Sergios Gatidis

All Publications

• Results from the autoPET challenge on fully automated lesion segmentation in oncologic PET/CT imaging NATURE MACHINE INTELLIGENCE Gatidis, S., Frueh, M., Fabritius, M. P., Gu, S., Nikolaou, K., La Fougere, C., Ye, J., He, J., Peng, Y., Bi, L., Ma, J., Wang, B., Zhang, J., Huang, Y., Heiliger, L., Marinov, Z., Stiefelhagen, R., Egger, J., Kleesiek, J., Sibille, L., Xiang, L., Bendazzoli, S., Astaraki, M., Ingrisch, M., Cyran, C. C., Kuestner, T. 2024

  View details for DOI 10.1038/s42256-024-00912-9

  View details for Web of Science ID 001344986700001

• Tumour-informed liquid biopsies to monitor advanced melanoma patients under immune checkpoint inhibition NATURE COMMUNICATIONS Schroeder, C., Gatidis, S., Kelemen, O., Schuetz, L., Bonzheim, I., Muyas, F., Martus, P., Admard, J., Armeanu-Ebinger, S., Gueckel, B., Kuestner, T., Garbe, C., Flatz, L., Pfannenberg, C., Ossowski, S., Forschner, A. 2024; 15 (1): 8750

  Abstract

  Immune checkpoint inhibitors (ICI) have significantly improved overall survival in melanoma patients. However, 60% experience severe adverse events and early response markers are lacking. Circulating tumour DNA (ctDNA) is a promising biomarker for treatment-response and recurrence detection. The prospective PET/LIT study included 104 patients with palliative combined or adjuvant ICI. Tumour-informed sequencing panels to monitor 30 patient-specific variants were designed and 321 liquid biopsies of 87 patients sequenced. Mean sequencing depth after deduplication using UMIs was 6000x and the error rate of UMI-corrected reads was 2.47×10-4. Variant allele fractions correlated with PET/CT MTV (rho=0.69), S100 (rho=0.72), and LDH (rho=0.54). A decrease of allele fractions between T1 and T2 was associated with improved PFS and OS in the palliative cohort (p = 0.008 and p < 0.001). ctDNA was detected in 76.9% of adjuvant patients with relapse (n = 10/13), while all patients without progression (n = 9) remained ctDNA negative. Tumour-informed liquid biopsies are a reliable tool for monitoring treatment response and early relapse in melanoma patients with ICI.

  View details for DOI 10.1038/s41467-024-52923-0

  View details for Web of Science ID 001335963600013

  View details for PubMedID 39384805

  View details for PubMedCentralID PMC11464631

• Attention-Aware Non-Rigid Image Registration for Accelerated MR Imaging. IEEE transactions on medical imaging Ghoul, A., Pan, J., Lingg, A., Kubler, J., Krumm, P., Hammernik, K., Rueckert, D., Gatidis, S., Kustner, T. 2024; 43 (8): 3013-3026

  Abstract

  Accurate motion estimation at high acceleration factors enables rapid motion-compensated reconstruction in Magnetic Resonance Imaging (MRI) without compromising the diagnostic image quality. In this work, we introduce an attention-aware deep learning-based framework that can perform non-rigid pairwise registration for fully sampled and accelerated MRI. We extract local visual representations to build similarity maps between the registered image pairs at multiple resolution levels and additionally leverage long-range contextual information using a transformer-based module to alleviate ambiguities in the presence of artifacts caused by undersampling. We combine local and global dependencies to perform simultaneous coarse and fine motion estimation. The proposed method was evaluated on in-house acquired fully sampled and accelerated data of 101 patients and 62 healthy subjects undergoing cardiac and thoracic MRI. The impact of motion estimation accuracy on the downstream task of motion-compensated reconstruction was analyzed. We demonstrate that our model derives reliable and consistent motion fields across different sampling trajectories (Cartesian and radial) and acceleration factors of up to 16x for cardiac motion and 30x for respiratory motion and achieves superior image quality in motion-compensated reconstruction qualitatively and quantitatively compared to conventional and recent deep learning-based approaches. The code is publicly available at https://github.com/lab-midas/GMARAFT.

  View details for DOI 10.1109/TMI.2024.3385024

  View details for PubMedID 39088484

• Merlin: A Vision Language Foundation Model for 3D Computed Tomography. Research square Blankemeier, L., Cohen, J. P., Kumar, A., Veen, D. V., Gardezi, S., Paschali, M., Chen, Z., Delbrouck, J. B., Reis, E., Truyts, C., Bluethgen, C., Jensen, M., Ostmeier, S., Varma, M., Valanarasu, J., Fang, Z., Huo, Z., Nabulsi, Z., Ardila, D., Weng, W. H., Junior, E. A., Ahuja, N., Fries, J., Shah, N., Johnston, A., Boutin, R., Wentland, A., Langlotz, C., Hom, J., Gatidis, S., Chaudhari, A. 2024

  Abstract

  Over 85 million computed tomography (CT) scans are performed annually in the US, of which approximately one quarter focus on the abdomen. Given the current shortage of both general and specialized radiologists, there is a large impetus to use artificial intelligence to alleviate the burden of interpreting these complex imaging studies while simultaneously using the images to extract novel physiological insights. Prior state-of-the-art approaches for automated medical image interpretation leverage vision language models (VLMs) that utilize both the image and the corresponding textual radiology reports. However, current medical VLMs are generally limited to 2D images and short reports. To overcome these shortcomings for abdominal CT interpretation, we introduce Merlin - a 3D VLM that leverages both structured electronic health records (EHR) and unstructured radiology reports for pretraining without requiring additional manual annotations. We train Merlin using a high-quality clinical dataset of paired CT scans (6+ million images from 15,331 CTs), EHR diagnosis codes (1.8+ million codes), and radiology reports (6+ million tokens) for training. We comprehensively evaluate Merlin on 6 task types and 752 individual tasks. The non-adapted (off-the-shelf) tasks include zero-shot findings classification (31 findings), phenotype classification (692 phenotypes), and zero-shot cross-modal retrieval (image to findings and image to impressions), while model adapted tasks include 5-year chronic disease prediction (6 diseases), radiology report generation, and 3D semantic segmentation (20 organs). We perform internal validation on a test set of 5,137 CTs, and external validation on 7,000 clinical CTs and on two public CT datasets (VerSe, TotalSegmentator). Beyond these clinically-relevant evaluations, we assess the efficacy of various network architectures and training strategies to depict that Merlin has favorable performance to existing task-specific baselines. We derive data scaling laws to empirically assess training data needs for requisite downstream task performance. Furthermore, unlike conventional VLMs that require hundreds of GPUs for training, we perform all training on a single GPU. This computationally efficient design can help democratize foundation model training, especially for health systems with compute constraints. We plan to release our trained models, code, and dataset, pending manual removal of all protected health information.

  View details for DOI 10.21203/rs.3.rs-4546309/v1

  View details for PubMedID 38978576

  View details for PubMedCentralID PMC11230513

• Applications of Artificial Intelligence for Pediatric Cancer Imaging. AJR. American journal of roentgenology Singh, S. B., Sarrami, A. H., Gatidis, S., Varniab, Z. S., Chaudhari, A., Daldrup-Link, H. E. 2024

  Abstract

  Artificial intelligence (AI) is transforming medical imaging of adult patients. However, its utilization in pediatric oncology imaging remains constrained, in part due to the inherent data scarcity associated with childhood cancers. Pediatric cancers are rare, and imaging technologies are evolving rapidly, leading to insufficient data of a particular type to effectively train these algorithms. The small market size of pediatrics compared to adults could also contribute to this challenge, as market size is a driver of commercialization. This article provides an overview of the current state of AI applications for pediatric cancer imaging, including applications for medical image acquisition, processing, reconstruction, segmentation, diagnosis, staging, and treatment response monitoring. While current developments are promising, impediments due to diverse anatomies of growing children and nonstandardized imaging protocols have led to limited clinical translation thus far. Opportunities include leveraging reconstruction algorithms to achieve accelerated low-dose imaging and automating the generation of metric-based staging and treatment monitoring scores. Transfer-learning of adult-based AI models to pediatric cancers, multi-institutional data sharing, and ethical data privacy practices for pediatric patients with rare cancers will be keys to unlocking AI's full potential for clinical translation and improved outcomes for these young patients.

  View details for DOI 10.2214/AJR.24.31076

  View details for PubMedID 38809123

• Adapted large language models can outperform medical experts in clinical text summarization. Nature medicine Van Veen, D., Van Uden, C., Blankemeier, L., Delbrouck, J. B., Aali, A., Bluethgen, C., Pareek, A., Polacin, M., Reis, E. P., Seehofnerová, A., Rohatgi, N., Hosamani, P., Collins, W., Ahuja, N., Langlotz, C. P., Hom, J., Gatidis, S., Pauly, J., Chaudhari, A. S. 2024

  Abstract

  Analyzing vast textual data and summarizing key information from electronic health records imposes a substantial burden on how clinicians allocate their time. Although large language models (LLMs) have shown promise in natural language processing (NLP) tasks, their effectiveness on a diverse range of clinical summarization tasks remains unproven. Here we applied adaptation methods to eight LLMs, spanning four distinct clinical summarization tasks: radiology reports, patient questions, progress notes and doctor-patient dialogue. Quantitative assessments with syntactic, semantic and conceptual NLP metrics reveal trade-offs between models and adaptation methods. A clinical reader study with 10 physicians evaluated summary completeness, correctness and conciseness; in most cases, summaries from our best-adapted LLMs were deemed either equivalent (45%) or superior (36%) compared with summaries from medical experts. The ensuing safety analysis highlights challenges faced by both LLMs and medical experts, as we connect errors to potential medical harm and categorize types of fabricated information. Our research provides evidence of LLMs outperforming medical experts in clinical text summarization across multiple tasks. This suggests that integrating LLMs into clinical workflows could alleviate documentation burden, allowing clinicians to focus more on patient care.

  View details for DOI 10.1038/s41591-024-02855-5

  View details for PubMedID 38413730

  View details for PubMedCentralID 5593724

• Pre-treatment 18F-FDG-PET/CT parameters as biomarkers for progression free survival, best overall response and overall survival in metastatic melanoma patients undergoing first-line immunotherapy PLOS ONE Peisen, F., Gerken, A., Dahm, I., Nikolaou, K., Eigentler, T., Amaral, T., Moltz, J. H., Othman, A. E., Gatidis, S., Dondi, F. 2024; 19 (1): e0296253

  Abstract

  Checkpoint inhibitors have drastically improved the therapy of patients with advanced melanoma. 18F-FDG-PET/CT parameters might act as biomarkers for response and survival and thus can identify patients that do not benefit from immunotherapy. However, little literature exists on the association of baseline 18F-FDG-PET/CT parameters with progression free survival (PFS), best overall response (BOR), and overall survival (OS).Using a whole tumor volume segmentation approach, we investigated in a retrospective registry study (n = 50) whether pre-treatment 18F-FDG-PET/CT parameters of three subgroups (tumor burden, tumor glucose uptake and non-tumoral hematopoietic tissue metabolism), can act as biomarkers for the primary endpoints PFS and BOR as well as for the secondary endpoint OS.Compared to the sole use of clinical parameters, baseline 18F-FDG-PET/CT parameters did not significantly improve a Cox proportional-hazard model for PFS (C-index/AIC: 0.70/225.17 and 0.68/223.54, respectively; p = 0.14). A binomial logistic regression analysis for BOR was not statistically significant (χ2(15) = 16.44, p = 0.35), with a low amount of explained variance (Nagelkerke's R2 = 0.38). Mean FDG uptake of the spleen contributed significantly to a Cox proportional-hazard model for OS (HR 3.55, p = 0.04).The present study could not confirm the capability of the pre-treatment 18F-FDG-PET/CT parameters tumor burden, tumor glucose uptake and non-tumoral hematopoietic tissue metabolism to act as biomarkers for PFS and BOR in metastatic melanoma patients receiving first-line immunotherapy. The documented potential of 18F-FDG uptake by immune-mediating tissues such as the spleen to act as a biomarker for OS has been reproduced.

  View details for DOI 10.1371/journal.pone.0296253

  View details for Web of Science ID 001153716700043

  View details for PubMedID 38180971

  View details for PubMedCentralID PMC10769042

• MEDALIGN: A Clinician-Generated Dataset for Instruction Following with Electronic Medical Records Fleming, S. L., Lozano, A., Haberkorn, W. J., Jindal, J. A., Reis, E., Thapa, R., Blankemeier, L., Genkins, J. Z., Steinberg, E., Nayak, A., Patel, B., Chiang, C., Callahan, A., Huo, Z., Gatidis, S., Adams, S., Fayanju, O., Shah, S. J., Savage, T., Goh, E., Chaudhari, A. S., Aghaeepour, N., Sharp, C., Pfeffer, M. A., Liang, P., Chen, J. H., Morse, K. E., Brunskill, E. P., Fries, J. A., Shah, N. H., Wooldridge, M., Dy, J., Natarajan, S. ASSOC ADVANCEMENT ARTIFICIAL INTELLIGENCE. 2024: 22021-22030

  View details for Web of Science ID 001239985800017

• Deep learning-based age estimation from clinical Computed Tomography image data of the thorax and abdomen in the adult population PLOS ONE Kerber, B., Hepp, T., Kuestner, T., Gatidis, S. 2023; 18 (11): e0292993

  Abstract

  Aging is an important risk factor for disease, leading to morphological change that can be assessed on Computed Tomography (CT) scans. We propose a deep learning model for automated age estimation based on CT- scans of the thorax and abdomen generated in a clinical routine setting. These predictions could serve as imaging biomarkers to estimate a "biological" age, that better reflects a patient's true physical condition. A pre-trained ResNet-18 model was modified to predict chronological age as well as to quantify its aleatoric uncertainty. The model was trained using 1653 non-pathological CT-scans of the thorax and abdomen of subjects aged between 20 and 85 years in a 5-fold cross-validation scheme. Generalization performance as well as robustness and reliability was assessed on a publicly available test dataset consisting of thorax-abdomen CT-scans of 421 subjects. Score-CAM saliency maps were generated for interpretation of model outputs. We achieved a mean absolute error of 5.76 ± 5.17 years with a mean uncertainty of 5.01 ± 1.44 years after 5-fold cross-validation. A mean absolute error of 6.50 ± 5.17 years with a mean uncertainty of 6.39 ± 1.46 years was obtained on the test dataset. CT-based age estimation accuracy was largely uniform across all age groups and between male and female subjects. The generated saliency maps highlighted especially the lumbar spine and abdominal aorta. This study demonstrates, that accurate and generalizable deep learning-based automated age estimation is feasible using clinical CT image data. The trained model proved to be robust and reliable. Methods of uncertainty estimation and saliency analysis improved the interpretability.

  View details for DOI 10.1371/journal.pone.0292993

  View details for Web of Science ID 001137006300001

  View details for PubMedID 37934735

  View details for PubMedCentralID PMC10629654

• Clinical Text Summarization: Adapting Large Language Models Can Outperform Human Experts. Research square Veen, D. V., Uden, C. V., Blankemeier, L., Delbrouck, J. B., Aali, A., Bluethgen, C., Pareek, A., Polacin, M., Reis, E. P., Seehofnerova, A., Rohatgi, N., Hosamani, P., Collins, W., Ahuja, N., Langlotz, C., Hom, J., Gatidis, S., Pauly, J., Chaudhari, A. 2023

  Abstract

  Sifting through vast textual data and summarizing key information from electronic health records (EHR) imposes a substantial burden on how clinicians allocate their time. Although large language models (LLMs) have shown immense promise in natural language processing (NLP) tasks, their efficacy on a diverse range of clinical summarization tasks has not yet been rigorously demonstrated. In this work, we apply domain adaptation methods to eight LLMs, spanning six datasets and four distinct clinical summarization tasks: radiology reports, patient questions, progress notes, and doctor-patient dialogue. Our thorough quantitative assessment reveals trade-offs between models and adaptation methods in addition to instances where recent advances in LLMs may not improve results. Further, in a clinical reader study with ten physicians, we show that summaries from our best-adapted LLMs are preferable to human summaries in terms of completeness and correctness. Our ensuing qualitative analysis highlights challenges faced by both LLMs and human experts. Lastly, we correlate traditional quantitative NLP metrics with reader study scores to enhance our understanding of how these metrics align with physician preferences. Our research marks the first evidence of LLMs outperforming human experts in clinical text summarization across multiple tasks. This implies that integrating LLMs into clinical workflows could alleviate documentation burden, empowering clinicians to focus more on personalized patient care and the inherently human aspects of medicine.

  View details for DOI 10.21203/rs.3.rs-3483777/v1

  View details for PubMedID 37961377

  View details for PubMedCentralID PMC10635391

• Can Whole-Body Baseline CT Radiomics Add Information to the Prediction of Best Response, Progression-Free Survival, and Overall Survival of Stage IV Melanoma Patients Receiving First-Line Targeted Therapy: A Retrospective Register Study DIAGNOSTICS Peisen, F., Gerken, A., Hering, A., Dahm, I., Nikolaou, K., Gatidis, S., Eigentler, T. K., Amaral, T., Moltz, J. H., Othman, A. E. 2023; 13 (20)

  Abstract

  The aim of this study was to investigate whether the combination of radiomics and clinical parameters in a machine-learning model offers additive information compared with the use of only clinical parameters in predicting the best response, progression-free survival after six months, as well as overall survival after six and twelve months in patients with stage IV malignant melanoma undergoing first-line targeted therapy.A baseline machine-learning model using clinical variables (demographic parameters and tumor markers) was compared with an extended model using clinical variables and radiomic features of the whole tumor burden, utilizing repeated five-fold cross-validation. Baseline CTs of 91 stage IV malignant melanoma patients, all treated in the same university hospital, were identified in the Central Malignant Melanoma Registry and all metastases were volumetrically segmented (n = 4727).Compared with the baseline model, the extended radiomics model did not add significantly more information to the best-response prediction (AUC [95% CI] 0.548 (0.188, 0.808) vs. 0.487 (0.139, 0.743)), the prediction of PFS after six months (AUC [95% CI] 0.699 (0.436, 0.958) vs. 0.604 (0.373, 0.867)), or the overall survival prediction after six and twelve months (AUC [95% CI] 0.685 (0.188, 0.967) vs. 0.766 (0.433, 1.000) and AUC [95% CI] 0.554 (0.163, 0.781) vs. 0.616 (0.271, 1.000), respectively).The results showed no additional value of baseline whole-body CT radiomics for best-response prediction, progression-free survival prediction for six months, or six-month and twelve-month overall survival prediction for stage IV melanoma patients receiving first-line targeted therapy. These results need to be validated in a larger cohort.

  View details for DOI 10.3390/diagnostics13203210

  View details for Web of Science ID 001094012400001

  View details for PubMedID 37892030

  View details for PubMedCentralID PMC10605712

• Quantification of intratumoural heterogeneity in mice and patients via machine-learning models trained on PET-MRI data NATURE BIOMEDICAL ENGINEERING Katiyar, P., Schwenck, J., Frauenfeld, L., Divine, M. R., Agrawal, V., Kohlhofer, U., Gatidis, S., Kontermann, R., Koenigsrainer, A., Quintanilla-Martinez, L., la Fougere, C., Schoelkopf, B., Pichler, B. J., Disselhorst, J. A. 2023

  Abstract

  In oncology, intratumoural heterogeneity is closely linked with the efficacy of therapy, and can be partially characterized via tumour biopsies. Here we show that intratumoural heterogeneity can be characterized spatially via phenotype-specific, multi-view learning classifiers trained with data from dynamic positron emission tomography (PET) and multiparametric magnetic resonance imaging (MRI). Classifiers trained with PET-MRI data from mice with subcutaneous colon cancer quantified phenotypic changes resulting from an apoptosis-inducing targeted therapeutic and provided biologically relevant probability maps of tumour-tissue subtypes. When applied to retrospective PET-MRI data of patients with liver metastases from colorectal cancer, the trained classifiers characterized intratumoural tissue subregions in agreement with tumour histology. The spatial characterization of intratumoural heterogeneity in mice and patients via multimodal, multiparametric imaging aided by machine-learning may facilitate applications in precision oncology.

  View details for DOI 10.1038/s41551-023-01047-9

  View details for Web of Science ID 001000747500001

  View details for PubMedID 37277483

  View details for PubMedCentralID 5378302

• AI Transformers for Radiation Dose Reduction in Serial Whole-Body PET Scans. Radiology. Artificial intelligence Wang, Y. J., Qu, L., Sheybani, N. D., Luo, X., Wang, J., Hawk, K. E., Theruvath, A. J., Gatidis, S., Xiao, X., Pribnow, A., Rubin, D., Daldrup-Link, H. E. 2023; 5 (3): e220246

  Abstract

  To develop a deep learning approach that enables ultra-low-dose, 1% of the standard clinical dosage (3 MBq/kg), ultrafast whole-body PET reconstruction in cancer imaging.In this Health Insurance Portability and Accountability Act-compliant study, serial fluorine 18-labeled fluorodeoxyglucose PET/MRI scans of pediatric patients with lymphoma were retrospectively collected from two cross-continental medical centers between July 2015 and March 2020. Global similarity between baseline and follow-up scans was used to develop Masked-LMCTrans, a longitudinal multimodality coattentional convolutional neural network (CNN) transformer that provides interaction and joint reasoning between serial PET/MRI scans from the same patient. Image quality of the reconstructed ultra-low-dose PET was evaluated in comparison with a simulated standard 1% PET image. The performance of Masked-LMCTrans was compared with that of CNNs with pure convolution operations (classic U-Net family), and the effect of different CNN encoders on feature representation was assessed. Statistical differences in the structural similarity index measure (SSIM), peak signal-to-noise ratio (PSNR), and visual information fidelity (VIF) were assessed by two-sample testing with the Wilcoxon signed rank t test.The study included 21 patients (mean age, 15 years ± 7 [SD]; 12 female) in the primary cohort and 10 patients (mean age, 13 years ± 4; six female) in the external test cohort. Masked-LMCTrans-reconstructed follow-up PET images demonstrated significantly less noise and more detailed structure compared with simulated 1% extremely ultra-low-dose PET images. SSIM, PSNR, and VIF were significantly higher for Masked-LMCTrans-reconstructed PET (P < .001), with improvements of 15.8%, 23.4%, and 186%, respectively.Masked-LMCTrans achieved high image quality reconstruction of 1% low-dose whole-body PET images.Keywords: Pediatrics, PET, Convolutional Neural Network (CNN), Dose Reduction Supplemental material is available for this article. © RSNA, 2023.

  View details for DOI 10.1148/ryai.220246

  View details for PubMedID 37293349

  View details for PubMedCentralID PMC10245181

• Local control and patient reported outcomes after online MR guided stereotactic body radiotherapy of liver metastases FRONTIERS IN ONCOLOGY Uder, L., Nachbar, M., Butzer, S., Boldt, J., Baumeister, S., Bitzer, M., Koenigsrainer, A., Seufferlein, T., Hoffmann, R., Gatidis, S., Nikolaou, K., Zips, D., Thorwarth, D., Gani, C., Boeke, S. 2023; 12: 1095633

  Abstract

  Stereotactic body radiotherapy (SBRT) is used to treat liver metastases with the intention of ablation. High local control rates were shown. Magnetic resonance imaging guided radiotherapy (MRgRT) provides the opportunity of a marker-less liver SBRT treatment due to the high soft tissue contrast. We report herein on one of the largest cohorts of patients treated with online MRgRT of liver metastases focusing on oncological outcome, toxicity, patient reported outcome measures (PROMs), quality of life.Patients treated for liver metastases with online MR-guided SBRT at a 1,5 T MR-Linac (Unity, Elekta, Crawley, UK) between March 2019 and December 2021 were included in this prospective study. UK SABR guidelines were used for organs at risk constraints. Oncological endpoints such as survival parameters (overall survival, progression-free survival) and local control as well as patient reported acceptance and quality of life data (EORTC QLQ-C30 questionnaire) were assessed. For toxicity scoring the Common Toxicity Criteria Version 5 were used.A total of 51 patients with 74 metastases were treated with a median of five fractions. The median applied BED GTV D98 was 84,1 Gy. Median follow-up was 15 months. Local control of the irradiated liver metastasis after 12 months was 89,6%, local control of the liver was 40,3%. Overall survival (OS) after 12 months was 85.1%. Progression free survival (PFS) after 12 months was 22,4%. Local control of the irradiated liver lesion was 100% after three years when a BED ≥100 Gy was reached. The number of treated lesions did not impact local control neither of the treated or of the hepatic control. Patient acceptance of online MRgSBRT was high. There were no acute grade ≥ 3 toxicities. Quality of life data showed no significant difference comparing baseline and follow-up data.Online MR guided radiotherapy is a noninvasive, well-tolerated and effective treatment for liver metastases. Further prospective trials with the goal to define patients who actually benefit most from an online adaptive workflow are currently ongoing.

  View details for DOI 10.3389/fonc.2022.1095633

  View details for Web of Science ID 000921644400001

  View details for PubMedID 36727060

  View details for PubMedCentralID PMC9885175

• Low-count whole-body PET/MRI restoration: an evaluation of dose reduction spectrum and five state-of-the-art artificial intelligence models. European journal of nuclear medicine and molecular imaging Wang, Y. J., Wang, P., Adams, L. C., Sheybani, N. D., Qu, L., Sarrami, A. H., Theruvath, A. J., Gatidis, S., Ho, T., Zhou, Q., Pribnow, A., Thakor, A. S., Rubin, D., Daldrup-Link, H. E. 2023

  Abstract

  To provide a holistic and complete comparison of the five most advanced AI models in the augmentation of low-dose 18F-FDG PET data over the entire dose reduction spectrum.In this multicenter study, five AI models were investigated for restoring low-count whole-body PET/MRI, covering convolutional benchmarks - U-Net, enhanced deep super-resolution network (EDSR), generative adversarial network (GAN) - and the most cutting-edge image reconstruction transformer models in computer vision to date - Swin transformer image restoration network (SwinIR) and EDSR-ViT (vision transformer). The models were evaluated against six groups of count levels representing the simulated 75%, 50%, 25%, 12.5%, 6.25%, and 1% (extremely ultra-low-count) of the clinical standard 3 MBq/kg 18F-FDG dose. The comparisons were performed upon two independent cohorts - (1) a primary cohort from Stanford University and (2) a cross-continental external validation cohort from Tübingen University - in order to ensure the findings are generalizable. A total of 476 original count and simulated low-count whole-body PET/MRI scans were incorporated into this analysis.For low-count PET restoration on the primary cohort, the mean structural similarity index (SSIM) scores for dose 6.25% were 0.898 (95% CI, 0.887-0.910) for EDSR, 0.893 (0.881-0.905) for EDSR-ViT, 0.873 (0.859-0.887) for GAN, 0.885 (0.873-0.898) for U-Net, and 0.910 (0.900-0.920) for SwinIR. In continuation, SwinIR and U-Net's performances were also discreetly evaluated at each simulated radiotracer dose levels. Using the primary Stanford cohort, the mean diagnostic image quality (DIQ; 5-point Likert scale) scores of SwinIR restoration were 5 (SD, 0) for dose 75%, 4.50 (0.535) for dose 50%, 3.75 (0.463) for dose 25%, 3.25 (0.463) for dose 12.5%, 4 (0.926) for dose 6.25%, and 2.5 (0.534) for dose 1%.Compared to low-count PET images, with near-to or nondiagnostic images at higher dose reduction levels (up to 6.25%), both SwinIR and U-Net significantly improve the diagnostic quality of PET images. A radiotracer dose reduction to 1% of the current clinical standard radiotracer dose is out of scope for current AI techniques.

  View details for DOI 10.1007/s00259-022-06097-w

  View details for PubMedID 36633614

• Self-supervised contrastive learning with random walks for medical image segmentation with limited annotations COMPUTERIZED MEDICAL IMAGING AND GRAPHICS Fischer, M., Hepp, T., Gatidis, S., Yang, B. 2023; 104: 102174

  Abstract

  Medical image segmentation has seen significant progress through the use of supervised deep learning. Hereby, large annotated datasets were employed to reliably segment anatomical structures. To reduce the requirement for annotated training data, self-supervised pre-training strategies on non-annotated data were designed. Especially contrastive learning schemes operating on dense pixel-wise representations have been introduced as an effective tool. In this work, we expand on this strategy and leverage inherent anatomical similarities in medical imaging data. We apply our approach to the task of semantic segmentation in a semi-supervised setting with limited amounts of annotated volumes. Trained alongside a segmentation loss in one single training stage, a contrastive loss aids to differentiate between salient anatomical regions that conform to the available annotations. Our approach builds upon the work of Jabri et al. (2020), who proposed cyclical contrastive random walks (CCRW) for self-supervision on palindromes of video frames. We adapt this scheme to operate on entries of paired embedded image slices. Using paths of cyclical random walks bypasses the need for negative samples, as commonly used in contrastive approaches, enabling the algorithm to discriminate among relevant salient (anatomical) regions implicitly. Further, a multi-level supervision strategy is employed, ensuring adequate representations of local and global characteristics of anatomical structures. The effectiveness of reducing the amount of required annotations is shown on three MRI datasets. A median increase of 8.01 and 5.90 pp in the Dice Similarity Coefficient (DSC) compared to our baseline could be achieved across all three datasets in the case of one and two available annotated examples per dataset.

  View details for DOI 10.1016/j.compmedimag.2022.102174

  View details for Web of Science ID 000923565500001

  View details for PubMedID 36640485

• Avoiding Shortcut-Learning by Mutual Information Minimization in Deep Learning-Based Image Processing IEEE ACCESS Fay, L., Cobos, E., Yang, B., Gatidis, S., Kuestner, T. 2023; 11: 64070-64086

  View details for DOI 10.1109/ACCESS.2023.3289397

  View details for Web of Science ID 001021944100001

• Impact of endorectal filling on interobserver variability of MRI based rectal primary tumor delineation CLINICAL AND TRANSLATIONAL RADIATION ONCOLOGY Lo Russo, M., Nachbar, M., Barry, A., Bhide, S., Chang, A., Hall, W., Intven, M., Marijnen, C., Peters, F., Minsky, B., Romesser, P. B., Sarkar, R., Tan, A., Boeke, S., Wegener, D., Butzer, S., Boldt, J., Gatidis, S., Nikolaou, K., Thorwarth, D., Zips, D., Gani, C. 2023; 38: 1-5

  Abstract

  Online adaptive MR-guided radiotherapy allows for the reduction of safety margins in dose escalated treatment of rectal tumors. With the use of smaller margins, precise tumor delineation becomes more critical. In the present study we investigated the impact of rectal ultrasound gel filling on interobserver variability in delineation of primary rectal tumor volumes.Six patients with locally advanced rectal cancer were scanned on a 1.5 T MRI-Linac without (MRI_e) and with application of 100 cc of ultrasound gel transanally (MRI_f). Eight international radiation oncologists expert in the treatment of gastrointestinal cancers delineated the gross tumor volume (GTV) on both MRI scans. MRI_f scans were provided to the participating centers after MRI_e scans had been returned. Interobserver variability was analyzed by either comparing the observers' delineations with a reference delineation (approach 1) and by building all possible pairs between observers (approach 2). Dice Similarity Index (DICE) and 95 % Hausdorff-Distance (95 %HD) were calculated.Rectal ultrasound gel filling was well tolerated by all patients. Overall, interobserver agreement was superior in MRI_f scans based on median DICE (0.81 vs 0.74, p < 0.005 for approach 1 and 0.76 vs 0.64, p < 0.0001 for approach 2) and 95 %HD (6.9 mm vs 4.2 mm for approach 1, p = 0.04 and 8.9 mm vs 6.1 mm, p = 0.04 for approach 2). Delineated median tumor volumes and inter-quartile ranges were 26.99 cc [18.01-50.34 cc] in MRI_e and 44.20 [19.72-61.59 cc] in MRI_f scans respectively, p = 0.012.Although limited by the small number of patients, in this study the application of rectal ultrasound gel resulted in higher interobserver agreement in rectal GTV delineation. The endorectal gel filling might be a useful tool for future dose escalation strategies.

  View details for DOI 10.1016/j.ctro.2022.09.002

  View details for Web of Science ID 000927150300001

  View details for PubMedID 36299279

  View details for PubMedCentralID PMC9589000

• A whole-body FDG-PET/CT Dataset with manually annotated Tumor Lesions. Scientific data Gatidis, S., Hepp, T., Fruh, M., La Fougere, C., Nikolaou, K., Pfannenberg, C., Scholkopf, B., Kustner, T., Cyran, C., Rubin, D. 2022; 9 (1): 601

  Abstract

  We describe a publicly available dataset of annotated Positron Emission Tomography/Computed Tomography (PET/CT) studies. 1014 whole body Fluorodeoxyglucose (FDG)-PET/CT datasets (501 studies of patients with malignant lymphoma, melanoma and non small cell lung cancer (NSCLC) and 513 studies without PET-positive malignant lesions (negative controls)) acquired between 2014 and 2018 were included. All examinations were acquired on a single, state-of-the-art PET/CT scanner. The imaging protocol consisted of a whole-body FDG-PET acquisition and a corresponding diagnostic CT scan. All FDG-avid lesions identified as malignant based on the clinical PET/CT report were manually segmented on PET images in a slice-per-slice (3D) manner. We provide the anonymized original DICOM files of all studies as well as the corresponding DICOM segmentation masks. In addition, we provide scripts for image processing and conversion to different file formats (NIfTI, mha, hdf5). Primary diagnosis, age and sex are provided as non-imaging information. We demonstrate how this dataset can be used for deep learning-based automated analysis of PET/CT data and provide the trained deep learning model.

  View details for DOI 10.1038/s41597-022-01718-3

  View details for PubMedID 36195599

• Standardised lesion segmentation for imaging biomarker quantitation: a consensus recommendation from ESR and EORTC INSIGHTS INTO IMAGING DeSouza, N. M., van Der Lugt, A., Deroose, C. M., Alberich-Bayarri, A., Bidaut, L., Fournier, L., Costaridou, L., Oprea-Lager, D. E., Kotter, E., Smits, M., Mayerhoefer, M. E., Boellaard, R., Caroli, A., De Geus-Oei, L., Kunz, W. G., Oei, E. H., Lecouvet, F., Franca, M., Loewe, C., Lopci, E., Caramella, C., Persson, A., Golay, X., Dewey, M., O'Connor, J. B., DeGraaf, P., Gatidis, S., Zahlmann, G., European Soc Radiology, European Org Res Treatment Canc 2022; 13 (1): 159

  Abstract

  Lesion/tissue segmentation on digital medical images enables biomarker extraction, image-guided therapy delivery, treatment response measurement, and training/validation for developing artificial intelligence algorithms and workflows. To ensure data reproducibility, criteria for standardised segmentation are critical but currently unavailable.A modified Delphi process initiated by the European Imaging Biomarker Alliance (EIBALL) of the European Society of Radiology (ESR) and the European Organisation for Research and Treatment of Cancer (EORTC) Imaging Group was undertaken. Three multidisciplinary task forces addressed modality and image acquisition, segmentation methodology itself, and standards and logistics. Devised survey questions were fed via a facilitator to expert participants. The 58 respondents to Round 1 were invited to participate in Rounds 2-4. Subsequent rounds were informed by responses of previous rounds.Items with ≥ 75% consensus are considered a recommendation. These include system performance certification, thresholds for image signal-to-noise, contrast-to-noise and tumour-to-background ratios, spatial resolution, and artefact levels. Direct, iterative, and machine or deep learning reconstruction methods, use of a mixture of CE marked and verified research tools were agreed and use of specified reference standards and validation processes considered essential. Operator training and refreshment were considered mandatory for clinical trials and clinical research. Items with a 60-74% agreement require reporting (site-specific accreditation for clinical research, minimal pixel number within lesion segmented, use of post-reconstruction algorithms, operator training refreshment for clinical practice). Items with ≤ 60% agreement are outside current recommendations for segmentation (frequency of system performance tests, use of only CE-marked tools, board certification of operators, frequency of operator refresher training). Recommendations by anatomical area are also specified.

  View details for DOI 10.1186/s13244-022-01287-4

  View details for Web of Science ID 000863839900001

  View details for PubMedID 36194301

  View details for PubMedCentralID PMC9532485

• Artificial Intelligence in Oncological Hybrid Imaging ROFO-FORTSCHRITTE AUF DEM GEBIET DER RONTGENSTRAHLEN UND DER BILDGEBENDEN VERFAHREN Feuerecker, B., Heimer, M. M., Geyer, T., Fabritius, M. P., Gu, S., Schachtner, B., Beyer, L., Ricke, J., Gatidis, S., Ingrisch, M., Cyran, C. C. 2023; 195 (02): 105-114

  Abstract

  Artificial intelligence (AI) applications have become increasingly relevant across a broad spectrum of settings in medical imaging. Due to the large amount of imaging data that is generated in oncological hybrid imaging, AI applications are desirable for lesion detection and characterization in primary staging, therapy monitoring, and recurrence detection. Given the rapid developments in machine learning (ML) and deep learning (DL) methods, the role of AI will have significant impact on the imaging workflow and will eventually improve clinical decision making and outcomes.The first part of this narrative review discusses current research with an introduction to artificial intelligence in oncological hybrid imaging and key concepts in data science. The second part reviews relevant examples with a focus on applications in oncology as well as discussion of challenges and current limitations.AI applications have the potential to leverage the diagnostic data stream with high efficiency and depth to facilitate automated lesion detection, characterization, and therapy monitoring to ultimately improve quality and efficiency throughout the medical imaging workflow. The goal is to generate reproducible, structured, quantitative diagnostic data for evidence-based therapy guidance in oncology. However, significant challenges remain regarding application development, benchmarking, and clinical implementation.· Hybrid imaging generates a large amount of multimodality medical imaging data with high complexity and depth.. · Advanced tools are required to enable fast and cost-efficient processing along the whole radiology value chain.. · AI applications promise to facilitate the assessment of oncological disease in hybrid imaging with high quality and efficiency for lesion detection, characterization, and response assessment. The goal is to generate reproducible, structured, quantitative diagnostic data for evidence-based oncological therapy guidance.. · Selected applications in three oncological entities (lung, prostate, and neuroendocrine tumors) demonstrate how AI algorithms may impact imaging-based tasks in hybrid imaging and potentially guide clinical decision making..· Feuerecker B, Heimer M, Geyer T et al. Artificial Intelligence in Oncological Hybrid Imaging. Fortschr Röntgenstr 2023; 195: 105 - 114.

