Professional Education


  • Postdoctoral Research Scholar, Stanford University, Radiology (2022)
  • Residency, Charité University Berlin, Department of Diagnostic and Interventional Radiology, Director: Prof. Dr. Bernd Hamm (2016-2021), German Board Certification as a Radiologist (2021)
  • 'Privatdozent', Charité University Berlin, Teaching, Research in Experimental Radiology, and Clinical Care (2020)
  • Doctor of Medicine, Charité University Berlin (2016)

Stanford Advisors


All Publications


  • ADAMTS4-specific MR probe to assess aortic aneurysms in vivo using synthetic peptide libraries NATURE COMMUNICATIONS Kaufmann, J. O., Brangsch, J., Kader, A., Saatz, J., Mangarova, D. B., Zacharias, M., Kempf, W. E., Schwaar, T., Ponader, M., Adams, L. C., Moeckel, J., Botnar, R. M., Taupitz, M., Maegdefessel, L., Traub, H., Hamm, B., Weller, M. G., Makowski, M. R. 2022; 13 (1): 2867

    Abstract

    The incidence of abdominal aortic aneurysms (AAAs) has substantially increased during the last 20 years and their rupture remains the third most common cause of sudden death in the cardiovascular field after myocardial infarction and stroke. The only established clinical parameter to assess AAAs is based on the aneurysm size. Novel biomarkers are needed to improve the assessment of the risk of rupture. ADAMTS4 (A Disintegrin And Metalloproteinase with ThromboSpondin motifs 4) is a strongly upregulated proteoglycan cleaving enzyme in the unstable course of AAAs. In the screening of a one-bead-one-compound library against ADAMTS4, a low-molecular-weight cyclic peptide is discovered with favorable properties for in vivo molecular magnetic resonance imaging applications. After identification and characterization, it's potential is evaluated in an AAA mouse model. The ADAMTS4-specific probe enables the in vivo imaging-based prediction of aneurysm expansion and rupture.

    View details for DOI 10.1038/s41467-022-30464-8

    View details for Web of Science ID 000802699200001

    View details for PubMedID 35606349

  • De Novo Radiomics Approach Using Image Augmentation and Features From T1 Mapping to Predict Gleason Scores in Prostate Cancer INVESTIGATIVE RADIOLOGY Makowski, M. R., Bressem, K. K., Franz, L., Kader, A., Niehues, S. M., Keller, S., Rueckert, D., Adams, L. C. 2021; 56 (10): 661-668

    Abstract

    The aims of this study were to discriminate among prostate cancers (PCa's) with Gleason scores 6, 7, and ≥8 on biparametric magnetic resonance imaging (bpMRI) of the prostate using radiomics and to evaluate the added value of image augmentation and quantitative T1 mapping.Eighty-five patients with subsequently histologically proven PCa underwent bpMRI at 3 T (T2-weighted imaging, diffusion-weighted imaging) with 66 patients undergoing additional T1 mapping at 3 T. The PCa lesions as well as the peripheral and transition zones were segmented pixel by pixel in multiple slices of the 3D MRI data sets (T2-weighted images, apparent diffusion coefficient, and T1 maps). To increase the size of the data set, images were augmented for contrast, brightness, noise, and perspective multiple times, effectively increasing the sample size 10-fold, and 322 different radiomics features were extracted before and after augmentation. Four different machine learning algorithms, including a random forest (RF), stochastic gradient boosting (SGB), support vector machine (SVM), and k-nearest neighbor, were trained with and without features from T1 maps to differentiate among 3 different Gleason groups (6, 7, and ≥8).Support vector machine showed the highest accuracy of 0.92 (95% confidence interval [CI], 0.62-1.00) for classifying the different Gleason scores, followed by RF (0.83; 95% CI, 0.52-0.98), SGB (0.75; 95% CI, 0.43-0.95), and k-nearest neighbor (0.50; 95% CI, 0.21-0.79). Image augmentation resulted in an average increase in accuracy between 0.08 (SGB) and 0.48 (SVM). Removing T1 mapping features led to a decline in accuracy for RF (-0.16) and SGB (-0.25) and a higher generalization error.When data are limited, image augmentations and features from quantitative T1 mapping sequences might help to achieve higher accuracy and lower generalization error for classification among different Gleason groups in bpMRI by using radiomics.

    View details for DOI 10.1097/RLI.0000000000000788

    View details for Web of Science ID 000697217100008

    View details for PubMedID 34047538

  • Deep-Learning-Based Diagnosis of Bedside Chest X-ray in Intensive Care and Emergency Medicine INVESTIGATIVE RADIOLOGY Niehues, S. M., Adams, L. C., Gaudin, R. A., Erxleben, C., Keller, S., Makowski, M. R., Vahldiek, J. L., Bressem, K. K. 2021; 56 (8): 525-534