  View details for DOI 10.1055/a-1909-7013

  View details for Web of Science ID 000860856200002

  View details for PubMedID 36170852

• Antibody-Guided Molecular Imaging of Aspergillus Lung Infections in Leukemia Patients JOURNAL OF NUCLEAR MEDICINE Schwenck, J., Maurer, A., Beziere, N., Fiz, F., Boschetti, F., Geistlich, S., Seyfried, D., Gunzer, M., Reischl, G., Wehrmueller, J., Ehrlichmann, W., Horger, M., Gatidis, S., Davies, G., Vogel, W., la Fougere, C., Pichler, B., Thornton, C. 2022; 63 (9): 1450-1451

  View details for DOI 10.2967/jnumed.121.263251

  View details for Web of Science ID 000859967100024

  View details for PubMedID 35863897

• Self-supervised learning for automated anatomical tracking in medical image data with minimal human labeling effort COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE Frueh, M., Kuestner, T., Nachbar, M., Thorwarth, D., Schilling, A., Gatidis, S. 2022; 225: 107085

  Abstract

  Tracking of anatomical structures in time-resolved medical image data plays an important role for various tasks such as volume change estimation or treatment planning. State-of-the-art deep learning techniques for automated tracking, while providing accurate results, require large amounts of human-labeled training data making their wide-spread use time- and resource-intensive. Our contribution in this work is the implementation and adaption of a self-supervised learning (SSL) framework that addresses this bottleneck of training data generation.To this end we adapted and implemented an SSL framework that allows for automated anatomical tracking without the necessity for human-labeled training data. We evaluated this method by comparison to conventional- and deep learning optical flow (OF)-based tracking methods. We applied all methods on three different time-resolved medical image datasets (abdominal MRI, cardiac MRI, and echocardiography) and assessed their accuracy regarding tracking of pre-defined anatomical structures within and across individuals.We found that SSL-based tracking as well as OF-based methods provide accurate results for simple, rigid and smooth motion patterns. However, regarding more complex motion, e.g. non-rigid or discontinuous motion patterns in the cardiac region, and for cross-subject anatomical matching, SSL-based tracking showed markedly superior performance.We conclude that automated tracking of anatomical structures on time-resolved medical image data with minimal human labeling effort is feasible using SSL and can provide superior results compared to conventional and deep learning OF-based methods.

  View details for DOI 10.1016/j.cmpb.2022.107085

  View details for Web of Science ID 000878991900011

  View details for PubMedID 36044801

• Combination of Whole-Body Baseline CT Radiomics and Clinical Parameters to Predict Response and Survival in a Stage-IV Melanoma Cohort Undergoing Immunotherapy CANCERS Peisen, F., Hansch, A., Hering, A., Brendlin, A. S., Afat, S., Nikolaou, K., Gatidis, S., Eigentler, T., Amaral, T., Moltz, J. H., Othman, A. E. 2022; 14 (12)

  Abstract

  This study investigated whether a machine-learning-based combination of radiomics and clinical parameters was superior to the use of clinical parameters alone in predicting therapy response after three months, and overall survival after six and twelve months, in stage-IV malignant melanoma patients undergoing immunotherapy with PD-1 checkpoint inhibitors and CTLA-4 checkpoint inhibitors.A random forest model using clinical parameters (demographic variables and tumor markers = baseline model) was compared to a random forest model using clinical parameters and radiomics (extended model) via repeated 5-fold cross-validation. For this purpose, the baseline computed tomographies of 262 stage-IV malignant melanoma patients treated at a tertiary referral center were identified in the Central Malignant Melanoma Registry, and all visible metastases were three-dimensionally segmented (n = 6404).The extended model was not significantly superior compared to the baseline model for survival prediction after six and twelve months (AUC (95% CI): 0.664 (0.598, 0.729) vs. 0.620 (0.545, 0.692) and AUC (95% CI): 0.600 (0.526, 0.667) vs. 0.588 (0.481, 0.629), respectively). The extended model was not significantly superior compared to the baseline model for response prediction after three months (AUC (95% CI): 0.641 (0.581, 0.700) vs. 0.656 (0.587, 0.719)).The study indicated a potential, but non-significant, added value of radiomics for six-month and twelve-month survival prediction of stage-IV melanoma patients undergoing immunotherapy.

  View details for DOI 10.3390/cancers14122992

  View details for Web of Science ID 000819643900001

  View details for PubMedID 35740659

  View details for PubMedCentralID PMC9221470

• 1.5T MR Linac for MR-guided stereotactic Radiotherapy of Patients with HCC: first clinical Results Uder, L., Boeke, S., Thorwarth, D., Nachbar, M., Butzer, S., Boldt, J., Bitzer, M., Koenigsrainer, A., Seufferlein, T., Hoffmann, R., Gatidis, S., Nikolaou, K., Gani, C., Zips, D. SPRINGER HEIDELBERG. 2022: S134

  View details for Web of Science ID 000791788000293

• Prospective Toxicity and Outcome Analysis after MR-guided stereotactic Radiotherapy (MRgSBRT) of Liver Metastases at 1.5 T MR Linac Uder, L., Boeke, S., Thorwarth, D., Nachbar, M., Butzer, S., Boldt, J., Bitzer, M., Koenigsrainer, A., Seufferlein, T., Hoffmann, R., Gatidis, S., Nikolaou, K., Gani, C., Zips, D. SPRINGER HEIDELBERG. 2022: S37-S38

  View details for Web of Science ID 000791788000070

• Inter-Observer Variability of MR-based Contouring of Rectal Cancer by MTAs compared to Radiation Oncologists Boldt, J., Gani, C., Boeke, S., Wegener, D., Russo, M. L., Nachbar, M., Moennich, D., Zips, D., Thorwarth, D., Gatidis, S., Nikolaou, K., Butzer, S. SPRINGER HEIDELBERG. 2022: S112

  View details for Web of Science ID 000791788000243

• Prediction of clinical Complete Remission by using functional MR Imaging during Chemoradiation in Rectal Cancer Russo, M. L., Nachbar, M., Boeke, S., Zips, D., Thorwarth, D., Gatidis, S., Nikolaou, K., Gani, C. SPRINGER HEIDELBERG. 2022: S58

  View details for Web of Science ID 000791788000113

• Interobserver Variability in Primary Tumor Contouring of Rectal Cancer to dose-escalated Radiotherapy Russo, M. L., Barry, A., Bhide, S., Chang, A., Hall, W., Intven, M., Marijnen, C., Minsky, B., Peters, F., Romesser, P., Sarker, R., Tan, A., Boeke, S., Wegener, D., Butzer, S., Boldt, J., Gatidis, S., Nikolaou, K., Zips, D., Gani, C. SPRINGER HEIDELBERG. 2022: S32

  View details for Web of Science ID 000791788000059

• Hybrid Cardiac Magnetic Resonance/Fluorodeoxyglucose Positron Emission Tomography to Differentiate Active From Chronic Cardiac Sarcoidosis JACC-CARDIOVASCULAR IMAGING Greulich, S., Gatidis, S., Graeni, C., Blankstein, R., Glatthaar, A., Mezger, K., Mueller, K. L., Castor, T., Mahrholdt, H., Haentschel, M., Hetzel, J., Dittmann, H., Nikolaou, K., Gawaz, M., la Fougere, C., Krumm, P. 2022; 15 (3): 445-456

  Abstract

  The purpose of this study was to investigate the diagnostic value of simultaneous hybrid cardiac magnetic resonance (CMR) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for detection and differentiation of active (aCS) from chronic (cCS) cardiac sarcoidosis.Late gadolinium enhancement (LGE) CMR and FDG-PET are both established imaging techniques for the detection of CS. However, there are limited data regarding the value of a comprehensive simultaneous hybrid CMR/FDG-PET imaging approach that includes CMR mapping techniques.Forty-three patients with biopsy-proven extracardiac sarcoidosis (median age: 48 years, interquartile range: 37-57 years, 65% male) were prospectively enrolled for evaluation of suspected CS. After dietary preparation for suppression of myocardial glucose metabolism, patients were evaluated on a 3-T hybrid PET/MR scanner. The CMR protocol included T1 and T2 mapping, myocardial function, and LGE imaging. We assumed aCS if PET and CMR (ie, LGE or T1/T2 mapping) were both positive (PET+/CMR+), cCS if PET was negative but CMR was positive (PET-/CMR+), and no CS if patients were CMR negative regardless of PET findings.Among the 43 patients, myocardial glucose uptake was suppressed successfully in 36 (84%). Hybrid CMR/FDG-PET revealed aCS in 13 patients (36%), cCS in 5 (14%), and no CS in 18 (50%). LGE was present in 14 patients (39%); T1 mapping was abnormal in 10 (27%) and T2 mapping abnormal in 2 (6%). CS was diagnosed based on abnormal T1 mapping in 4 out of 18 CS patients (22%) who were LGE negative. PET FDG uptake was present in 17 (47%) patients.Comprehensive simultaneous hybrid CMR/FDG-PET imaging is useful for the detection of CS and provides additional value for identifying active disease. Our results may have implications for enhanced diagnosis as well as improved identification of patients with aCS in whom anti-inflammatory therapy may be most beneficial.

  View details for DOI 10.1016/j.jcmg.2021.08.018

  View details for Web of Science ID 000782633300003

  View details for PubMedID 34656480

• Real Time Landmark Detection for Within- and Cross Subject Tracking With Minimal Human Supervision IEEE ACCESS Frueh, M., Schilling, A., Gatidis, S., Kuestner, T. 2022; 10: 81192-81202

  View details for DOI 10.1109/ACCESS.2022.3195211

  View details for Web of Science ID 000840563100001

• LAPNet: Non-Rigid Registration Derived in k-Space for Magnetic Resonance Imaging IEEE TRANSACTIONS ON MEDICAL IMAGING Kuestner, T., Pan, J., Qi, H., Cruz, G., Gilliam, C., Blu, T., Yang, B., Gatidis, S., Botnar, R., Prieto, C. 2021; 40 (12): 3686-3697

  Abstract

  Physiological motion, such as cardiac and respiratory motion, during Magnetic Resonance (MR) image acquisition can cause image artifacts. Motion correction techniques have been proposed to compensate for these types of motion during thoracic scans, relying on accurate motion estimation from undersampled motion-resolved reconstruction. A particular interest and challenge lie in the derivation of reliable non-rigid motion fields from the undersampled motion-resolved data. Motion estimation is usually formulated in image space via diffusion, parametric-spline, or optical flow methods. However, image-based registration can be impaired by remaining aliasing artifacts due to the undersampled motion-resolved reconstruction. In this work, we describe a formalism to perform non-rigid registration directly in the sampled Fourier space, i.e. k-space. We propose a deep-learning based approach to perform fast and accurate non-rigid registration from the undersampled k-space data. The basic working principle originates from the Local All-Pass (LAP) technique, a recently introduced optical flow-based registration. The proposed LAPNet is compared against traditional and deep learning image-based registrations and tested on fully-sampled and highly-accelerated (with two undersampling strategies) 3D respiratory motion-resolved MR images in a cohort of 40 patients with suspected liver or lung metastases and 25 healthy subjects. The proposed LAPNet provided consistent and superior performance to image-based approaches throughout different sampling trajectories and acceleration factors.

  View details for DOI 10.1109/TMI.2021.3096131

  View details for Web of Science ID 000724511900038

  View details for PubMedID 34242163

• Detection of lung lesions in breath-hold VIBE and free-breathing Spiral VIBE MRI compared to CT INSIGHTS INTO IMAGING Olthof, S., Reinert, C., Nikolaou, K., Pfannenberg, C., Gatidis, S., Benkert, T., Kuestner, T., Krumm, P. 2021; 12 (1): 175

  Abstract

  Detection of pulmonary nodules in MRI requires fast imaging strategies without respiratory motion impairment, such as single-breath-hold Cartesian VIBE. As patients with pulmonary diseases have limited breath-hold capacities, this study investigates the clinical feasibility of non-Cartesian Spiral VIBE under free-breathing compared to CT as the gold standard.Prospective analysis of 27 oncological patients examined in PET/CT and PET/MR. A novel motion-robust 3D ultrashort-echo-time (UTE) MR sequence was evaluated in comparison with CT and conventional breath-hold MR. CT scans were performed under breath-hold in end-expiratory and end-inspiratory position (CT ex, CT in). MR data was acquired with non-contrast-enhanced breath-hold Cartesian VIBE followed by a free-breathing 3D UTE Spiral VIBE. Impact of respiratory motion on pulmonary evaluation was investigated by two readers in Cartesian VIBE, followed by UTE Spiral VIBE and CT ex and the reference standard of CT in. Diagnostic accuracy was calculated, and visual image quality assessed.Higher detection rate and sensitivity of pulmonary nodules in free-breathing UTE Spiral VIBE in comparison with breath-hold Cartesian VIBE were found for lesions > 10 mm (UTE Spiral VIBE/VIBE/CT ex): 93%/54%/100%; Lesions 5-10 mm: 67%/25%/ 92%; Lesions < 5 mm: 11%/11%/78%. Lobe-based analysis revealed sensitivities and specificities of 64%/96%/41% and 96%/93%/100% for UTE Spiral VIBE/VIBE/CT ex.Free-breathing UTE Spiral VIBE indicates higher sensitivity for detection of pulmonary nodules than breath-hold Cartesian VIBE and is a promising but time-consuming approach. However, sensitivity and specificity of inspiratory CT remain superior in comparison and should be preferred for detection of pulmonary lesions.

  View details for DOI 10.1186/s13244-021-01124-0

  View details for Web of Science ID 000722208600002

  View details for PubMedID 34817715

  View details for PubMedCentralID PMC8613318

• MRI-Derived Radiomics Features of Hepatic Fat Predict Metabolic States in Individuals without Cardiovascular Disease ACADEMIC RADIOLOGY Gutmann, D. P., Rospleszcz, S., Rathmann, W., Schlett, C. L., Peters, A., Wachinger, C., Gatidis, S., Bamberg, F. 2021; 28: S1-S10

  Abstract

  To investigate radiomics features of hepatic fat as potential biomarkers of type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) in individuals without overt cardiovascular disease, and benchmarking against hepatic proton density fat fraction (PDFF) and the body mass index (BMI).This study collected liver radiomics features of 310 individuals that were part of a case-controlled imaging substudy embedded in a prospective cohort. Individuals had known T2DM (n = 39; 12.6 %) and MetS (n = 107; 34.5 %) status, and were divided into stratified training (n = 232; 75 %) and validation (n = 78; 25 %) sets. Six hundred eighty-four MRI radiomics features were extracted for each liver volume of interest (VOI) on T1-weighted dual-echo Dixon relative fat water content (rfwc) maps. Test-retest and inter-rater variance was simulated by additionally extracting radiomics features using noise augmented rfwc maps and deformed volume of interests. One hundred and seventy-one features with test-retest reliability (ICC(1,1)) and inter-rater agreement (ICC(3,k)) of ≥0.85 on the training set were considered stable. To construct predictive random forest (RF) models, stable features were filtered using univariate RF analysis followed by sequential forward aggregation. The predictive performance was evaluated on the independent validation set with area under the curve of the receiver operating characteristic (AUROC) and balanced accuracy (AccuracyB).On the validation set, the radiomics RF models predicted T2DM with AUROC of 0.835 and AccuracyB of 0.822 and MetS with AUROC of 0.838 and AccuracyB of 0.787, outperforming the RF models trained on the benchmark parameters PDFF and BMI.Hepatic radiomics features may serve as potential imaging biomarkers for T2DM and MetS.

  View details for DOI 10.1016/j.acra.2020.06.030

  View details for Web of Science ID 000719455800001

  View details for PubMedID 32800693

• Effectiveness of Chest CT in Children: CT Findings in Relation to the Clinical Question ROFO-FORTSCHRITTE AUF DEM GEBIET DER RONTGENSTRAHLEN UND DER BILDGEBENDEN VERFAHREN Esser, M., Tsiflikas, I., Kraus, M., Hess, S., Gatidis, S., Schaefer, J. F. 2022; 194 (03): 281-290

  Abstract

  To estimate the effectiveness and efficiency of chest CT in children based on the suspected diagnosis in relation to the number of positive, negative, and inconclusive CT results.In this monocentric retrospective study at a university hospital with a division of pediatric radiology, 2019 chest CT examinations (973 patients; median age: 10.5 years; range: 2 days to 17.9 years) were analyzed with regards to clinical data, including the referring department, primary questions or suspected diagnosis, and CT findings. It was identified if the clinical question was answered, whether the suspected diagnosis was confirmed or ruled out, and if additional findings (clinically significant or minor) were detected.The largest clinical subgroup was the hematooncological subgroup (n = 987), with frequent questions for inflammation/pneumonia (66 % in this subgroup). Overall, CT provided conclusive results in 97.6 % of all scans. In 1380 scans (70 %), the suspected diagnosis was confirmed. In 406/2019 cases (20 %), the CT scan was negative also in terms of an additional finding. In 8 of 9 clinical categories, the proportion of positive results was over 50 %. There were predominantly negative results (110/179; 61 %) in pre-stem cell transplant evaluation. In the subgroup of trauma management, 81/144 exams (57 %) showed positive results, including combined injuries (n = 23). 222/396 (56 %) of all additional findings were estimated to be clinically significant.In a specialized center, the effectiveness of pediatric chest CT was excellent when counting the conclusive results. However, to improve efficiency, the clinical evaluation before imaging appears crucial to prevent unnecessary CT examinations.· Pediatric chest CT in specialized centers has a high diagnostic value.. · CT identifies relevant changes besides the working hypothesis in clinically complex situations.. · Pre-CT clinical evaluation is crucial, especially in the context of suspected pneumonia..· Esser M, Tsiflikas I, Kraus MS et al. Effectiveness of Chest CT in Children: CT Findings in Relation to the Clinical Question. Fortschr Röntgenstr 2022; 194: 281 - 290.

  View details for DOI 10.1055/a-1586-3023

  View details for Web of Science ID 000707988800004

  View details for PubMedID 34649290

• PET/MRI Improves Management of Children with Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Baratto, L., Hawk, K. E., States, L., Qi, J., Gatidis, S., Kiru, L., Daldrup-Link, H. E. 2021; 62 (10): 1334-1340

  Abstract

  Integrated PET/MRI has shown significant clinical value for staging and restaging of children with cancer by providing functional and anatomic tumor evaluation with a 1-stop imaging test and with up to 80% reduced radiation exposure compared with 18F-FDG PET/CT. This article reviews clinical applications of 18F-FDG PET/MRI that are relevant for pediatric oncology, with particular attention to the value of PET/MRI for patient management. Early adopters from 4 different institutions share their insights about specific advantages of PET/MRI technology for the assessment of young children with cancer. We discuss how whole-body PET/MRI can be of value in the evaluation of certain anatomic regions, such as soft tissues and bone marrow, as well as specific PET/MRI interpretation hallmarks in pediatric patients. We highlight how whole-body PET/MRI can improve the clinical management of children with lymphoma, sarcoma, and neurofibromatosis, by reducing the number of radiologic examinations needed (and consequently the radiation exposure), without losing diagnostic accuracy. We examine how PET/MRI can help in differentiating malignant tumors versus infectious or inflammatory diseases. Future research directions toward the use of PET/MRI for treatment evaluation of patients undergoing immunotherapy and assessment of different theranostic agents are also briefly explored. Lessons learned from applications in children might also be extended to evaluations of adult patients.

  View details for DOI 10.2967/jnumed.120.259747

  View details for PubMedID 34599010

• A novel approach for radiotherapy dose escalation in rectal cancer using online MR-guidance and rectal ultrasound gel filling-Rationale and first in human RADIOTHERAPY AND ONCOLOGY Gani, C., Lo Russo, M., Boeke, S., Wegener, D., Gatidis, S., Butzer, S., Boldt, J., Moennich, D., Thorwarth, D., Nikolaou, K., Zips, D., Nachbar, M. 2021; 164: 37-42

  Abstract

  Dose escalated radiotherapy has previously been investigated as a strategy to increase complete response rates in rectal cancer. However large safety margins are required using cone-beam computed tomography guided radiotherapy leading to high doses to organs at risk or insufficient target volume coverage in order to keep dose constraints. We herein present the first clinical application of a new technique for dose escalation in rectal cancer using online magnetic resonance (MR)-guidance and rectal ultrasound gel filling.A 73-year-old patient with distal cT3a cN0 cM0 rectal cancer was referred for definitive radiochemotherapy with the goal of organ preservation after multidisciplinary discussion. A dose of 45 Gy in 25 fractions with a stereotactic integrated boost to the primary tumor of 50 Gy with concomitant 5-fluorouracil was prescribed. Furthermore, a boost to the primary tumor with 3 Gy per fraction using the adapt-to-shape workflow on a 1.5 T MR-Linac was planned once weekly. For the boost fractions 100 cc of ultrasound gel was applied rectally in order to improve tumor visibility and distancing of uninvolved rectal mucosa. In order to determine the required planning target volume margin diagnostic scans of ten rectal cancer patients conducted with rectal ultrasound gel filling were studied.Based on the ten diagnostic scans an average isotropic margin of 4 mm was found to be sufficient to cover 95% of the target volume during an online adaptive workflow. Three boost fractions were applied, mean treatment duration was 22:34 min. Treatment was well tolerated by the patient with no more than PRO-CTCAE grade I° toxicity of any kind. The rectal ultrasound gel filling resulted in superior visibility of the tumor and reduced the dose to the involved mucosa especially in the high dose range compared with a boost plan calculated without any filling. A considerable tumor shrinkage was observed during treatment from 17.43 cc at baseline to 4 cc in week four.This novel method appears to be a simple but effective strategy for dose escalated radiotherapy in rectal cancer. Based on the encouraging observation, a prospective trial is currently under preparation.

  View details for DOI 10.1016/j.radonc.2021.09.002

  View details for Web of Science ID 000708441100001

  View details for PubMedID 34534612

• Overcoming barriers to data sharing with medical image generation: a comprehensive evaluation NPJ DIGITAL MEDICINE Schuette, A., Hetzel, J., Gatidis, S., Hepp, T., Dietz, B., Bauer, S., Schwab, P. 2021; 4 (1): 141

  Abstract

  Privacy concerns around sharing personally identifiable information are a major barrier to data sharing in medical research. In many cases, researchers have no interest in a particular individual's information but rather aim to derive insights at the level of cohorts. Here, we utilise generative adversarial networks (GANs) to create medical imaging datasets consisting entirely of synthetic patient data. The synthetic images ideally have, in aggregate, similar statistical properties to those of a source dataset but do not contain sensitive personal information. We assess the quality of synthetic data generated by two GAN models for chest radiographs with 14 radiology findings and brain computed tomography (CT) scans with six types of intracranial haemorrhages. We measure the synthetic image quality by the performance difference of predictive models trained on either the synthetic or the real dataset. We find that synthetic data performance disproportionately benefits from a reduced number of classes. Our benchmark also indicates that at low numbers of samples per class, label overfitting effects start to dominate GAN training. We conducted a reader study in which trained radiologists discriminate between synthetic and real images. In accordance with our benchmark results, the classification accuracy of radiologists improves with an increasing resolution. Our study offers valuable guidelines and outlines practical conditions under which insights derived from synthetic images are similar to those that would have been derived from real data. Our results indicate that synthetic data sharing may be an attractive alternative to sharing real patient-level data in the right setting.

  View details for DOI 10.1038/s41746-021-00507-3

  View details for Web of Science ID 000698951100001

  View details for PubMedID 34561528

  View details for PubMedCentralID PMC8463544

• Targeting extracellular and juxtamembrane FGFR2 mutations in chemotherapy-refractory cholangiocarcinoma NPJ PRECISION ONCOLOGY Bitzer, M., Spahn, S., Babaei, S., Horger, M., Singer, S., Schulze-Osthoff, K., Missios, P., Gatidis, S., Nann, D., Mattern, S., Scheble, V., Nikolaou, K., Armeanu-Ebinger, S., Schulze, M., Schroeder, C., Biskup, S., Beha, J., Claassen, M., Ruhm, K., Poso, A., Malek, N. P. 2021; 5 (1): 80

  Abstract

  Intrahepatic cholangiocarcinoma (iCCA) has emerged as a promising candidate for precision medicine, especially in the case of activating FGFR2 gene fusions. In addition to fusions, a considerable fraction of iCCA patients reveals FGFR2 mutations, which might lead to uncontrolled activation of the FGFR2 pathway but are mostly of unknown functional significance. A current challenge for molecular tumor boards (MTB) is to predict the functional consequences of such FGFR2 alterations to guide potential treatment decisions. We report two iCCA patients with extracellular and juxtamembrane FGFR2 mutations. After in silico investigation of the alterations and identification of activated FGFR2 downstream targets in tumor specimens by immunohistochemistry and transcriptome analysis, the MTB recommended treatment with an FGFR-inhibiting tyrosine kinase inhibitor. Both patients developed a rapidly detectable and prolonged partial response to treatment. These two cases suggest an approach to characterize further detected FGFR2 mutations in iCCA to enable patients´ selection for a successful application of the FGFR -inhibiting drugs.

  View details for DOI 10.1038/s41698-021-00220-0

  View details for Web of Science ID 000694237900001

  View details for PubMedID 34480077

  View details for PubMedCentralID PMC8417271

• Dynamic whole-body F-18-FDG PET/CT in patients with unclear lung tumors - evaluation of multiparametric dynamic imaging in a clinical setting Weissinger, M., Atmanspacher, M., Dittmann, H., Gatidis, S., Zender, L., La Fougere, C. SPRINGER. 2021: S479

  View details for Web of Science ID 000709355001337

• Weakly supervised segmentation of tumor lesions in PET-CT hybrid imaging JOURNAL OF MEDICAL IMAGING Frueh, M., Fischer, M., Schilling, A., Gatidis, S., Hepp, T. 2021; 8 (5): 054003

  Abstract

  Purpose: We introduce and evaluate deep learning methods for weakly supervised segmentation of tumor lesions in whole-body fluorodeoxyglucose-positron emission tomography (FDG-PET) based solely on binary global labels ("tumor" versus "no tumor"). Approach: We propose a three-step approach based on (i) a deep learning framework for image classification, (ii) subsequent generation of class activation maps (CAMs) using different CAM methods (CAM, GradCAM, GradCAM++, ScoreCAM), and (iii) final tumor segmentation based on the aforementioned CAMs. A VGG-based classification neural network was trained to distinguish between PET image slices with and without FDG-avid tumor lesions. Subsequently, the CAMs of this network were used to identify the tumor regions within images. This proposed framework was applied to FDG-PET/CT data of 453 oncological patients with available manually generated ground-truth segmentations. Quantitative segmentation performance was assessed for the different CAM approaches and compared with the manual ground truth segmentation and with supervised segmentation methods. In addition, further biomarkers (MTV and TLG) were extracted from the segmentation masks. Results: A weakly supervised segmentation of tumor lesions was feasible with satisfactory performance [best median Dice score 0.47, interquartile range (IQR) 0.35] compared with a fully supervised U-Net model (median Dice score 0.72, IQR 0.36) and a simple threshold based segmentation (Dice score 0.29, IQR 0.28). CAM, GradCAM++, and ScoreCAM yielded similar results. However, GradCAM led to inferior results (median Dice score: 0.12, IQR 0.21) and was likely to ignore multiple instances within a given slice. CAM, GradCAM++, and ScoreCAM yielded accurate estimates of metabolic tumor volume (MTV) and tumor lesion glycolysis. Again, worse results were observed for GradCAM. Conclusions: This work demonstrated the feasibility of weakly supervised segmentation of tumor lesions and accurate estimation of derived metrics such as MTV and tumor lesion glycolysis.

  View details for DOI 10.1117/1.JMI.8.5.054003

  View details for Web of Science ID 000720829600019

  View details for PubMedID 34660843

  View details for PubMedCentralID PMC8510879

• Uncertainty estimation and explainability in deep learning-based age estimation of the human brain: Results from the German National Cohort MRI study COMPUTERIZED MEDICAL IMAGING AND GRAPHICS Hepp, T., Blum, D., Armanious, K., Schoelkopf, B., Stern, D., Yang, B., Gatidis, S. 2021; 92: 101967

  Abstract

  Brain ageing is a complex neurobiological process associated with morphological changes that can be assessed on MRI scans. Recently, Deep learning (DL)-based approaches have been proposed for the prediction of chronological brain age from MR images yielding high accuracy. These approaches, however, usually do not address quantification of uncertainty and, therefore, intrinsic physiological variability. Considering uncertainty is essential for the interpretation of the difference between predicted and chronological age. In addition, DL-based models lack in explainability compared to classical approaches like voxel-based morphometry. In this study, we aim to address both, modeling uncertainty and providing visual explanations to explore physiological patterns in brain ageing. T1-weighted brain MRI datasets of 10691 participants of the German National Cohort Study, drawn from the general population, were included in this study (chronological age from 20 to 72 years). A regression model based on a 3D Convolutional Neural Network taking into account aleatoric noise was implemented for global as well as regional brain age estimation. We observed high overall accuracy of global brain age estimation with a mean absolute error of 3.2 ± 2.5 years and mean uncertainty of 2.9 ± 0.6 years. Regional brain age estimation revealed higher estimation accuracy and lower uncertainty in central compared to peripheral brain regions. Visual explanations illustrating the importance of brain sub-regions were generated using Grad-CAM: the derived saliency maps showed a high relevance of the lateral and third ventricles, the insular lobe as well as parts of the basal ganglia and the internal capsule.

  View details for DOI 10.1016/j.compmedimag.2021.101967

  View details for Web of Science ID 000694676100001

  View details for PubMedID 34392229

• Lymph Node Staging with a Combined Protocol of F-18-FDG PET/MRI and Sentinel Node SPECT/CT: A Prospective Study in Patients with FIGO I/II Cervical Carcinoma JOURNAL OF NUCLEAR MEDICINE Weissinger, M., Taran, F., Gatidis, S., Kommoss, S., Nikolaou, K., Sahbai, S., la Fougere, C., Brucker, S., Dittmann, H. 2021; 62 (8): 1062-1067

  Abstract

  Lymph node metastasis (LNM) is present in a minority of patients with early stages of cervical carcinomas. As conventional imaging including PET/CT has shown limited sensitivity, systematic lymphadenectomies are often conducted for staging purposes. Therefore, the aim of this prospective study was to analyze the impact of 18F-FDG PET/MRI in addition to sentinel lymph node (SLN) biopsy on lymph node (LN) status. Methods: Forty-two women with an initial diagnosis of Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) IA-IIB cervical carcinoma were included between March 2016 and April 2019. Each patient underwent preoperative whole-body 18F-FDG PET/MRI and SLN imaging with SPECT/CT after intracervical injection of 99mTc-labeled nanocolloid. Systematic lymphadenectomy and SLN biopsy served as the reference standard. Staging using PET/MRI was performed by nuclear medicine and radiology experts working in consensus. Results: One patient was excluded from surgical staging because of liver metastases newly diagnosed on PET/MRI. The overall prevalence of LNM in the remaining 41 patients was 29.3% (12/41). Five of 12 patients with LNM had solely small metastases with a maximum diameter of 5 mm. The consensus interpretation showed PET/MRI to have a specificity of 100% (29/29; 95% CI, 88.3%-100%) for LNM staging but a low sensitivity, 33.3% (4/12; 95% CI, 12.8%-60.9%). LN size was the most important factor for the detectability of metastases, since only LNMs larger than 5 mm could be identified by PET/MRI (sensitivity, 57.1% for >5 mm and 0% for ≤5 mm). Paraaortic LNM was evaluated accurately in 3 of the 4 patients with paraaortic LN metastasis. SLNs were detectable by SPECT/CT in 82.9% of the patients or 69.0% of the hemipelves. In cases with an undetectable SLN on SPECT/CT, the malignancy rate was considerably higher (31.2% vs. 19.3%). The combination of PET/MRI and SLN SPECT/CT improved the detection of pelvic LNM from 33.3% to 75%. Conclusion:18F-FDG PET/MRI is a highly specific N-staging method and improves LNM detection. Because of the limited sensitivity in frequently occurring small LNMs, PET/MRI should be combined with SLN mapping. The proposed combined protocol helps to decide whether extensive surgical staging is necessary in patients with FIGO I/II cervical cancer.

  View details for DOI 10.2967/jnumed.120.255919

  View details for Web of Science ID 000711570000014

  View details for PubMedID 33509973

  View details for PubMedCentralID PMC8833872

• F-18-Fluoride PET/CT Imaging of Medication-Related Osteonecrosis of the Jaw in Conservative Treatment-A Case Report FRONTIERS IN ONCOLOGY Reinert, C., Pfannenberg, C., Gatidis, S., la Fougere, C., Nikolaou, K., Hoefert, S. 2021; 11: 700397

  Abstract

  Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect in antiresorptive treatment. Treatment of MRONJ is considered primarily conservative with oral mouth rinses and antibiotics but may demand surgery, depending on the complaints and general condition of the patient, the extent of the necrosis, and the overall prognosis with respect to the underlying disease. A 77 year old female patient with invasive ductal breast cancer and bone metastases was treated with intravenous bisphosphonate (BP) zoledronic acid. During therapy, she developed MRONJ in the mandible with severe pain. Clinical examination revealed confluent exposed bone of the lower left jaw and a fistula at the right molar region. The panoramic radiograph revealed a mandibular osseous involvement with diffuse radiopaque areas between radiolucent areas. For preoperative planning, 18F-fluoride positron emission tomography/computed tomography (PET/CT) of the jaw was performed, showing substantially increased 18F-fluoride uptake in regions 38 to 47 of the mandible with a focal gap in region 36 (area of clinically exposed bone). CT revealed medullary sclerosis and cortical thickening with confluent periosteal reaction and focal cortical erosion in the regions 37 to 42, whereas the regions 43 to 47 were only subtly sclerotic without cortical thickening. After systemic antibiotic therapy with sultamicillin following significant symptom and pain relief, 18F-fluoride PET/CT imaging was performed again after 5 months. No changes in either CT and PET were observed in regions 38 to 42, whereas the bony sclerosis was slightly increased in regions 43 to 47 with a slight reduction of 18F-fluoride uptake. 18F-fluoride PET/CT showed no significant changes assessing the extent of MRONJ prior and after systemic antibiotic therapy, providing no evidence that conservative treatment reduced the extent of the MRONJ-affected jawbone. The additional information of 18F-fluoride PET enables to identify the true extent of MRONJ which may be underestimated by CT imaging alone. Patients with MRONJ undergoing conservative treatment could benefit because additional imaging may be avoided as the pre-therapeutic 18F-fluoride PET/CT delivers all information needed for further treatment. Our findings support the recommendation of a surgical approach as long-term antibiotics cannot downsize the extent of MRONJ.

  View details for DOI 10.3389/fonc.2021.700397

  View details for Web of Science ID 000673662300001

  View details for PubMedID 34277447

  View details for PubMedCentralID PMC8281890

• Age-Net: An MRI-Based Iterative Framework for Brain Biological Age Estimation IEEE TRANSACTIONS ON MEDICAL IMAGING Armanious, K., Abdulatif, S., Shi, W., Salian, S., Kustner, T., Weiskopf, D., Hepp, T., Gatidis, S., Yang, B. 2021; 40 (7): 1778-1791

  Abstract

  The concept of biological age (BA) - although important in clinical practice - is hard to grasp mainly due to the lack of a clearly defined reference standard. For specific applications, especially in pediatrics, medical image data are used for BA estimation in a routine clinical context. Beyond this young age group, BA estimation is mostly restricted to whole-body assessment using non-imaging indicators such as blood biomarkers, genetic and cellular data. However, various organ systems may exhibit different aging characteristics due to lifestyle and genetic factors. Thus, a whole-body assessment of the BA does not reflect the deviations of aging behavior between organs. To this end, we propose a new imaging-based framework for organ-specific BA estimation. In this initial study we focus mainly on brain MRI. As a first step, we introduce a chronological age (CA) estimation framework using deep convolutional neural networks (Age-Net). We quantitatively assess the performance of this framework in comparison to existing state-of-the-art CA estimation approaches. Furthermore, we expand upon Age-Net with a novel iterative data-cleaning algorithm to segregate atypical-aging patients (BA [Formula: see text] CA) from the given population. We hypothesize that the remaining population should approximate the true BA behavior. We apply the proposed methodology on a brain magnetic resonance image (MRI) dataset containing healthy individuals as well as Alzheimer's patients with different dementia ratings. We demonstrate the correlation between the predicted BAs and the expected cognitive deterioration in Alzheimer's patients. A statistical and visualization-based analysis has provided evidence regarding the potential and current challenges of the proposed methodology.

  View details for DOI 10.1109/TMI.2021.3066857

  View details for Web of Science ID 000668842500004

  View details for PubMedID 33729932

• 1.5 T MR-linac Planning Study comparing two different Rectum-Boost Strategies in Patients with locally advanced Rectal Cancer Bonomo, P., Lo Russo, M., Nachbar, M., Boeke, S., Gatidis, S., Zips, D., Thorwarth, D., Gani, C. SPRINGER HEIDELBERG. 2021: S151-S152

  View details for Web of Science ID 000664126100271

• Deep Learning-Based Automated Abdominal Organ Segmentation in the UK Biobank and German National Cohort Magnetic Resonance Imaging Studies INVESTIGATIVE RADIOLOGY Kart, T., Fischer, M., Kuestner, T., Hepp, T., Bamberg, F., Winzeck, S., Glocker, B., Rueckert, D., Gatidis, S. 2021; 56 (6): 401-408

  Abstract

  The aims of this study were to train and evaluate deep learning models for automated segmentation of abdominal organs in whole-body magnetic resonance (MR) images from the UK Biobank (UKBB) and German National Cohort (GNC) MR imaging studies and to make these models available to the scientific community for analysis of these data sets.A total of 200 T1-weighted MR image data sets of healthy volunteers each from UKBB and GNC (400 data sets in total) were available in this study. Liver, spleen, left and right kidney, and pancreas were segmented manually on all 400 data sets, providing labeled ground truth data for training of a previously described U-Net-based deep learning framework for automated medical image segmentation (nnU-Net). The trained models were tested on all data sets using a 4-fold cross-validation scheme. Qualitative analysis of automated segmentation results was performed visually; performance metrics between automated and manual segmentation results were computed for quantitative analysis. In addition, interobserver segmentation variability between 2 human readers was assessed on a subset of the data.Automated abdominal organ segmentation was performed with high qualitative and quantitative accuracy on UKBB and GNC data. In more than 90% of data sets, no or only minor visually detectable qualitative segmentation errors occurred. Mean Dice scores of automated segmentations compared with manual reference segmentations were well higher than 0.9 for the liver, spleen, and kidneys on UKBB and GNC data and around 0.82 and 0.89 for the pancreas on UKBB and GNC data, respectively. Mean average symmetric surface distance was between 0.3 and 1.5 mm for the liver, spleen, and kidneys and between 2 and 2.2 mm for pancreas segmentation. The quantitative accuracy of automated segmentation was comparable with the agreement between 2 human readers for all organs on UKBB and GNC data.Automated segmentation of abdominal organs is possible with high qualitative and quantitative accuracy on whole-body MR imaging data acquired as part of UKBB and GNC. The results obtained and deep learning models trained in this study can be used as a foundation for automated analysis of thousands of MR data sets of UKBB and GNC and thus contribute to tackling topical and original scientific questions.

  View details for DOI 10.1097/RLI.0000000000000755

  View details for Web of Science ID 000650001200008

  View details for PubMedID 33930003

• The International Radiomics Platform - An Initiative of the German and Austrian Radiological Societies (vol 193, pg 276, 2021) ROFO-FORTSCHRITTE AUF DEM GEBIET DER RONTGENSTRAHLEN UND DER BILDGEBENDEN VERFAHREN Overhoff, D., Kohlmann, P., Frydrychowicz, A., Gatidis, S., Loewe, C., Moltz, J., Kuhnigk, J., Gutberlet, M., Winter, H., Volker, M., Hahn, H., Schoenberg, S. O., Attenberger, U., Bamberg, F., Baessler, B., Barkhausen, J., Forsting, M., Furtner-Srajer, J., Gatidis, S., Gutberlet, M., Hahn, H. K., Herold, C., Kaindl, A., Kather, J., Kikinis, R., Kohlmann, P., Krause, B. J., Krombach, G., Ladd, M. E., Langs, G., Lohwasser, S., Lotz, J., Pinto dos Santos, D., Prosch, H., Schoenberg, S. O., Volker, M., Winther, H., Zimmermann, M., Antoch, G., Anton, F., Barkhausen, J., Dorfler, A., Korber, F., Layer, G., Neumann, S., Schoenberg, S. O., Wessling, J., Wucherer, M., Forstner, R., Gizewski, E. R., Hausegger, K. A., Heinz, G., Herold, C., Loewe, C., Prosch, H., Sorantin, E., Wicke, K. 2021; 193 (03): E3

  View details for Web of Science ID 000642290300001

  View details for PubMedID 33890252

• Case Report: Combined CDK4/6 and MEK Inhibition in Refractory CDKN2A and NRAS Mutant Melanoma FRONTIERS IN ONCOLOGY Forschner, A., Sinnberg, T., Mroz, G., Schroeder, C., Reinert, C., Gatidis, S., Bitzer, M., Eigentler, T., Garbe, C., Niessner, H., Rocken, M., Roggia, C., Armeanu-Ebinger, S., Riess, O., Mattern, S., Nann, D., Bonzheim, I. 2021; 11: 643156

  Abstract

  There are only limited treatment options for metastatic NRAS mutant melanoma patients with resistance to immune checkpoint inhibitors. Besides activation of the mitogen-activated protein (MAP) kinase pathway, they often have additional disturbances in cell cycle regulation. However, unlike BRAF mutant melanoma, no targeted therapy has yet been approved for NRAS mutant melanoma so far. Here we present a NRAS mutant melanoma patient with response to combined binimetinib and ribociclib therapy following characterization of the molecular defects of the tumor by panel sequencing. Next generation sequencing (708 cancer genes) of a soft tissue metastasis revealed a homozygous deletion of CDKN2A in addition to the previously known NRAS mutation, as well as amplification of CCNE1 and CDK6. Immunohistochemical staining of the altered cell cycle genes confirmed loss of p16, reduced expression of p21 and high expression of CDK6 and cyclin D1. As the patient had been progressive on combined immunotherapy, targeted therapy with combined MEK and CDK4/6 inhibition was initiated as recommended by the molecular tumor board. Response to treatment was monitored with PET/CT and liquid biopsy, serum LDH, and S100. In addition, a patient-derived xenograft (PDX) was used to prove the efficacy of the two drugs in combination. Furthermore, senescence-associated beta-galactosidase staining showed that more cells were senescent under the combination treatment of binimetinib and ribociclib. Our case demonstrates how an individualized, molecular-based therapeutic approach could be found based on next-generation sequencing results. Furthermore our report highlights the fruitful and efficient collaboration of dermatooncologists, human geneticists, molecular pathologists, biochemists, radiologists, and nuclear physicians. Further studies are urgently needed to expand the very limited therapeutic landscape of NRAS mutated melanoma.

  View details for DOI 10.3389/fonc.2021.643156

  View details for Web of Science ID 000628892500001

  View details for PubMedID 33732653

  View details for PubMedCentralID PMC7959243

• Artificial intelligence enables whole-body positron emission tomography scans with minimal radiation exposure. European journal of nuclear medicine and molecular imaging Wang, Y. J., Baratto, L., Hawk, K. E., Theruvath, A. J., Pribnow, A., Thakor, A. S., Gatidis, S., Lu, R., Gummidipundi, S. E., Garcia-Diaz, J., Rubin, D., Daldrup-Link, H. E. 2021

  Abstract

  PURPOSE: To generate diagnostic 18F-FDG PET images of pediatric cancer patients from ultra-low-dose 18F-FDG PET input images, using a novel artificial intelligence (AI) algorithm.METHODS: We used whole-body 18F-FDG-PET/MRI scans of 33 children and young adults with lymphoma (3-30years) to develop a convolutional neural network (CNN), which combines inputs from simulated 6.25% ultra-low-dose 18F-FDG PET scans and simultaneously acquired MRI scans to produce a standard-dose 18F-FDG PET scan. The image quality of ultra-low-dose PET scans, AI-augmented PET scans, and clinical standard PET scans was evaluated by traditional metrics in computer vision and by expert radiologists and nuclear medicine physicians, using Wilcoxon signed-rank tests and weighted kappa statistics.RESULTS: The peak signal-to-noise ratio and structural similarity index were significantly higher, and the normalized root-mean-square error was significantly lower on the AI-reconstructed PET images compared to simulated 6.25% dose images (p<0.001). Compared to the ground-truth standard-dose PET, SUVmax values of tumors and reference tissues were significantly higher on the simulated 6.25% ultra-low-dose PET scans as a result of image noise. After the CNN augmentation, the SUVmax values were recovered to values similar to the standard-dose PET. Quantitative measures of the readers' diagnostic confidence demonstrated significantly higher agreement between standard clinical scans and AI-reconstructed PET scans (kappa=0.942) than 6.25% dose scans (kappa=0.650).CONCLUSIONS: Our CNN model could generate simulated clinical standard 18F-FDG PET images from ultra-low-dose inputs, while maintaining clinically relevant information in terms of diagnostic accuracy and quantitative SUV measurements.

  View details for DOI 10.1007/s00259-021-05197-3

  View details for PubMedID 33527176

• Impact of PET/CT on management of patients with esophageal cancer-results from a PET/CT registry study EUROPEAN JOURNAL OF RADIOLOGY Reinert, C., Sekler, J., Gani, C., Nikolaou, K., la Fougere, C., Pfannenberg, C., Gatidis, S. 2021; 136: 109524

  Abstract

  To investigate the impact of positron emission tomography/computed tomography (PET/CT) on clinical management in patients with esophageal cancer and its link to overall survival (OS) in a real-world setting.A patient cohort with advanced esophageal cancer undergoing PET/CT was prospectively enrolled in a registry study between 04/2013 and 06/2019. Intended patient management prior and after PET/CT was documented based on standardized questionnaire data. Management changes after PET/CT were recorded including major changes concerning the treatment goal (curative vs. palliative) and minor changes (therapy adjustments). OS was analyzed for subgroups with squamous cell carcinomas (SCC) or adenocarcinomas (AC) and stratified for extent of metastatic disease and treatment goals.257 patients (53 female;65.5 ± 10.0 yr.) were included. After PET/CT, major changes of intended therapy were observed in 34/257 patients (13.2%), from curative to palliative (8.2%), palliative to curative (1.9%) and from "not finally determined" to a curative (1.9%) or palliative (1.2%) concept. Minor changes were found in 62/257 patients (24.1%). Invasive procedures and additional imaging were intended in 70/257 (27.2%) and 94/257 (36.6%) patients before PET/CT and 20/257 (7.8%) and 8/257 (3.1%) patients after PET/CT. Curative therapy concepts based on PET/CT were associated with a longer OS (3.5 yr.[95%CI 3.1-3.8 yr.]) as compared to palliative concepts (0.9 yr.[95%CI 0.6-1.2 yr.];p < 0.0001). Patients with SCC had a worse prognosis (2.4 yr.[95%CI 2.0-2.9 yr.]) as compared to patients with AC (3.2 yr.[95%CI 2.7-3.7 yr.];p = 0.01).In patients with advanced esophageal cancer, PET/CT has a significant impact on clinical management by improving the selection of individualized treatment strategies and avoiding additional diagnostic procedures.

  View details for DOI 10.1016/j.ejrad.2021.109524

  View details for Web of Science ID 000620374400013

  View details for PubMedID 33434862

• Uncertainty-Guided Progressive GANs for Medical Image Translation Upadhyay, U., Chen, Y., Hepp, T., Gatidis, S., Akata, Z., DeBruijne, M., Cattin, P. C., Cotin, S., Padoy, N., Speidel, S., Zheng, Y., Essert, C. SPRINGER INTERNATIONAL PUBLISHING AG. 2021: 614-624

  View details for DOI 10.1007/978-3-030-87199-4_58

  View details for Web of Science ID 000712025000058

• Marker-less online MR-guided stereotactic body radiotherapy of liver metastases at a 1.5 T MR-Linac - Feasibility, workflow data and patient acceptance CLINICAL AND TRANSLATIONAL RADIATION ONCOLOGY Gani, C., Boeke, S., McNair, H., Ehlers, J., Nachbar, M., Moennich, D., Stolte, A., Boldt, J., Marks, C., Winter, J., Kuenzel, L. A., Gatidis, S., Bitzer, M., Thorwarth, D., Zips, D. 2021; 26: 55-61

  Abstract

  Stereotactic body radiotherapy (SBRT) is an established ablative treatment for liver tumors with excellent local control rates. Magnetic resonance imaging guided radiotherapy (MRgRT) provides superior soft tissue contrast and may therefore facilitate a marker-less liver SBRT workflow. The goal of the present study was to investigate feasibility, workflow parameters, toxicity and patient acceptance of MRgSBRT on a 1.5 T MR-Linac.Ten consecutive patients with liver metastases treated on a 1.5 T MR-Linac were included in this prospective trial. Tumor delineation was performed on four-dimensional computed tomography scans and both exhale triggered and free-breathing T2 MRI scans from the MR-Linac. An internal target volume based approach was applied. Organ at risk constraints were based on the UKSABR guidelines (Version 6.1). Patient acceptance regarding device specific aspects was assessed and toxicity was scored according to the common toxicity criteria of adverse events, version 5.Nine of ten tumors were clearly visible on the 1.5 T MR-Linac. No patient had fiducial markers placed for treatment. All patients were treated with three or five fractions. Median dose to 98% of the gross tumor volume was 38.5 Gy. The median time from "patient identity check" until "beam-off" was 31 min. Median beam on time was 9.6 min. Online MRgRT was well accepted in general and no treatment had to be interrupted on patient request. No event of symptomatic radiation induced liver disease was observed after a median follow-up of ten month (range 3-17 months).Our early experience suggests that online 1.5 T MRgSBRT of liver metastases represents a promising new non-invasive marker-free treatment modality based on high image quality, clinically reasonable in-room times and high patient acceptance. Further studies are necessary to assess clinical outcome, to validate advanced motion management and to explore the benefit of online response adaptive liver SBRT.

  View details for DOI 10.1016/j.ctro.2020.11.014

  View details for Web of Science ID 000600587800009

  View details for PubMedID 33319073

  View details for PubMedCentralID PMC7723999

• 1.5 T MR-linac planning study to compare two different strategies of rectal boost irradiation CLINICAL AND TRANSLATIONAL RADIATION ONCOLOGY Bonomo, P., Lo Russo, M., Nachbar, M., Boeke, S., Gatidis, S., Zips, D., Thorwarth, D., Gani, C. 2021; 26: 86-91

  Abstract

  To compare treatment plans of two different rectal boost strategies: up-front versus adaptive boost at the 1.5 T MR-Linac.Patients with locally advanced rectal cancer (LARC) underwent standard neoadjuvant radiochemotherapy with 50.4 Gy in 28 fractions. T2-weighted MRI prior and after the treatment session were acquired to contour gross tumor volumes (GTVs) and organs at risk (OARs). The datasets were used to simulate four different boost strategies (all with 15 Gy/5 fractions in addition to 50.4 Gy): up-front boost (5 daily fractions in the first week of treatment) and an adaptive boost (one boost fraction per week). Both strategies were planned using standard and reduced PTV margins. Intra-fraction motion was assessed by pre- and post-treatment MRI-based contours.Five patients were included and a total of 44 MRI sets were evaluated. The median PTV volumes of the adaptive boost were significantly smaller than for the up-front boost (81.4 cm3 vs 44.4 cm3 for PTV with standard margins; 31.2 cm3 vs 15 cm3 for PTV with reduced margins; p = 0.031). With reduced margins the rectum was significantly better spared with an adaptive boost rather than with an up-front boost: V60Gy and V65Gy were 41.2% and 24.8% compared with 59% and 29.9%, respectively (p = 0.031). Median GTV intra-fractional motion was 2 mm (range 0-8 mm).The data suggest that the adaptive boost strategy exploiting tumor-shrinkage and reduced margin might result in better sparing of rectum and anal canal. Individual margin assessment, motion management and real-time adaptive radiotherapy appear attractive applications of the 1.5 T MR-Linac for further testing of individualized and safe dose escalation in patients with rectal cancer.

  View details for DOI 10.1016/j.ctro.2020.11.016

  View details for Web of Science ID 000600587800013

  View details for PubMedID 33336086

  View details for PubMedCentralID PMC7732969

• Feature-based Response Prediction to Immunotherapy of late-stage Melanoma Patients Using PET/MR Imaging Liebgott, A., Gatidis, S., Viet Chau Vu, Haueise, T., Nikolaou, K., Yang, B., IEEE IEEE. 2021: 1229-1233

  View details for Web of Science ID 000632622300247

• UNCERTAINTY-BASED BIOLOGICAL AGE ESTIMATION OF BRAIN MRI SCANS Armanious, K., Abdulatif, S., Shi, W., Hepp, T., Gatidis, S., Yang, B., IEEE IEEE. 2021: 1100-1104

  View details for DOI 10.1109/ICASSP39728.2021.9414112

  View details for Web of Science ID 000704288401069

• AUTOMATED MULTI-ORGAN SEGMENTATION IN PET IMAGES USING CASCADED TRAINING OF A 3D U-NET AND CONVOLUTIONAL AUTOENCODER Liebgott, A., Lorenz, C., Gatidis, S., Viet Chau Vu, Nikolaou, K., Yang, B., IEEE IEEE. 2021: 1145-1149

  View details for DOI 10.1109/ICASSP39728.2021.9414700

  View details for Web of Science ID 000704288401078

• The International Radiomics Platform - An Initiative of the German and Austrian Radiological Societies First Application Examples ROFO-FORTSCHRITTE AUF DEM GEBIET DER RONTGENSTRAHLEN UND DER BILDGEBENDEN VERFAHREN Overhoff, D., Kohlmann, P., Frydrychowicz, A., Gatidis, S., Loewe, C., Moltz, J., Kuhnigk, J., Gutberlet, M., Winter, H., Voelker, M., Hahn, H., Schoenberg, S. O. 2021; 193 (03): 276-287

  Abstract

   The DRG-ÖRG IRP (Deutsche Röntgengesellschaft-Österreichische Röntgengesellschaft international radiomics platform) represents a web-/cloud-based radiomics platform based on a public-private partnership. It offers the possibility of data sharing, annotation, validation and certification in the field of artificial intelligence, radiomics analysis, and integrated diagnostics. In a first proof-of-concept study, automated myocardial segmentation and automated myocardial late gadolinum enhancement (LGE) detection using radiomic image features will be evaluated for myocarditis data sets. The DRG-ÖRP IRP can be used to create quality-assured, structured image data in combination with clinical data and subsequent integrated data analysis and is characterized by the following performance criteria: Possibility of using multicentric networked data, automatically calculated quality parameters, processing of annotation tasks, contour recognition using conventional and artificial intelligence methods and the possibility of targeted integration of algorithms. In a first study, a neural network pre-trained using cardiac CINE data sets was evaluated for segmentation of PSIR data sets. In a second step, radiomic features were applied for segmental detection of LGE of the same data sets, which were provided multicenter via the IRP. First results show the advantages (data transparency, reliability, broad involvement of all members, continuous evolution as well as validation and certification) of this platform-based approach. In the proof-of-concept study, the neural network demonstrated a Dice coefficient of 0.813 compared to the expert's segmentation of the myocardium. In the segment-based myocardial LGE detection, the AUC was 0.73 and 0.79 after exclusion of segments with uncertain annotation.The evaluation and provision of the data takes place at the IRP, taking into account the FAT (fairness, accountability, transparency) and FAIR (findable, accessible, interoperable, reusable) criteria. It could be shown that the DRG-ÖRP IRP can be used as a crystallization point for the generation of further individual and joint projects. The execution of quantitative analyses with artificial intelligence methods is greatly facilitated by the platform approach of the DRG-ÖRP IRP, since pre-trained neural networks can be integrated and scientific groups can be networked.In a first proof-of-concept study on automated segmentation of the myocardium and automated myocardial LGE detection, these advantages were successfully applied.Our study shows that with the DRG-ÖRP IRP, strategic goals can be implemented in an interdisciplinary way, that concrete proof-of-concept examples can be demonstrated, and that a large number of individual and joint projects can be realized in a participatory way involving all groups.  · The DRG-ÖRG IRP is a web/cloud-based radiomics platform based on a public-private partnership.. · The DRG-ÖRG IRP can be used for the creation of quality-assured, structured image data in combination with clinical data and subsequent integrated data analysis.. · First results show the applicability of left ventricular myocardial segmentation using a neural network and segment-based LGE detection using radiomic image features.. · The DRG-ÖRG IRP offers the possibility of integrating pre-trained neural networks and networking of scientific groups..· Overhoff D, Kohlmann P, Frydrychowicz A et al. The International Radiomics Platform - An Initiative of the German and Austrian Radiological Societies. Fortschr Röntgenstr 2021; 193: 276 - 287.

  View details for DOI 10.1055/a-1244-2775

  View details for Web of Science ID 000592809200002

  View details for PubMedID 33242898

• Serial DWI in HNC treated on a 1.5 T MR-Linac and benchmark to a reference 3 T diagnostic MR-scanner Boeke, S., Winter, R. M., Nachbar, M., Clasen, K., Gani, C., Stolte, A., Boldt, J., Marks, C., Gatidis, S., Nikolaou, K., Zips, D., Thorwarth, D. ELSEVIER IRELAND LTD. 2020: S927-S928

  View details for Web of Science ID 000648572703205

• Fully Automated Segmentation and Shape Analysis of the Thoracic Aorta in Non-contrast-enhanced Magnetic Resonance Images of the German National Cohort Study JOURNAL OF THORACIC IMAGING Hepp, T., Fischer, M., Winkelmann, M. T., Baldenhofer, S., Kuestner, T., Nikolaou, K., Yang, B., Gatidis, S. 2020; 35 (6): 389-398

  Abstract

  The purpose of this study was to develop and validate a deep learning-based framework for automated segmentation and vessel shape analysis on non-contrast-enhanced magnetic resonance (MR) data of the thoracic aorta within the German National Cohort (GNC) MR study.One hundred data sets acquired in the GNC MR study were included (56 men, average age 53 y [22 to 72 y]). All participants had undergone non-contrast-enhanced MR imaging of the thoracic vessels. Automated vessel segmentation of the thoracic aorta was performed using a Convolutional Neural Network in a supervised setting with manually annotated data sets as the ground truth. Seventy data sets were used for training; 30 data sets were used for quantitative and qualitative evaluation. Automated shape analysis based on centerline extraction from segmentation masks was performed to derive a diameter profile of the vessel. For comparison, 2 radiologists measured vessel diameters manually.Overall, automated aortic segmentation was successful, providing good qualitative analyses with only minor irregularities in 29 of 30 data sets. One data set with severe MR artifacts led to inadequate automated segmentation results. The mean Dice score of automated vessel segmentation was 0.85. Automated aortic diameter measurements were similar to manual measurements (average difference -0.9 mm, limits of agreement: -5.4 to 3.9 mm), with minor deviations in the order of the interreader agreement between the 2 radiologists (average difference -0.5 mm, limits of agreement: -5.8 to 4.8 mm).Automated segmentation and shape analysis of the thoracic aorta is feasible with high accuracy on non-contrast-enhanced MR imaging using the proposed deep learning approach.

  View details for DOI 10.1097/RTI.0000000000000522

  View details for Web of Science ID 000583403600013

  View details for PubMedID 32349056

• Noninvasive, longitudinal imaging-based analysis of body adipose tissue and water composition in a melanoma mouse model and in immune checkpoint inhibitor-treated metastatic melanoma patients CANCER IMMUNOLOGY IMMUNOTHERAPY Thaiss, W. M., Gatidis, S., Sartorius, T., Machann, J., Peter, A., Eigentler, T. K., Nikolaou, K., Pichler, B. J., Kneilling, M. 2021; 70 (5): 1263-1275

  Abstract

  As cancer cachexia (CC) is associated with cancer progression, early identification would be beneficial. The aim of this study was to establish a workflow for automated MRI-based segmentation of visceral (VAT) and subcutaneous adipose tissue (SCAT) and lean tissue water (LTW) in a B16 melanoma animal model, monitor diseases progression and transfer the protocol to human melanoma patients for therapy assessment.For in vivo monitoring of CC B16 melanoma-bearing and healthy mice underwent longitudinal three-point DIXON MRI (days 3, 12, 17 after subcutaneous tumor inoculation). In a prospective clinical study, 18 metastatic melanoma patients underwent MRI before, 2 and 12 weeks after onset of checkpoint inhibitor therapy (CIT; n = 16). We employed an in-house MATLAB script for automated whole-body segmentation for detection of VAT, SCAT and LTW.B16 mice exhibited a CC phenotype and developed a reduced VAT volume compared to baseline (B16 - 249.8 µl, - 25%; controls + 85.3 µl, + 10%, p = 0.003) and to healthy controls. LTW was increased in controls compared to melanoma mice. Five melanoma patients responded to CIT, 7 progressed, and 6 displayed a mixed response. Responding patients exhibited a very limited variability in VAT and SCAT in contrast to others. Interestingly, the LTW was decreased in CIT responding patients (- 3.02% ± 2.67%; p = 0.0034) but increased in patients with progressive disease (+ 1.97% ± 2.19%) and mixed response (+ 4.59% ± 3.71%).MRI-based segmentation of fat and water contents adds essential additional information for monitoring the development of CC in mice and metastatic melanoma patients during CIT or other treatment approaches.

  View details for DOI 10.1007/s00262-020-02765-8

  View details for Web of Science ID 000583119500001

  View details for PubMedID 33130917

  View details for PubMedCentralID PMC8053172

• Fully Automated and Standardized Segmentation of Adipose Tissue Compartments via Deep Learning in 3D Whole-Body MRI of Epidemiologic Cohort Studies RADIOLOGY-ARTIFICIAL INTELLIGENCE Kuestner, T., Hepp, T., Fischer, M., Schwartz, M., Fritsche, A., Haering, H., Nikolaou, K., Bamberg, F., Yang, B., Schick, F., Gatidis, S., Machann, J. 2020; 2 (6): e200010

  Abstract

  To enable fast and reliable assessment of subcutaneous and visceral adipose tissue compartments derived from whole-body MRI.Quantification and localization of different adipose tissue compartments derived from whole-body MR images is of high interest in research concerning metabolic conditions. For correct identification and phenotyping of individuals at increased risk for metabolic diseases, a reliable automated segmentation of adipose tissue into subcutaneous and visceral adipose tissue is required. In this work, a three-dimensional (3D) densely connected convolutional neural network (DCNet) is proposed to provide robust and objective segmentation. In this retrospective study, 1000 cases (average age, 66 years ± 13 [standard deviation]; 523 women) from the Tuebingen Family Study database and the German Center for Diabetes research database and 300 cases (average age, 53 years ± 11; 152 women) from the German National Cohort (NAKO) database were collected for model training, validation, and testing, with transfer learning between the cohorts. These datasets included variable imaging sequences, imaging contrasts, receiver coil arrangements, scanners, and imaging field strengths. The proposed DCNet was compared to a similar 3D U-Net segmentation in terms of sensitivity, specificity, precision, accuracy, and Dice overlap.Fast (range, 5-7 seconds) and reliable adipose tissue segmentation can be performed with high Dice overlap (0.94), sensitivity (96.6%), specificity (95.1%), precision (92.1%), and accuracy (98.4%) from 3D whole-body MRI datasets (field of view coverage, 450 × 450 × 2000 mm). Segmentation masks and adipose tissue profiles are automatically reported back to the referring physician.Automated adipose tissue segmentation is feasible in 3D whole-body MRI datasets and is generalizable to different epidemiologic cohort studies with the proposed DCNet.Supplemental material is available for this article.© RSNA, 2020.

  View details for DOI 10.1148/ryai.2020200010

  View details for Web of Science ID 000826480100008

  View details for PubMedID 33937847

  View details for PubMedCentralID PMC8082356

• Simultaneous whole-body PET/MRI with integrated multiparametric MRI for primary staging of high-risk prostate cancer WORLD JOURNAL OF UROLOGY Kaufmann, S., Kruck, S., Gatidis, S., Hepp, T., Thaiss, W. M., Hennenlotter, J., Schwenck, J., Scharpf, M., Nikolaou, K., Stenzl, A., Reischl, G., la Fougere, C., Bedke, J. 2020; 38 (10): 2513-2521

  Abstract

  Whole-body positron emission tomography/magnetic resonance imaging (wbPET/MRI) is a promising diagnostic tool of recurrent prostate cancer (PC), but its role in primary staging of high-risk PC (hrPC) is not well defined. Thus, the aim was to compare the diagnostic accuracy for T-staging of PET-blinded reading (PBR) and PET/MRI.In this prospective study, hrPC patients scheduled to radical prostatectomy (RPx) with extended lymphadenectomy (eLND) were staged with wbPET/MRI and either 68Ga-PSMA-11 or 11C-choline including simultaneous multiparametric MRI (mpMRI). Images were assessed in two sessions, first as PBR (mpMRI and wbMRI) and second as wbPET/MRI. Prostate Imaging Reporting and Data System criteria (PIRADS v2) were used for T-staging. Results were correlated with the exact anatomical localization and extension as defined by histopathology. Diagnostic accuracy of cTNM stage according to PBR was compared to pathological pTNM stage as reference standard.Thirty-four patients underwent wbPET/MRI of 68Ga-PSMA-11 (n = 17) or 11C-choline (n = 17). Twenty-four patients meeting the inclusion criteria of localized disease ± nodal disease based on imaging results underwent RPx and eLND, whereas ten patients were excluded from analysis due to metastatic disease. T-stage was best defined by mpMRI with underestimation of tumor lesion size by PET for both tracers. N-stage yielded a per patient sensitivity/specificity comparable to PBR.MpMRI is the primary modality for T-staging in hrPC as PET underestimated T-stage in direct comparison to final pathology. In this selected study, cohort MRI shows no inferiority compared to wbPET/MRI considering N-staging.

  View details for DOI 10.1007/s00345-019-03066-1

  View details for Web of Science ID 000571851500019

  View details for PubMedID 31907632

  View details for PubMedCentralID 26742998

• Structured reporting in oncologic hybrid imaging: a consensus recommendation NUKLEARMEDIZIN-NUCLEAR MEDICINE Derlin, T., Gatidis, S., Krause, B., Antoch, G., Kotzerke, J., dos Santos, D., Eiber, M., Weber, M., Giesel, F., Pfannenberg, C., Schlemmer, H., Persigehl, T., Herrmann, K., Umutlu, L., Anton, F., Barkhausen, J., Bartenstein, P., Luster, M., Neumann, S., Schoenberg, S. O. 2020; 59 (04): 288-293

  Abstract

  Since the clinical introduction of PET/CT in the year of 2001 and PET/MRI in the year of 2010, hybrid imaging-guided precision medicine has become an important component of diagnostic algorithms in oncology. The written report represents the primary mode of communication between the referring physician and both the nuclear medicine physician and the radiologist. Reports have considerable impact on patient management and patient outcome, and serve as a legal documentation of the services provided and the expert impression of the interpreting physician. A high-quality hybrid imaging study should result in a likewise high-quality, structured written report which satisfactorily answers the clinical question of the referring physician. In this manuscript, consensus recommendations for structure and content of oncologic hybrid imaging reports and conclusive impressions are provided. Moreover, exemplary structured reports are provided. The recommendations for structured reporting provided in this document should foster further standardization and harmonization of oncologic reports in the context of hybrid imaging. They should also simplify communication with referring physicians and support both acceptance and appreciation of the clinical value of oncologic hybrid imaging. CITATION FORMAT: · Derlin T, Gatidis S, Krause BJ et al. Konsensusempfehlung zur strukturierten Befunderstellung onkologischer PET-Hybridbildgebung. Nuklearmedizin 2020; 59: DOI:10.1055/a-1176-0275.

  View details for DOI 10.1055/a-1176-0275

  View details for Web of Science ID 000555834600001

  View details for PubMedID 32544954

• Structured reporting in oncologic hybrid imaging: a consensus recommendation ROFO-FORTSCHRITTE AUF DEM GEBIET DER RONTGENSTRAHLEN UND DER BILDGEBENDEN VERFAHREN Derlin, T., Gatidis, S., Krause, B., Antoch, G., Kotzerke, J., dos Santos, D., Eiber, M., Weber, M., Giesel, F., Pfannenberg, C., Schlemmer, H., Persigehl, T., Herrmann, K., Umutlu, L., Anton, F., Barkhausen, J., Bartenstein, P., Luster, M., Neumann, S., Schoenberg, S. O., Vorstand Interdisziplinaren AG Hyb, Deutsch Rontgengesell DRG, Deutsch Gesell Nukl Med DGN 2020; 192 (8): 739-744

  Abstract

  Since the clinical introduction of PET/CT in the year of 2001 and PET/MRI in the year of 2010, hybrid imaging-guided precision medicine has become an important component of diagnostic algorithms in oncology. The written report represents the primary mode of communication between the referring physician and both the nuclear medicine physician and the radiologist. Reports have considerable impact on patient management and patient outcome, and serve as a legal documentation of the services provided and the expert impression of the interpreting physician. A high-quality hybrid imaging study should result in a likewise high-quality, structured written report which satisfactorily answers the clinical question of the referring physician. In this manuscript, consensus recommendations for structure and content of oncologic hybrid imaging reports and conclusive impressions are provided. Moreover, exemplary structured reports are provided. The recommendations for structured reporting provided in this document should foster further standardization and harmonization of oncologic reports in the context of hybrid imaging. They should also simplify communication with referring physicians and support both acceptance and appreciation of the clinical value of oncologic hybrid imaging. CITATION FORMAT: · Derlin T, Gatidis S, Krause BJ et al. Konsensusempfehlung zur strukturierten Befunderstellung onkologischer PET-Hybridbildgebung. Fortschr Röntgenstr 2020; 192: DOI:10.1055/a-1179-6603.

  View details for DOI 10.1055/a-1179-6603

  View details for Web of Science ID 000590148400002

  View details for PubMedID 32544953

• Clinical and prognostic value of tumor volumetric parameters in melanoma patients undergoing(18)F-FDG-PET/CT: a comparison with serologic markers of tumor burden and inflammation CANCER IMAGING Reinert, C., Gatidis, S., Sekler, J., Dittmann, H., Pfannenberg, C., la Fougere, C., Nikolaou, K., Forschner, A. 2020; 20 (1): 44

  Abstract

  To investigate the association of tumor volumetric parameters in melanoma patients undergoing 18F-FDG-PET/CT with serologic tumor markers and inflammatory markers and the role as imaging predictors for overall survival.A patient cohort with advanced melanoma undergoing 18F-FDG-PET/CT for planning metastasectomy between 04/2013 and 01/2015 was retrospectively included. The volumetric PET parameters whole-body MTV and whole-body TLG as well as the standard uptake value (SUV) peak were quantified using 50%-isocontour volumes of interests (VOIs) and then correlated with the serologic parameters lactate dehydrogenase (LDH), S-100 protein, c-reactive protein (CRP) and alkaline phosphatase (AP). PET parameters were dichotomized by their respective medians and correlated with overall survival (OS) after PET/CT. OS was compared between patients with or without metastases and increased or not-increased serologic parameters.One hundred seven patients (52 female; 65 ± 13.1yr.) were included. LDH was strongly associated with MTV (rP = 0.73, p <  0.001) and TLG (rP = 0.62, p <  0.001), and moderately associated with SUVpeak (rP = 0.55, p <  0.001). S-100 protein showed a moderate association with MTV (rP = 0.54, p <  0.001) and TLG (rP = 0.48, p <  0.001) and a weak association with SUVpeak (rP = 0.42, p <  0.001). A strong association was observed between CRP and MTV (rP = 0.66, p <  0.001) and a moderate to weak association between CRP and TLG (rP = 0.53, p <  0.001) and CRP and SUVpeak (rP = 0.45, p <  0.001). For differentiation between patients with or without metastases, receiver operating characteristic (ROC) analysis revealed a cut-off value of 198 U/l for serum LDH (AUC 0.81, sensitivity 0.80, specificity 0.72). Multivariate analysis for OS revealed that both MTV and TLG were strong independent prognostic factors. TLG, MTV and SUVpeak above patient median were accompanied with significantly reduced estimated OS compared to the PET parameters below patient median (e.g. TLG: 37.1 ± 3.2 months vs. 55.9 ± 2.5 months, p <  0.001). Correspondingly, both elevated serum LDH and S-100 protein were accompanied with significantly reduced OS (36.5 ± 4.9 months and 37.9 ± 4.4 months) compared to normal serum LDH (49.2 ± 2.4 months, p = 0.01) and normal S-100 protein (49.0 ± 2.5 months, p = 0.01).Tumor volumetric parameters in 18F-FDG-PET/CT serve as prognostic imaging biomarkers in patients with advanced melanoma which are associated with established serologic tumor markers and inflammatory markers.

  View details for DOI 10.1186/s40644-020-00322-1

  View details for Web of Science ID 000552723100001

  View details for PubMedID 32631431

  View details for PubMedCentralID PMC7339397

• Independent attenuation correction of whole body [F-18]FDG-PET using a deep learning approach with Generative Adversarial Networks EJNMMI RESEARCH Armanious, K., Hepp, T., Kuestnert, T., Dittmann, H., Nikolaou, K., La Fougere, C., Yang, B., Gatidis, S. 2020; 10 (1): 53

  Abstract

  Attenuation correction (AC) of PET data is usually performed using a second imaging for the generation of attenuation maps. In certain situations however-when CT- or MR-derived attenuation maps are corrupted or CT acquisition solely for the purpose of AC shall be avoided-it would be of value to have the possibility of obtaining attenuation maps only based on PET information. The purpose of this study was to thus develop, implement, and evaluate a deep learning-based method for whole body [18F]FDG-PET AC which is independent of other imaging modalities for acquiring the attenuation map.The proposed method is investigated on whole body [18F]FDG-PET data using a Generative Adversarial Networks (GAN) deep learning framework. It is trained to generate pseudo CT images (CTGAN) based on paired training data of non-attenuation corrected PET data (PETNAC) and corresponding CT data. Generated pseudo CTs are then used for subsequent PET AC. One hundred data sets of whole body PETNAC and corresponding CT were used for training. Twenty-five PET/CT examinations were used as test data sets (not included in training). On these test data sets, AC of PET was performed using the acquired CT as well as CTGAN resulting in the corresponding PET data sets PETAC and PETGAN. CTGAN and PETGAN were evaluated qualitatively by visual inspection and by visual analysis of color-coded difference maps. Quantitative analysis was performed by comparison of organ and lesion SUVs between PETAC and PETGAN.Qualitative analysis revealed no major SUV deviations on PETGAN for most anatomic regions; visually detectable deviations were mainly observed along the diaphragm and the lung border. Quantitative analysis revealed mean percent deviations of SUVs on PETGAN of - 0.8 ± 8.6% over all organs (range [- 30.7%, + 27.1%]). Mean lesion SUVs showed a mean deviation of 0.9 ± 9.2% (range [- 19.6%, + 29.2%]).Independent AC of whole body [18F]FDG-PET is feasible using the proposed deep learning approach yielding satisfactory PET quantification accuracy. Further clinical validation is necessary prior to implementation in clinical routine applications.