    Abstract

    Validation of deep learning models should separately consider bedside chest radiographs (CXRs) as they are the most challenging to interpret, while at the same time the resulting diagnoses are important for managing critically ill patients. Therefore, we aimed to develop and evaluate deep learning models for the identification of clinically relevant abnormalities in bedside CXRs, using reference standards established by computed tomography (CT) and multiple radiologists.In this retrospective study, a dataset consisting of 18,361 bedside CXRs of patients treated at a level 1 medical center between January 2009 and March 2019 was used. All included CXRs occurred within 24 hours before or after a chest CT. A deep learning algorithm was developed to identify 8 findings on bedside CXRs (cardiac congestion, pleural effusion, air-space opacification, pneumothorax, central venous catheter, thoracic drain, gastric tube, and tracheal tube/cannula). For the training dataset, 17,275 combined labels were extracted from the CXR and CT reports by a deep learning natural language processing (NLP) tool. In case of a disagreement between CXR and CT, human-in-the-loop annotations were used. The test dataset consisted of 583 images, evaluated by 4 radiologists. Performance was assessed by area under the receiver operating characteristic curve analysis, sensitivity, specificity, and positive predictive value.Areas under the receiver operating characteristic curve for cardiac congestion, pleural effusion, air-space opacification, pneumothorax, central venous catheter, thoracic drain, gastric tube, and tracheal tube/cannula were 0.90 (95% confidence interval [CI], 0.87-0.93; 3 radiologists on the receiver operating characteristic [ROC] curve), 0.95 (95% CI, 0.93-0.96; 3 radiologists on the ROC curve), 0.85 (95% CI, 0.82-0.89; 1 radiologist on the ROC curve), 0.92 (95% CI, 0.89-0.95; 1 radiologist on the ROC curve), 0.99 (95% CI, 0.98-0.99), 0.99 (95% CI, 0.98-0.99), 0.98 (95% CI, 0.97-0.99), and 0.99 (95% CI, 0.98-1.00), respectively.A deep learning model used specifically for bedside CXRs showed similar performance to expert radiologists. It could therefore be used to detect clinically relevant findings during after-hours and help emergency and intensive care physicians to focus on patient care.

    View details for DOI 10.1097/RLI.0000000000000771

    View details for Web of Science ID 000669537500008

    View details for PubMedID 33826549

  • Targeting the Extracellular Matrix in Abdominal Aortic Aneurysms Using Molecular Imaging Insights INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Adams, L., Brangsch, J., Hamm, B., Makowski, M. R., Keller, S. 2021; 22 (5)

    Abstract

    This review outlines recent preclinical and clinical advances in molecular imaging of abdominal aortic aneurysms (AAA) with a focus on molecular magnetic resonance imaging (MRI) of the extracellular matrix (ECM). In addition, developments in pharmacologic treatment of AAA targeting the ECM will be discussed and results from animal studies will be contrasted with clinical trials. Abdominal aortic aneurysm (AAA) is an often fatal disease without non-invasive pharmacologic treatment options. The ECM, with collagen type I and elastin as major components, is the key structural component of the aortic wall and is recognized as a target tissue for both initiation and the progression of AAA. Molecular imaging allows in vivo measurement and characterization of biological processes at the cellular and molecular level and sets forth to visualize molecular abnormalities at an early stage of disease, facilitating novel diagnostic and therapeutic pathways. By providing surrogate criteria for the in vivo evaluation of the effects of pharmacological therapies, molecular imaging techniques targeting the ECM can facilitate pharmacological drug development. In addition, molecular targets can also be used in theranostic approaches that have the potential for timely diagnosis and concurrent medical therapy. Recent successes in preclinical studies suggest future opportunities for clinical translation. However, further clinical studies are needed to validate the most promising molecular targets for human application.

    View details for DOI 10.3390/ijms22052685

    View details for Web of Science ID 000628249200001

    View details for PubMedID 33799971

    View details for PubMedCentralID PMC7962044

  • Highly accurate classification of chest radiographic reports using a deep learning natural language model pre-trained on 3.8 million text reports BIOINFORMATICS Bressem, K. K., Adams, L. C., Gaudin, R. A., Troeltzsch, D., Hamm, B., Makowski, M. R., Schuele, C., Vahldiek, J. L., Niehues, S. M. 2020; 36 (21): 5255-5261

    Abstract

    The development of deep, bidirectional transformers such as Bidirectional Encoder Representations from Transformers (BERT) led to an outperformance of several Natural Language Processing (NLP) benchmarks. Especially in radiology, large amounts of free-text data are generated in daily clinical workflow. These report texts could be of particular use for the generation of labels in machine learning, especially for image classification. However, as report texts are mostly unstructured, advanced NLP methods are needed to enable accurate text classification. While neural networks can be used for this purpose, they must first be trained on large amounts of manually labelled data to achieve good results. In contrast, BERT models can be pre-trained on unlabelled data and then only require fine tuning on a small amount of manually labelled data to achieve even better results.Using BERT to identify the most important findings in intensive care chest radiograph reports, we achieve areas under the receiver operation characteristics curve of 0.98 for congestion, 0.97 for effusion, 0.97 for consolidation and 0.99 for pneumothorax, surpassing the accuracy of previous approaches with comparatively little annotation effort. Our approach could therefore help to improve information extraction from free-text medical reports. Availability  and implementationWe make the source code for fine-tuning the BERT-models freely available at https://github.com/fast-raidiology/bert-for-radiology.Supplementary data are available at Bioinformatics online.

    View details for DOI 10.1093/bioinformatics/btaa668

    View details for Web of Science ID 000635348000017

    View details for PubMedID 32702106

  • Simultaneous molecular MRI of extracellular matrix collagen and inflammatory activity to predict abdominal aortic aneurysm rupture SCIENTIFIC REPORTS Adams, L. C., Brangsch, J., Reimann, C., Kaufmann, J. O., Buchholz, R., Karst, U., Botnar, R. M., Hamm, B., Makowski, M. R. 2020; 10 (1): 15206

    Abstract

    Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease with an up to 80% mortality in case of rupture. Current biomarkers fail to account for size-independent risk of rupture. By combining the information of different molecular probes, multi-target molecular MRI holds the potential to enable individual characterization of AAA. In this experimental study, we aimed to examine the feasibility of simultaneous imaging of extracellular collagen and inflammation for size-independent prediction of risk of rupture in murine AAA. The study design consisted of: (1) A outcome-based longitudinal study with imaging performed once after one week with follow-up and death as the end-point for assessment of rupture risk. (2) A week-by-week study for the characterization of AAA development with imaging after 1, 2, 3 and 4 weeks. For both studies, the animals were administered a type 1 collagen-targeted gadolinium-based probe (surrogate marker for extracellular matrix (ECM) remodeling) and an iron oxide-based probe (surrogate marker for inflammatory activity), in one imaging session. In vivo measurements of collagen and iron oxide probes showed a significant correlation with ex vivo histology (p < 0.001) and also corresponded well to inductively-coupled plasma-mass spectrometry and laser-ablation inductively-coupled plasma mass spectrometry. Combined evaluation of collagen-related ECM remodeling and inflammatory activity was the most accurate predictor for AAA rupture (sensitivity 80%, specificity 100%, area under the curve 0.85), being superior to information from the individual probes alone. Our study supports the feasibility of a simultaneous assessment of collagen-related extracellular matrix remodeling and inflammatory activity in a murine model of AAA.

    View details for DOI 10.1038/s41598-020-71817-x

    View details for Web of Science ID 000573768800014

    View details for PubMedID 32939002

    View details for PubMedCentralID PMC7494914

  • The role of visceral adiposity in the severity of COVID-19: Highlights from a unicenter cross-sectional pilot study in Germany METABOLISM-CLINICAL AND EXPERIMENTAL Petersen, A., Bressem, K., Albrecht, J., Thiess, H., Vahldiek, J., Hamm, B., Makowski, M. R., Niehues, A., Niehues, S. M., Adams, L. C. 2020; 110: 154317

    Abstract

    Overall obesity has recently been established as an independent risk factor for critical illness in patients with coronavirus disease 2019 (COVID-19). The role of fat distribution and especially that of visceral fat, which is often associated with metabolic syndrome, remains unclear. Therefore, this study aims at investigating the association between fat distribution and COVID-19 severity.Thirty patients with COVID-19 and a mean age of 65.6 ± 13.1 years from a level-one medical center in Berlin, Germany, were included in the present cross-sectional analysis. COVID-19 was confirmed by polymerase chain reaction (PCR) from nasal and throat swabs. A severe clinical course of COVID-19 was defined by hospitalization in the intensive care unit (ICU) and/or invasive mechanical ventilation. Fat was measured at the level of the first lumbar vertebra on routinely acquired low-dose chest computed tomography (CT).An increase in visceral fat area (VFA) by ten square centimeters was associated with a 1.37-fold higher likelihood of ICU treatment and a 1.32-fold higher likelihood of mechanical ventilation (adjusted for age and sex). For upper abdominal circumference, each additional centimeter of circumference was associated with a 1.13-fold higher likelihood of ICU treatment and a 1.25-fold higher likelihood of mechanical ventilation.Our proof-of-concept study suggests that visceral adipose tissue and upper abdominal circumference specifically increase the likelihood of COVID-19 severity. CT-based quantification of visceral adipose tissue and upper abdominal circumference in routine chest CTs may therefore be a simple tool for risk assessment in COVID-19 patients.

    View details for DOI 10.1016/j.metabol.2020.154317

    View details for Web of Science ID 000563770500007

    View details for PubMedID 32673651

    View details for PubMedCentralID PMC7358176

  • Quantitative 3D Assessment of Ga-68-DOTATOC PET/MRI with Diffusion-Weighted Imaging to Assess Imaging Markers for Gastroenteropancreatic Neuroendocrine Tumors: Preliminary Results JOURNAL OF NUCLEAR MEDICINE Adams, L. C., Bressem, K. K., Brangsch, J., Reimann, C., Nowak, K., Brenner, W., Makowski, M. R. 2020; 61 (7): 1021-1027

    Abstract

    68Ga-DOTATOC PET/MRI combines the advantages of PET in the acquisition of metabolic-functional information with the high soft-tissue contrast of MRI. SUVs in tumors have been suggested to be a measure of somatostatin receptor expression. A challenge with receptor ligands is that the distribution volume is confined to tissues with tracer uptake, potentially limiting SUV quantification. In this study, various functional 3-dimensional SUV apparent diffusion coefficient (ADC) parameters and arterial tumor enhancement were tested for ability to characterize gastroenteropancreatic (GEP) neuroendocrine tumors (NETs). Methods: For this single-center, cross-sectional study, 22 patients with 24 histologically confirmed GEP NET lesions (15 men and 7 women; median age, 61 y; range, 43-81 y) who underwent hybrid 68Ga-DOTA PET/MRI at 3 T between January 2017 and July 2019 met the eligibility criteria. SUV, tumor-to-background ratio, total functional tumor volume, and mean and minimum ADC were measured on the basis of volumes of interest and examined with receiver-operating-characteristic analysis to determine cutoffs for differentiation between low- and intermediate-grade GEP NETs. The Spearman rank correlation coefficient was used to assess correlations between functional imaging parameters. Results: The ratio of PET-derived SUVmean and diffusion-weighted imaging-derived minimum ADC was introduced as a combined variable to predict tumor grade, outperforming single predictors. On the basis of a threshold ratio of 0.03, tumors could be classified as grade 2 with a sensitivity of 86% and a specificity of 100%. SUV and functional ADCs, as well as arterial contrast enhancement parameters, showed nonsignificant and mostly negligible correlations. Conclusion: Because receptor density and tumor cellularity appear to be independent, potentially complementary phenomena, the combined ratio of PET/MRI and SUVmean/ADCmin may be used as a novel biomarker allowing differentiation between grade 1 and grade 2 GEP NETs.