  View details for DOI 10.1186/s13550-020-00644-y

  View details for Web of Science ID 000536942500002

  View details for PubMedID 32449036

  View details for PubMedCentralID PMC7246235

• Combined positron emission tomography and magnetic resonance imaging (PET/MRI) in children and adolescents MONATSSCHRIFT KINDERHEILKUNDE Schaefer, J. F., Tsiflikas, I., Esser, M., Dittmann, H., Bender, B., Gatidis, S. 2020; 168 (5): 416-426

  View details for DOI 10.1007/s00112-020-00889-w

  View details for Web of Science ID 000523062500001

• PET/MRI and genetic intrapatient heterogeneity in head and neck cancers STRAHLENTHERAPIE UND ONKOLOGIE Clasen, K., Leibfarth, S., Hilke, F. J., Admard, J., Winter, R. M., Welz, S., Gatidis, S., Nann, D., Ossowski, S., Breuer, T., la Fougere, C., Nikolaou, K., Riess, O., Zips, D., Schroeder, C., Thorwarth, D. 2020; 196 (6): 542-551

  Abstract

  The relation between functional imaging and intrapatient genetic heterogeneity remains poorly understood. The aim of our study was to investigate spatial sampling and functional imaging by FDG-PET/MRI to describe intrapatient tumour heterogeneity.Six patients with oropharyngeal cancer were included in this pilot study. Two tumour samples per patient were taken and sequenced by next-generation sequencing covering 327 genes relevant in head and neck cancer. Corresponding regions were delineated on pretherapeutic FDG-PET/MRI images to extract apparent diffusion coefficients and standardized uptake values.Samples were collected within the primary tumour (n = 3), within the primary tumour and the involved lymph node (n = 2) as well as within two independent primary tumours (n = 1). Genetic heterogeneity of the primary tumours was limited and most driver gene mutations were found ubiquitously. Slightly increasing heterogeneity was found between primary tumours and lymph node metastases. One private predicted driver mutation within a primary tumour and one in a lymph node were found. However, the two independent primary tumours did not show any shared mutations in spite of a clinically suspected field cancerosis. No conclusive correlation between genetic heterogeneity and heterogeneity of PET/MRI-derived parameters was observed.Our limited data suggest that single sampling might be sufficient in some patients with oropharyngeal cancer. However, few driver mutations might be missed and, if feasible, spatial sampling should be considered. In two independent primary tumours, both lesions should be sequenced. Our data with a limited number of patients do not support the concept that multiparametric PET/MRI features are useful to guide biopsies for genetic tumour characterization.

  View details for DOI 10.1007/s00066-020-01606-y

  View details for Web of Science ID 000521726000004

  View details for PubMedID 32211941

• Association between metabolic syndrome and hip osteoarthritis in middle-aged men and women from the general population PLOS ONE Walter, S. S., Wintermeyer, E., Klinger, C., Lorbeer, R., Rathmann, W., Peters, A., Schlett, C. L., Thorand, B., Gatidis, S., Nikolaou, K., Bamberg, F., Notohamiprodjo, M. 2020; 15 (3): e0230185

  Abstract

  To investigate the impact of metabolic syndrome and its components on osteoarthritis of the hip joints compared to a healthy cohort in the KORA MRI-study.Randomly selected men and women from the general population were classified as having metabolic syndrome, defined as presence of central obesity plus two of the following four components: elevated blood pressure (BP), elevated fasting glucose, elevated triglycerides (TG) and low HDL-cholesterol (HDL-c), or as controls without metabolic syndrome. Therefore, each subject underwent detailed assessment of waist circumference as well as fasting glucose, systolic and diastolic BP, TG, and HDL-c concentrations as well as a full-body MR scan. MR measurements were performed on a 3 Tesla scanner (Magnetom Skyra, Siemens) including a dual-echo Dixon and a T2 SS-FSE sequence for anatomical structures. In order to quantify osteoarthritis of the hip, assessment was performed by two independent, experienced radiologists for joint gap narrowing, osteophytic lipping and subchondral changes (e.g. sclerosis, pseudocysts). Associations between metabolic syndrome components and hip degeneration were estimated by logistic regression models providing odds ratios.Among 354 included participants (mean age: 56.1 ± 9.2 years; 55.4% male), 119 (34%) had metabolic syndrome, while 235 (66%) were part of the control group. Except for elevated blood glucose (p = 0.02), none of the metabolic syndromes' component was independently associated with osteoarthritis. Multivariable adjusted ORs for osteoarthritis of the right hip were 1.00 (95% CI 0.98;1.03), 1.00 (95% CI 0.99;1.00), 1.01 (95% CI 0.99;1.03), 1.00 (95% CI 0.97;1.04) and 1.01 (95% CI 0.96;1.06), and for the left hip 1.00 (95% CI 0.98;1.03), 1.00 (95% CI 1.00;1.01), 1.01 (95% CI 0.99;1.03), 0.99 (95% CI 0.96;1.02) and 1.04 (95% CI 0.99;1.09) for waist circumference, triglyceride, HDL-c and systolic and diastolic BP, respectively. Blood glucose was a borderline non-dependent factor for osteoarthritis of the right hip (OR: 1.02 (95% CI 1.0;1.04); p = 0.05). Furthermore, the compound metabolic syndrome was not significantly associated (OR left hip: 1.53 (95% CI 0.8;2.92), p = 0.20; OR right hip: 1.33 (95% CI 0.72;2.45), p = 0.37) with osteoarthritis of the hip joint. Age as well as gender (left hip) were the only parameters in univariate and multivariate analysis to be significantly associated with osteoarthritis of the hip joint.The compound metabolic syndrome showed no association with osteoarthritis of the hip joint. Age was the only parameter to be dependently and independently associated to osteoarthritis of both hip joints, while elevated blood glucose was independently associated with degeneration of the right hip joint.

  View details for DOI 10.1371/journal.pone.0230185

  View details for Web of Science ID 000535278500071

  View details for PubMedID 32155212

  View details for PubMedCentralID PMC7064195

• Effects of simulated dose variation on contrast-enhanced CT-based radiomic analysis for Non-Small Cell Lung Cancer EUROPEAN JOURNAL OF RADIOLOGY Hepp, T., Othman, A., Liebgott, A., Kim, J., Pfannenberg, C., Gatidis, S. 2020; 124: 108804

  Abstract

  To examine the potential effect of CT dose variation on radiomic features in vivo using simulated contrast-enhanced CT dose reduction in patients with non-small lung cell cancer (NSCLC).In this retrospective study, we included 69 patients (25 females, 44 males, median age 66 years) with histologically proven NSCLC who underwent a whole contrast-enhanced body FDG-PET/CT for primary staging. To simulate different CT dose levels, we used an algorithm to simulate low-dose CT images based on a noise model derived from phantom experiments. The tumor lesions and reference regions in the paraspinal muscle were manually segmented to obtain three-dimensional regions of interest. Radiomic feature extraction was performed using the PyRadiomics toolbox. The median relative feature value deviation was assessed for each feature and each dose level.The mean segmented tumor volume was 340 ml. T-stages of the primary tumors were primarily T3/4. For NSCLCs, the median relative feature value deviation in the lowest dose images varied for the calculated features from 52.2% to -49.5%. In general, dose-dependent deviations of feature values showed a monotonous increase or decrease with decreasing dose levels. Statistical analyses revealed significant differences between the dose levels in 91% of features.We examined the effects of simulated CT dose reduction on the values of radiomic features in primary NSCLC and showed significant deviations of varying degrees in numerous feature classes. This is a theoretical indicator of potential influence under real conditions, which should be taken into account in clinical use.

  View details for DOI 10.1016/j.ejrad.2019.108804

  View details for Web of Science ID 000512890500006

  View details for PubMedID 31926387

• Impact of PET/CT on clinical management in patients with cancer of unknown primary-a PET/CT registry study EUROPEAN RADIOLOGY Reinert, C., Sekler, J., la Fougere, C., Pfannenberg, C., Gatidis, S. 2020; 30 (3): 1325-1333

  Abstract

  To evaluate the impact of PET/CT on clinical management in patients with cancer of unknown primary (CUP).A cohort of patients with CUP undergoing PET/CT was prospectively enrolled in a local PET/CT registry study between April 2013 and June 2018. Questionnaire data from referring physicians on intended patient management prior and after PET/CT were recorded including items on the intended treatment concept and intended additional diagnostics. Changes in management after PET/CT were recorded. Patient outcome of different cohorts was analyzed for overall survival drawn from patient records.One hundred fifty-five patients (53 female; 63.4 ± 12.1 years) were included. Intended therapeutic management was revised in 45.8% of patients after PET/CT, including major changes affecting the intended treatment goal in 26.5% of patients and minor changes (therapy adjustments) in 19.3% of patients. Invasive and additional diagnostic procedures were intended in 25.8% and 63.2% prior PET/CT and 13.5% and 6.5% after PET/CT. PET/CT-based curative therapy concepts were associated with significantly longer patient survival (4.7 ± 0.3 years) than palliative therapy concepts (1.8 ± 0.5 years, p = .0001). Patients with cervical CUP showed a significantly longer survival (4.3 ± 0.3 years) than patients with extracervical CUP (3.5 ± 0.5 years, p = .01). The identification of the primary did not significantly affect survival.This registry study confirms previous studies reporting that PET/CT significantly influences clinical management in patients with CUP, helping physicians to select a more individualized treatment and to avoid additional diagnostics. Furthermore, we could confirm that tumor localization and extent as shown by PET/CT have a significant impact on patient prognosis.• PET/CT significantly influences intended clinical management in patients with CUP, helping physicians to select a more individualized treatment and to avoid additional diagnostics. • Tumor localization and extent as shown by PET/CT have a significant impact on patient prognosis. • The identification of the primary tumor has no significant impact on overall patient survival.

  View details for DOI 10.1007/s00330-019-06518-9

  View details for Web of Science ID 000517458800004

  View details for PubMedID 31728688

• New severity assessment in cystic fibrosis: signal intensity and lung volume compared to LCI and FEV1: preliminary results EUROPEAN RADIOLOGY Fleischer, S., Kraus, M., Gatidis, S., Baden, W., Hector, A., Hartl, D., Tsiflikas, I., Schaefer, J. 2020; 30 (3): 1350-1358

  Abstract

  Magnetic resonance imaging (MRI) aids diagnosis in cystic fibrosis (CF) but its use in quantitative severity assessment is under research. This study aims to assess changes in signal intensity (SI) and lung volumes (Vol) during functional MRI and their use as a severity assessment tool in CF patients.The CF intra-hospital standard chest 1.5 T MRI protocol comprises of very short echo-time sequences in submaximal in- and expiration for functional information. Quantitative measurements (Vol/SI at in- and expiration, relative differences (Vol_delta/SI_delta), and cumulative histograms for normalized SI values across the expiratory lung volume) were assessed for correlation to pulmonary function: lung clearance index (LCI) and forced expiratory volume in 1 s (FEV1).In 49 patients (26 male, mean age 17 ± 7 years) significant correlation of Vol_delta and SI_delta (R = 0.86; p < 0.0001) during respiration was observed. Individual cumulated histograms enabled severity disease differentiation (mild, severe) to be visualized (defined by functional parameter: LCI > 10). The expiratory volume at a relative SI of 100% correlated significantly to LCI (R = 0.676 and 0.627; p < 0.0001) and FEV1 (R = - 0.847 and - 0.807; p < 0.0001). Clustering patients according to Vol_SI_100 showed that an amount of ≤ 4% was related to normal, while an amount of > 4% was associated with pathological pulmonary function values.Functional pulmonary MRI provides a radiation-free severity assessment tool and can contribute to early detection of lung impairment in CF. Lung volume with SI below 100% of the inspiratory volume represents overinflated tissue; an amount of 4% of the expiratory lung volume was a relevant turning point.• Signal intensity and lung volumes are used as potential metric parameters for lung impairment. • Quantification of trapped air impacts on therapy management. • Functional pulmonary MRI can contribute to early detection of lung impairment.

  View details for DOI 10.1007/s00330-019-06462-8

  View details for Web of Science ID 000517458800007

  View details for PubMedID 31728685

• Paraneoplastic syndrome in undifferentiated embryonic sarcoma of the liver EJNMMI RESEARCH Perl, R., Haering, A., Horger, M., Pfannenberg, C., Gatidis, S. 2020; 10 (1): 11

  Abstract

  The undifferentiated embryonic sarcoma of the liver (UESL) is a rare, aggressive tumor mainly affecting children. Since UESL has no specific clinical symptoms or imaging characteristics, many cases of UESL are diagnosed late. The paraneoplastic leukemoid reaction (PLR) is a very rare concomitant of oncological patients associated with poor prognosis. This report describes the clinical course of a patient combining these two rare entities and describes the diagnostic challenges and dynamics of paraneoplastic syndrome.We report a case of UESL in a 46-year-old male who became clinically conspicuous due to pronounced B symptoms. CT and MRI showed a suspicious unifocal liver lesion. As the histological analysis of a tissue sample did not reveal a clear result, an 18F-FDG-PET-CT examination was performed. In addition to a high glucose metabolism of the liver lesion, an increased glucose metabolism in the entire bone marrow was observed. This finding was considered as pronounced paraneoplasia and laparotomy with liver segment resection followed. Immediately after resection of the tumor the paraneoplastic symptoms completely declined and the patient showed no signs of recurrence in the 1-year follow-up.Although UESL is rare and predominantly affects children, this diagnosis should always be considered for unclear unifocal cystic liver lesions, regardless of the patient's age, as appropriate treatment has a good prognosis.

  View details for DOI 10.1186/s13550-020-0602-x

  View details for Web of Science ID 000514803100001

  View details for PubMedID 32072333

  View details for PubMedCentralID PMC7028890

• Therapy Response Assessment of Pediatric Tumors with Whole-Body Diffusion-weighted MRI and FDG PET/MRI. Radiology Theruvath, A. J., Siedek, F. n., Muehe, A. M., Garcia-Diaz, J. n., Kirchner, J. n., Martin, O. n., Link, M. P., Spunt, S. n., Pribnow, A. n., Rosenberg, J. n., Herrmann, K. n., Gatidis, S. n., Schäfer, J. F., Moseley, M. n., Umutlu, L. n., Daldrup-Link, H. E. 2020: 192508

  Abstract

  Background Whole-body diffusion-weighted (DW) MRI can help detect cancer with high sensitivity. However, the assessment of therapy response often requires information about tumor metabolism, which is measured with fluorine 18 fluorodeoxyglucose (FDG) PET. Purpose To compare tumor therapy response with whole-body DW MRI and FDG PET/MRI in children and young adults. Materials and Methods In this prospective, nonrandomized multicenter study, 56 children and young adults (31 male and 25 female participants; mean age, 15 years ± 4 [standard deviation]; age range, 6-22 years) with lymphoma or sarcoma underwent 112 simultaneous whole-body DW MRI and FDG PET/MRI between June 2015 and December 2018 before and after induction chemotherapy (ClinicalTrials.gov identifier: NCT01542879). The authors measured minimum tumor apparent diffusion coefficients (ADCs) and maximum standardized uptake value (SUV) of up to six target lesions and assessed therapy response after induction chemotherapy according to the Lugano classification or PET Response Criteria in Solid Tumors. The authors evaluated agreements between whole-body DW MRI- and FDG PET/MRI-based response classifications with Krippendorff α statistics. Differences in minimum ADC and maximum SUV between responders and nonresponders and comparison of timing for discordant and concordant response assessments after induction chemotherapy were evaluated with the Wilcoxon test. Results Good agreement existed between treatment response assessments after induction chemotherapy with whole-body DW MRI and FDG PET/MRI (α = 0.88). Clinical response prediction according to maximum SUV (area under the receiver operating characteristic curve = 100%; 95% confidence interval [CI]: 99%, 100%) and minimum ADC (area under the receiver operating characteristic curve = 98%; 95% CI: 94%, 100%) were similar (P = .37). Sensitivity and specificity were 96% (54 of 56 participants; 95% CI: 86%, 99%) and 100% (56 of 56 participants; 95% CI: 54%, 100%), respectively, for DW MRI and 100% (56 of 56 participants; 95% CI: 93%, 100%) and 100% (56 of 56 participants; 95% CI: 54%, 100%) for FDG PET/MRI. In eight of 56 patients who underwent imaging after induction chemotherapy in the early posttreatment phase, chemotherapy-induced changes in tumor metabolism preceded changes in proton diffusion (P = .002). Conclusion Whole-body diffusion-weighted MRI showed significant agreement with fluorine 18 fluorodeoxyglucose PET/MRI for treatment response assessment in children and young adults. © RSNA, 2020 Online supplemental material is available for this article.

  View details for DOI 10.1148/radiol.2020192508

  View details for PubMedID 32368961

• MedGAN: Medical image translation using GANs COMPUTERIZED MEDICAL IMAGING AND GRAPHICS Armanious, K., Jiang, C., Fischer, M., Kuestner, T., Nikolaou, K., Gatidis, S., Yang, B. 2020; 79: 101684

  Abstract

  Image-to-image translation is considered a new frontier in the field of medical image analysis, with numerous potential applications. However, a large portion of recent approaches offers individualized solutions based on specialized task-specific architectures or require refinement through non-end-to-end training. In this paper, we propose a new framework, named MedGAN, for medical image-to-image translation which operates on the image level in an end-to-end manner. MedGAN builds upon recent advances in the field of generative adversarial networks (GANs) by merging the adversarial framework with a new combination of non-adversarial losses. We utilize a discriminator network as a trainable feature extractor which penalizes the discrepancy between the translated medical images and the desired modalities. Moreover, style-transfer losses are utilized to match the textures and fine-structures of the desired target images to the translated images. Additionally, we present a new generator architecture, titled CasNet, which enhances the sharpness of the translated medical outputs through progressive refinement via encoder-decoder pairs. Without any application-specific modifications, we apply MedGAN on three different tasks: PET-CT translation, correction of MR motion artefacts and PET image denoising. Perceptual analysis by radiologists and quantitative evaluations illustrate that the MedGAN outperforms other existing translation approaches.

  View details for DOI 10.1016/j.compmedimag.2019.101684

  View details for Web of Science ID 000514014200007

  View details for PubMedID 31812132

• UNSUPERVISED ADVERSARIAL CORRECTION OF RIGID MR MOTION ARTIFACTS Armanious, K., Tanwar, A., Abdulatif, S., Kuestner, T., Gatidis, S., Bin Yang, IEEE IEEE. 2020: 1494-1498

  View details for Web of Science ID 000578080300309

• Bayesian Neural Networks for Uncertainty Estimation of Imaging Biomarkers Senapati, J., Roy, A., Polsterl, S., Gutmann, D., Gatidis, S., Schlett, C., Peters, A., Bamberg, F., Wachinger, C., Liu, M., Yan, P., Lian, C., Cao SPRINGER INTERNATIONAL PUBLISHING AG. 2020: 270-280

  View details for DOI 10.1007/978-3-030-59861-7_28

  View details for Web of Science ID 000927856100028

• ipA-MedGAN: INPAINTING OF ARBITRARY REGIONS IN MEDICAL IMAGING Armanious, K., Kumar, V., Abdulatif, S., Hepp, T., Gatidis, S., Yang, B., IEEE IEEE. 2020: 3005-3009

  View details for Web of Science ID 000646178503023

• Deep-learning based motion-corrected image reconstruction in 4D magnetic resonance imaging of the body trunk Kuestner, T., Pan, J., Gilliam, C., Qi, H., Cruz, G., Hammernik, K., Yang, B., Blu, T., Rueckert, D., Botnar, R., Prieto, C., Gatidis, S., IEEE IEEE. 2020: 976-985

  View details for Web of Science ID 000678729400168

• Baseline clinical and imaging predictors of treatment response and overall survival of patients with metastatic melanoma undergoing immunotherapy EUROPEAN JOURNAL OF RADIOLOGY Schraag, A., Klumpp, B., Afat, S., Gatidis, S., Nikolaou, K., Eigentler, T. K., Othman, A. E. 2019; 121: 108688

  Abstract

  We aimed to identify predictive clinical and CT imaging biomarkers and assess their predictive capacity regarding overall survival (OS) and treatment response in patients with metastatic melanoma undergoing immunotherapy.The local institutional ethics committee approved this retrospective study and waived informed patient consent. 103 patients with immunotherapy for metastatic melanoma were randomly divided into training (n = 69) and validation cohort (n = 34). Baseline tumor markers (LDH, S100B), baseline CT imaging biomarkers (tumor burden, Choi density) and CT texture parameters (Entropy, Kurtosis, Skewness, uniformity, MPP, UPP) of the largest target lesion were extracted. To identify treatment response predictors, binary logistic regression analysis was performed in the training cohort and tested in the validation cohort. For OS, Cox regression and Kaplan Maier analyses were performed in the training cohort. Bivariate and multivariate models were established. Goodness of fit was assessed with Harrell's C-index. Potential predictors were tested in the validation cohort also using Cox-regression and Kaplan-Meier analyses.Baseline S100B (Hazard ratio(HR) = 2.543, p0.018), tumor burden (HR = 1.657, p = 0.002) and Kurtosis (HR = 2.484, p < 0.001) were independent predictors of OS and were confirmed in the validation cohort (p < 0.048). Tumor burden and Kurtosis showed incremental predictive capacity allowing a good predictive model when combined with baseline S100B levels (C-index = 0.720). Only S100B was predictive of treatment response (OR ≤ 0.630, p ≤ 0.022). Imaging biomarkers did not predict treatment response.We identified easily obtainable baseline clinical (S100B) and CT predictors (tumor burden and Kurtosis) of OS in patients with metastatic melanoma undergoing immunotherapy. However, imaging predictors did not predict treatment response.

  View details for DOI 10.1016/j.ejrad.2019.108688

  View details for Web of Science ID 000500465900006

  View details for PubMedID 31704599

• Assessment of Hepatic Perfusion Using GRASP MRI Bringing Liver MRI on a New Level INVESTIGATIVE RADIOLOGY Weiss, J., Ruff, C., Grosse, U., Groezinger, G., Horger, M., Nikolaou, K., Gatidis, S. 2019; 54 (12): 737-743

  Abstract

  The aim of this study was to demonstrate the feasibility of hepatic perfusion imaging using dynamic contrast-enhanced (DCE) golden-angle radial sparse parallel (GRASP) magnetic resonance imaging (MRI) for characterizing liver parenchyma and hepatocellular carcinoma (HCC) before and after transarterial chemoembolization (TACE) as a potential alternative to volume perfusion computed tomography (VPCT).Between November 2017 and September 2018, 10 patients (male = 8; mean age, 66.5 ± 8.6 years) with HCC were included in this prospective, institutional review board-approved study. All patients underwent DCE GRASP MRI with high spatiotemporal resolution after injection of liver-specific MR contrast agent before and after TACE. In addition, VPCT was acquired before TACE serving as standard of reference. From the dynamic imaging data of DCE MRI and VPCT, perfusion maps (arterial liver perfusion [mL/100 mL/min], portal liver perfusion [mL/100 mL/min], hepatic perfusion index [%]) were calculated using a dual-input maximum slope model and compared with assess perfusion measures, lesion characteristics, and treatment response using Wilcoxon signed-rank test. To evaluate interreader agreement for measurement repeatability, the interclass correlation coefficient (ICC) was calculated.Perfusion maps could be successfully generated from all DCE MRI and VPCT data. The ICC was excellent for all perfusion maps (ICC ≥ 0.88; P ≤ 0.001). Image analyses revealed perfusion parameters for DCE MRI and VPCT within the same absolute range for tumor and liver tissue. Dynamic contrast-enhanced MRI further enabled quantitative assessment of treatment response showing a significant decrease (P ≤ 0.01) of arterial liver perfusion and hepatic perfusion index in the target lesion after TACE.Dynamic contrast-enhanced GRASP MRI allows for a reliable and robust assessment of hepatic perfusion parameters providing quantitative results comparable to VPCT and enables characterization of HCC before and after TACE, thus posing the potential to serve as an alternative to VPCT.

  View details for DOI 10.1097/RLI.0000000000000586

  View details for Web of Science ID 000497657600001

  View details for PubMedID 31206392

• Retrospective correction of motion-affected MR images using deep learning frameworks MAGNETIC RESONANCE IN MEDICINE Kuestner, T., Armanious, K., Yang, J., Yang, B., Schick, F., Gatidis, S. 2019; 82 (4): 1527-1540

  Abstract

  Motion is 1 extrinsic source for imaging artifacts in MRI that can strongly deteriorate image quality and, thus, impair diagnostic accuracy. In addition to involuntary physiological motion such as respiration and cardiac motion, intended and accidental patient movements can occur. Any impairment by motion artifacts can reduce the reliability and precision of the diagnosis and a motion-free reacquisition can become time- and cost-intensive. Numerous motion correction strategies have been proposed to reduce or prevent motion artifacts. These methods have in common that they need to be applied during the actual measurement procedure with a-priori knowledge about the expected motion type and appearance. For retrospective motion correction and without the existence of any a-priori knowledge, this problem is still challenging.We propose the use of deep learning frameworks to perform retrospective motion correction in a reference-free setting by learning from pairs of motion-free and motion-affected images. For this image-to-image translation problem, we propose and compare a variational auto encoder and generative adversarial network. Feasibility and influences of motion type and optimal architecture are investigated by blinded subjective image quality assessment and by quantitative image similarity metrics.We observed that generative adversarial network-based motion correction is feasible producing near-realistic motion-free images as confirmed by blinded subjective image quality assessment. Generative adversarial network-based motion correction accordingly resulted in images with high evaluation metrics (normalized root mean squared error <0.08, structural similarity index >0.8, normalized mutual information >0.9).Deep learning-based retrospective restoration of motion artifacts is feasible resulting in near-realistic motion-free images. However, the image translation task can alter or hide anatomical features and, therefore, the clinical applicability of this technique has to be evaluated in future studies.

  View details for DOI 10.1002/mrm.27783

  View details for Web of Science ID 000483917000025

  View details for PubMedID 31081955

• Independent brain F-18-FDG PET attenuation correction using a deep learning approach with Generative Adversarial Networks HELLENIC JOURNAL OF NUCLEAR MEDICINE Armanious, K., Kuestner, T., Reimold, M., Nikolaou, K., La Fougere, C., Yang, B., Gatidis, S. 2019; 22 (3): 179-186

  Abstract

  Attenuation correction (AC) of positron emission tomography (PET) data poses a challenge when no transmission data or computed tomography (CT) data are available, e.g. in stand alone PET scanners or PET/magnetic resonance imaging (MRI). In these cases, external imaging data or morphological imaging data are normally used for the generation of attenuation maps. Newly introduced machine learning methods however may allow for direct estimation of attenuation maps from non attenuation-corrected PET data (PETNAC). Our purpose was thus to establish and evaluate a method for independent AC of brain fluorine-18-fluorodeoxyglucose (18F-FDG) PET images only based on PETNAC using Generative Adversarial Networks (GAN).After training of the deep learning GAN framework on a paired training dataset of PETNAC and the corresponding CT images of the head from 50 patients, pseudo-CT images were generated from PETNAC of 40 validation patients, of which 20 were used for technical validation and 20 stemming from patients with CNS disorders were used for clinical validation. Pseudo-CT was used for subsequent AC of these validation data sets resulting in independently attenuation-corrected PET data.Visual inspection revealed a high degree of resemblance of generated pseudo-CT images compared to the acquired CT images in all validation data sets, with minor differences in individual anatomical details. Quantitative analyses revealed minimal underestimation below 5% of standardized uptake value (SUV) in all brain regions in independently attenuation-corrected PET data compared to the reference PET images. Color-coded error maps showed no regional bias and only minimal average errors around ±0%. Using independently attenuation-corrected PET data, no differences in image-based diagnoses were observed in 20 patients with neurological disorders compared to the reference PET images.Independent AC of brain 18F-FDG PET is feasible with high accuracy using the proposed, easy to implement deep learning framework. Further evaluation in clinical cohorts will be necessary to assess the clinical performance of this method.

  View details for Web of Science ID 000506147400004

  View details for PubMedID 31587027

• Comprehensive metabolic and morphologic disease characterization in systemic sclerosis: initial results using combined positron emission tomography and magnetic resonance imaging QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Sauter, A. W., Gatidis, S., Schwenzer, N. F., La Fougere, C., Nikolaou, K., Henes, J. C., Horger, M. 2019; 63 (2): 207-215

  Abstract

  The aim of this study was to evaluate the role of metabolic and morphologic parameters derived from simultaneous hybrid PET/MRI in correlation to clinical criteria for an image-based characterization of musculoskeletal, esophagus and lymph node involvement in systemic sclerosis (SSc).Between November 2013 and May 2015, simultaneous whole-body hybrid PET/MRI was performed in 13 prospectively recruited patients with SSc. A mean dose of 241.3 MBq 2-deoxy-2-[18F]fluoro-D-glucose (FDG) was injected. SUVmean and SUVmax values were measured in the spinal bone marrow, spleen, joints, muscles, fasciae, mediastinal lymph nodes and esophagus. MRI abnormalities were scored as 0 (absent), 1 (moderate) and 2 (marked). In addition, organ and skin involvement were graded with clinical sum score (CSS) and modified Rodnan skin score (mRSS), respectively.Results indicate positive correlations between mRSS and fascial FDG-uptake values (fascia summed SUVmax ρ=0.67; fascia summed SUVmean ρ=0.66) that performed better than the MRI sum score (ρ=0.50). Fascial FDG-uptake is also useful in the differentiation between diffuse and limited SSc. Additionally, FDG-PET detected patients with active mediastinal lymphadenopathy and MRI proved to be useful for the delineation of esophagus involvement.Fascial FDG-uptake has a strong correlation with mRSS and can discriminate between limited and diffuse SSc. These results and the detection of active lymphadenopathy and esophagus involvement can identify patients with advanced scleroderma. Combined PET/MRI therefore provides complementary information on the complex pathophysiology and may integrate several imaging procedures in one.

  View details for DOI 10.23736/S1824-4785.17.02966-1

  View details for Web of Science ID 000486419900012

  View details for PubMedID 28478666

• Genetic and imaging intratumoral Heterogeneity in Patients with Head and Neck Tumors Zwirner, K., Leibfarth, S., Hilke, F. J., Matthes, J., Winter, R., Welz, S., Gatidis, S., Nann, D., Ossowski, S., Breuer, T., La Fougere, C., Nikolaou, K., Riess, O., Schroeder, C., Thorwarth, D., Zips, D. SPRINGER HEIDELBERG. 2019: S130

  View details for Web of Science ID 000468853300276

• State of affairs of hybrid imaging in Europe: two multi-national surveys from 2017 INSIGHTS INTO IMAGING Gatidis, S., Beyer, T., Becker, M., Riklund, K., Nikolaou, K., Cyran, C., Pfannenberg, C. 2019; 10 (1): 57

  Abstract

  To assess the current state of hybrid imaging in Europe with respect to operations, reading and reporting, as well as qualification and training.The first survey (LOCAL) was sent to the heads of the departments of radiology and nuclear medicine in Europe in 2017, including 15 questions regarding the organisation of hybrid imaging operations, reporting strategies for PET/CT and the existence of relevant training programmes. The second survey (NATIONAL) consisted of 10 questions and was directed to the national ministries of health of 37 European countries addressing combined training options in radiology and nuclear medicine.In the LOCAL survey, 61 valid responses from 26 European countries were received. In almost half of the institutions, hybrid imaging was performed within a single department, mainly in nuclear medicine departments (31%). In half of the centres (51%), PET/CT reports were performed jointly, while in 20% of the centres, reporting was performed by nuclear medicine physicians. Radiologists were responsible for presenting hybrid imaging results in clinical boards in 34% of responding sites. Integrated hybrid imaging training was available in 41% sites. In the NATIONAL survey, responses from 34 countries were received and demonstrated a heterogeneous landscape of official training possibilities in radiology and nuclear medicine with limited opportunities for additional qualifications in hybrid imaging.The results of these surveys demonstrate a notable heterogeneity in the current practice of hybrid imaging throughout Europe. This heterogeneity exists despite the general consensus that strong professional cooperation is required in order to ensure high clinical quality and to strengthen the clinical role of hybrid imaging.

  View details for DOI 10.1186/s13244-019-0741-7

  View details for Web of Science ID 000468757300003

  View details for PubMedID 31115706

  View details for PubMedCentralID PMC6529476

• FDG-PET/MRI combined with SPECT/CT guided sentinel lymph node mapping for lymph node staging in patients with early stage cervical and endometrial carcinoma: a prospective study. Weissinger, M., Taran, F., Brucker, S., Reimold, M., Gatidis, S., Pfannenberg, C., Nikolaou, K., La Fougare, C., Dittmann, H. SOC NUCLEAR MEDICINE INC. 2019

  View details for Web of Science ID 000473116800550

• Whole-Body [18F]-FDG-PET/MRI for Oncology: A Consensus Recommendation ROFO-FORTSCHRITTE AUF DEM GEBIET DER RONTGENSTRAHLEN UND DER BILDGEBENDEN VERFAHREN Umutlu, L., Beyer, T., Grueneisen, J., Rischpler, C., Quick, H. H., Veit-Haibach, P., Eiber, M., Purz, S., Antoch, G., Gatidis, S., Nikolaou, K., Schaefer, J. F., Rausch, I., Herrmann, K., Herrmann, K., Krause, B. J., Schoenberg, S. O., Umutlu, L., Anton, F., Antoch, G., Hacker, M., Krause, B. J., Luster, M., Neumann, S., Schoenberg, S. O., Vorwerk, D., Schoenberg, S., Vorwerk, D., Antoch, G., Anton, F., Neumann, S., Deutschen Rontgengesell DRG, DGN 2019; 191 (4): 289-297

  Abstract

  Combined PET/MR imaging (PET/MRI) was proposed for patient management in 2006 with first commercial versions of integrated whole-body systems becoming available as of 2010. PET/MRI followed the prior evolution of hybrid imaging as attested by the successful adoption of combined PET/CT and SPECT/CT since the early 2000 s. Today, around 150 whole-body PET/MRI systems have become operational worldwide. One of the main application fields of PET/MRI is oncologic imaging. Despite the increasing use of PET/MRI, little governance regarding standardized PET/MRI protocols has been provided to date. Standardization and harmonization of imaging protocols is, however, mandatory for efficient on-site patient management and multi-center studies. This document summarizes consensus recommendations on key aspects of patient referral and preparation, PET/MRI workflow and imaging protocols, as well as reporting strategies for whole-body [18F]-FDG-PET/MRI. These recommendations were created by early adopters and key experts in the field of PET, MRI and PET/MRI. This document is intended to provide guidance for the harmonization and standardization of PET/MRI today and to support wider clinical adoption of this imaging modality for the benefit of patients. CITATION FORMAT: · Umutlu L, Beyer T, Grueneisen JS et al. Whole-Body [18F]-FDG-PET/MRI for Oncology: A Consensus Recommendation. Fortschr Röntgenstr 2019; 191: 289 - 297.

  View details for DOI 10.1055/a-0828-8654

  View details for Web of Science ID 000463102800003

  View details for PubMedID 30818411

• Whole-Body [18F]-FDG-PET/MRI for Oncology: A Consensus Recommendation NUKLEARMEDIZIN-NUCLEAR MEDICINE Umutlu, L., Beyer, T., Grueneisen, J., Rischpler, C., Quick, H. H., Veit-Halbach, P., Eiber, M., Purz, S., Antoch, G., Gatidis, S., Nikolaou, K., Schaefer, J. F., Rausch, I., Herrmann, K., Herrmann, K., Krause, B. J., Schoenberg, S. O., Umutlu, L., Anton, F., Antoch, G., Hacker, M., Krause, B. J., Luster, M., Neumann, S., Schoenberg, S. O., Vorwerk, D. 2019; 58 (2): 68-76

  Abstract

  Combined PET/MR imaging (PET/MRI) was proposed for patient management in 2006 with first commercial versions of integrated whole-body systems becoming available as of 2010. PET/MRI followed the prior evolution of hybrid imaging as attested by the successful adoption of combined PET/CT and SPECT/CT since the early 2000 s. Today, around 150 whole-body PET/MRI systems have become operational worldwide. One of the main application fields of PET/MRI is oncologic imaging. Despite the increasing use of PET/MRI, little governance regarding standardized PET/MRI protocols has been provided to date. Standardization and harmonization of imaging protocols is, however, mandatory for efficient on-site patient management and multi-center studies. This document summarizes consensus recommendations on key aspects of patient referral and preparation, PET/MRI workflow and imaging protocols, as well as reporting strategies for whole-body [18F]-FDG-PET/MRI. These recommendations were created by early adopters and key experts in the field of PET, MRI and PET/MRI. This document is intended to provide guidance for the harmonization and standardization of PET/ MRI today and to support wider clinical adoption of this imaging modality for the benefit of patients. CITATION FORMAT:: Umutlu L, Beyer T, Grueneisen JS et al. Whole-Body [18F]-FDG-PET/MRI for Oncology: A Consensus Recommendation. Nuklearmedizin 2019, 58: 1-9.

  View details for DOI 10.1055/a-0830-4453

  View details for Web of Science ID 000463226700002

  View details for PubMedID 30818412

• Comprehensive anatomical and functional imaging in patients with type I neurofibromatosis using simultaneous FDG-PET/MRI EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Reinert, C., Schuhmann, M., Bender, B., Gugel, I., la Fougere, C., Schaefer, J., Gatidis, S. 2019; 46 (3): 776-787

  Abstract

  To demonstrate the clinical use of FDG-PET/MRI for monitoring enlargement and metabolism of plexiform neurofibromas (PNF) in patients with neurofibromatosis type 1 (NF1), in whom the development of a malignant peripheral nerve sheath tumor (MPNST) is often a life limiting event.NF1 patients who underwent a simultaneous FDG-PET/MRI examination in our institution from September 2012 to February 2018 were included. Indication was suspicion of malignant transformation of a PNF to MPNST. A maximum of six peripheral nerve lesions per patient were defined as targets. Standardized uptake values (SUV) and apparent diffusion coefficients (ADC) were measured. The presence of target sign and contrast-medium enhancement was visually recorded. Growth rates were estimated comparing prior or follow-up examinations and correlated with FDG uptake and ADC values. The presence of CNS lesions in cerebral T2 weighted images was recorded.In 28 NF1 patients a total number of 83 peripheral nerve tumors, 75 benign PNFs and eight MPNSTs, were selected as target lesions. The SUVs of MPNSTs were significantly higher than the SUVs of PNF (3.84 ± 3.98 [SUVmean MPNSTs] vs. 1.85 ± 1.03 [SUVmean PNF], P < .01). Similarly, lesion SUVmean-to-liver SUVmean ratios significantly differed between MPNSTs and PNF (3.20 ± 2.70 [MPNSTs] vs. 1.23 ± 0.61 [PNF]; P < .01). For differentiation between still benign PNF and MPNSTs, we defined SUVmax ≥ 2.78 as a significant cut-off value. Growth rate of PNF correlated significantly positively with SUVmean (rs = .41; P = .003). MRI parameters like ADCmean (1.87 ± 0.24 × 10-3 mm2/s [PNF] vs. 1.76 ± 0.11 × 10-3 mm2/s [MPNSTs]; P > .05], contrast medium enhancement (P = .50) and target sign (P = .86) did not differ between groups.Simultaneous FDG-PET/MRI is a comprehensive imaging modality for monitoring PNF in NF1 patients. The combined acquisition of both morphologic information in MRI and metabolic information in PET enables the correlation of lesion growth rates with metabolic activity and to define SUV thresholds of significance to identify malignant transformation, which is of utmost clinical significance.

  View details for DOI 10.1007/s00259-018-4227-5

  View details for Web of Science ID 000457151600024

  View details for PubMedID 30535768

• Prediction of FDG uptake in Lung Tumors from CT Images Using Generative Adversarial Networks Liebgott, A., Hindere, D., Armanious, K., Bartler, A., Nikolaou, K., Gatidis, S., Yang, B., IEEE IEEE. 2019

  View details for Web of Science ID 000604567700258

• Practice-based evidence for the clinical benefit of PET/CT-results of the first oncologic PET/CT registry in Germany EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Pfannenberg, C., Gueckel, B., Wang, L., Gatidis, S., Olthof, S., Vach, W., Reimold, M., la Fougere, C., Nikolaou, K., Martus, P. 2019; 46 (1): 54-64

  Abstract

  The purpose of this study was to evaluate the impact of PET/CT on clinical management of cancer patients based on a prospective data registry. The study was developed to inform consultations with public health insurances on PET/CT coverage.We evaluated a prospective patient cohort having a clinically indicated PET/CT at a single German University Center from April 2013 to August 2016. The registry collected questionnaire data from requesting physicians on intended patient management before and after PET/CT. A total of 4,504 patients with 5,939 PET/CT examinations were enrolled in the registry, resulting in evaluable data from 3,724 patients receiving 4,754 scans. The impact of PET/CT on patient management was assessed across 22 tumor types, for different indications (diagnosis, staging, suspected recurrence) and different categories of management including treatment (curative or palliative) and non-treatment (watchful waiting, additional imaging, invasive tests).The most frequent PET/CT indication was tumor staging (59.7%). Melanoma, lung cancer, lymphoma, neuroendocrine tumor and prostate cancer accounted for 70% of cases. Overall, the use of PET/CT resulted in a 37.1% change of clinical management (95% CI, 35.7-38.5), most frequently (30.6%) from an intended non-treatment strategy before PET/CT to active treatment after PET/CT. The frequency of changes ranged from 28.3% for head and neck cancers up to 46.0% for melanomas. The impact of PET/CT was greatest in reducing demands for additional imaging which decreased from 66.1% before PET/CT to 6.1% after PET/CT. Pre-PET/CT planned invasive tests could be avoided in 72.7% of cases. The treatment goal changed after PET/CT in 21.7% of cases, in twice as many cases from curative to palliative therapy than vice versa.The data of this large prospective registry confirm that physicians often change their intended management on the basis of PET/CT by initiating treatment and reducing additional imaging as well as invasive tests. This applies to various cancer types and indications.

  View details for DOI 10.1007/s00259-018-4156-3

  View details for Web of Science ID 000450924400009

  View details for PubMedID 30269155

• Value of CT iterative metal artifact reduction in PET/CT-clinical evaluation in 100 patients BRITISH JOURNAL OF RADIOLOGY Reinert, C., La Fougere, C., Nikolaou, K., Pfannenberg, C., Gatidis, S. 2019; 92 (1096): 20180756

  Abstract

  To assess the technical feasibility and diagnostic benefit of CT iterative metal artifact reduction (iMAR) in patients with metal implants undergoing positron emission tomography (PET/CT.PET/CTs of 100 patients with metal implants in different anatomical localization were retrospectively analyzed. CT data were reconstructed with iMAR and without iMAR (noMAR) and used in comparison for PET attenuation correction, generating iMAR-corrected and noMAR PET data. The effect of iMAR on quantitative CT and PET analysis was assessed by measurements of Hounsfield units (HUs) and standard uptake values (SUV) in predefined anatomical structures and pathological lesions in the vicinity of metal implants. Diagnostic confidence for lesion delineation was assessed using a 3-point scale.For artifact-affected structures, mean HU of iMAR corrected CT significantly differed compared to noMAR CT and standard deviations were significantly lower [e.g. M. masseter: 71.01 ± 22.34 HU (iMAR) vs 98.89 ± 92.18 HU (noMAR), p < .01]. SUVs did not significantly differ in artifact-affected structures [e.g. M. masseter: SUVmean 0.96 ± 0.54 (iMAR) vs 0.97 ± 0.55 (noMAR); p > .89] and pathological findings [SUVmean 10.78 (iMAR) vs 10.81 (noMAR); p > .98] between iMAR and noMAR PET. Qualitatively, delineation was significantly improved in iMAR corrected CT for the interpretation of anatomical and pathological structures [e.g. score of pathologic lesions: 2.80 (iMAR) vs 2.31 (noMAR); p < .01].The use of iMAR in PET/CT significantly improves delineation of anatomical and pathological structures in the vicinity of metal implants in CT. PET quantification and PET image quality are not significantly affected by the use of iMAR-based attenuation correction independent of the presence of metal implants.IMAR is a feasible algorithm in PET/CT improving CT image quality in the vicinity of metal implants without affecting PET quantification and can therefore be implemented in the clinical routine.

  View details for DOI 10.1259/bjr.20180756

  View details for Web of Science ID 000462033100010

  View details for PubMedID 30618270

  View details for PubMedCentralID PMC6540858

• MRI-based assessment and characterization of epicardial and paracardial fat depots in the context of impaired glucose metabolism and subclinical left-ventricular alterations BRITISH JOURNAL OF RADIOLOGY Rado, S. D., Lorbeer, R., Gatidis, S., Machann, J., Storz, C., Nikolaou, K., Rathmann, W., Hoffmann, U., Peters, A., Bamberg, F., Schlett, C. L. 2019; 92 (1096): 20180562

  Abstract

  To analyze the associations between epicardial and paracardial fat and impaired glucose tolerance as well as left ventricular (LV) alterations.400 subjects underwent 3 T MRI and fat depots were delineated in the four chamber-view of the steady-state free precession cine sequence (repetition time: 29.97 ms; echo time 1.46 ms). LV parameters were also derived from MRI. Oral glucose tolerance tests were performed.Epi- and paracardial fat was derived in 372 (93%) subjects (220 healthy controls, 100 persons with prediabetes, 52 with diabetes). Epi- and paracardial fat increased from normal glucose tolerance (NGT) to prediabetes and diabetes (7.7 vs 9.2 vs 10.3 cm2 and 14.3 vs 20.3 vs 27.4 cm2, respectively; all p < 0.001). However, the association between impaired glucose metabolism and cardiac fat attenuated after adjustment, mainly confounded by visceral adipose tissue (VAT). 93 subjects (27%) had LV impairment, defined as late gadolinium enhancement, ejection fraction < 55% or LV concentricity index > 1.3 g ml-1 . Mean epicardial fat was higher in subjects with LV impairment (11.0 vs 8.1 cm2, p < 0.001). This association remained independent after adjustment for traditional risk factors and VAT [β: 1.13 (0.22; 2.03), p = 0.02].Although epicardial and paracardial fat are increased in prediabetes and diabetes, the association is mostly confounded by VAT. Epicardial fat is independently associated with subclinical LV impairment in subjects without known cardiovascular disease.This study contributes to the picture of epicardial fat as a pathogenic local fat depot that is independently associated with MR-derived markers of left ventricular alterations.

  View details for DOI 10.1259/bjr.20180562

  View details for Web of Science ID 000462033100005

  View details for PubMedID 30633543

  View details for PubMedCentralID PMC6540853

• ADVERSARIAL INPAINTING OF MEDICAL IMAGE MODALITIES Armanious, K., Mecky, Y., Gatidis, S., Yang, B., IEEE IEEE. 2019: 3267-3271

  View details for Web of Science ID 000482554003098

• RETROSPECTIVE CORRECTION OF RIGID AND NON-RIGID MR MOTION ARTIFACTS USING GANS Armanious, K., Gatidis, S., Nikolaou, K., Yang, B., Kuestner, T., IEEE IEEE. 2019: 1550-1554

  View details for Web of Science ID 000485040000328

• Unsupervised Medical Image Translation Using Cycle-MedGAN Armanious, K., Jiang, C., Abdulatif, S., Kuestner, T., Gatidis, S., Yang, B., IEEE IEEE. 2019

  View details for Web of Science ID 000604567700221

• Optimierung der Strahlendosis in der Thorax-CT des Kindes: Einflussfaktoren der Strahlenexposition aus 1695 CT-Untersuchungen in sieben Jahren. RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin Esser, M., Hess, S., Teufel, M., Kraus, M. S., SchneeweiSS, S., Gatidis, S., Schaefer, J. F., Tsiflikas, I. 2018; 190 (12): 1131-1140

  Abstract

  PURPOSE: To analyze possible influencing factors on radiation exposure in pediatric chest CT using different approaches for radiation dose optimization and to determine major indicators for dose development.MATERIALS AND METHODS: In this retrospective study at a clinic with maximum care facilities including pediatric radiology, 1695 chest CT examinations in 768 patients (median age: 10years; range: 2 days to 17.9 years) were analyzed. Volume CT dose indices, effective dose, size-specific dose estimate, automatic dose modulation (AEC), and high-pitch protocols (pitch ≥ 3.0) were evaluated by univariate analysis. The image quality of low-dose examinations was compared to higher dose protocols by non-inferiority testing.RESULTS: Median dose-specific values annually decreased by an average of 12 %. High-pitch mode (n = 414) resulted in lower dose parameters (p < 0.001). In unenhanced CT, AEC delivered higher dose values compared to scans with fixed parameters (p < 0.001). In contrast-enhanced CT, the use of AEC yielded a significantly lower radiation dose only in patients older than 16years (p = 0.04). In the age group 6 to 15 years, the values were higher (p < 0.001). The diagnostic image quality of low-dose scans was non-inferior to high-dose scans (2.18 vs. 2.14).CONCLUSION: Radiation dose of chest CT was reduced without loss of image quality in the last decade. High-pitch scanning was an independent factor in this context. Dose reduction by AEC was limited and only relevant for patients over 16 years.KEY POINTS: · The radiation dose of pediatric chest CT was reduced in the last decade.. · High-pitch scanning is an independent factor of dose optimization.. · Dose reduction by AEC is limited and only relevant for older children..CITATION FORMAT: · Esser M, Hess S, Teufel M et al. Radiation Dose Optimization in Pediatric Chest CT: Major Indicators of Dose Exposure in 1695 CT Scans over Seven Years. Fortschr Rontgenstr 2018; 190: 1131 - 1140.

  View details for DOI 10.1055/a-0628-7222

  View details for PubMedID 30308691

• ImFEATbox: a toolbox for extraction and analysis of medical image features INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY Liebgott, A., Kuestner, T., Strohmeier, H., Hepp, T., Mangold, P., Martirosian, P., Bamberg, F., Nikolaou, K., Yang, B., Gatidis, S. 2018; 13 (12): 1881-1893

  Abstract

  In medical imaging, the digital post-processing and analysis of acquired images has become an important research field. Topics include various applications of image processing and machine learning aiming to assist radiologists in their diagnostic work. A crucial step in successfully implementing such systems is finding appropriate mathematical descriptions to reflect characteristics of acquired images. Which features are the most meaningful ones strongly depends on the underlying scientific/diagnostic question and the image itself. This makes researching, implementing and testing features time-consuming and cost-intensive. In our work, we aim to address this issue by creating ImFEATbox, a publicly available toolbox to extract and analyze image features for a wide range of applications.To reduce the amount of time spent for choosing the right features, we provide an assortment of feature extraction algorithms which are suitable for a broad variety of medical image processing problems. The toolbox includes both global and local features as well as feature descriptors. While being primarily developed in MATLAB, the majority of our algorithms is also available in Python to enable access to a wider range of researchers.We tested the applicability of ImFEATbox on an FDG-PET/CT data set of 12 patients diagnosed with lung cancer and an MRI data set of 50 patients with prostate lesions. Employing the implemented algorithms in an exemplary manner, we are able to demonstrate its potential for different scientific problems, e.g., show differences between features, indicate redundancies in extracted feature sets by means of a correlation analysis and training a SVM to distinguish between high-risk and low-risk prostate lesions.ImFEATbox provides a variety of feature extraction algorithms suitable for a large number of post-processing and analysis applications in medical imaging. The toolbox is publicly available and can thus be beneficial to a wide range of researchers working on medical image analysis.

  View details for DOI 10.1007/s11548-018-1859-7

  View details for Web of Science ID 000449775700002

  View details for PubMedID 30229363

• A machine-learning framework for automatic reference-free quality assessment in MRI MAGNETIC RESONANCE IMAGING Kuestner, T., Gatidis, S., Liebgott, A., Schwartz, M., Mauch, L., Martirosian, P., Schmidt, H., Schwenzer, N. F., Nikolaou, K., Bamberg, F., Yang, B., Schick, F. 2018; 53: 134-147

  Abstract

  Magnetic resonance (MR) imaging offers a wide variety of imaging techniques. A large amount of data is created per examination which needs to be checked for sufficient quality in order to derive a meaningful diagnosis. This is a manual process and therefore time- and cost-intensive. Any imaging artifacts originating from scanner hardware, signal processing or induced by the patient may reduce the image quality and complicate the diagnosis or any image post-processing. Therefore, the assessment or the ensurance of sufficient image quality in an automated manner is of high interest. Usually no reference image is available or difficult to define. Therefore, classical reference-based approaches are not applicable. Model observers mimicking the human observers (HO) can assist in this task. Thus, we propose a new machine-learning-based reference-free MR image quality assessment framework which is trained on HO-derived labels to assess MR image quality immediately after each acquisition. We include the concept of active learning and present an efficient blinded reading platform to reduce the effort in the HO labeling procedure. Derived image features and the applied classifiers (support-vector-machine, deep neural network) are investigated for a cohort of 250 patients. The MR image quality assessment framework can achieve a high test accuracy of 93.7% for estimating quality classes on a 5-point Likert-scale. The proposed MR image quality assessment framework is able to provide an accurate and efficient quality estimation which can be used as a prospective quality assurance including automatic acquisition adaptation or guided MR scanner operation, and/or as a retrospective quality assessment including support of diagnostic decisions or quality control in cohort studies.

  View details for DOI 10.1016/j.mri.2018.07.003

  View details for Web of Science ID 000445591900018

  View details for PubMedID 30036653

• Assessment of image quality of a radiotherapy-specific hardware solution for PET/MRI in head and neck cancer patients RADIOTHERAPY AND ONCOLOGY Winter, R. M., Leibfarth, S., Schmidt, H., Zwirner, K., Moennich, D., Welz, S., Schwenzer, N. F., la Fougere, C., Nikolaou, K., Gatidis, S., Zips, D., Thorwarth, D. 2018; 128 (3): 485-491

  Abstract

  Functional PET/MRI has great potential to improve radiotherapy planning (RTP). However, data integration requires imaging with radiotherapy-specific patient positioning. Here, we investigated the feasibility and image quality of radiotherapy-customized PET/MRI in head-and-neck cancer (HNC) patients using a dedicated hardware setup.Ten HNC patients were examined with simultaneous PET/MRI before treatment, with radiotherapy and diagnostic scan setup, respectively. We tested feasibility of radiotherapy-specific patient positioning and compared the image quality between both setups by pairwise image analysis of 18F-FDG-PET, T1/T2-weighted and diffusion-weighted MRI. For image quality assessment, similarity measures including average symmetric surface distance (ASSD) of PET and MR-based tumor contours, MR signal-to-noise ratio (SNR) and mean apparent diffusion coefficient (ADC) value were used.PET/MRI in radiotherapy position was feasible - all patients were successfully examined. ASSD (median/range) of PET and MR contours was 0.6 (0.4-1.2) and 0.9 (0.5-1.3) mm, respectively. For T2-weighted MRI, a reduced SNR of -26.2% (-39.0--11.7) was observed with radiotherapy setup. No significant difference in mean ADC was found.Simultaneous PET/MRI in HNC patients using radiotherapy positioning aids is clinically feasible. Though SNR was reduced, the image quality obtained with a radiotherapy setup meets RTP requirements and the data can thus be used for personalized RTP.

  View details for DOI 10.1016/j.radonc.2018.04.018

  View details for Web of Science ID 000444505600014

  View details for PubMedID 29747873

  View details for PubMedCentralID PMC6141811

• Voxel-wise correlation of functional imaging parameters in HNSCC patients receiving PET/MRI in an irradiation setup STRAHLENTHERAPIE UND ONKOLOGIE Zwirner, K., Thorwarth, D., Winter, R. M., Welz, S., Weiss, J., Schwenzer, N. F., Schmidt, H., la Fougere, C., Nikolaou, K., Zips, D., Gatidis, S. 2018; 194 (8): 719-726

  Abstract

  The purpose of this study was to demonstrate the feasibility of voxel-wise multiparametric characterization of head and neck squamous cell carcinomas (HNSCC) using hybrid multiparametric magnetic resonance imaging and positron emission tomography with [18F]-fluorodesoxyglucose (FDG-PET/MRI) in a radiation treatment planning setup.Ten patients with locally advanced HNSCC were examined with a combined FDG-PET/MRI in an irradiation planning setup. The multiparametric imaging protocol consisted of FDG-PET, T2-weighted transverse short tau inversion recovery sequence (STIR) and diffusion-weighted MRI (DWI). Primary tumours were manually segmented and quantitative imaging parameters were extracted. PET standardized uptake values (SUV) and DWI apparent diffusion coefficients (ADC) were correlated on a voxel-wise level.Images acquired in this specialised radiotherapy planning setup achieved good diagnostic quality. Median tumour volume was 4.9 [1.1-42.1] ml. Mean PET SUV and ADC of the primary tumours were 5 ± 2.5 and 1.2 ± 0.3 10-3 mm2/s, respectively. In voxel-wise correlation between ADC values and corresponding FDG SUV of the tumours, a significant negative correlation was observed (r = -0.31 ± 0.27, p < 0.05).Multiparametric voxel-wise characterization of HNSCC is feasible using combined PET/MRI in a radiation planning setup. This technique may provide novel insights into tumour biology with regard to radiation therapy in the future.

  View details for DOI 10.1007/s00066-018-1292-4

  View details for Web of Science ID 000439933100003

  View details for PubMedID 29564483

• Translational theranostic imaging of lymphoma using radiolabeled alpha CD19-antibodies Sonanini, D., Schwenck, J., Schmitt, J., Maurer, A., Gatidis, S., Seitz, C., Reischl, G., Kneilling, M., Jung, G., Lang, P., Kanz, L., Nikolaou, K., Handgretinger, R., la Fougere, C., Pichler, B. J. AMER ASSOC CANCER RESEARCH. 2018

  View details for DOI 10.1158/1538-7445.AM2018-658

  View details for Web of Science ID 000468818902169

• 1.5 Tesla MR-Linac Treatment Plans for a Hypoxia-based Dose Escalation in Head and Neck Tumors Welz, S., Moennich, D., Nachbar, M., Neuhaus, E., Boeke, S., Zips, D., Grosse, U., Gatidis, S., Schick, F., Nikolaou, K., Thorwarth, D., Gani, C. SPRINGER HEIDELBERG. 2018: S65

  View details for Web of Science ID 000435675600131

• Phenotypic Multiorgan Involvement of Subclinical Disease as Quantified by Magnetic Resonance Imaging in Subjects With Prediabetes, Diabetes, and Normal Glucose Tolerance INVESTIGATIVE RADIOLOGY Storz, C., Rospleszcz, S., Lorbeer, R., Hetterich, H., Auweter, S. D., Sommer, W., Machann, J., Gatidis, S., Rathmann, W., Heier, M., Linkohr, B., Meisinger, C., Reiser, M., Hoffmann, U., Peters, A., Schlett, C. L., Bamberg, F. 2018; 53 (6): 357-364

  Abstract

  Detailed mechanisms in the pathophysiology of diabetes disease are poorly understood, but structural alterations in various organ systems incur an elevated risk for cardiovascular events and adverse outcome. The aim of this study was to compare multiorgan subclinical disease phenotypes by magnetic resonance (MR) imaging to study differences between subjects with prediabetes, diabetes, and normal controls.Subjects without prior cardiovascular disease were enrolled in a prospective case-control study and underwent multiorgan MR for the assessment of metabolic and arteriosclerotic alterations, including age-related white matter changes, hepatic proton density fat fraction, visceral adipose tissue volume, left ventricular remodeling index, carotid plaque, and late gadolinium enhancement. Magnetic resonance features were summarized in a phenotypic-based score (range, 0-6). Univariate, multivariate correlation, and unsupervised clustering were performed.Among 243 subjects with complete multiorgan MR data sets included in the analysis (55.6 ± 8.9 years, 62% males), 48 were classified as subjects with prediabetes and 38 as subjects with diabetes. The MR phenotypic score was significantly higher in subjects with prediabetes and diabetes as compared with controls (mean score, 3.00 ± 1.04 and 2.69 ± 0.98 vs 1.22 ± 0.98, P < 0.001 respectively), also after adjustment for potential confounders. We identified 2 clusters of MR phenotype patterns associated with glycemic status (P < 0.001), independent of the MR score (cluster II-metabolic specific: odds ratio, 2.49; 95% CI, 1.00-6.17; P = 0.049).Subjects with prediabetes and diabetes have a significantly higher phenotypic-based score with a distinctive multiorgan phenotypic pattern, which may enable improved disease characterization.

  View details for DOI 10.1097/RLI.0000000000000451

  View details for Web of Science ID 000432188500006

  View details for PubMedID 29494349

• Plan Comparison Study between a 1.5 T MR-Linac and a Standard-Linac for the definitive Chemoradiotherapy of thoracic Esophageal Cancer Gani, C., Nachbar, M., Moennich, D., Kalwa, P., Grosse, U., Gatidis, S., Schick, F., Nikolaou, K., Thorwarth, D., Zips, D. SPRINGER HEIDELBERG. 2018: S151

  View details for Web of Science ID 000435675600334

• Clinical use of cardiac PET/MRI: current state-of-the-art and potential future applications JAPANESE JOURNAL OF RADIOLOGY Krumm, P., Mangold, S., Gatidis, S., Nikolaou, K., Nensa, F., Bamberg, F., la Fougere, C. 2018; 36 (5): 313-323

  Abstract

  Combined PET/MRI is a novel imaging method integrating the advances of functional and morphological MR imaging with PET applications that include assessment of myocardial viability, perfusion, metabolism of inflammatory tissue and tumors, as well as amyloid deposition imaging. As such, PET/MRI is a promising tool to detect and characterize ischemic and non-ischemic cardiomyopathies. To date, the greatest benefit may be expected for diagnostic evaluation of systemic diseases and cardiac masses that remain unclear in cardiac MRI, as well as for clinical and scientific studies in the setting of ischemic cardiomyopathies. Diagnosis and therapeutic monitoring of cardiac sarcoidosis has the potential of a possible 'killer-application' for combined cardiac PET/MRI. In this article, we review the current evidence and discuss current and potential future applications of cardiac PET/MRI.

  View details for DOI 10.1007/s11604-018-0727-2

  View details for Web of Science ID 000430656100001

  View details for PubMedID 29524169

• Automated reference-free detection of motion artifacts in magnetic resonance images MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE Kuestner, T., Liebgott, A., Mauch, L., Martirosian, P., Bamberg, F., Nikolaou, K., Yang, B., Schick, F., Gatidis, S. 2018; 31 (2): 243-256

  Abstract

  Our objectives were to provide an automated method for spatially resolved detection and quantification of motion artifacts in MR images of the head and abdomen as well as a quality control of the trained architecture.T1-weighted MR images of the head and the upper abdomen were acquired in 16 healthy volunteers under rest and under motion. Images were divided into overlapping patches of different sizes achieving spatial separation. Using these patches as input data, a convolutional neural network (CNN) was trained to derive probability maps for the presence of motion artifacts. A deep visualization offers a human-interpretable quality control of the trained CNN. Results were visually assessed on probability maps and as classification accuracy on a per-patch, per-slice and per-volunteer basis.On visual assessment, a clear difference of probability maps was observed between data sets with and without motion. The overall accuracy of motion detection on a per-patch/per-volunteer basis reached 97%/100% in the head and 75%/100% in the abdomen, respectively.Automated detection of motion artifacts in MRI is feasible with good accuracy in the head and abdomen. The proposed method provides quantification and localization of artifacts as well as a visualization of the learned content. It may be extended to other anatomic areas and used for quality assurance of MR images.

  View details for DOI 10.1007/s10334-017-0650-z

  View details for Web of Science ID 000428612800002

  View details for PubMedID 28932991

• Implementation of a 5-Minute Magnetic Resonance Imaging Screening Protocol for Prostate Cancer in Men With Elevated Prostate-Specific Antigen Before Biopsy INVESTIGATIVE RADIOLOGY Weiss, J., Martirosian, P., Notohamiprodjo, M., Kaufmann, S., Othman, A. E., Grosse, U., Nikolaou, K., Gatidis, S. 2018; 53 (3): 186-190

  Abstract

  The aims of this study were to establish a 5-minute magnetic resonance (MR) screening protocol for prostate cancer in men before biopsy and to evaluate effects on Prostate Imaging Reporting and Data System (PI-RADS) V2 scoring in comparison to a conventional, fully diagnostic multiparametric MR imaging (mpMRI) approach.Fifty-two patients with elevated prostate-specific antigen levels and without prior biopsy were prospectively included in this institutional review board-approved study. In all patients, an mpMRI protocol according to the PI-RADS recommendations was acquired on a 3 T MRI system. In addition, an accelerated diffusion-weighted imaging sequence was acquired using simultaneous multislice technique (DW-EPISMS). Two readers independently evaluated the images for the presence/absence of prostate cancer according to the PI-RADS criteria and for additional findings. In a first reading session, only the screening protocol consisting of axial T2-weighted and DW-EPISMS images was made available. In a subsequent reading session, the mpMRI protocol was assessed blinded to the results of the first reading, serving as reference standard.Both readers successfully established a final diagnosis according to the PI-RADS criteria in the screening and mpMRI protocol. Mean lesion size was 1.2 cm in the screening and 1.4 cm in the mpMRI protocol (P = 0.4) with 35% (18/52) of PI-RADS IV/V lesions. Diagnostic performance of the screening protocol was excellent with a sensitivity and specificity of 100% for both readers with no significant differences in comparison to the mpMRI standard (P = 1.0). In 3 patients, suspicious lymph nodes were reported as additional finding, which were equally detectable in the screening and mpMRI protocol.A 5-minute MR screening protocol for prostate cancer in men with elevated prostate-specific antigen levels before biopsy is applicable for clinical routine with similar diagnostic performance as the full diagnostic mpMRI approach.

  View details for DOI 10.1097/RLI.0000000000000427

  View details for Web of Science ID 000425366500008

  View details for PubMedID 29077588

• Graphical User Interface for Medical Deep Learning - Application to Magnetic Resonance Imaging Milde, S., Liebgott, A., Wu, Z., Feng, W., Yang, J., Mauch, L., Martirosian, P., Bamberg, F., Nikolaou, K., Gatidis, S., Schick, F., Yang, B., Kuestner, T., IEEE IEEE. 2018: 838-847

  View details for Web of Science ID 000468383400134

• A semiquantitative MRI-Score can predict loss of lung function in patients with cystic fibrosis: Preliminary results EUROPEAN RADIOLOGY Schaefer, J. F., Hector, A., Schmidt, K., Teufel, M., Fleischer, S., Graepler-Mainka, U., Riethmueller, J., Gatidis, S., Schaefer, S., Nikolaou, K., Hartl, D., Tsiflikas, I. 2018; 28 (1): 74-84

  Abstract

  To evaluate the applicability of a semiquantitative MRI scoring system (MR-CF-S) as a prognostic marker for clinical course of cystic fibrosis (CF) lung disease.This observational study of a single-centre CF cohort included a group of 61 patients (mean age 12.9 ± 4.7 years) receiving morphological and functional pulmonary MRI, pulmonary function testing (PFT) and follow-up of 2 years. MRI was analysed by three raters using MR-CF-S. The inter-rater agreement, correlation of score categories with forced expiratory volume in 1 s (FEV1) at baseline, and the predictive value of clinical parameters, and score categories was assessed for the whole cohort and a subgroup of 40 patients with moderately impaired lung function.The inter-rater agreement of MR-CF-S was sufficient (mean intraclass correlation coefficient 0.92). MR-CF-S (-0.62; p < 0.05) and most of the categories significantly correlated with FEV1. Differences between patients with relevant loss of FEV1 (>3%/year) and normal course were only significant for MR-CF-S (p < 0.05) but not for clinical parameters. Centrilobular opacity (CO) was the most promising score category for prediction of a decline of FEV1 (area under curve: whole cohort 0.69; subgroup 0.86).MR-CF-S is promising to predict a loss of lung function. CO seems to be a particular finding in CF patients with an abnormal course.• Lung imaging is essential in the diagnostic work-up of CF patients • MRI serves as a powerful, radiation-free modality in paediatric CF patients • Observational single-centre study showed significant correlation of MR-CF score and FEV 1 • MR-CF score is promising in predicting a loss of lung function.

  View details for DOI 10.1007/s00330-017-4870-4

  View details for Web of Science ID 000417150600011

  View details for PubMedID 28664245

• The role of visceral and subcutaneous adipose tissue measurements and their ratio by magnetic resonance imaging in subjects with prediabetes, diabetes and healthy controls from a general population without cardiovascular disease BRITISH JOURNAL OF RADIOLOGY Storz, C., Heber, S. D., Rospleszcz, S., Machann, J., Sellner, S., Nikolaou, K., Lorbeer, R., Gatidis, S., Elser, S., Peters, A., Schlett, C. L., Bamberg, F. 2018; 91 (1089): 20170808

  Abstract

  To study the relationship of area- and volumetric-based visceral and subcutaneous adipose tissue (VAT and SAT) by MRI and their ratio in subjects with impaired glucose metabolism from the general population.Subjects from a population-based cohort with established prediabetes, diabetes and healthy controls without prior cardiovascular diseases underwent 3 T MRI. VAT and SAT were assessed as total volume and area on a single slice, and their ratio (VAT/SAT) was calculated. Clinical covariates and cardiovascular risk factors, such as hypertension and glycemic state were assessed in standardized fashion. Univariate and adjusted analyses were conducted.Among 384 subjects (age: 56.2 ± 9.2 years, 58.1% male) with complete MRI data available, volumetric and single-slice VAT, SAT and VAT/SAT ratio were strongly correlated (all >r = 0.89). Similarly, VAT/SATvolume ratio was strongly correlated with VATvolume but not with SAT (r = 0.72 and r = -0.21, respectively). Significant higher levels of VAT, SAT and VAT/SAT ratio were found in subjects with impaired glucose metabolism (all p ≤ 0.01). After adjustment for potential cardiovascular confounders, VATvolume and VAT/SATvolume ratio remained significantly higher in subjects with impaired glucose metabolism (VATvolume = 6.9 ± 2.5 l and 3.4 ± 2.3 l; VAT/SATvolume ratio = 0.82 ± 0.34 l and 0.49 ± 0.29 l in patients with diabetes and controls, respectively, all p < 0.02), whereas the association for SATvolume attenuated. Additionally, there was a decreasing effect of glycemic status on VAT/SATvolume ratio with increasing body mass index and waist circumference (p < 0.05).VATvolume and VAT/SATvolume ratio are associated with impaired glucose metabolism, independent of cardiovascular risk factors or MRI-based quantification technique, with a decreasing effect of VAT/SATvolume ratio in obese subjects. Advances in knowledge: Quantification of VATvolume and VAT/SATvolume ratio by MRI represents a reproducable biomarker associated with cardiometabolic risk factors in subjects with impaired glucose metabolism, while the association of VAT/SATvolume ratio with glycemic state is attenuated in obese subjects.

  View details for DOI 10.1259/bjr.20170808

  View details for Web of Science ID 000443131900013

  View details for PubMedID 29388794

  View details for PubMedCentralID PMC6223151

• AUTOMATIC MOTION ARTIFACT DETECTION FOR WHOLE-BODY MAGNETIC RESONANCE IMAGING Kuestner, T., Jandt, M., Liebgott, A., Mauch, L., Martirosian, P., Bamberg, F., Nikolaou, K., Gatidis, S., Schick, F., Yang, B., IEEE IEEE. 2018: 995-999

  View details for Web of Science ID 000446384601038

• AUTOMATED DETECTION OF HIGH FDG UPTAKE REGIONS IN CT IMAGES Liebgott, A., Gatidis, S., Liebgott, F., Nikolaou, K., Yang, B., IEEE IEEE. 2018: 1065-1069

  View details for Web of Science ID 000446384601051

• SEMANTIC ORGAN SEGMENTATION IN 3D WHOLE-BODY MR IMAGES Kuestner, T., Mueller, S., Fischer, M., Weiss, J., Nikolaou, K., Bamberg, F., Yang, B., Schick, F., Gatidis, S., IEEE IEEE. 2018: 3498-3502

  View details for Web of Science ID 000455181503123

• MR-based respiratory and cardiac motion correction for PET imaging MEDICAL IMAGE ANALYSIS Kuestner, T., Schwartz, M., Martirosian, P., Gatidis, S., Seith, F., Gilliam, C., Blu, T., Fayad, H., Visvikis, D., Schick, F., Yang, B., Schmidt, H., Schwenzer, N. F. 2017; 42: 129-144

  Abstract

  To develop a motion correction for Positron-Emission-Tomography (PET) using simultaneously acquired magnetic-resonance (MR) images within 90 s.A 90 s MR acquisition allows the generation of a cardiac and respiratory motion model of the body trunk. Thereafter, further diagnostic MR sequences can be recorded during the PET examination without any limitation. To provide full PET scan time coverage, a sensor fusion approach maps external motion signals (respiratory belt, ECG-derived respiration signal) to a complete surrogate signal on which the retrospective data binning is performed. A joint Compressed Sensing reconstruction and motion estimation of the subsampled data provides motion-resolved MR images (respiratory + cardiac). A 1-POINT DIXON method is applied to these MR images to derive a motion-resolved attenuation map. The motion model and the attenuation map are fed to the Customizable and Advanced Software for Tomographic Reconstruction (CASToR) PET reconstruction system in which the motion correction is incorporated. All reconstruction steps are performed online on the scanner via Gadgetron to provide a clinically feasible setup for improved general applicability. The method was evaluated on 36 patients with suspected liver or lung metastasis in terms of lesion quantification (SUVmax, SNR, contrast), delineation (FWHM, slope steepness) and diagnostic confidence level (3-point Likert-scale).A motion correction could be conducted for all patients, however, only in 30 patients moving lesions could be observed. For the examined 134 malignant lesions, an average improvement in lesion quantification of 22%, delineation of 64% and diagnostic confidence level of 23% was achieved.The proposed method provides a clinically feasible setup for respiratory and cardiac motion correction of PET data by simultaneous short-term MRI. The acquisition sequence and all reconstruction steps are publicly available to foster multi-center studies and various motion correction scenarios.