    View details for DOI 10.2967/jnumed.119.234062

    View details for Web of Science ID 000548809100014

    View details for PubMedID 31862798

    View details for PubMedCentralID PMC7383081

  • Assessment of the extracellular volume fraction for the grading of clear cell renal cell carcinoma: first results and histopathological findings EUROPEAN RADIOLOGY Adams, L. C., Jurmeister, P., Ralla, B., Bressem, K. K., Fahlenkam, U. L., Engel, G., Siepmann, S., Wagner, M., Hamm, B., Busch, J., Makowski, M. R. 2019; 29 (11): 5832-5843

    Abstract

    To assess the potential of T1 mapping-based extracellular volume fraction (ECV) for the identification of higher grade clear cell renal cell carcinoma (cRCC), based on histopathology as the reference standard.For this single-center, institutional review board-approved prospective study, 27 patients (17 men, median age 62 ± 12.4 years) with pathologic diagnosis of cRCC (nucleolar International Society of Urological Pathology (ISUP) grading) received abdominal MRI scans at 1.5 T using a modified Look-Locker inversion recovery (MOLLI) sequence between January 2017 and June 2018. Quantitative T1 values were measured at different time points (pre- and postcontrast agent administration) and quantification of the ECV was performed on MRI and histological sections (H&E staining).Reduction in T1 value after contrast agent administration and MR-derived ECV were reliable predictors for differentiating higher from lower grade cRCC. Postcontrast T1diff values (T1diff = T1 difference between the native and nephrogenic phase) and MR-derived ECV were significantly higher for higher grade cRCC (ISUP grades 3-4) compared with lower grade cRCC (ISUP grades 1-2) (p < 0.001). A cutoff value of 700 ms could distinguish higher grade from lower grade tumors with 100% (95% CI 0.69-1.00) sensitivity and 82% (95% CI 0.57-0.96) specificity. There was a positive and strong correlation between MR-derived ECV and histological ECV (p < 0.01, r = 0.88). Interobserver agreement for quantitative longitudinal relaxation times in the T1 maps was excellent.T1 mapping with ECV measurement could represent a novel in vivo biomarker for the classification of cRCC regarding their nucleolar grade, providing incremental diagnostic value as a quantitative MR marker.• Reduction in MRI T1 relaxation times after contrast agent administration and MR-derived extracellular volume fraction are useful parameters for grading of clear cell renal cell carcinoma (cRCC). • T1 differences between the native and the nephrogenic phase are higher for higher grade cRCC compared with lower grade cRCC and MRI-derived extracellular volume fraction (ECV) and histological ECV show a strong correlation. • T1 mapping with ECV measurement may be helpful for the noninvasive assessment of cRCC pathology, being a safe and feasible method, and it has potential to optimize individualized treatment options, e.g., in the decision of active surveillance.

    View details for DOI 10.1007/s00330-019-06087-x

    View details for Web of Science ID 000490625400011

    View details for PubMedID 30887194

  • Native T1 Mapping as an In Vivo Biomarker for the Identification of Higher-Grade Renal Cell Carcinoma Correlation With Histopathological Findings INVESTIGATIVE RADIOLOGY Adams, L. C., Ralla, B., Jurmeister, P., Bressem, K. K., Fahlenkamp, U. L., Ilamm, B., Busch, J., Makowski, M. R. 2019; 54 (2): 118-128

    Abstract

    The aims of this study were to identify higher-grade clear cell renal cell carcinoma (cRCC) with native T1 mapping and to histologically correlate the results with the collagen volume fraction.For this institutional review board-approved, single-center prospective study, 68 consecutive patients received abdominal magnetic resonance imaging scans at 1.5 T between January 2017 and July 2018, using a Modified Look-Locker Inversion Recovery (MOLLI) sequence. Thirty patients with cRCC (20 men; mean age, 61.9 ± 13.1 years) who underwent partial or radical nephrectomy and histological grading according to the International Society of Urological Pathology (ISUP) classification and a separate healthy cohort of 30 individuals without renal malignancies or complex cysts (16 men; mean age, 59.7 ± 14.6 years) met the eligibility criteria. T1 values were quantitatively measured with region of interest measurements in T1 maps. Quantification of the collagen volume fraction was performed on histological sections (picrosirius red staining).Native T1 values were significantly lower for lower-grade cRCC (ISUP 1 and 2) compared with higher-grade cRCC (ISUP 3 and 4; P < 0.001). A cutoff value of 1101 milliseconds distinguished higher-grade from lower-grade tumors with a sensitivity of 100% (95% confidence interval [CI], 0.69-1.00), a specificity of 85% (95% CI, 0.62-0.97), and an accuracy of 90% (95% CI, 0.73-0.98). Native T1 values were significantly associated with the histological collagen volume fraction (P < 0.05). Furthermore, T1 times in the renal cortex, medulla, and tumor tissue showed an excellent interobserver agreement.Native T1 mapping could represent an in vivo biomarker for the differentiation of lower- and higher-grade cRCCs, providing incremental diagnostic value beyond qualitative magnetic resonance imaging features.

    View details for DOI 10.1097/RLI.0000000000000515

    View details for Web of Science ID 000455897200009

    View details for PubMedID 30379727

  • Iron Oxide Nanoparticles for Visualization of Prostate Cancer in MRI. Cancers Kader, A., Kaufmann, J. O., Mangarova, D. B., Moeckel, J., Brangsch, J., Adams, L. C., Zhao, J., Reimann, C., Saatz, J., Traub, H., Buchholz, R., Karst, U., Hamm, B., Makowski, M. R. 2022; 14 (12)

    Abstract

    Prostate cancer (PCa) is one of the most common cancers in men. For detection and diagnosis of PCa, non-invasive methods, including magnetic resonance imaging (MRI), can reduce the risk potential of surgical intervention. To explore the molecular characteristics of the tumor, we investigated the applicability of ferumoxytol in PCa in a xenograft mouse model in two different tumor volumes, 500 mm3 and 1000 mm3. Macrophages play a key role in tumor progression, and they are able to internalize iron-oxide particles, such as ferumoxytol. When evaluating T2*-weighted sequences on MRI, a significant decrease of signal intensity between pre- and post-contrast images for each tumor volume (n = 14; p < 0.001) was measured. We, furthermore, observed a higher signal loss for a tumor volume of 500 mm3 than for 1000 mm3. These findings were confirmed by histological examinations and laser ablation inductively coupled plasma-mass spectrometry. The 500 mm3 tumors had 1.5% iron content (n = 14; σ = 1.1), while the 1000 mm3 tumors contained only 0.4% iron (n = 14; σ = 0.2). In vivo MRI data demonstrated a correlation with the ex vivo data (R2 = 0.75). The results of elemental analysis by inductively coupled plasma-mass spectrometry correlated strongly with the MRI data (R2 = 0.83) (n = 4). Due to its long retention time in the blood, biodegradability, and low toxicity to patients, ferumoxytol has great potential as a contrast agent for visualization PCa.

    View details for DOI 10.3390/cancers14122909

    View details for PubMedID 35740575

  • Microscopic multifrequency magnetic resonance elastography of ex vivo abdominal aortic aneurysms for extracellular matrix imaging in a mouse model ACTA BIOMATERIALIA Mangarova, D. B., Bertalan, G., Jordan, J., Brangsch, J., Kader, A., Moeckel, J., Adams, L. C., Sack, I., Taupitz, M., Hamm, B., Braun, J., Makowski, M. R. 2022; 140: 389-397

    Abstract

    An abdominal aortic aneurysm (AAA) is a permanent dilatation of the abdominal aorta, usually accompanied by thrombus formation. The current clinical imaging modalities cannot reliably visualize the thrombus composition. Remodeling of the extracellular matrix (ECM) during AAA development leads to stiffness changes, providing a potential imaging marker. 14 apolipoprotein E-deficient mice underwent surgery for angiotensin II-loaded osmotic minipump implantation. 4 weeks post-op, 5 animals developed an AAA. The aneurysm was imaged ex vivo by microscopic multifrequency magnetic resonance elastography (µMMRE) with an in-plane resolution of 40 microns. Experiments were performed on a 7-Tesla preclinical magnetic resonance imaging scanner with drive frequencies between 1000 Hz and 1400 Hz. Shear wave speed (SWS) maps indicating stiffness were computed based on tomoelastography multifrequency inversion. As control, the aortas of 5 C57BL/6J mice were examined with the same imaging protocol. The regional variation of SWS in the thrombus ranging from 0.44 ± 0.07 to 1.20 ± 0.31 m/s was correlated fairly strong with regional histology-quantified ECM accumulation (R2 = 0.79). Our results suggest that stiffness changes in aneurysmal thrombus reflect ECM remodeling, which is critical for AAA risk assessment. In the future, µMMRE could be used for a mechanics-based clinical characterization of AAAs in patients. STATEMENT OF SIGNIFICANCE: To our knowledge, this is the first study mapping the stiffness of abdominal aortic aneurysms with microscopic resolution of 40 µm. Our work revealed that stiffness critically changes due to extracellular matrix (ECM) remodeling in the aneurysmal thrombus. We were able to image various levels of ECM remodeling in the aneurysm reflected in distinct shear wave speed patterns with a strong correlation to regional histology-quantified ECM accumulation. The generated results are significant for the application of microscopic multifrequency magnetic resonance elastography for quantification of pathological remodeling of the ECM and may be of great interest for detailed characterization of AAAs in patients.