  View details for DOI 10.1016/j.media.2017.08.002

  View details for Web of Science ID 000415778100009

  View details for PubMedID 28800546

• Simulation of Tracer Dose Reduction in F-18-FDG PET/MRI: Effects on Oncologic Reading, Image Quality, and Artifacts JOURNAL OF NUCLEAR MEDICINE Seith, F., Schmidt, H., Kunz, J., Kuestner, T., Gatidis, S., Nikolaou, K., la Fougere, C., Schwenzer, N. 2017; 58 (10): 1699-1705

  Abstract

  The aim of our study was to evaluate the effect of stepwise-reduced doses on objective and subjective image parameters and on oncologic readings in whole-body 18F-FDG PET/MRI. Methods: We retrospectively simulated the stepwise reduction of 18F-FDG doses of 19 patients (mean age ± SD, 50.9 ± 11.7 y; mean body mass index ± SD, 22.8 ± 3.2 kg/m2) who received a whole-body PET/MRI examination from 3 to 0.5 MBq/kg of body weight (kgBW) in intervals of 0.25. Objective imaging parameters were assessed by measuring the SUV and coefficient of variation in different regions (aorta, liver, spleen, kidney, small bowel, lumbar vertebra, psoas muscle, urinary bladder) as well as the noise-equivalent counting rates in each bed position. Subjective image quality was evaluated with a masked reading of each simulated PET compared with the dose of 2 MBq/kgBW. Oncologic reading was performed first according to PERCIST in each dose and second by defining malignant lesions in doses of 2 MBq/kgBW and the maximum dose image (gold standard). The diagnostic confidence of each lesion was measured using a Likert scale. Results: With decreasing doses, regions in the mid abdomen showed a stronger decrease of SUVmean and noise-equivalent counting rates than regions in the upper abdomen (SUVmean, -45% and -15% on average in the small bowel and the liver, respectively). The coefficient of variation showed a nonlinear increase, pronounced below 1.5 MBq/kgBW. Subjective image quality was stable over a range between 1.25 and 2.75 MBq/kgBW compared with 2 MBq/kgBW. However, large photopenic areas in the mid abdomen were observed in 2 patients. In the PERCIST reading, target lesions were above the liver threshold with a stable SUVpeak in all cases down to 2 MBq/kgBW. Eighty-six of 90 lesions were identified correctly with a dose of 2 MBq/kgBW; Likert scores did not differ significantly. Conclusion: A reduction of doses in 18F-FDG PET/MRI might be possible down to 2 MBq/kgBW in oncologic whole-body examinations. The image quality in the mid abdomen seems to be more affected by lower doses than in the upper abdomen, and in single cases large photopenic areas can occur. Therefore, we do not recommend reducing doses below 3 MBq/kgBW in adults at this time.

  View details for DOI 10.2967/jnumed.116.184440

  View details for Web of Science ID 000411985900031

  View details for PubMedID 28360205

• Combination of integrated dynamic shimming and readout-segmented echo planar imaging for diffusion weighted MRI of the head and neck region at 3 Tesla MAGNETIC RESONANCE IMAGING Walter, S. S., Liu, W., Stemmer, A., Martirosian, P., Nikolaou, K., Notohamiprodjo, M., Gatidis, S. 2017; 42: 32-36

  Abstract

  To evaluate the performance of combined integrated slice-by-slice shimming and readout-segmented EPI (irsEPI) for diffusion-weighted MR imaging (DWI) of the neck at 3Tesla.This study was approved by the local ethics committee. An anthropometric phantom of the head/neck region incorporating compartments with different diffusivities was constructed. In vivo measurements were performed in 10 healthy volunteers. DWI of the phantom and volunteers was performed on a 3Tesla MR scanner using single shot EPI (sEPI), a prototype single shot EPI with integrated slice-by-slice shimming (iEPI), readout segmented EPI (rsEPI) and a prototype readout segmented EPI with integrated shimming irsEPI. Apparent diffusion coefficients (ADC) and spatial distortions of phantom compartments were quantified. For phantom and volunteer measurements, the presence of geometric distortions, signal losses, ghosting artifacts as well as overall image quality were visually assessed on a 4-point scale by two radiologists in consensus. In addition, failure of fat saturation was assessed in volunteer data.Quantification of ADC within the phantom compartments was comparable using the different EPI techniques without significant variations. Using irsEPI, spatial distortions in phase-encoding direction were markedly reduced compared to iEPI, rsEPI and especially sEPI. irsEPI yielded significantly better overall image quality compared to sEPI, iEPI and rsEPI in phantom data as well as volunteer measurements. Markedly reduced geometric distortions and signal loss as well as better fat saturation were observed using irsEPI.The use of irsEPI significantly improves image quality and reduces artifacts caused by magnetic field inhomogeneities in EPI based DWI of the head/neck at 3Tesla.

  View details for DOI 10.1016/j.mri.2017.05.004

  View details for Web of Science ID 000410872600005

  View details for PubMedID 28526430

• PET/MRI in children EUROPEAN JOURNAL OF RADIOLOGY Gatidis, S., Bender, B., Reimold, M., Schaefer, J. F. 2017; 94: A64-A70

  Abstract

  During the past decade, combined PET/MRI has been translated from a basic technical concept to a clinical research tool and a clinically applied hybrid imaging modality. Numerous clinical and scientific applications have been proposed for this novel hybrid modality including oncologic, neurologic and cardiovascular imaging. Among these, PET/MRI in children has emerged as a key application, not only due to possible diagnostic advantages but also because of reduced radiation exposure compared to alternative techniques. A variety of clinical indications exists for the use of PET/MR imaging in children mainly in but not limited to the field of paediatric oncology. The purpose of this review article is to discuss possible applications of combined PET/MR in paediatric imaging and to illustrate these by presenting cases from clinical practice.

  View details for DOI 10.1016/j.ejrad.2017.01.018

  View details for Web of Science ID 000411459400008

  View details for PubMedID 28131593

• Cardiac CT for Guiding Mitral Valve Interventions CURRENT CARDIOVASCULAR IMAGING REPORTS Storz, C., Mangold, S., Mueller, K. L., Lausberg, H., Gatidis, S., Heber, S. D., Schlett, C. L., Nikolaou, K., Bamberg, F. 2017; 10 (9)

  View details for DOI 10.1007/s12410-017-9428-y

  View details for Web of Science ID 000411116800001

• Self-navigated 4D cartesian imaging of periodic motion in the body trunk using partial k-space compressed sensing MAGNETIC RESONANCE IN MEDICINE Kuestner, T., Wuerslin, C., Schwartz, M., Martirosian, P., Gatidis, S., Brendle, C., Seith, F., Schick, F., Schwenzer, N. F., Yang, B., Schmidt, H. 2017; 78 (2): 632-644

  Abstract

  To enable fast and flexible high-resolution four-dimensional (4D) MRI of periodic thoracic/abdominal motion for motion visualization or motion-corrected imaging.We proposed a Cartesian three-dimensional k-space sampling scheme that acquires a random combination of k-space lines in the ky/kz plane. A partial Fourier-like constraint compacts the sampling space to one half of k-space. The central k-space line is periodically acquired to allow an extraction of a self-navigated respiration signal used to populate a k-space of multiple breathing positions. The randomness of the acquisition (induced by periodic breathing pattern) yields a subsampled k-space that is reconstructed using compressed sensing. Local image evaluations (coefficient of variation and slope steepness through organs) reveal information about motion resolvability. Image quality is inspected by a blinded reading. Sequence and reconstruction method are made publicly available.The method is able to capture and reconstruct 4D images with high image quality and motion resolution within a short scan time of less than 2 min. These findings are supported by restricted-isometry-property analysis, local image evaluation, and blinded reading.The proposed method provides a clinical feasible setup to capture periodic respiratory motion with a fast acquisition protocol and can be extended by further surrogate signals to capture additional periodic motions. Retrospective parametrization allows for flexible tuning toward the targeted applications. Magn Reson Med 78:632-644, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

  View details for DOI 10.1002/mrm.26406

  View details for Web of Science ID 000405637000021

  View details for PubMedID 27667730

• Population-based imaging biobanks as source of big data RADIOLOGIA MEDICA Gatidis, S., Heber, S. D., Storz, C., Bamberg, F. 2017; 122 (6): 430-436

  Abstract

  Advances of computational sciences over the last decades have enabled the introduction of novel methodological approaches in biomedical research. Acquiring extensive and comprehensive data about a research subject and subsequently extracting significant information has opened new possibilities in gaining insight into biological and medical processes. This so-called big data approach has recently found entrance into medical imaging and numerous epidemiological studies have been implementing advanced imaging to identify imaging biomarkers that provide information about physiological processes, including normal development and aging but also on the development of pathological disease states. The purpose of this article is to present existing epidemiological imaging studies and to discuss opportunities, methodological and organizational aspects, and challenges that population imaging poses to the field of big data research.

  View details for DOI 10.1007/s11547-016-0684-8

  View details for Web of Science ID 000401765500005

  View details for PubMedID 27613426

• SUV-quantification of physiological lung tissue in an integrated PET/MR-system: Impact of lung density and bone tissue PLOS ONE Seith, F., Schmidt, H., Gatidis, S., Bezrukov, I., Schraml, C., Pfannenberg, C., la Fougere, C., Nikolaou, K., Schwenzer, N. 2017; 12 (5): e0177856

  Abstract

  The aim of the study was to investigate the influence of lung density changes as well as bone proximity on the attenuation correction of lung standardized uptake values (SUVs).15 patients with mostly oncologic diseases were examined in 18F-FDG-PET/CT and subsequently in a fully integrated PET/MR scanner. From each PET dataset acquired in PET/MR, four different PET reconstructions were computed using different attenuation maps (μ-maps): i) CT-based μ-map (gold standard); ii) CT-based μ-map in which the linear attenuation coefficients (LAC) of the lung tissue was replaced by the lung LAC from the MR-based segmentation method; iii) based on reconstruction ii), the LAC of bone structures was additionally replaced with the LAC from the MR-based segmentation method; iv) the vendor-provided MR-based μ-map (segmentation-based method). Those steps were performed using MATLAB. CT Hounsfield units (HU) and SUVmean was acquired in different levels and regions of the lung. Relative differences between the differently corrected PETs were computed.Compared to the gold standard, reconstruction ii), iii) and iv) led to a relative underestimation of SUV in the posterior regions of -9.0%, -13.4% and -14.0%, respectively. Anterior and middle regions were less affected with an overestimation of about 6-8% in reconstructions ii)-iv).It could be shown that both, differences in lung density and the vicinity of bone tissue in the μ-map may have an influence on SUV, mostly affecting the posterior lung regions.

  View details for DOI 10.1371/journal.pone.0177856

  View details for Web of Science ID 000402608700030

  View details for PubMedID 28562622

  View details for PubMedCentralID PMC5451041

• Diffusion-weighted echo planar MR imaging of the neck at 3 T using integrated shimming: comparison of MR sequence techniques for reducing artifacts caused by magnetic-field inhomogeneities MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE Gatidis, S., Graf, H., Weiss, J., Stemmer, A., Kiefer, B., Nikolaou, K., Notohamiprodjo, M., Martirosian, P. 2017; 30 (1): 57-63

  Abstract

  Our objective was to compare available techniques reducing artifacts in echo planar imaging (EPI)-based diffusion-weighed magnetic resonance imaging MRI (DWI) of the neck at 3 Tesla caused by B0-field inhomogeneities.A cylindrical fat-water phantom was equipped with a Maxwell coil allowing for additional linear B0-field variations in z-direction. The effect of increasing strength of this superimposed gradient on image quality was observed using a standard single-shot EPI-based DWI sequence (sEPI), a zoomed single-shot EPI sequence (zEPI), a readout-segmented EPI sequence (rsEPI), and an sEPI sequence with integrated dynamic shimming (intEPI) on a 3-Tesla system. Additionally, ten volunteers were examined over the neck region using these techniques. Image quality was assessed by two radiologists. Scan durations were recorded.With increasing strength of the external gradient, marked distortions, signal loss, and failure of fat suppression were observed using sEPI, zEPI, and rsEPI. These artifacts were markedly reduced using intEPI. Significantly better in vivo image quality was also observed using intEPI compared with the other techniques. Scan time of intEPI was similar to sEPI and zEPI and shorter than rsEPI.The use of integrated 2D shim and frequency adjustment for EPI-based DWI results in a significant improvement in image quality of the head/neck region at 3 Tesla. Combining integrated shimming with rsEPI or zEPI can be expected to provide additional improvements.

  View details for DOI 10.1007/s10334-016-0582-z

  View details for Web of Science ID 000394155100005

  View details for PubMedID 27503308

• The Spatial Relationship between Apparent Diffusion Coefficient and Standardized Uptake Value of F-18-Fluorodeoxyglucose Has a Crucial Influence on the Numeric Correlation of Both Parameters in PET/MRI of Lung Tumors CONTRAST MEDIA & MOLECULAR IMAGING Sauter, A. W., Stieltjes, B., Weikert, T., Gatidis, S., Wiese, M., Klarhofer, M., Wild, D., Lardinois, D., Bremerich, J., Sommer, G. 2017: 8650853

  Abstract

  The minimum apparent diffusion coefficient (ADCmin) derived from diffusion-weighted MRI (DW-MRI) and the maximum standardized uptake value (SUVmax) of FDG-PET are markers of aggressiveness in lung cancer. The numeric correlation of the two parameters has been extensively studied, but their spatial interplay is not well understood. After FDG-PET and DW-MRI coregistration, values and location of ADCmin- and SUVmax-voxels were analyzed. The upper limit of the 95% confidence interval for registration accuracy of sequential PET/MRI was 12 mm, and the mean distance (D) between ADCmin- and SUVmax-voxels was 14.0 mm (average of two readers). Spatial mismatch (D > 12 mm) between ADCmin and SUVmax was found in 9/25 patients. A considerable number of mismatch cases (65%) was also seen in a control group that underwent simultaneous PET/MRI. In the entire patient cohort, no statistically significant correlation between SUVmax and ADCmin was seen, while a moderate negative linear relationship (r = -0.5) between SUVmax and ADCmin was observed in tumors with a spatial match (D ≤ 12 mm). In conclusion, spatial mismatch between ADCmin and SUVmax is found in a considerable percentage of patients. The spatial connection of the two parameters SUVmax and ADCmin has a crucial influence on their numeric correlation.

  View details for DOI 10.1155/2017/8650853

  View details for Web of Science ID 000419020200001

  View details for PubMedID 29391862

  View details for PubMedCentralID PMC5748125

• Improving CT-Based PET Attenuation Correction in the Vicinity of Metal Implants by an Iterative Metal Artifact Reduction Algorithm of CT Data and Its Comparison to Dual-Energy-Based Strategies A Phantom Study INVESTIGATIVE RADIOLOGY Schabel, C., Gatidis, S., Bongers, M., Huettig, F., Bier, G., Kupferschlaeger, J., Bamberg, F., la Fougere, C., Nikolaou, K., Pfannenberg, C. 2017; 52 (1): 61-65

  Abstract

  The aim of this study was to evaluate the potential of iterative metal artifact reduction (IMAR) for the improvement of computed tomography (CT)-based position emission tomography (PET) attenuation correction in the vicinity of metal implants and compare it with dual-energy-based metal artifact reduction strategies.A dedicated dental phantom was constructed consisting of a cylindrical tube filled with [18-F]FDG solution (5300 mL and 50.9 MBq) containing 2 artificial jaws with 1 nonprecious alloy fixed dental prosthesis and 3 single tooth crowns in the lower jaw.Computed tomography measurements of the phantom were acquired on a stand-alone dual-energy CT scanner equipped with IMAR capabilities. A series of 24 CT data sets were obtained using different scan parameters and monoenergetic extrapolation of dual-energy CT acquisitions with and without IMAR reconstruction.Position emission tomography measurements of the phantom were performed on a state-of-art PET/CT scanner. Position emission tomography data were reconstructed using all 24 previously acquired CT data sets.Relative errors in the quantification of activity concentrations using the different CT scanning and reconstruction parameters were quantified by placement of regions of interest within the phantom.Metal artifacts of different extent were observed in all CT data sets. A marked reduction in CT metal artifacts was observed using IMAR. In general, activity concentrations were overestimated/underestimated in areas of high/low-density metal artifacts, respectively.Relative errors in PET quantification ranged between -71% and +70% without IMAR. Using IMAR, these errors were reduced to a range between -40% and +12%. Averaged absolute values of relative PET quantification errors were 27% and 7% without and with the use of IMAR (P < 0.001), respectively. Iterative metal artifact reduction was superior compared with dual-energy-based metal artifact reduction strategies, and the combination of both strategies did not result in further significant improvement of PET quantification.The use of IMAR in PET/CT is a promising approach for markedly improving image quality and PET quantification in the vicinity of metal implants. Further clinical studies are necessary to assess the clinical performance of this algorithm in patients.

  View details for DOI 10.1097/RLI.0000000000000306

  View details for Web of Science ID 000390940300007

  View details for PubMedID 27416330

• Contrast-Enhanced High-Pitch Computed Tomography in Pediatric Patients Without Electrocardiography Triggering and Sedation: Comparison of Cardiac Image Quality With Conventional Multidetector Computed Tomography JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY Esser, M., Gatidis, S., Teufel, M., Ketelsen, I., Nikolaou, K., Schaefer, J. F., Tsiflikas, I. 2017; 41 (1): 165-171

  Abstract

  The aim of this study was to compare image quality of anatomical cardiac details without electrocardiography triggering, sedation, or heart rate-regulating drugs in contrast-enhanced pediatric chest computed tomography (CT), using high-pitch CT (HPCT) versus conventional pitch-mode technique (multidetector CT [MDCT]).After written informed consent, 55 patients (median age, 11 years; range, 3-17 years) were prospectively included in this institutional review board-approved study. Patients underwent clinically indicated, contrast-enhanced MDCT or HPCT of the chest.Image quality was assessed evaluating morphological criteria on a 3-point scale (from 1, high, to 3, low detail) and summed up in a global score (from 4, best, to 12, poor image quality). Artifacts were analyzed correspondingly (from 3, low, to 9, severe artifacts). Effective dose and size-specific dose estimate were calculated for all scans.Cardiac image quality was higher in HPCT than in MDCT (7.1 [1.6] vs 8.8 [1.9], P < 0.001). Nevertheless, HPCT showed limitations in image quality, especially concerning the heart valves (2.5 [0.6] and 1.7 [0.5]) and coronary arteries (1.8 [0.6). Artifact score (3.4 [0.6 vs 5.1 [0.9, P < 0.001), effective dose (1.6 [1.3] vs 2.3 [1.6] mSv, P = 0.047), and size-specific dose estimate (2.5 [1.7] vs 4.1 [2.3] mGy, P = 0.002) were lower in HPCT compared with those in MDCT.In pediatric patients, contrast-enhanced HPCT of the chest provides high image quality without electrocardiography triggering or sedation, although image quality is somewhat limited for a detailed depiction of cardiac anatomy.

  View details for DOI 10.1097/RCT.0000000000000482

  View details for Web of Science ID 000392819500027

  View details for PubMedID 27680418

• AN EASY-TO-USE IMAGE LABELING PLATFORM FOR AUTOMATIC MAGNETIC RESONANCE IMAGE QUALITY ASSESSMENT Kuestner, T., Wolf, P., Schwartz, M., Liebgott, A., Schick, F., Gatidis, S., Yang, B., IEEE IEEE. 2017: 754-757

  View details for Web of Science ID 000414283200175

• Distortion correction of diffusion-weighted magnetic resonance imaging of the head and neck in radiotherapy position ACTA ONCOLOGICA Winter, R. M., Schmidt, H., Leibfarth, S., Zwirner, K., Welz, S., Schwenzer, N. F., la Fougere, C., Nikolaou, K., Gatidis, S., Zips, D., Thorwarth, D. 2017; 56 (11): 1659-1663

  View details for DOI 10.1080/0284186X.2017.1377347

  View details for Web of Science ID 000423464400049

  View details for PubMedID 28927335

• Defining optimal tracer activities in pediatric oncologic whole-body F-18-FDG-PET/MRI EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Gatidis, S., Schmidt, H., La Fougere, C., Nikolaou, K., Schwenzer, N. F., Schaefer, J. F. 2016; 43 (13): 2283-2289

  Abstract

  To explore the feasibility of reducing administered tracer activities and to assess optimal activities for combined 18F-FDG-PET/MRI in pediatric oncology.30 18F-FDG-PET/MRI examinations were performed on 24 patients with known or suspected solid tumors (10 girls, 14 boys, age 12 ± 5.6 [1-18] years; PET scan duration: 4 min per bed position). Low-activity PET images were retrospectively simulated from the originally acquired data sets using randomized undersampling of list mode data. PET data of different simulated administered activities (0.25-2.5 MBq/kg body weight) were reconstructed with or without point spread function (PSF) modeling. Mean and maximum standardized uptake values (SUVmean and SUVmax) as well as SUV variation (SUVvar) were measured in physiologic organs and focal FDG-avid lesions. Detectability of organ structures and of focal 18F-FDG-avid lesions as well as the occurrence of false-positive PET lesions were assessed at different simulated tracer activities.Subjective image quality steadily declined with decreasing tracer activities. Compared to the originally acquired data sets, mean relative deviations of SUVmean and SUVmax were below 5 % at 18F-FDG activities of 1.5 MBq/kg or higher. Over 95 % of anatomic structures and all pathologic focal lesions were detectable at 1.5 MBq/kg 18F-FDG. Detectability of anatomic structures and focal lesions was significantly improved using PSF. No false-positive focal lesions were observed at tracer activities of 1 MBq/kg 18F-FDG or higher. Administration of 18F-FDG activities of 1.5 MBq/kg is, thus, feasible without obvious diagnostic shortcomings, which is equivalent to a dose reduction of more than 50 % compared to current recommendations.Significant reduction in administered 18F-FDG tracer activities is feasible in pediatric oncologic PET/MRI. Appropriate activities of 18F-FDG or other tracers for specific clinical questions have to be further established in selected patient populations.

  View details for DOI 10.1007/s00259-016-3503-5

  View details for Web of Science ID 000387478500003

  View details for PubMedID 27565153

• MR Image Reconstruction Using a Combination of Compressed Sensing and Partial Fourier Acquisition: ESPReSSo IEEE TRANSACTIONS ON MEDICAL IMAGING Kuestner, T., Wuerslin, C., Gatidis, S., Martirosian, P., Nikolaou, K., Schwenzer, N., Schick, F., Yang, B., Schmidt, H. 2016; 35 (11): 2447-2458

  Abstract

  A Cartesian subsampling scheme is proposed incorporating the idea of PF acquisition and variable-density Poisson Disc (vdPD) subsampling by redistributing the sampling space onto a smaller region aiming to increase k-space sampling density for a given acceleration factor. Especially the normally sparse sampled high-frequency components benefit from this sampling redistribution, leading to improved edge delineation. The prospective subsampled and compacted k-space can be reconstructed by a seamless combination of a CS-algorithm with a Hermitian symmetry constraint accounting for the missing part of the k-space. This subsampling and reconstruction scheme is called Compressed Sensing Partial Subsampling (ESPReSSo) and was tested on in-vivo abdominal MRI datasets. Different reconstruction methods and regularizations are investigated and analyzed via global (intensity-based) and local (region-of-interest and line evaluation) image metrics, to conclude a clinical feasible setup. Results substantiate that ESPReSSo can provide improved edge delineation and regional homogeneity for multidimensional and multi-coil MRI datasets and is therefore useful in applications depending on well-defined tissue boundaries, such as image registration and segmentation or detection of small lesions in clinical diagnostics.

  View details for DOI 10.1109/TMI.2016.2577642

  View details for Web of Science ID 000388503400008

  View details for PubMedID 27295659

• Bronchial Artery Embolization in Hemoptysis: 10-Year Survival and Recurrence-Free Survival in Benign and Malignant Etiologies - A Retrospective Study ROFO-FORTSCHRITTE AUF DEM GEBIET DER RONTGENSTRAHLEN UND DER BILDGEBENDEN VERFAHREN Syha, R., Benz, T., Hetzel, J., Spengler, W., Kohlhaeufl, M. J., Gatidis, S., Groezinger, G., Horger, M., Nikolaou, K., Ketelsen, D. 2016; 188 (11): 1061-1066

  Abstract

  Purpose: The aim of the study was to evaluate safety, effectiveness, recurrence rate and 10-year survival after bronchial artery embolization (BAE) in benign and malignant etiologies. Methods: The retrospective study includes 100 BAE procedures in 88 patients. Underlying disease was classified as benign (n = 67) and malignant (n = 21) etiologies. Immediate bleeding control and procedure safety were evaluated in all patients. In 51 (58 %) patients, follow-up data with a median follow-up time of 1015 days (range, 494 to 3727 days) were acquired to assess overall survival, time-to-recurrence of bleeding and recurrence-free survival, using Kaplan-Maier estimates to compare differences between both subgroups. Results: Immediate bleeding control was achieved after 96/100 procedures (96 %), with a minor complication rate of 5.0 %. No major complications occurred. The overall survival was 74 % after 1 year and 59 % after 5 years and 10 years. There was a significant difference in survival between the malignant and benign groups (p < 0.0001). Survival was 90 %, 80 % and 76 % at 1 year, 3 years and 10 years, respectively, in the benign group and 18 % and 0 % at 1 year and 3 years, respectively in the malignant group. The median time to recurrence of bleeding and recurrence-free survival were 239 days and 94 % after 1 year and 87 % after 10 years in the benign group, compared to 66 days and 34 % after 1 year and 0 % after 3 years in the malignant group (p = 0.0107). Conclusion: BAE is a safe and highly effective treatment option in hemoptysis. However, the recurrence rate and survival are highly dependent on the underlying disease. Key Points: • BAE is a safe and highly effective treatment option in hemoptysis.• Recurrence rate and survival are strongly dependent on the underlying disease with significantly impaired results in patients with malignant diseases. • Coil embolization is an effective BAE treatment method. Nevertheless, it should be mentioned, that reinterventions can be impeded, if embolization is performed in the proximal part of bronchial arteries. Citation Format: • Syha R, Benz T, Hetzel J et al. Bronchial Artery Embolization in Hemoptysis: 10-Year Survival and Recurrence-Free Survival in Benign and Malignant Etiologies - A Retrospective Study. Fortschr Röntgenstr 2016; 188: 1061 - 1066.

  View details for DOI 10.1055/s-0042-112227

  View details for Web of Science ID 000387237500008

  View details for PubMedID 27760440

• MR-based in vivo follow-up study of Achilles tendon volume and hydration state after ankle-loading activity SCANDINAVIAN JOURNAL OF MEDICINE & SCIENCE IN SPORTS Grosse, U., Syha, R., Gatidis, S., Groezinger, G., Martirosian, P., Partovi, S., Nikolaou, K., Robbin, M. R., Schick, F., Springer, F. 2016; 26 (10): 1200-1208

  Abstract

  The purpose of this study was to evaluate temporal alterations of the Achilles tendon volume and hydration state after cross-country-running. Achilles tendons of six untrained participants were examined on a 3T MR-scanner before running, immediately afterwards, and in the following 24, 48, and 72 h. Using a 3D-UTE sequence, caudal (CA) and cranial (CR) mid-portion tendon areas were examined with off-resonance saturation ratios (OSR) and T2* relaxation times. Tendon volume was measured with a self-written Matlab-based automated contour detection algorithm (AVAT) in submillimeter T2-weighted MR images. A significant influence of running in caudal (P = 0.017) and cranial OSR values (P = 0.001), tendon volume (P = 0.024), and cranial T2* measurements (P = 0.046), but not in caudal T2* values (P = 0.298) were found. In detail, mean individual OSR and tendon volume measurements demonstrated a similar but inverted course in their values after exercise: initially, OSR values increased after running (and tendon volume decreased), while subsequently a decrease of OSR values (with an increase of tendon volume) could be observed. OSR and tendon volume measurements are able to detect a physiological response of tendons to a mechanical stimulus. After a transient decrease of free water in the Achilles tendon, an increase with a maximum free water content 48 h after ankle loading and a tendency toward normalization after 72 h was found.

  View details for DOI 10.1111/sms.12550

  View details for Web of Science ID 000386937200008

  View details for PubMedID 26369754

• Systematic Evaluation of Amide Proton Chemical Exchange Saturation Transfer at 3 T: Effects of Protein Concentration, pH, and Acquisition Parameters INVESTIGATIVE RADIOLOGY Schmidt, H., Schwenzer, N. F., Gatidis, S., Kuestner, T., Nikolaou, K., Schick, F., Martirosian, P. 2016; 51 (10): 635-646

  Abstract

  The goal of this work was to systematically evaluate the reproducibility of amide proton transfer chemical exchange saturation transfer (APT-CEST) at 3 T and its signal dependence on pH, protein concentration, and acquisition parameters. An in vitro system based on bovine serum albumin (BSA) was used, and its limitations were tested by comparing it to in vivo measurements. The contribution of small endogenous metabolites on the APT-CEST signal at 3 T was also investigated. In addition, the reliability of different z-spectrum interpolations as well as the use of only a few frequency offset data points instead of a whole z-spectrum were tested.We created both a BSA phantom at different concentrations and pH values and a metabolite phantom with different small molecules. Chemical exchange saturation transfer data were acquired using a 2-dimensional fast spoiled gradient-echo sequence with pulsed CEST preparation at different saturation durations and power levels. Healthy volunteer measurements were taken for comparison. Z-spectra were interpolated using a 24th-order polynomial (Poly), an eighth-order Fourier series (Fourier), and a smoothing Spline (sSpline) algorithm. To evaluate reduced data sets, only 6 to 14 frequency offsets of the z-spectrum were used and interpolated via a cubic Spline. Region of interest (ROI) evaluations were used to investigate the reproducibility of amide magnetization transfer ratio asymmetry [MTRasym(3.5 ppm)] and to analyze the MTRasym and z-spectra.Interscan standard deviations of MTRasym(3.5 ppm) were always below 0.3%. MTRasym(3.5 ppm) increased when the BSA concentrations increased and decreased when the pH increased. The amine MTRasym signal of small molecules was very small compared with BSA and was only detectable using short saturation times and higher power levels. The MTRasym(3.5 ppm) between BSA concentration steps and between nearly all pH steps was significantly different for all 3 fitting methods. The Fourier and sSpline methods showed no statistically significant differences; however, the results for the Poly method were significantly higher at some concentrations and pH values. Using only few frequency offsets resulted in less significant differences compared with fitting the complete z-spectrum. In general, MTRasym(3.5 ppm) of gray matter, white matter, and ventricle ROIs from volunteer scans increased with an increase in saturation power and partially decreased with an increase in saturation duration. Intra-ROI covariances of MTRasym(3.5 ppm) revealed the highest variations for Poly, whereas using reduced spectral data resulted in an increased signal variation.Amide proton transfer-CEST imaging is a highly reproducible method in which absolute signal differences of approximately 0.5% are detectable in principle. For in vivo applications, Fourier or sSpline interpolations of z-spectra are preferable. Using reduced data sets delivers similar results but with increased variation and therefore decreased (pH/concentration) differentiation capability. Differentiation capability increases with increases in the saturation duration and power level. The results from the in vitro BSA system cannot be directly transferred to the in vivo situation due to different chemical environments resulting in, for example, higher asymmetric macromolecular cMT effects in vivo. Amine signals from small molecules are unlikely to contribute to APT-CEST at 3 T (except for creatine); however, signals can be enhanced by using short saturation times and higher power levels.

  View details for DOI 10.1097/RLI.0000000000000292

  View details for Web of Science ID 000384454000006

  View details for PubMedID 27272542

• C-arm computed tomography and volume perfusion computed tomography (VPCT)-based assessment of blood volume changes in hepatocellular carcinoma in prediction of midterm tumor response to transarterial chemoembolization: a single center retrospective trial CANCER IMAGING Syha, R., Gatidis, S., Groezinger, G., Grosse, U., Maurer, M., Zender, L., Horger, M., Nikolaou, K., Ketelsen, D. 2016; 16: 30

  Abstract

  This study aims to evaluate immediate changes in perfusion parameters in hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE) in C-arm computed tomography (CT) and volume perfusion CT (VPCT) and prediction of midterm tumor response.Twenty-five patients (median age 66, range 61 to 75 years) with 62 HCC lesions undergoing TACE received immediate pre- and post-interventional assessment by C-arm CT and VPCT. Cross-sectional imaging was analyzed at baseline and approximately 12 weeks after TACE according to modified RECIST criteria. Outcome was defined as objective response (OR, > 30 % reduction of viable tumor) or non-OR. Perfusion parameters were evaluated in C-arm CT [parenchymal blood volume (PBV)] and VPCT [blood volume (BV) and blood flow (BF)]. Ratios of perfusion parameters before and after TACE within the tumor and the non-affected liver parenchyma were calculated.Correlation between tumor PBV and BV revealed a moderate correlation (rho = 0.45, p = 0.005). In non-affected liver parenchyma, a significant decrease in PBV was seen, compared to a significant increase in BF and BV. Perfusion ratios in HCC lesions were significantly (p < 0.05) increased in OR group compared to non-OR patients in C-arm CT and VPCT: PBV ratio (0.95 (0.06) to 0.67 (0.38), BV ratio 0.63 (0.34) to 0.15 (0.6), and BF ratio 0.6 (0.32) to 0.22 (0.51). Logistic regression including PBV and BF allowed prediction of OR (sensitivity 88 %/specificity of 83 %).Perfusion parameters acquired by C-arm CT and VPCT cannot simply be substituted by each other, but show similar capability in prediction of midterm tumor response.

  View details for DOI 10.1186/s40644-016-0088-y

  View details for Web of Science ID 000393703300001

  View details for PubMedID 27654658

  View details for PubMedCentralID PMC5031258

• Diagnosing Lung Nodules on Oncologic MR/PET Imaging: Comparison of Fast T1-Weighted Sequences and Influence of Image Acquisition in Inspiration and Expiration Breath-Hold KOREAN JOURNAL OF RADIOLOGY Schwenzer, N. F., Seith, F., Gatidis, S., Brendle, C., Schmidt, H., Pfannenberg, C. A., laFougere, C., Nikolaou, K., Schraml, C. 2016; 17 (5): 684-694

  Abstract

  First, to investigate the diagnostic performance of fast T1-weighted sequences for lung nodule evaluation in oncologic magnetic resonance (MR)/positron emission tomography (PET). Second, to evaluate the influence of image acquisition in inspiration and expiration breath-hold on diagnostic performance.The study was approved by the local Institutional Review Board. PET/CT and MR/PET of 44 cancer patients were evaluated by 2 readers. PET/CT included lung computed tomography (CT) scans in inspiration and expiration (CTin, CTex). MR/PET included Dixon sequence for attenuation correction and fast T1-weighted volumetric interpolated breath-hold examination (VIBE) sequences (volume interpolated breath-hold examination acquired in inspiration [VIBEin], volume interpolated breath-hold examination acquired in expiration [VIBEex]). Diagnostic performance was analyzed for lesion-, lobe-, and size-dependence. Diagnostic confidence was evaluated (4-point Likert-scale; 1 = high). Jackknife alternative free-response receiver-operating characteristic (JAFROC) analysis was performed.Seventy-six pulmonary lesions were evaluated. Lesion-based detection rates were: CTex, 77.6%; VIBEin, 53.3%; VIBEex, 51.3%; and Dixon, 22.4%. Lobe-based detection rates were: CTex, 89.6%; VIBEin, 58.3%; VIBEex, 60.4%; and Dixon, 31.3%. In contrast to CT, inspiration versus expiration did not alter diagnostic performance in VIBE sequences. Diagnostic confidence was best for VIBEin and CTex and decreased in VIBEex and Dixon (1.2 ± 0.6; 1.2 ± 0.7; 1.5 ± 0.9; 1.7 ± 1.1, respectively). The JAFROC figure-of-merit of Dixon was significantly lower. All patients with malignant lesions were identified by CTex, VIBEin, and VIBEex, while 3 patients were false-negative in Dixon.Fast T1-weighted VIBE sequences allow for identification of patients with malignant pulmonary lesions. The Dixon sequence is not recommended for lung nodule evaluation in oncologic MR/PET patients. In contrast to CT, inspiration versus expiratory breath-hold in VIBE sequences was less crucial for lung nodule evaluation but was important for diagnostic confidence.

  View details for DOI 10.3348/kjr.2016.17.5.684

  View details for Web of Science ID 000383357700012

  View details for PubMedID 27587957

  View details for PubMedCentralID PMC5007395

• Simultaneous whole-body PET-MRI in pediatric oncology. More than just reducing radiation? RADIOLOGE Gatidis, S., Gueckel, B., la Fougere, C., Schmitt, J., Schaefer, J. F. 2016; 56 (7): 622-630

  Abstract

  Diagnostic imaging plays an essential role in pediatric oncology with regard to diagnosis, therapy-planning, and the follow-up of solid tumors. The current imaging standard in pediatric oncology includes a variety of radiological and nuclear medicine imaging modalities depending on the specific tumor entity. The introduction of combined simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) has opened up new diagnostic options in pediatric oncology. This novel modality combines the excellent anatomical accuracy of MRI with the metabolic information of PET. In initial clinical studies, the technical feasibility and possible diagnostic advantages of combined PET-MRI have been in comparison with alternative imaging techniques. It was shown that a reduction in radiation exposure of up to 70 % is achievable compared with PET-CT. Furthermore, it has been shown that the number of imaging studies necessary can be markedly reduced using combined PET-MRI. Owing to its limited availability, combined PET-MRI is currently not used as a routine procedure. However, this new modality has the potential to become the imaging reference standard in pediatric oncology in the future. This review article summarizes the central aspects of pediatric oncological PET-MRI based on existing literature. Typical pediatric oncological PET-MRI cases are also presented.