    View details for DOI 10.1016/j.actbio.2021.11.026

    View details for Web of Science ID 000755615300009

    View details for PubMedID 34818577

  • Editorial for "An Unsupervised Deep Learning Approach for Dynamic-Exponential Intravoxel Incoherent Motion MRI Modeling and Parameter Estimation in the Liver" JOURNAL OF MAGNETIC RESONANCE IMAGING Adams, L. C., Bressem, K. K. 2022

    View details for DOI 10.1002/jmri.28075

    View details for Web of Science ID 000745069900001

    View details for PubMedID 35061299

  • Do submillisievert-chest CT protocols impact diagnostic quality in suspected COVID-19 patients? ACTA RADIOLOGICA OPEN Thiess, H., Bressem, K. K., Adams, L., Boening, G., Vahldiek, J. L., Niehues, S. M. 2022; 11 (1): 20584601211073864

    Abstract

    During the ongoing global SARS-CoV-2 pandemic, there is a high demand for quick and reliable methods for early identification of infected patients. Due to its widespread availability, chest-CT is commonly used to detect early pulmonary manifestations and for follow-ups.This study aims to analyze image quality and reproducibility of readings of scans using low-dose chest CT protocols in patients suspected of SARS-CoV-2 infection.Two radiologists retrospectively analyzed 100 low-dose chest CT scans of patients suspected of SARS-CoV-2 infection using two protocols on devices from two vendors regarding image quality based on a Likert scale. After 3 weeks, quality ratings were repeated to allow for analysis of intra-reader in addition to the inter-reader agreement. Furthermore, radiation dose and presence as well as distribution of radiological features were noted.The exams' effective radiation doses were in median in the submillisievert range (median of 0.53 mSv, IQR: 0.35 mSv). While most scans were rated as being of optimal quality, 38% of scans were scored as suboptimal, yet only one scan was non-diagnostic. Inter-reader and intra-reader reliability showed almost perfect agreement with Cohen's kappa of 0.82 and 0.87.Overall, in this study, we present two protocols for submillisievert low-dose chest CT demonstrating appropriate or better image quality with almost perfect inter-reader and intra-reader agreement in patients suspected of SARS-CoV-2 infection.

    View details for DOI 10.1177/20584601211073864

    View details for Web of Science ID 000748439400001

    View details for PubMedID 35096416

    View details for PubMedCentralID PMC8796096

  • Detection of radiographic sacroiliitis with an artificial neural network in patients with suspicion of axial spondyloarthritis RHEUMATOLOGY Poddubnyy, D., Proft, F., Hermann, K. A., Spiller, L., Niehues, S. M., Adams, L. C., Protopopov, M., Rodriguez, V., Muche, B., Rademacher, J., Torgutalp, M., Bressem, K. K., Vahldiek, J. L. 2021; 60 (12): 5868-5869

    View details for DOI 10.1093/rheumatology/keab636

    View details for Web of Science ID 000746212300058

    View details for PubMedID 34363456

  • Visualization and Quantification of the Extracellular Matrix in Prostate Cancer Using an Elastin Specific Molecular Probe BIOLOGY-BASEL Kader, A., Brangsch, J., Reimann, C., Kaufmann, J. O., Mangarova, D. B., Moeckel, J., Adams, L. C., Zhao, J., Saatz, J., Traub, H., Buchholz, R., Karst, U., Hamm, B., Makowski, M. R. 2021; 10 (11)

    Abstract

    Human prostate cancer (PCa) is a type of malignancy and one of the most frequently diagnosed cancers in men. Elastin is an important component of the extracellular matrix and is involved in the structure and organization of prostate tissue. The present study examined prostate cancer in a xenograft mouse model using an elastin-specific molecular probe for magnetic resonance molecular imaging. Two different tumor sizes (500 mm3 and 1000 mm3) were compared and analyzed by MRI in vivo and histologically and analytically ex vivo. The T1-weighted sequence was used in a clinical 3-T scanner to calculate the relative contrast enhancement before and after probe administration. Our results show that the use of an elastin-specific probe enables better discrimination between tumors and surrounding healthy tissue. Furthermore, specific binding of the probe to elastin fibers was confirmed by histological examination and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Smaller tumors showed significantly higher signal intensity (p > 0.001), which correlates with the higher proportion of elastin fibers in the histological evaluation than in larger tumors. A strong correlation was seen between relative enhancement (RE) and Elastica-van Gieson staining (R2 = 0.88). RE was related to inductively coupled plasma-mass spectrometry data for Gd and showed a correlation (R2 = 0.78). Thus, molecular MRI could become a novel quantitative tool for the early evaluation and detection of PCa.

    View details for DOI 10.3390/biology10111217

    View details for Web of Science ID 000727716500001

    View details for PubMedID 34827210

    View details for PubMedCentralID PMC8615039

  • Assessment of Albumin ECM Accumulation and Inflammation as Novel In Vivo Diagnostic Targets for Multi-Target MR Imaging BIOLOGY-BASEL Moeckel, J., Brangsch, J., Reimann, C., Kaufmann, J. O., Sack, I., Mangarova, D. B., Kader, A., Taupitz, M., Adams, L. C., Keller, S., Ludwig, A., Hamm, B., Botnar, R. M., Makowski, M. R. 2021; 10 (10)

    Abstract

    Atherosclerosis is a progressive inflammatory vascular disease characterized by endothelial dysfunction and plaque burden. Extracellular matrix (ECM)-associated plasma proteins play an important role in disease development. Our magnetic resonance imaging (MRI) study investigates the feasibility of using two different molecular MRI probes for the simultaneous assessment of ECM-associated intraplaque albumin deposits caused by endothelial damage and progressive inflammation in atherosclerosis. Male apolipoprotein E-deficient (ApoE-/-)-mice were fed a high-fat diet (HFD) for 2 or 4 months. Another ApoE-/--group was treated with pravastatin and received a HFD for 4 months. T1- and T2*-weighted MRI was performed before and after albumin-specific MRI probe (gadofosveset) administration and a macrophage-specific contrast agent (ferumoxytol). Thereafter, laser ablation inductively coupled plasma mass spectrometry and histology were performed. With advancing atherosclerosis, albumin-based MRI signal enhancement and ferumoxytol-induced signal loss areas in T2*-weighted MRI increased. Significant correlations between contrast-to-noise-ratio (CNR) post-gadofosveset and albumin stain (R2 = 0.78, p < 0.05), and signal loss areas in T2*-weighted MRI with Perls' Prussian blue stain (R2 = 0.83, p < 0.05) were observed. No interference of ferumoxytol with gadofosveset enhancement was detectable. Pravastatin led to decreased inflammation and intraplaque albumin. Multi-target MRI combining ferumoxytol and gadofosveset is a promising method to improve diagnosis and treatment monitoring in atherosclerosis.

    View details for DOI 10.3390/biology10100964

    View details for Web of Science ID 000711467900001

    View details for PubMedID 34681063

    View details for PubMedCentralID PMC8533611

  • Detection of Radiographic Sacroiliitis with an Artificial Neural Network in Patients with Suspicion of Axial Spondyloarthritis Poddubnyy, D., Proft, F., Hermann, K., Spiller, L., Niehues, S., Adams, L., Protopopov, M., Rodriguez, V., Muche, B., Rademacher, J., Torgutalp, M., Bressem, K., Vahldiek, J. WILEY. 2021: 4010-4012
  • Artificial Neural Network for the Recognition of Active Inflammatory Changes Compatible with Axial Spondyloarthritis on Magnetic Resonance Imaging of Sacroiliac Joints Poddubnyy, D., Vahldiek, J., Adams, L., Diekhoff, T., Proft, F., Protopopov, M., Rademacher, J., Rodriguez, V., Torgutalp, M., Niehues, S., Bressem, K. WILEY. 2021: 1880-1882
  • Evaluation of potential tissue heating during percutaneous drill-assisted bone sampling in an in vivo porcine study SKELETAL RADIOLOGY Niehues, S. M., Elezkurtaj, S., Bresssem, K. K., Hamm, B., Erxleben, C., Vahldiek, J., Adams, L. C. 2022; 51 (4): 829-836

    Abstract

    Minimally invasive, battery-powered drilling systems have become the preferred tool for obtaining representative samples from bone lesions. However, the heat generated during battery-powered bone drilling for bone biopsies has not yet been sufficiently investigated. Thermal necrosis can occur if the bone temperature exceeds a critical threshold for a certain period of time.To investigate heat production as a function of femur temperature during and after battery-powered percutaneous bone drilling in a porcine in vivo model.We performed 16 femur drillings in 13 domestic pigs with an average age of 22 weeks and an average body temperature of 39.7 °C, using a battery-powered drilling system and an intraosseous temperature monitoring device. The standardized duration of the drilling procedure was 20 s. The bone core specimens obtained were embedded in 4% formalin, stained with haematoxylin and eosin (H&E) and sent for pathological analysis of tissue quality and signs of thermal damage.No significant changes in the pigs' local temperature were observed after bone drilling with a battery-powered drill device. Across all measurements, the median change in temperature between the initial measurement and the temperature measured after drilling (at 20 s) was 0.1 °C. Histological examination of the bone core specimens revealed no signs of mechanical or thermal damage.Overall, this preliminary study shows that battery-powered, drill-assisted harvesting of bone core specimens does not appear to cause mechanical or thermal damage.

    View details for DOI 10.1007/s00256-021-03890-w

    View details for Web of Science ID 000691165700001

    View details for PubMedID 34462782

    View details for PubMedCentralID PMC8854298

  • Value of susceptibility-weighted imaging for the assessment of angle measurements reflecting hip morphology (vol 10, 20899, 2021) SCIENTIFIC REPORTS Boeker, S. M., Adams, L. C., Fahlenkamp, U., Diederichs, G., Hamm, B., Makowski, M. R. 2021; 11 (1): 17580

    View details for DOI 10.1038/s41598-021-96788-5

    View details for Web of Science ID 000691009100005

    View details for PubMedID 34453108

    View details for PubMedCentralID PMC8397764

  • AN ARTIFICIAL NEURAL NETWORK FOR THE DETECTION OF DEFINITE RADIOGRAPHIC SACROILIITIS WITH HIGH SPECIFICITY IN THE DIAGNOSTIC SETTING Vahldiek, J. L., Bressem, K. K., Niehues, S., Adams, L., Spiller, L., Protopopov, M., Rodriguez, V., Muche, B., Rademacher, J., Haibel, H., Torgutalp, M., Proft, F., Poddubnyy, D. BMJ PUBLISHING GROUP. 2021: 155-156
  • Correlation of Native Liver Parenchyma T1 and T2 Relaxation Times and Liver Synthetic Function Tests: A Pilot Study DIAGNOSTICS Fahlenkamp, U., Kunkel, J., Ziegeler, K., Neumann, K., Adams, L., Engel, G., Boker, S., Makowski, M. 2021; 11 (6)

    Abstract

    MR relaxometry increasingly contributes to liver imaging. Studies on native relaxation times mainly describe relation to the presence of fibrosis. The hypothesis was that relaxation times are also influenced by other inherent factors, including changes in liver synthesis function. With the approval of the local ethics committee and written informed consent, data from 94 patients referred for liver MR imaging, of which 20 patients had cirrhosis, were included. Additionally to standard sequences, both native T1 and T2 parametric maps and T1 maps in the hepatobiliary phase of gadoxetate disodium were acquired. Associations with laboratory variables were assessed. Altogether, there was a negative correlation between albumin and all acquired relaxation times in cirrhotic patients. In non-cirrhotic patients, only T1 values exhibited a negative correlation with albumin. In all patients, bilirubin correlated significantly with post-contrast T1 relaxation times, whereas native relaxation times correlated only in cirrhotic patients. Evaluating patients with pathological INR values, post-contrast relaxation times were significantly higher, whereas native relaxation times did not correlate. In conclusion, apart from confirming the value of hepatobiliary phase T1 mapping, our results show a correlation of native T1 with serum albumin even in non-cirrhotic liver parenchyma, suggesting a direct influence of liver's synthesis capacity on T1 relaxation times.