  View details for DOI 10.1007/s00117-016-0122-x

  View details for Web of Science ID 000379708100008

  View details for PubMedID 27306199

• Ultra low-dose VCUG in children using a modern flat detectorunit EUROPEAN RADIOLOGY Linke, S. S., Tsiflikas, I., Herz, K., Szavay, P., Gatidis, S., Schaefer, J. F. 2016; 26 (6): 1678-1685

  Abstract

  To assess dose area products (DAP) and effective doses (ED) of voiding cystourethrography (VCUG) in children using optimized protocols on a modern flat detector unit.DAP and ED were evaluated in 651 VCUG (316 girls, median age: 2.25 years) between 2009 and 2012. DAP was analyzed in relation to patient characteristics (gender, age, presence of pathological findings) and experience of performing physician using analysis of variance. ED values were estimated using adapted conversion factors from the literature. Diagnostic image quality was validated by two experienced physicians using a 3-point scale.Median DAP/ED was 0.5 cGycm(2)/4.56 μSv (boys: 0.6 cGycm(2)/6.16 μSv; girls: 0.4 cGycm(2)/3.54 μSv). In 300 studies without pathologic findings DAP was 0.35 cGycm(2), whereas 351 studies with pathologic findings had a median DAP of 0.7 cGycm(2). No significant relationship between DAP and experience of radiologist was observed. Image validation resulted in an overall good to excellent rating.DAP and ED can be markedly reduced in paediatric VCUG performed with optimized protocols on modern equipment without a noticeable decrease in diagnostic image quality.• Voiding cystourethrography is a comprehensive examination in diagnosing vesicoureteral reflux (VUR). • Radiation reduction is achieved in VCUG through modern equipment and optimized protocols. • Low-dose VCUG is possible without noticeable decrease in diagnostic image quality.

  View details for DOI 10.1007/s00330-015-3996-5

  View details for Web of Science ID 000376100100020

  View details for PubMedID 26385801

• Pediatric Oncologic Imaging: A Key Application of Combined PET/MRI ROFO-FORTSCHRITTE AUF DEM GEBIET DER RONTGENSTRAHLEN UND DER BILDGEBENDEN VERFAHREN Gatidis, S., la Fougere, C., Schaefer, J. F. 2016; 188 (4): 359-364

  Abstract

  Pediatric imaging has been identified as a key application of combined whole-body PET/MRI. First studies have revealed the clinical feasibility and possible advantages of PET/MRI over PET/CT and MRI. Besides a significant reduction in radiation exposure of about 50 - 75 %, combined whole-body PET/MRI offers the diagnostic advantage of the multiparametric characterization of pathophysiologic processes and helps reduce the number of necessary imaging studies. However, very few studies focusing on pediatric PET/MRI have been published to date. Additional studies are necessary in order to fully appreciate the clinical impact of this novel method. This review article shall summarize the existing literature concerning pediatric PET/MRI and give insight into the practical experience derived from over 160 pediatric PET/MRI examinations that were performed in Tübingen.•Combined PET/MR is a promising imaging modality in pediatric oncology. •Using combined PET/MRI, diagnostic radiation exposure of pediatric patients and the number of necessary imaging studies can be reduced. •Further clinical studies are necessary in order to define specific indications for combined PET/MRI in pediatric radiology.

  View details for DOI 10.1055/s-0041-109513

  View details for Web of Science ID 000373075000002

  View details for PubMedID 27002497

• Prostate cancer gene 3 (PCA3) is of additional predictive value in patients with PI-RADS grade III (intermediate) lesions in the MR-guided re-biopsy setting for prostate cancer WORLD JOURNAL OF UROLOGY Kaufmann, S., Bedke, J., Gatidis, S., Hennenlotter, J., Kramer, U., Notohamiprodjo, M., Nikolaou, K., Stenzl, A., Kruck, S. 2016; 34 (4): 509-515

  Abstract

  Multiparametric magnetic resonance imaging (mpMRI) improves diagnostic accuracy in re-biopsies of men with prostate cancer (PC) suspicion, but predictive value is limited despite the use of the new Prostate Imaging Reporting and Data System (PI-RADS). Prognostic value of the PC-specific biomarker prostate cancer gene 3 (PCA3) added to the PI-RADS score was evaluated.The study was a retrospective analysis of the institutional database for men with MR-guided biopsy (MR-GB) for suspicious lesion in mpMRI and who had an additional pre-MR-GB PCA3 testing for ongoing PC suspicion. All men had ≥ 1 negative ultrasound GB. Lesions were retrospectively scored by PI-RADS in three MRI sequences (T2w, DCE, and DWI). PCA3 was analyzed with cutoffs of 25 and 35. The prognostic value of mpMRI and PCA3 and the additional value of both were explored.Tumor detection rate (49 men, mean PSA 10 ng/ml, lesion size 40 mm(2)) was 45 % (22/49 patients). In the subgroup of PI-RADS IV°, 17/17 patients had PC; in PI-RADS III° (intermediate) 5/15 had PC, and all 5 had a PCA3 > 35. PCA3 > 35 had no additional prognostic value in the whole cohort. Out of the 10/15 PC negative patients (PI-RADS III°), PCA3 was < 35 in 6. The inclusion of PCA3 value in PI-RADS III° patients improved predictive accuracy to 91.8 %.MpMRI and subsequent grading to PI-RADS significantly improves PC detection in the re-biopsy setting. The diagnostic uncertainty in the PI-RADS intermediate group can be ameliorated by the addition of PCA3 cutoff of 35 to avoid potential unnecessary biopsies.

  View details for DOI 10.1007/s00345-015-1655-8

  View details for Web of Science ID 000372626700007

  View details for PubMedID 26267808

• Apparent diffusion coefficient-dependent voxelwise computed diffusion-weighted imaging: An approach for improving SNR and reducing T-2 shine-through effects JOURNAL OF MAGNETIC RESONANCE IMAGING Gatidis, S., Schmidt, H., Martirosian, P., Nikolaou, K., Schwenzer, N. F. 2016; 43 (4): 824-832

  Abstract

  To introduce and evaluate a method for signal-to-noise ratio (SNR) improvement and T2 shine-through effect reduction in diffusion-weighted magnetic resonance imaging (DWI).The proposed method uses quantitative information given by the voxel apparent diffusion coefficient (ADC) to derive voxelwise-computed DWI (vcDWI). Behavior of signal intensity variations was simulated and correlated with measurements using a dedicated phantom for DWI allowing for independent adjustment of T2 -relaxivity and diffusivity. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were measured and compared to the method of computed DWI (cDWI). Image signal was correlated with ADCs to appreciate the extent of T2 shine-through effects. Additionally, the proposed method was retrospectively applied to whole-body DWI data of 20 patients with metastatic malignancies. vcDWI was compared to cDWI and measured DWI with respect to image quality, lesion detectability, and lesion diffusivity assessment.Theoretically predicted signal intensity variations showed a high correlation with measured phantom data (r > 0.96). The proposed method yielded lower background signal intensity variation and higher contrast (+144%) and CNR (+358%) for diffusion-restricted phantom compartments than cDWI. Signal intensities of vcDWI showed an increased inverse correlation with phantom ADC values compared to cDWI (r = -0.86 vs. r = -0.73). Application to patient data showed higher image quality (P < 0.001) and lesion detectability (P = 0.011) using vcDWI compared to cDWI, and higher confidence for the correct identification of diffusion-restricted lesions compared to measured DWI (80/80 vs. 60/81; P = 0.013).vcDWI is a promising approach for the reduction of T2 shine-through effects and improvement of SNR and CNR in DWI. The clinical significance of these improvements, especially regarding lesion detection, needs to be evaluated in larger prospective clinical studies.

  View details for DOI 10.1002/jmri.25044

  View details for Web of Science ID 000373000500005

  View details for PubMedID 26348708

• Is It Possible to Detect Activated Brown Adipose Tissue in Humans Using Single-Time-Point Infrared Thermography under Thermoneutral Conditions? Impact of BMI and Subcutaneous Adipose Tissue Thickness PLOS ONE Gatidis, S., Schmidt, H., Pfannenberg, C. A., Nikolaou, K., Schick, F., Schwenzer, N. F. 2016; 11 (3): e0151152

  Abstract

  To evaluate the feasibility to detect activated brown adipose tissue (BAT) using single-time-point infrared thermography of the supraclavicular skin region under thermoneutral conditions. To this end, infrared thermography was compared with 18-F-FDG PET, the current reference standard for the detection of activated BAT.120 patients were enrolled in this study. After exclusion of 18 patients, 102 patients (44 female, 58 male, mean age 58±17 years) were included for final analysis. All patients underwent a clinically indicated 18F-FDG-PET/CT examination. Immediately prior to tracer injection skin temperatures of the supraclavicular, presternal and jugular regions were measured using spatially resolved infrared thermography at room temperature. The presence of activated BAT was determined in PET by typical FDG uptake within the supraclavicular adipose tissue compartments. Local thickness of supraclavicular subcutaneous adipose tissue (SCAT) was measured on CT. Measured skin temperatures were statistically correlated with the presence of activated BAT and anthropometric data.Activated BAT was detected in 9 of 102 patients (8.8%). Local skin temperature of the supraclavicular region was significantly higher in individuals with active BAT compared to individuals without active BAT. However, after statistical correction for the influence of BMI, no predictive value of activated BAT on skin temperature of the supraclavicular region could be observed. Supraclavicular skin temperature was significantly negatively correlated with supraclavicular SCAT thickness.We conclude that supraclavicular SCAT thickness influences supraclavicular skin temperature and thus makes a specific detection of activated BAT using single-time-point thermography difficult. Further studies are necessary to evaluate the possibility of BAT detection using alternative thermographic methods, e.g. dynamic thermography or MR-based thermometry taking into account BMI as a confounding factor.

  View details for DOI 10.1371/journal.pone.0151152

  View details for Web of Science ID 000371989200033

  View details for PubMedID 26967519

  View details for PubMedCentralID PMC4788460

• ACTIVE LEARNING FOR MAGNETIC RESONANCE IMAGE QUALITY ASSESSMENT Liebgott, A., Kuestner, T., Gatidis, S., Schick, F., Yang, B., IEEE IEEE. 2016: 922-926

  View details for Web of Science ID 000388373401012

• Comprehensive Oncologic Imaging in Infants and Preschool Children With Substantially Reduced Radiation Exposure Using Combined Simultaneous F-18-Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Imaging A Direct Comparison to F-18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography INVESTIGATIVE RADIOLOGY Gatidis, S., Schmidt, H., Guecke, B., Bezrukov, I., Seitz, G., Ebinger, M., Reimold, M., Pfannenberg, C. A., Nikolaou, K., Schwenzer, N. F., Schaefer, J. F. 2016; 51 (1): 7-14

  Abstract

  The aim of this study was to evaluate the clinical applicability and technical feasibility of fluorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) compared with FDG PET/computed tomography (CT) in young children focusing on lesion detection, PET quantification, and potential savings in radiation exposure.Twenty examinations (10 PET/CT and 10 PET/MRI examinations) were performed prospectively in 9 patients with solid tumors (3 female, 6 male; mean age, 4.8 [1-6] years). Fluorodeoxyglucose PET/CT and FDG PET/MRI were performed sequentially after a single tracer injection. Lesion detection and analysis were performed independently in PET/CT and PET/MRI. Potential changes in diagnostic or therapeutic patient management were recorded. Positron emission tomography quantification in PET/MRI was evaluated by comparing standardized uptake values resulting from MRI-based and CT-based attenuation correction. Effective radiation doses of PET and CT were estimated.Twenty-one PET-positive lesions were found congruently in PET/CT and PET/MRI. Magnetic resonance imaging enabled significantly better detection of morphologic PET correlates compared with CT. Eight suspicious PET-negative lesions were identified by MRI, of which one was missed in CT. Sensitivity, specificity, and accuracy for correct lesion classification were not significantly different (90%, 47%, and 62% in PET/CT; 100%, 68%, and 79% in PET/MRI, respectively). In 4 patients, the use of PET/MRI resulted in a potential change in diagnostic management compared with PET/CT, as local and whole-body staging could be performed within 1 single examination. In 1 patient, PET/MRI initiated a change in therapeutic management. Positron emission tomography quantification using MRI-based attenuation correction was accurate compared with CT-based attenuation correction. Higher standardized uptake value deviations of about 18% were observed in the lungs due to misclassification in MRI-based attenuation maps. Potential reduction in radiation dose was 48% in PET/MRI compared with PET/CT (P < 0.05).FDG PET/MRI is at least equivalent to FDG PET/CT for oncologic imaging in young children. Specifically, superior soft tissue contrast of MRI results in higher confidence in lesion interpretation. Substantial savings in radiation exposure can be achieved, and the number of necessary imaging examinations can be reduced using PET/MRI compared with PET/CT.

  View details for DOI 10.1097/RLI.0000000000000200

  View details for Web of Science ID 000366824600002

  View details for PubMedID 26309185

• Comparison of Positron Emission Tomography Quantification Using Magnetic Resonance- and Computed Tomography-Based Attenuation Correction in Physiological Tissues and Lesions A Whole-Body Positron Emission Tomography/Magnetic Resonance Study in 66 Patients INVESTIGATIVE RADIOLOGY Seith, F., Gatidis, S., Schmidt, H., Bezrukov, I., la Fougere, C., Nikolaou, K., Pfannenberg, C., Schwenzer, N. 2016; 51 (1): 66-71

  Abstract

  Attenuation correction (AC) in fully integrated positron emission tomography (PET)/magnetic resonance (MR) systems plays a key role for the quantification of tracer uptake. The aim of this prospective study was to assess the accuracy of standardized uptake value (SUV) quantification using MR-based AC in direct comparison with computed tomography (CT)-based AC of the same PET data set on a large patient population.Sixty-six patients (22 female; mean [SD], 61 [11] years) were examined by means of combined PET/CT and PET/MR (11C-choline, 18F-FDG, or 68Ga-DOTATATE) subsequently. Positron emission tomography images from PET/MR examinations were corrected with MR-derived AC based on tissue segmentation (PET(MR)). The same PET data were corrected using CT-based attenuation maps (μ-maps) derived from PET/CT after nonrigid registration of the CT to the MR-based μ-map (PET(MRCT)). Positron emission tomography SUVs were quantified placing regions of interest or volumes of interest in 6 different body regions as well as PET-avid lesions, respectively.The relative differences of quantitative PET values when using MR-based AC versus CT-based AC were varying depending on the organs and body regions assessed. In detail, the mean (SD) relative differences of PET SUVs were as follows: -7.8% (11.5%), blood pool; -3.6% (5.8%), spleen; -4.4% (5.6%)/-4.1% (6.2%), liver; -0.6% (5.0%), muscle; -1.3% (6.3%), fat; -40.0% (18.7%), bone; 1.6% (4.4%), liver lesions; -6.2% (6.8%), bone lesions; and -1.9% (6.2%), soft tissue lesions. In 10 liver lesions, distinct overestimations greater than 5% were found (up to 10%). In addition, overestimations were found in 2 bone lesions and 1 soft tissue lesion adjacent to the lung (up to 28.0%).Results obtained using different PET tracers show that MR-based AC is accurate in most tissue types, with SUV deviations generally of less than 10%. In bone, however, underestimations can be pronounced, potentially leading to inaccurate SUV quantifications. In addition, SUV overestimations were found for some lesions close to lung borders. This has to be taken into account when comparing PET/CT- and PET/MR-derived SUVs.

  View details for DOI 10.1097/RLI.0000000000000208

  View details for Web of Science ID 000366824600009

  View details for PubMedID 26348596

• Imaging-based characterization of cardiometabolic phenotypes focusing on whole-body MRI-an approach to disease prevention and personalized treatment BRITISH JOURNAL OF RADIOLOGY Gatidis, S., Schlett, C. L., Notohamiprodjo, M., Bamberg, F. 2016; 89 (1059): 20150829

  Abstract

  Metabolic syndrome and cardiovascular disorders pose a challenge to global healthcare systems. Too often, patients with metabolic syndrome are diagnosed in advanced disease stages, where disease-associated damage is irreversible and treatment options are limited. Thus, prevention plays an increasingly important role in the management of cardiometabolic disorders. The main challenge of prevention is to identify patient groups who are at risk for developing overt disease and who might benefit from early therapeutic intervention. In this context, imaging-based phenotyping can add significant information to clinical evaluations, revealing anatomical and physiological changes that reflect intrinsic and extrinsic risk factors. The purpose of this review article was to provide an overview of the current state of imaging-based phenotyping of metabolic syndrome and cardiovascular disorders and to discuss current and potential developments in this field.

  View details for DOI 10.1259/bjr.20150829

  View details for Web of Science ID 000372202900030

  View details for PubMedID 26780657

  View details for PubMedCentralID PMC4986500

• Towards tracer dose reduction in PET studies: Simulation of dose reduction by retrospective randomized undersampling of list-mode data HELLENIC JOURNAL OF NUCLEAR MEDICINE Gatidis, S., Wuerslin, C., Seith, F., Schaefer, J. F., la Fougere, C., Nikolaou, K., Schwenzer, N. F., Schmidt, H. 2016; 19 (1): 15-18

  Abstract

  Optimization of tracer dose regimes in positron emission tomography (PET) imaging is a trade-off between diagnostic image quality and radiation exposure. The challenge lies in defining minimal tracer doses that still result in sufficient diagnostic image quality. In order to find such minimal doses, it would be useful to simulate tracer dose reduction as this would enable to study the effects of tracer dose reduction on image quality in single patients without repeated injections of different amounts of tracer. The aim of our study was to introduce and validate a method for simulation of low-dose PET images enabling direct comparison of different tracer doses in single patients and under constant influencing factors.(18)F-fluoride PET data were acquired on a combined PET/magnetic resonance imaging (MRI) scanner. PET data were stored together with the temporal information of the occurrence of single events (list-mode format). A predefined proportion of PET events were then randomly deleted resulting in undersampled PET data. These data sets were subsequently reconstructed resulting in simulated low-dose PET images (retrospective undersampling of list-mode data). This approach was validated in phantom experiments by visual inspection and by comparison of PET quality metrics contrast recovery coefficient (CRC), background-variability (BV) and signal-to-noise ratio (SNR) of measured and simulated PET images for different activity concentrations. In addition, reduced-dose PET images of a clinical (18)F-FDG PET dataset were simulated using the proposed approach.(18)F-PET image quality degraded with decreasing activity concentrations with comparable visual image characteristics in measured and in corresponding simulated PET images. This result was confirmed by quantification of image quality metrics. CRC, SNR and BV showed concordant behavior with decreasing activity concentrations for measured and for corresponding simulated PET images. Simulation of dose-reduced datasets based on clinical (18)F-FDG PET data demonstrated the clinical applicability of the proposed data.Simulation of PET tracer dose reduction is possible with retrospective undersampling of list-mode data. Resulting simulated low-dose images have equivalent characteristics with PET images actually measured at lower doses and can be used to derive optimal tracer dose regimes.

  View details for Web of Science ID 000377667300006

  View details for PubMedID 26929936

• Bile Acid-Induced Suicidal Erythrocyte Death CELLULAR PHYSIOLOGY AND BIOCHEMISTRY Lang, E., Pozdeev, V. I., Gatidis, S., Qadri, S. M., Haeussinger, D., Kubitz, R., Herebian, D., Mayatepek, E., Lang, F., Lang, K. S., Lang, P. A. 2016; 38 (4): 1500-1509

  Abstract

  In nucleated cells, bile acids may activate cation channels subsequently leading to entry of Ca2+. In erythrocytes, increase of cytosolic Ca2+ activity triggers eryptosis, the suicidal death of erythrocytes characterized by phosphatidylserine exposure at the cell surface and cell shrinkage. Eryptosis is triggered by bile duct ligation, an effect partially attributed to conjugated bilirubin. The present study explored, whether bile acids may stimulate eryptosis.Phosphatidylserine exposing erythrocytes have been identified utilizing annexin V binding, cell volume estimated from forward scatter, cytosolic Ca2+ activity determined using Fluo-3 fluorescence, and ceramide abundance at the erythrocyte surface utilizing specific antibodies.The exposure of human erythrocytes to glycochenodesoxycholic (GCDC) and taurochenodesoxycholic (TCDC) acid was followed by a significant decrease of forward scatter and significant increase of Fluo-3 fluorescence, ceramide abundance as well as annexin V binding. The effect on annexin V binding was significantly blunted, but not abolished by removal of extracellular Ca2+.Bile acids stimulate suicidal cell death, an effect paralleled by and in part due to Ca2+ entry and ceramide. The bile acid induced eryptosis may in turn lead to accelerated clearance of circulating erythrocytes and, thus, may contribute to anemia in cholestatic patients.

  View details for DOI 10.1159/000443091

  View details for Web of Science ID 000375787000019

  View details for PubMedID 27050423

• Multiparametric imaging with simultaneousMRI/PET. Methodological aspects and possible clinical applications ZEITSCHRIFT FUR RHEUMATOLOGIE Gatidis, S., Schmidt, H., Claussen, C. D., Schwenzer, N. F. 2015; 74 (10): 878-885

  Abstract

  Combined MRI/PET enables the acquisition of a variety of imaging parameters during one examination, including anatomical and functional information such as perfusion, diffusion, and metabolism.The present article summarizes these methods and their applications in multiparametric imaging via MRI/PET.Numerous studies have shown that the combination of these parameters can improve diagnostic accuracy for many applications, including the imaging of oncological, neurological, and inflammatory conditions. Because of the amount and the complexity of the acquired multiparametric data, there is a need for advanced analysis tools, such as methods of parameter selection and data classification.Currently, the clinical application of this process still has limitations. On the one hand, software for the fast calculation and standardized evaluation of the imaging data acquired is still lacking. On the other hand, there are deficiencies when comparing the results because of a lack of standardization of the assessment and diagnostic procedure.

  View details for DOI 10.1007/s00393-015-0011-0

  View details for Web of Science ID 000365812300007

  View details for PubMedID 26589201

• Noninfectious Generalized Bronchiolitis in the Setting of Allogeneic Stem Cell Transplantation: A Potential Mimic. of Lower Respiratory Tract Infection ACADEMIC RADIOLOGY Kloth, C., Grosse, U., Wirths, S., Gatidis, S., Bethge, W., Nikolaou, K., Horger, M. 2015; 22 (12): 1546-1554

  Abstract

  To describe a little-known therapy-related small-airway phenomenon presumably caused by mucosal irritation in patients undergoing allogeneic stem cell transplantation (allo-SCT).Retrospective database search at our institution identified 739 hematologic patients who underwent chemotherapy + allo-SCT between September 2004 and March 2014. After infectious pulmonary complications were excluded, 75 patients (female = 24; male = 51; median age = 47 years) with signs of generalized bronchiolitis (GB) on chest high-resolution computed tomography were identified. Computed tomography (CT) was performed proximate to chemotherapy onset; 92% had follow-up CT (mean, 1.9 weeks). The presence of centrilobular nodules, bronchial wall thickening (BWT), tree-in-bud (distributed diffuse vs. focal), ground-glass opacity, airspace opacification, luminal impactions, and air trapping was correlated with occurrence and duration of oral mucositis and therapy characteristics. Intensity of tree-in-bud and centrilobular nodules was graded absent (grade = 0), moderate (grade = 1), or marked (grade = 2).Overall incidence of GB among allo-SCT patients was 10.14%. GB was diagnosed at the time point of transplantation with a mean duration of CT findings of 4 weeks (±2.7). Tree-in-bud (17% [grade 2] and 83% [grade 1]) and BWT were present in 100% of the patients. Centrilobular nodules diffusely distributed were found in 45.5% of patients (20% [grade 2], 24% [grade 1], and 56% [none]). Air trapping and mosaic pattern were found in 13% and 16% of the patients, respectively. Resolution of GB was spontaneous. GB and its severity correlated with the temporal course and grade of oral mucositis; frequency and degree were not significantly influenced by the chemotherapy regimen. The incidence of GB in high-resolution computed tomography was statistically and significantly higher in patients with oral mucositis (P < 0.035).GB is frequent during chemotherapy for allo-SCT and is characterized by an even distribution of tree-in-bud, BWT, centrilobular nodules, mild clinical symptoms, and spontaneous resolution.

  View details for DOI 10.1016/j.acra.2015.08.025

  View details for Web of Science ID 000364612600013

  View details for PubMedID 26482262

• Multiparametric Analysis of Bone Marrow in Cancer Patients Using Simultaneous PET/MR Imaging: Correlation of Fat Fraction, Diffusivity, Metabolic Activity, and Anthropometric Data JOURNAL OF MAGNETIC RESONANCE IMAGING Schraml, C., Schmid, M., Gatidis, S., Schmidt, H., la Fougere, C., Nikolaou, K., Schwenzer, N. F. 2015; 42 (4): 1048-1056

  Abstract

  To analyze the regional composition of bone marrow (BM) in correlation with metabolic activity and diffusivity using simultaneous positron emission tomography (PET)/MRI.Retrospective analysis of 18F-FDG-PET/MR scans of 110 patients was performed. A three-dimensional gradient-echo sequence with Dixon-based fat-water separation was used for fat quantification. Dixon images, diffusion-weighted images (DWI) and 18F-FDG-PET were co-registered. Mean values of fat fraction (FF), standardized uptake value (SUV), and apparent diffusion coefficient (ADC) of BM were measured in different anatomical regions. Correlation of FF, SUV, and ADC and association of BM fat content and metabolic activity with anthropometric data was analyzed (Pearson). BM fat content and metabolic activity was compared in patients with and without chemotherapy (t-test).Regional differences in BM were found with highest fat content (93 ± 8%) and lowest ADC (0.22 ± 0.18 × 10(-3) mm(2) /s) in the peripheral skeleton and highest SUV in the spine (1.77 ± 0.6). There was a significant inverse correlation between FF and SUV (r = -0.73; P < 0.0001) and a significant inverse correlation between FF and ADC (r = -0.62; P < 0.0001). In patients with chemotherapy, a tendency to higher fat content and lower metabolic activity was observed in the proximal skeleton, although no statistical significance was reached.BM shows distinct regional variations in FF, SUV, and ADC. The inverse correlation of FF and SUV in BM suggests that BM adipose tissue does not have a comparable high metabolic activity as brown adipose tissue.

  View details for DOI 10.1002/jmri.24865

  View details for Web of Science ID 000363281500021

  View details for PubMedID 25683203

• Patient Comfort During Positron Emission Tomography/Magnetic Resonance and Positron Emission Tomography/Computed Tomography Examinations Subjective Assessments With Visual Analog Scales INVESTIGATIVE RADIOLOGY Gueckel, B., Gatidis, S., Enck, P., Schaefer, J., Bisdas, S., Pfannenberg, C., Schwenzer, N. 2015; 50 (10): 726-732

  Abstract

  The aims of this study were to investigate subjective perceptions and sensory side effects during whole-body positron emission tomography (PET)/magnetic resonance (MR) examinations and to evaluate differences between PET/MR and standard PET/computed tomography (CT) examinations.During prospective clinical trials using a PET/MR hybrid system after a standard PET/CT examination, 266 patients (including 19 juveniles) were asked to complete questionnaires on causes of discomfort and side effects after both examinations (self-assessment). In case of complaints regarding causes of discomfort, physicians were also asked to complete the questionnaires to provide an external assessment. Visual analog scales were used for the ratings.Seventy-four percent (183/247) of all adult patients and 68% (13/19) of all teenage patients completed the questionnaires. In most of the cases, patient compliance was good and allowed for the acquisition of diagnostic images. Most patients did not report side effects or discomfort at all. Only 11 of 247 PET/MR scans of adult patients (4.4%) and 4 of 19 scans of juvenile patients (21%) were aborted prematurely by the patients' requests; however, this did not influence the final PET/MR diagnoses in most cases (12/15). In terms of noise levels and examination times, patients rated the PET/MR significantly lower than the PET/CT. With the exception of male patients not tolerating the examination time as well as female patients, no significant influences of sex, age, body mass index, and real scan times were observed. The attending physicians tended to underestimate their patient's discomfort, particularly when the discomfort was because of time (in the case of children) or noise exposure (all patients).Patient comfort should drive the design and development of optimized scanner types, workflow processes, and scan protocols. For PET/MR, the most important aim should be to shorten the scan time. However, patient-centered management may be the best instrument to improve patient compliance.

  View details for DOI 10.1097/RLI.0000000000000177

  View details for Web of Science ID 000362086700007

  View details for PubMedID 26039772

• Quantitative Evaluation of Segmentation- and Atlas-Based Attenuation Correction for PET/MR on Pediatric Patients JOURNAL OF NUCLEAR MEDICINE Bezrukov, I., Schmidt, H., Gatidis, S., Mantlik, F., Schaefer, J. F., Schwenzer, N., Pichler, B. J. 2015; 56 (7): 1067-1074

  Abstract

  Pediatric imaging is regarded as a key application for combined PET/MR imaging systems. Because existing MR-based attenuation-correction methods were not designed specifically for pediatric patients, we assessed the impact of 2 potentially influential factors: inter- and intrapatient variability of attenuation coefficients and anatomic variability. Furthermore, we evaluated the quantification accuracy of 3 methods for MR-based attenuation correction without (SEGbase) and with bone prediction using an adult and a pediatric atlas (SEGwBONEad and SEGwBONEpe, respectively) on PET data of pediatric patients.The variability of attenuation coefficients between and within pediatric (5-17 y, n = 17) and adult (27-66 y, n = 16) patient collectives was assessed on volumes of interest (VOIs) in CT datasets for different tissue types. Anatomic variability was assessed on SEGwBONEad/pe attenuation maps by computing mean differences to CT-based attenuation maps for regions of bone tissue, lungs, and soft tissue. PET quantification was evaluated on VOIs with physiologic uptake and on 80% isocontour VOIs with elevated uptake in the thorax and abdomen/pelvis. Inter- and intrapatient variability of the bias was assessed for each VOI group and method.Statistically significant differences in mean VOI Hounsfield unit values and linear attenuation coefficients between adult and pediatric collectives were found in the lungs and femur. The prediction of attenuation maps using the pediatric atlas showed a reduced error in bone tissue and better delineation of bone structure. Evaluation of PET quantification accuracy showed statistically significant mean errors in mean standardized uptake values of -14% ± 5% and -23% ± 6% in bone marrow and femur-adjacent VOIs with physiologic uptake for SEGbase, which could be reduced to 0% ± 4% and -1% ± 5% using SEGwBONEpe attenuation maps. Bias in soft-tissue VOIs was less than 5% for all methods. Lung VOIs showed high SDs in the range of 15% for all methods. For VOIs with elevated uptake, mean and SD were less than 5% except in the thorax.The use of a dedicated atlas for the pediatric patient collective resulted in improved attenuation map prediction in osseous regions and reduced interpatient bias variation in femur-adjacent VOIs. For the lungs, in which intrapatient variation was higher for the pediatric collective, a patient- or group-specific attenuation coefficient might improve attenuation map accuracy. Mean errors of -14% and -23% in bone marrow and femur-adjacent VOIs can affect PET quantification in these regions when bone tissue is ignored.

  View details for DOI 10.2967/jnumed.114.149476

  View details for Web of Science ID 000357754600039

  View details for PubMedID 25952739

• Combined unsupervised-supervised classification of multiparametric PET/MRI data: application to prostate cancer NMR IN BIOMEDICINE Gatidis, S., Scharpf, M., Martirosian, P., Bezrukov, I., Kuestner, T., Hennenlotter, J., Kruck, S., Kaufmann, S., Schraml, C., la Fougere, C., Schwenzer, N. F., Schmidt, H. 2015; 28 (7): 914-922

  Abstract

  Multiparametric medical imaging data can be large and are often complex. Machine learning algorithms can assist in image interpretation when reliable training data exist. In most cases, however, knowledge about ground truth (e.g. histology) and thus training data is limited, which makes application of machine learning algorithms difficult. The purpose of this study was to design and implement a learning algorithm for classification of multidimensional medical imaging data that is robust and accurate even with limited prior knowledge and that allows for generalization and application to unseen data. Local prostate cancer was chosen as a model for application and validation. 16 patients underwent combined simultaneous [(11) C]-choline positron emission tomography (PET)/MRI. The following imaging parameters were acquired: T2 signal intensities, apparent diffusion coefficients, parameters Ktrans and Kep from dynamic contrast-enhanced MRI, and PET standardized uptake values (SUVs). A spatially constrained fuzzy c-means algorithm (sFCM) was applied to the single datasets and the resulting labeled data were used for training of a support vector machine (SVM) classifier. Accuracy and false positive and false negative rates of the proposed algorithm were determined in comparison with manual tumor delineation. For five of the 16 patients rates were also determined in comparison with the histopathological standard of reference. The combined sFCM/SVM algorithm proposed in this study revealed reliable classification results consistent with the histopathological reference standard and comparable to those of manual tumor delineation. sFCM/SVM generally performed better than unsupervised sFCM alone. We observed an improvement in accuracy with increasing number of imaging parameters used for clustering and SVM training. In particular, including PET SUVs as an additional parameter markedly improved classification results. A variety of applications are conceivable, especially for imaging of tissues without easily available histopathological correlation.

  View details for DOI 10.1002/nbm.3329

  View details for Web of Science ID 000356672100016

  View details for PubMedID 26014883

• Comparison of chest-CT findings of Influenza virus-associated pneumonia in immunocompetent vs. immunocompromised patients EUROPEAN JOURNAL OF RADIOLOGY Kloth, C., Forler, S., Gatidis, S., Beck, R., Spira, D., Nikolaou, K., Horger, M. 2015; 84 (6): 1177-1183

  Abstract

  To retrospectively compare CT-patterns of pulmonary infiltration caused by different Influenza virus types and subtypes in immunocompetent and immunocompromised patients for possible discrimination.Retrospective database search at our institution yielded 237 patients who were tested positive for Influenza virus type A or type B by bronchoalveolar lavage between January 2009 and April 2014. Fifty-six of these patients (female 26; male 30; median age 55.8 y, range 17-86 y; SD ± 14.4 y) underwent chest-HRCT due to a more severe clinical course of pulmonary infection. We registered all CT-findings compatible with pulmonary infection classifying them as airway predominant (tree-in-bud, centrilobular nodules, bronchial wall thickening ± peribronchial ground-glass opacity and consolidation) vs. interstitial-parenchymal predominant (bilateral, symmetrical GGO, consolidation, crazy paving and/or interlobular septal thickening). Twenty-six patients (46.4%) had follow-up CT-studies (0.78 mean, SD ± 5.8 scans).Thirty-six patients were immunocompromised (group I) whereas 20 patients were immunocompetent (group II). An airway-centric pattern of infection was found in 15 patients (group I) and 14 patients (group II) whereas an interstitial-parenchymal predominant pattern was found in 14 patients (group I) and 2 patients (group II). Eleven patients had a mixed pattern with no clear assignment to one group. At FU, 12 patients from group I and 3 from group II showed transitional infiltration patterns: in 10 patients from interstitial-parenchymal into airway predominant pattern and in five patients from airway predominant into interstitial-parenchymal. No significant differences in the pattern of pulmonary infection were found between different types and subtypes of Influenza viruses.Patterns of pulmonary infiltration caused by Influenza viruses do not significantly differ between immunocompetent and immunocompromised patients or between different types and subtypes of Influenza virus. One possible explanation for this could be the temporarily interchangeable character of pulmonary infiltration in this infection.

  View details for DOI 10.1016/j.ejrad.2015.02.014

  View details for Web of Science ID 000354027400024

  View details for PubMedID 25796425

• Evaluation of MR imaging properties of a dedicated RT positioning solution for combined PET/MR imaging Winter, R., Leibfarth, S., Gatidis, S., Schmidt, H., Schwenzer, N., Zips, D., Thorwarth, D. ELSEVIER IRELAND LTD. 2015: S222

  View details for Web of Science ID 000688178300453

• Diagnostic Value of T-1 and T-2* Relaxation Times and Off-Resonance Saturation Effects in the Evaluation of Achilles Tendinopathy by MRI at 3T JOURNAL OF MAGNETIC RESONANCE IMAGING Grosse, U., Syha, R., Hein, T., Gatidis, S., Groezinger, G., Schabel, C., Martirosian, P., Schick, F., Springer, F. 2015; 41 (4): 964-973

  Abstract

  To evaluate and compare the diagnostic value of T1 , T2 * relaxation times and off-resonance saturation ratios (OSR) in healthy controls and patients with different clinical and morphological stages of Achilles tendinopathy.Forty-two healthy Achilles tendons and 34 tendons of 17 patients with symptomatic and asymptomatic tendinopathy were investigated clinically with conventional magnetic resonance imaging (MRI) sequences on a 3T whole-body MR scanner and a dynamic ultrasound examination. In addition, T1 and T2 * relaxation times were assessed using an ultrashort echo time (UTE) imaging sequence with flip angle and echo time variation. For the calculation of OSR values a Gaussian off-resonance saturation pulse (frequency offset: 750-5000 Hz) was used. The diagnostic value of the derived MR values was assessed and compared using receiver operating characteristic (ROC) curves.ROC curves demonstrate the highest overall test performance for OSR values at 2000 Hz off-resonance in differentiating slightly (OSR-2000 [AUC: 0.930] > T2 * [AUC: 0.884] > T1 [AUC: 0.737]) and more severe pathologically altered tendon areas (OSR-2000 [AUC: 0.964] > T2 * [AUC: 0.917] > T1 [AUC: 0.819]) from healthy ones.OSR values at a frequency offset of 2000 Hz demonstrated a better sensitivity and specificity for detecting mild and severe stages of tendinopathy compared to T2 * and particularly when compared to T1 relaxation times.

  View details for DOI 10.1002/jmri.24657

  View details for Web of Science ID 000351521700014

  View details for PubMedID 24817378

• Direct Comparison of Targeted MRI-Guided Biopsy with Systematic Transrectal Ultrasound-Guided Biopsy in Patients with Previous Negative Prostate Biopsies UROLOGIA INTERNATIONALIS Kaufmann, S., Kruck, S., Kramer, U., Gatidis, S., Stenzl, A., Roethke, M., Scharpf, M., Schilling, D. 2015; 94 (3): 319-325

  Abstract

  To directly compare the diagnostic performance of targeted MRI-guided biopsy (MR-GB) and systematic transrectal ultrasound-guided biopsy (TRUS-GB).Thirty-five patients with at least one negative TRUS-GB, persistently elevated or rising prostate-specific antigen and a lesion suspicious for prostate cancer (PC) on multiparametric MRI (mpMRI) scored by using the Prostate Imaging Reporting and Data System (PI-RADS) were included. A median of three targeted biopsies per lesion were obtained and systematic TRUS-GB was performed subsequently by an independent urologist without knowledge of the MRI findings. Definite pathology reports were analyzed for anatomical location and criteria of clinical significance.The tumor detection rate was significantly higher with MR-GB compared with TRUS-GB (16/35, 46% and 8/35, 23%, respectively, p < 0.05). MR-GB detected PC in all patients with positive TRUS-GB. All tumors detected by MR-GB exhibited at least one criterion of clinical significance. PC lesions showed a significantly higher PI-RADS sum score compared with benign lesions.MR-GB is more effective compared with TRUS-GB in detecting clinically significant PC in men after previous negative TRUS-GB. PI-RADS scores give additional information and could be part of the decision-making process when considering retrial biopsy. Additional systematic biopsy can be omitted in patients undergoing targeted MR-GB.

  View details for DOI 10.1159/000365397

  View details for Web of Science ID 000352882700009

  View details for PubMedID 25227711

• Impact of Measurement Parameters on Apparent Diffusion Coefficient Quantification in Diffusion-Weighted-Magnetic Resonance Imaging INVESTIGATIVE RADIOLOGY Schmidt, H., Gatidis, S., Schwenzer, N. F., Martirosian, P. 2015; 50 (1): 46-56

  Abstract

  The scope of this work was to systematically evaluate the reproducibility of diffusion-weighted imaging and the impact of b values used for apparent diffusion coefficient (ADC) calculation as well as the echo time (TE) on the resulting ADC in phantom studies. We attempted to find a minimum upper b value needed for reliable ADC measurements. In addition, we were able to investigate these impacts not only for different diffusivities but also for different T2 relaxation times. The influence of different b values on ADC calculations for different organs was also assessed in a volunteer study.Diffusion-weighted imaging of a phantom consisting of 16 compartments with combinations of 4 different diffusivities and 4 different T2 relaxation times was conducted 5 times using 11 b values (0-1000 s/mm) and 5 different TEs. Apparent diffusion coefficient was calculated from the 16 compartment regions of interest using 42 different combinations of b values. Reproducibility of ADC was assessed from the coefficient of variation of the 5 measurements. The ADC stability was determined from a voxel-based coefficient of variation (CVsta) and the signal-to-noise ratio (SNR) to find the minimum upper b values for a reliable ADC quantification. The influence of TE on ADC quantification was assessed for 9 different b value combinations. The influence of 9 different b value combinations on ADC was evaluated by a region of interest analysis of 7 organs in 12 volunteers.The found coefficient of variation was between 10.2% and 1.4%, decreasing with increasing upper b value and increasing diffusivities. Accordingly, CVsta and SNR showed the same trend. Using an upper b value of 600 s/mm gives already reliable ADC results showing a maximum CVsta of 7.5%, whereas an upper b value of 1000 s/mm revealed a maximum CVsta of 5.5%. Values of ADC reduced with increasing upper b value in phantom as well as in human data. Apparent diffusion coefficient also reduced with increasing TE and tended to increase for increasing T2 relaxation times and increasing diffusion restriction.Apparent diffusion coefficient can be measured with high reproducibility but strongly depends on b values used and TE, which should be kept constant in each examination protocol. Whereas upper b values as low as 400 s/mm can be used for examinations of tissues with low diffusivities, very high b values (>1000 s/mm) are needed to reach an optimal SNR for high diffusive tissues. An upper b value of 600 s/mm is a good compromise regarding ADC stability, SNR, and measurement time for all tissue types.

  View details for Web of Science ID 000346150100007

  View details for PubMedID 25247326

• Is the standard uptake value (SUV) appropriate for quantification in clinical PET imaging? - Variability induced by different SUV measurements and varying reconstruction methods EUROPEAN JOURNAL OF RADIOLOGY Brendle, C., Kupferschlaeger, J., Nikolaou, K., la Fougere, C., Gatidis, S., Pfannenberg, C. 2015; 84 (1): 158-162

  Abstract

  PET quantification using the standard uptake value (SUV) is very prone to variations by technical factors of the scanner system and patient specific characteristics. Aim of the study was to investigate the reproducibility of SUV values between different measures and different reconstruction algorithms in a PET/CT scanner of the newest generation.The time-of-flight PET datasets of 27 consecutive oncological patients were reconstructed with OSEM3D in two different matrix sizes (200 × 200 and 400 × 400) as well as in a matrix size of 400 × 400 and additional point-spread-reconstruction. The standardized uptake values SUVmax, SUVmean and SUVpeak in 60 lesions were compared concerning their variability in the three reconstructions.The addition of point-spread-reconstruction causes a significant increase of SUV values in comparison to OSEM 3D. SUVpeak showed the highest reproducibility between the different reconstruction algorithms. The variability of SUVmax and SUVmean increases in small lesions <5 ml, while SUVpeak remains more stable.SUVmax, SUVmean and SUVpeak can be used for PET quantification in principle. However, quantification of small lesions is difficult. SUVpeak is the most robust method when using varying reconstruction methods, especially in small lesions.

  View details for DOI 10.1016/j.ejrad.2014.10.018

  View details for Web of Science ID 000346386100021

  View details for PubMedID 25467224

• Conjugated Bilirubin Triggers Anemia by Inducing Erythrocyte Death HEPATOLOGY Lang, E., Gatidis, S., Freise, N. F., Bock, H., Kubitz, R., Lauermann, C., Orth, H., Klindt, C., Schuier, M., Keitel, V., Reich, M., Liu, G., Schmidt, S., Xu, H. C., Qadri, S. M., Herebian, D., Pandyra, A. A., Mayatepek, E., Gulbins, E., Lang, F., Haeussinger, D., Lang, K. S., Foeller, M., Lang, P. A. 2015; 61 (1): 275-284

  Abstract

  Hepatic failure is commonly associated with anemia, which may result from gastrointestinal bleeding, vitamin deficiency, or liver-damaging diseases, such as infection and alcohol intoxication. At least in theory, anemia during hepatic failure may result from accelerated clearance of circulating erythrocytes. Here we show that bile duct ligation (BDL) in mice leads to severe anemia despite increased reticulocyte numbers. Bilirubin stimulated suicidal death of human erythrocytes. Mechanistically, bilirubin triggered rapid Ca(2+) influx, sphingomyelinase activation, formation of ceramide, and subsequent translocation of phosphatidylserine to the erythrocyte surface. Consistent with our in vitro and in vivo findings, incubation of erythrocytes in serum from patients with liver disease induced suicidal death of erythrocytes in relation to their plasma bilirubin concentration. Consistently, patients with hyperbilirubinemia had significantly lower erythrocyte and significantly higher reticulocyte counts compared to patients with low bilirubin levels.Bilirubin triggers suicidal erythrocyte death, thus contributing to anemia during liver disease.

  View details for DOI 10.1002/hep.27338

  View details for Web of Science ID 000347005100034

  View details for PubMedID 25065608

  View details for PubMedCentralID PMC4303990

• Single-Source Dual-Energy Computed Tomography Use of Monoenergetic Extrapolation for a Reduction of Metal Artifacts INVESTIGATIVE RADIOLOGY Mangold, S., Gatidis, S., Luz, O., Koenig, B., Schabel, C., Bongers, M. N., Flohr, T. G., Claussen, C. D., Thomas, C. 2014; 49 (12): 788-793

  Abstract

  The objective of this study was to retrospectively determine the potential of virtual monoenergetic (ME) reconstructions for a reduction of metal artifacts using a new-generation single-source computed tomographic (CT) scanner.The ethics committee of our institution approved this retrospective study with a waiver of the need for informed consent. A total of 50 consecutive patients (29 men and 21 women; mean [SD] age, 51.3 [16.7] years) with metal implants after osteosynthetic fracture treatment who had been examined using a single-source CT scanner (SOMATOM Definition Edge; Siemens Healthcare, Forchheim, Germany; consecutive dual-energy mode with 140 kV/80 kV) were selected. Using commercially available postprocessing software (syngo Dual Energy; Siemens AG), virtual ME data sets with extrapolated energy of 130 keV were generated (medium smooth convolution kernel D30) and compared with standard polyenergetic images reconstructed with a B30 (medium smooth) and a B70 (sharp) kernel. For quantification of the beam hardening artifacts, CT values were measured on circular lines surrounding bone and the osteosynthetic device, and frequency analyses of these values were performed using discrete Fourier transform. A high proportion of low frequencies to the spectrum indicates a high level of metal artifacts. The measurements in all data sets were compared using the Wilcoxon signed rank test.The virtual ME images with extrapolated energy of 130 keV showed significantly lower contribution of low frequencies after the Fourier transform compared with any polyenergetic data set reconstructed with D30, B70, and B30 kernels (P < 0.001).Sequential single-source dual-energy CT allows an efficient reduction of metal artifacts using high-energy ME extrapolation after osteosynthetic fracture treatment.

  View details for Web of Science ID 000345293000005

  View details for PubMedID 24979325

• Measurement of Apparent Diffusion Coefficient With Simultaneous MR/Positron Emission Tomography in Patients With Peritoneal Carcinomatosis: Comparison With 18F-FDG-PET JOURNAL OF MAGNETIC RESONANCE IMAGING Schwenzer, N. F., Schmidt, H., Gatidis, S., Brendle, C., Mueller, M., Koenigsrainer, I., Claussen, C. D., Pfannenberg, A. C., Schraml, C. 2014; 40 (5): 1121-1128

  Abstract

  To characterize peritoneal carcinomatosis (PC) of different histologically proven primary tumors based on diffusion-weighted imaging (DWI) and (18) F-FDG positron emission tomography (PET).Forty-one patients underwent simultaneous MR/PET after clinically indicated (18) F-FDG-PET/CT. For all patients, histology of the primary tumor was obtained. MR protocol comprised anatomical imaging and axial DWI. Apparent diffusion coefficient (ADC) maps and FDG-PET were co-registered for evaluation of ADC and standard uptake value (SUV) of peritoneal lesions. Both lesion- and patient-based analysis was performed. Up to four peritoneal lesions were evaluated per patient. Mean and maximum standard uptake value (SUVmean , SUVmax ), mean and minimum ADC (ADCmean , ADCmin ) of each lesion were assessed. Spearman rank correlation (rs ) of ADC and SUV were calculated. SUV and ADC of ovarian and colorectal cancer lesions were compared using Wilcoxon test.Measurable lesions (n = 52) were found in 20 of 41 PC patients. Moderate, but significant correlation existed between ADC and SUV in the lesion-based as well as the patient-based analysis (lesion-based: SUVmean versus ADCmean rs = -0.58; SUVmax versus ADCmin rs = -0.56, all P < 0.0001; patient-based: SUVmean versus ADCmean rs = -0.64, P = 0.002; SUVmax versus ADCmin rs = -0.60, P = 0.005). ADC and SUV differed significantly between ovarian and colorectal cancer lesions (ADCmin : P < 0.0001; ADCmean : P < 0.0001; SUVmax : P = 0.002; SUVmean : P = 0.005). Overall, mucinous tumor entities showed a tendency to higher ADC and lower SUV.PC lesions showed significant differences in glucose uptake and diffusion characteristics depending on primary tumor histology. These differences should be considered when interpreting FDG-PET and DWI in PC patients.

  View details for DOI 10.1002/jmri.24497

  View details for Web of Science ID 000344005800013

  View details for PubMedID 24923481

• Simultaneous Whole-Body PET/MR Imaging in Comparison to PET/CT in Pediatric Oncology: Initial Results RADIOLOGY Schaefer, J. F., Gatidis, S., Schmidt, H., Gueckel, B., Bezrukov, I., Pfannenberg, C. A., Reimold, M., Ebinger, M., Fuchs, J., Claussen, C. D., Schwenzer, N. F. 2014; 273 (1): 220-231

  Abstract

  To compare positron emission tomography (PET)/magnetic resonance (MR) imaging and PET/computed tomography (CT) for lesion detection and interpretation, quantification of fluorine 18 ((18)F) fluorodeoxyglucose (FDG) uptake, and accuracy of MR-based PET attenuation correction in pediatric patients with solid tumors. Materials and Methods This prospective study had local ethics committee and German Federal Institute for Drugs and Medical Devices approval. Written informed consent was obtained from all patients and legal guardians. Twenty whole-body (18)F-FDG PET/CT and (18)F-FDG PET/MR examinations were performed in 18 pediatric patients (median age, 14 years; range, 11-17 years). (18)F-FDG PET/CT and (18)F-FDG PET/MR data were acquired sequentially on the same day for all patients. PET standardized uptake values (SUVs) were quantified with volume of interest measurements in lesions and healthy tissues. MR-based PET attenuation correction was compared with CT-derived attenuation maps (µ-maps). Lesion detection was assessed with separate reading of PET/CT and PET/MR data. Estimates of radiation dose were derived from the applied doses of (18)F-FDG and CT protocol parameters. Descriptive statistical analyses were performed to report correlation coefficients and relative deviations for comparison of SUVs, rates of lesion detection, and percentage reductions in radiation dose.PET SUVs showed strong correlations between PET of PET/CT (PETCT) and PET of PET/MR (PETMR) (r > 0.85 for most tissues). Apart from drawbacks of MR-based PET attenuation correction in osseous structures and lungs, similar SUVs were found on PET images corrected with CT-based µ-maps (13.1% deviation of SUVs for bone marrow and <5% deviation for other tissues). Lesion detection rate with PET/MR imaging was equivalent to that with PET/CT (61 areas of focal uptake on PETMR images vs 62 areas on PETCT images). Advantages of PET/MR were observed especially in soft-tissue regions. Furthermore, PET/MR offered significant dose reduction (73%) compared with PET/CT.Pediatric oncologic PET/MR is technically feasible, showing satisfactory performance for PET quantification with SUVs similar to those of PET/CT. Compared with PET/CT, PET/MR demonstrates equivalent lesion detection rates while offering markedly reduced radiation exposure. Thus, PET/MR is a promising modality for the clinical work-up of pediatric malignancies. Online supplemental material is available for this article.

  View details for DOI 10.1148/radiol.14131732

  View details for Web of Science ID 000344232100025

  View details for PubMedID 24877983

• Impact of Endobronchial Coiling for Lung Volume Reduction on Pulmonary Volume and Attenuation: Preinterventional and Postinterventional Computed Tomography-Quantification Using Separate Lobe Measurements JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY Grosse, U., Hetzel, J., Guendel, L., Gatidis, S., Syha, R., Schabel, C., Springer, F., Horger, M. 2014; 38 (5): 779-785

  Abstract

  The aim of this study was to objectify changes in volume and density of treated and untreated pulmonary lobes following endobronchial coiling for lung volume reduction by comparison with clinical (6-m walk test) and pulmonary function tests.Twenty-two lobes in 17 patients (8 men, 9 women) were treated by endobronchial coiling and underwent preinterventional and postinterventional computed tomography examinations (inspiratory and expiratory phase) as well as pulmonary function test measurements.Responders (n = 14) presented a significant increase (70 ± 11 m) in the walking distance (6-m walk test) and FEV1 (forced expiratory volume in 1 second) values (61 ± 21 mL). Only in responders inspiratory volume (VolIn) of the target lobe significantly decreased (10.0% ± 16.4%; P = 0.0245), and VolIn of the nontreated ipsilateral lobe significantly increased (5.5% ± 9.1%; P = 0.0209).Our results objectify volume reduction of the treated lobe coupled by a significant volume expansion of the ipsilateral lobe as a sole correlate for clinical improvement in responders.

  View details for DOI 10.1097/RCT.0000000000000121

  View details for Web of Science ID 000342669300024

  View details for PubMedID 24979262

• Development of an MRI Phantom for Diffusion-Weighted Imaging with Independent Adjustment of Apparent Diffusion Coefficient Values and T2 Relaxation Times MAGNETIC RESONANCE IN MEDICINE Gatidis, S., Schmidt, H., Martirosian, P., Schwenzer, N. F. 2014; 72 (2): 459-463

  Abstract

  To design a phantom for diffusion-weighted imaging (DWI) with defined apparent diffusion coefficients (ADC) and T2 relaxation times.Varying concentrations of polyethylene glycol (PEG) were used for the adjustment of diffusivity. T2 relaxation times were tuned by adding of the MR contrast agent gadobutrol. Relaxation times and apparent diffusion coefficients were quantified using a multiecho spin echo sequence and an echo planar imaging (EPI) DWI sequence, respectively, on a 3T clinical scanner.Increasing concentrations of PEG led to a marked impairment of diffusivity accompanied by only moderate changes of T2 relaxation times. Adding gadobutrol to the PEG solutions allowed for adjustment of transverse relaxation times to predefined values. Thus, a broad range of defined ADC values and T2 relaxation times could be accurately achieved in the final phantom.The proposed phantom allows for standardized in vitro studies of DWI methods and protocols. The obtained MR image contrasts are similar to a variety of biological tissues, which can contribute to optimization of imaging techniques with respect to specific clinical questions. Due to the simplicity of design and the accessibility of the contained compounds, this phantom may also serve as a tool for standardization and calibration.

  View details for DOI 10.1002/mrm.24944

  View details for Web of Science ID 000339714900018

  View details for PubMedID 24123316

• Preclinical and Translational PET/MR Imaging JOURNAL OF NUCLEAR MEDICINE Wehrl, H. F., Wiehr, S., Divine, M. R., Gatidis, S., Gullberg, G. T., Maier, F. C., Rolle, A., Schwenck, J., Thaiss, W. M., Pichler, B. J. 2014; 55: 11S-18S

  Abstract

  Combined PET and MR imaging (PET/MR imaging) has progressed tremendously in recent years. The focus of current research has shifted from technologic challenges to the application of this new multimodal imaging technology in the areas of oncology, cardiology, neurology, and infectious diseases. This article reviews studies in preclinical and clinical translation. The common theme of these initial results is the complementary nature of combined PET/MR imaging that often provides additional insights into biologic systems that were not clearly feasible with just one modality alone. However, in vivo findings require ex vivo validation. Combined PET/MR imaging also triggers a multitude of new developments in image analysis that are aimed at merging and using multimodal information that ranges from better tumor characterization to analysis of metabolic brain networks. The combination of connectomics information that maps brain networks derived from multiparametric MR data with metabolic information from PET can even lead to the formation of a new research field that we would call cometomics that would map functional and metabolic brain networks. These new methodologic developments also call for more multidisciplinarity in the field of molecular imaging, in which close interaction and training among clinicians and a variety of scientists is needed.

  View details for DOI 10.2967/jnumed.113.129221

  View details for Web of Science ID 000336830000003

  View details for PubMedID 24833493

• Assessment of Relapse in Patients with Peritoneal Carcinomatosis after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy using F-18-FDG-PET/CT ROFO-FORTSCHRITTE AUF DEM GEBIET DER RONTGENSTRAHLEN UND DER BILDGEBENDEN VERFAHREN Klumpp, B., Schwenzer, N. F., Gatidis, S., Koenigsrainer, I., Koenigsrainer, A., Beckert, S., Mueller, M., Claussen, C. D., Pfannenberg, C. 2014; 186 (4): 359-366

  Abstract

  In patients with peritoneal carcinomatosis (PC), cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is an evolving therapeutic approach with curative intention. The differentiation between posttherapeutic findings after HIPEC and relapse of PC is challenging. We evaluated the diagnostic value of F-18-FDG-PET/CT in patients with relapse of PC after HIPEC.36 patients with recurring PC after HIPEC were examined on a whole-body PET/CT system (44 examinations). The examination included 3 D F-18-FDG-PET and contrast-enhanced CT. Images were assessed by two experienced readers regarding the presence and the extent of PC using the peritoneal carcinomatosis index (PCI). Imaging results were correlated with surgical findings or follow-up.Relapse was suspected in 40 of 44 examinations. Relapse was missed by F-18-FDG PET/CT in 4 patients and significantly underestimated in 8 patients. The diagnostic accuracy for the detection of PC on a patient basis was 91 %, the sensitivity was 91 % and the positive predictive value was 100 %. The mean PCI was 11.4 ± 11.9 for PET/CT, 8.4 ± 10.3 for CT and 16.6 ± 15.0 in the case of surgical exploration. The extent of PC was underestimated by PET/CT and even more by CT alone (p < 0.05).The diagnostic value of F-18-FDG PET/CT after cytoreductive surgery and HIPEC in the detection of recurring PC is superior to contrast-enhanced CT. However, the quantification of the extent of PC is limited due to post-therapeutic tissue alterations.• Imaging of recurrent PC after HIPEC is challenging due to posttherapeutic tissue alterations.• The extent of recurrent PC after HIPEC is systematically underestimated by F-18-FDG PET/CT.• F-18-FDG PET/CT provides improved sensitivity for recurrent PC compared to contrast-enhanced CT.• The correlation of the extent of recurrent PC depicted by F-18-FDG PET/CT and surgical exploration is better than that of contrast-enhanced CT and surgical exploration.

  View details for DOI 10.1055/s-0034-1366041

  View details for Web of Science ID 000333566100004

  View details for PubMedID 24683168

• Hypoxia imaging and functional MR using combined FMISO PET/MRI in head and neck cancer (HNC) Thorwarth, D., Boeke, S., Leibfarth, S., Schmidt, H., Gatidis, S., Schwenzer, N., Welz, S., Zips, D. ELSEVIER IRELAND LTD. 2014: S53

  View details for Web of Science ID 000688272900129

• Evaluation of a dedicated radiotherapy positioning solution for combined PET/MR imaging Winter, R., Leibfarth, S., Paulus, D. H., Quick, H. H., Gatidis, S., Schmidt, H., Schwenzer, N., Zips, D., Thorwarth, D. ELSEVIER IRELAND LTD. 2014: S33

  View details for Web of Science ID 000688272900079

• Multiparametric imaging with simultaneous MR/PET RADIOLOGE Gatidis, S., Schmidt, H., Claussen, C. D., Schwenzer, N. F. 2013; 53 (8): 669-675

  Abstract

  Combined magnetic resonance imaging-positron emission tomography (MR/PET) enables acquisition of a variety of imaging parameters during a single examination including anatomical as well as functional information, such as perfusion, diffusion and metabolism. Numerous studies have shown that the combination of these parameters can improve the diagnostic accuracy for many applications especially in oncological imaging. Due to the amount and the complexity of the acquired multiparametric data there is a need for advanced analytical tools, such as methods of parameter selection and data classification. The present article summarizes these methods and their applications in multiparametric imaging via MR/PET.

  View details for DOI 10.1007/s00117-013-2496-3

  View details for Web of Science ID 000323251300003

  View details for PubMedID 23949435

• Increased platelet Ca2+ channel Orai1 expression upon platelet activation and in patients with acute myocardial infarction THROMBOSIS AND HAEMOSTASIS Tolios, A., Gatidis, S., Muenzer, P., Liu, G., Towhid, S. T., Karathanos, A., Tavlaki, E., Geisler, T., Seizer, P., May, A. E., Bigalke, B., Borst, O., Gawaz, M., Lang, F. 2013; 110 (2): 386-389

  View details for DOI 10.1160/TH12-09-0701

  View details for Web of Science ID 000323019100020

  View details for PubMedID 23703676

• Multiparametric Hypoxia Imaging with combined [18F]-FMISO MR/PET in Head and Neck Cancer for individualization of Radiotherapy Thorwarth, D., Welz, S., Schwenzer, N., Gatidis, S., Schmidt, H., Pfannenberg, C., Zips, D. URBAN & VOGEL. 2013: 31

  View details for Web of Science ID 000317982100063

• Tin-filter Enhanced Dual-Energy-CT: Image Quality and Accuracy of CT Numbers in Virtual Noncontrast Imaging ACADEMIC RADIOLOGY Kaufmann, S., Sauter, A., Spira, D., Gatidis, S., Ketelsen, D., Heuschmid, M., Claussen, C. D., Thomas, C. 2013; 20 (5): 596-603

  Abstract

  To measure and compare the objective image quality of true noncontrast (TNC) images with virtual noncontrast (VNC) images acquired by tin-filter-enhanced, dual-source, dual-energy computed tomography (DECT) of upper abdomen.Sixty-three patients received unenhanced abdominal CT and enhanced abdominal DECT (100/140 kV with tin filter) in portal-venous phase. VNC images were calculated from the DECT datasets using commercially available software. The mean attenuation of relevant tissues and image quality were compared between the TNC and VNC images. Image quality was rated objectively by measuring image noise and the sharpness of object edges using custom-designed software. Measurements were compared using Student two-tailed t-test. Correlation coefficients for tissue attenuation measurements between TNC and VNC were calculated and the relative deviations were illustrated using Bland-Altman plots.Mean attenuation differences between TNC and VNC (HUTNC - HUVNC) image sets were as follows: right liver lobe -4.94 Hounsfield units (HU), left liver lobe -3.29 HU, vena cava -2.19 HU, spleen -7.46 HU, pancreas 1.29 HU, fat -11.14 HU, aorta 1.29 HU, bone marrow 36.83 HU (all P < .05); right kidney 0.46 HU, left kidney 0.56 HU, vena portae -0.48 HU and muscle -0.62 HU (nonsignificant). Good correlations between VNC and TNC series were observed for liver, vena portae, kidneys, pancreas, muscle and bone marrow (Pearson's correlation coefficient ≥0.75). Mean image noise was significantly higher in TNC images (P < .0001). Measurements of edge sharpness revealed no significant differences between VNC and TNC images (P = .19).The Hounsfield units in VNC images closely resemble TNC images in the majority of the organs of the upper abdomen (kidneys, liver, pancreas). In spleen and fat, Hounsfield numbers in VNC images are tend to be higher than in TNC images. VNC images show a low image noise and satisfactory edge sharpness. Other criteria of image quality and the depiction of certain lesions need to be evaluated additionally.

  View details for DOI 10.1016/j.acra.2013.01.010

  View details for Web of Science ID 000317801000011

  View details for PubMedID 23490736

• The Inflammatory Chemokine CXC Motif Ligand 16 Triggers Platelet Activation and Adhesion Via CXC Motif Receptor 6-Dependent Phosphatidylinositide 3-Kinase/Akt Signaling CIRCULATION RESEARCH Borst, O., Muenzer, P., Gatidis, S., Schmidt, E., Schoenberger, T., Schmid, E., Towhid, S. T., Stellos, K., Seizer, P., May, A. E., Lang, F., Gawaz, M. 2012; 111 (10): 1297-U151

  Abstract

  The recently discovered chemokine CXC motif ligand 16 (CXCL16) is highly expressed in atherosclerotic lesions and is a potential pathogenic mediator in coronary artery disease.The aim of this study was to test the role of CXCL16 on platelet activation and vascular adhesion, as well as the underlying mechanism and signaling pathway.Reverse-transcriptase polymerase chain reaction, Western blotting, confocal microscopy, and flow cytometry revealed that CXCL16-specific receptor, CXC motif receptor 6, is highly expressed in platelets. According to flow cytometry and confocal microscopy, stimulation of platelets with CXCL16 induced platelet degranulation, integrin α(IIb)β(3) activation, and shape change. CXCL16 increased Akt phosphorylation (Thr(308)/Ser(473)), an effect abrogated by phosphatidylinositide 3-kinase inhibitors wortmannin (100 nmol/L) and LY294002 (25 µmol/L). The phosphatidylinositide 3-kinase inhibitors and Akt inhibitor SH-6 (20 µmol/L) further diminished CXCL16-induced platelet activation. CXCL16-mediated platelet degranulation, integrin α(IIb)β(3) activation, and Akt phosphorylation were blunted in platelets lacking CXCL16-specific receptor CXC motif receptor 6. CXCL16-induced platelet activation was abrogated in Akt1- or Akt2-deficient platelets. CXCL16 enhanced platelet adhesion to endothelium in vitro after high arterial shear stress (2000(-s)) and to injured vascular wall in vivo after carotid ligation. CXCL16-induced stimulation of platelet adhesion again was prevented by phosphatidylinositide 3-kinase and Akt inhibitors. Apyrase and antagonists of platelet purinergic receptors P(2)Y(1) (MRS2179, 100 µmol/L) and especially P(2)Y(12) (Cangrelor, 10 µmol/L) blunted CXCL16-triggered platelet activation as well as CXCL16-induced platelet adhesion under high arterial shear stress in vitro and after carotid ligation in vivo.The inflammatory chemokine CXCL16 triggers platelet activation and adhesion via CXC motif receptor 6-dependent phosphatidylinositide 3-kinase/Akt signaling and paracrine activation, suggesting a decisive role for CXCL16 in linking vascular inflammation and thrombo-occlusive diseases.

  View details for DOI 10.1161/CIRCRESAHA.112.276444

  View details for Web of Science ID 000310501300011

  View details for PubMedID 22927331

• Computed tomography angiography in patients with suspected pulmonary embolism-too often considered? AMERICAN JOURNAL OF EMERGENCY MEDICINE Haap, M. M., Gatidis, S., Horger, M., Riessen, R., Lehnert, H., Haas, C. S. 2012; 30 (2): 325-330

  Abstract

  Pulmonary embolism (PE) is a major cause of morbidity and mortality associated with surgery and medical illnesses. In recent years, pulmonary computed tomography angiography (CTA) has become the diagnostic method of choice. However, it remains unclear when to perform CTA and how often a decision based on clinical judgment results in positive or negative findings.In a retrospective study, 261 patients admitted for suspected PE were evaluated with pulmonary CTA. Decisions to order CTA were based on clinical judgment and optionally quantitative d-dimer assays. Clinical, radiologic, and laboratory data were revisited and compared in patients with and without proven PE.The patients' mean age was 63 ± 1 years; almost 30% of all participants had at least a moderately reduced renal function. Pulmonary CTA demonstrated PE in only 14.9%; both age and sex distribution was comparable in the PE and non-PE group. Proximal deep vein thrombosis or pathologic chest x-rays were significantly more likely in patients with PE (P < .001 and P < .05), whereas echocardiography results were comparable. d-dimer values were noticeably higher in the PE group (P < .001); however, C-reactive protein and troponin T levels were not helpful.Pulmonary CTA confirmed PE in only a minority of patients and may be overused. Clinical judgment in conjunction with d-dimer evaluation was of limited help to predict positive results but surprisingly comparable with previous results using pretest probability scoring systems. Using present and previous data, a simplified enhanced algorithm is proposed to reduce use of CTA.

  View details for DOI 10.1016/j.ajem.2010.12.013

  View details for Web of Science ID 000300237200008

  View details for PubMedID 21277141

• Phlorhizin Protects against Erythrocyte Cell Membrane Scrambling JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY Gatidis, S., Meier, A., Jilani, K., Lang, E., Zelenak, C., Qadri, S. M., Lang, F. 2011; 59 (15): 8524-8530

  Abstract

  Phlorhizin interferes with glucose transport. Glucose depletion triggers suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling. Eryptosis is further triggered by oxidative stress. The present study explored whether phlorhizin influences eryptosis following glucose depletion or oxidative stress. Cell membrane scrambling was estimated from annexin binding, cell volume from forward scatter (FSC), and cytosolic Ca(2+) concentration from Fluo-3 fluorescence. Phlorhizin (10-100 μM) added alone did not modify scrambling, FSC, or Fluo-3 fluorescence. Glucose depletion (48 h) significantly increased Fluo-3 fluorescence, decreased FSC, and increased annexin binding, effects in part significantly blunted by phlorhizin (annexin binding ≥ 10 μM, FSC ≥ 50 μM). Oxidative stress (30 min 0.3 mM tert-butylhydroperoxide) again significantly increased Fluo-3 fluorescence and triggered annexin binding, effects again in part significantly blunted by phlorhizin (Fluo-3 fluorescence ≥ 50 μM, annexin-binding ≥ 10 μM). Phlorhizin did not blunt the cell shrinkage induced by oxidative stress. The present observations disclose a novel effect of phlorhizin, that is, an influence on suicidal erythrocyte death following energy depletion and oxidative stress.

  View details for DOI 10.1021/jf201938d

  View details for Web of Science ID 000293355000061

  View details for PubMedID 21707031

• p38 MAPK Activation and Function following Osmotic Shock of Erythrocytes CELLULAR PHYSIOLOGY AND BIOCHEMISTRY Gatidis, S., Zelenak, C., Fajol, A., Lang, E., Jilani, K., Michael, D., Qadri, S. M., Lang, F. 2011; 28 (6): 1279-1286

  Abstract

  p38 protein kinase is activated by hyperosmotic shock, participates in the regulation of cell volume sensitive transport and metabolism and is involved in the regulation of various physiological functions including cell proliferation and apoptosis. Similar to apoptosis of nucleated cells, erythrocytes may undergo suicidal death or eryptosis, which is paralleled by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Triggers of eryptosis include hyperosmotic shock, which increases cytosolic Ca(2+) activity and ceramide formation. The present study explored whether p38 kinase is expressed in human erythrocytes, is activated by hyperosmotic shock and participates in the regulation of eryptosis. Western blotting was utilized to determine phosphorylation of p38 kinase, forward scatter to estimate cell volume, annexin V binding to depict phosphatidylserine exposure and Fluo3 fluorescence to estimate cytosolic Ca(2+) activity. As a result, erythrocytes express p38 kinase, which is phosphorylated upon osmotic shock (+550 mM sucrose). Osmotic shock decreased forward scatter, increased annexin V binding and increased Fluo3 fluorescence, all effects significantly blunted by the p38 kinase inhibitors SB203580 (2 μM) and p38 Inh III (1 μM). In conclusion, p38 kinase is expressed in erythrocytes and participates in the machinery triggering eryptosis following hyperosmotic shock.

  View details for DOI 10.1159/000335859

  View details for Web of Science ID 000298490200021

  View details for PubMedID 22179015

• Effect of osmotic shock and urea on phosphatidylserine scrambling in thrombocyte cell membranes AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY Gatidis, S., Borst, O., Foeller, M., Lang, F. 2010; 299 (1): C111-C118

  Abstract

  Blood passing the renal medulla enters a strongly hypertonic environment challenging functional properties and survival of blood cells. In erythrocytes, exposure to hyperosmotic shock stimulates Ca(2+) entry and ceramide formation with subsequent cell membrane scrambling, an effect partially reversed by high concentrations of Cl(-) or urea. Cell membrane scrambling with phosphatidylserine exposure is part of the procoagulant phenotype of platelets. Coagulation in the hypertonic renal medulla would jeopardize blood flow in the vasa recta. The present study thus explored whether hypertonic environment and urea modify phosphatidylserine exposure of human platelets. FACS analysis was employed to estimate cytosolic Ca(2+) activity with Fluo3 fluorescence, ceramide formation, P-selectin, and glycoprotein IIb/IIIa activation with fluorescent antibodies and phosphatidylserine exposure with annexin V-binding. The spontaneous platelet aggregation was measured by impedance aggregometry. Hyperosmotic shock (addition of 500 mM sucrose or 250 mM NaCl) significantly enhanced cytosolic Ca(2+) activity, ceramide formation, phosphatidylserine exposure, platelet degranulation, and aggregability. Addition of 500 mM urea to isotonic saline did not significantly modify cytosolic Ca(2+) activity, ceramide abundance, or annexin V-binding but significantly blunted the respective effects of hypertonic shock following addition of 500 mM sucrose. In isotonic solutions, both ceramide (20 microM) and Ca(2+) ionophore ionomycin (0.5 microM) increased annexin V-binding, effects again significantly blunted by 500 mM urea. Moreover, oxidative stress by addition of 0.5 mM peroxynitrite increased cytosolic Ca(2+) activity and triggered annexin V-binding, effects again blunted in the presence of 500 mM urea. The observations reveal that hyperosmotic shock and oxidative stress trigger a procoagulant platelet phenotype, an effect blunted by the presence of high urea concentrations.

  View details for DOI 10.1152/ajpcell.00477.2009

  View details for Web of Science ID 000278887800014

  View details for PubMedID 20237147

• Hemin-induced suicidal erythrocyte death ANNALS OF HEMATOLOGY Gatidis, S., Foeller, M., Lang, F. 2009; 88 (8): 721-726

  Abstract

  Several diseases, such as malaria, sickle cell disease, and ischemia/reperfusion may cause excessive formation of hemin, which may in turn trigger hemolysis. A variety of drugs and diseases leading to hemolysis triggers suicidal erythrocyte death or eryptosis, i.e., cell membrane scrambling and cell shrinkage. Eryptosis is elicited by increased cytosolic Ca(2+) activity and by ceramide. The present study explored whether hemin stimulates eryptosis. Cell membrane scrambling was estimated from annexin V-binding to phosphatidylserine exposed at the cell surface, cell shrinkage from forward scatter in fluorescence-activated cell sorter analysis, cytosolic Ca(2+) activity from Fluo3 fluorescence and ceramide formation from fluorescence-labeled antibody binding. Exposure to hemin (1-10 microM) within 48 h significantly increased annexin V-binding, decreased forward scatter, increased cytosolic Ca(2+) activity, and stimulated ceramide formation. In conclusion, hemin stimulates suicidal cell death, which may in turn contribute to the clearance of circulating erythrocytes and thus to anemia.

  View details for DOI 10.1007/s00277-009-0697-7

  View details for Web of Science ID 000267095100002

  View details for PubMedID 19184015