    View details for DOI 10.3390/diagnostics11061125

    View details for Web of Science ID 000665538500001

    View details for PubMedID 34203008

    View details for PubMedCentralID PMC8233916

  • Simultaneous molecular MRI of extracellular matrix collagen and inflammatory activity to predict abdominal aortic aneurysm rupture (vol 10, 15206, 2020) SCIENTIFIC REPORTS Adams, L. C., Brangsch, J., Reimann, C., Kaufmann, J. O., Buchholz, R., Karst, U., Botnar, R. M., Hamm, B., Makowski, M. R. 2021; 11 (1): 9860

    View details for DOI 10.1038/s41598-021-89154-y

    View details for Web of Science ID 000656375400001

    View details for PubMedID 33947952

    View details for PubMedCentralID PMC8096974

  • Noninvasive imaging of vascular permeability to predict the risk of rupture in abdominal aortic aneurysms using an albumin-binding probe (vol 10, 3231, 2020) SCIENTIFIC REPORTS Adams, L. C., Brangsch, J., Reimann, C., Kaufmann, J. O., Nowak, K., Buchholz, R., Karst, U., Botnar, R. M., Hamm, B., Makowski, M. R. 2021; 11 (1): 9675

    View details for DOI 10.1038/s41598-021-89153-z

    View details for Web of Science ID 000656499600002

    View details for PubMedID 33931707

    View details for PubMedCentralID PMC8087688

  • Effect of Doxycycline on Survival in Abdominal Aortic Aneurysms in a Mouse Model CONTRAST MEDIA & MOLECULAR IMAGING Adams, L. C., Brangsch, J., Kaufmann, J. O., Mangarova, D. B., Moeckel, J., Kader, A., Buchholz, R., Karst, U., Botnar, R. M., Hamm, B., Makowski, M. R., Keller, S. 2021; 2021: 9999847

    Abstract

    Currently, there is no reliable nonsurgical treatment for abdominal aortic aneurysm (AAA). This study, therefore, investigates if doxycycline reduces AAA growth and the number of rupture-related deaths in a murine ApoE-/- model of AAA and whether gadofosveset trisodium-based MRI differs between animals with and without doxycycline treatment.Nine ApoE-/- mice were implanted with osmotic minipumps continuously releasing angiotensin II and treated with doxycycline (30 mg/kg/d) in parallel. After four weeks, MRI was performed at 3T with a clinical dose of the albumin-binding probe gadofosveset (0.03 mmol/kg). Results were compared with previously published wild-type control animals and with previously studied ApoE-/- animals without doxycycline treatment. Differences in mortality were also investigated between these groups.In a previous study, we found that approximately 25% of angiotensin II-infused ApoE-/- mice died, whereas in the present study, only one out of 9 angiotensin II-infused and doxycycline-treated ApoE-/- mice (11.1%) died within 4 weeks. Furthermore, doxycycline-treated ApoE-/- mice showed significantly lower contrast-to-noise (CNR) values (p=0.017) in MRI compared to ApoE-/- mice without doxycycline treatment. In vivo measurements of relative signal enhancement (CNR) correlated significantly with ex vivo measurements of albumin staining (R 2 = 0.58). In addition, a strong visual colocalization of albumin-positive areas in the fluorescence albumin staining with gadolinium distribution in LA-ICP-MS was shown. However, no significant difference in aneurysm size was observed after doxycycline treatment.The present experimental in vivo study suggests that doxycycline treatment may reduce rupture-related deaths in AAA by slowing endothelial damage without reversing aneurysm growth.

    View details for DOI 10.1155/2021/9999847

    View details for Web of Science ID 000655051900001

    View details for PubMedID 34007253

    View details for PubMedCentralID PMC8099506

  • Deep learning for detection of radiographic sacroiliitis: achieving expert-level performance ARTHRITIS RESEARCH & THERAPY Bressem, K. K., Vahldiek, J. L., Adams, L., Niehues, S., Haibel, H., Rodriguez, V., Torgutalp, M., Protopopov, M., Proft, F., Rademacher, J., Sieper, J., Rudwaleit, M., Hamm, B., Makowski, M. R., Hermann, K., Poddubnyy, D. 2021; 23 (1): 106

    Abstract

    Radiographs of the sacroiliac joints are commonly used for the diagnosis and classification of axial spondyloarthritis. The aim of this study was to develop and validate an artificial neural network for the detection of definite radiographic sacroiliitis as a manifestation of axial spondyloarthritis (axSpA).Conventional radiographs of the sacroiliac joints obtained in two independent studies of patients with axSpA were used. The first cohort comprised 1553 radiographs and was split into training (n = 1324) and validation (n = 229) sets. The second cohort comprised 458 radiographs and was used as an independent test dataset. All radiographs were assessed in a central reading session, and the final decision on the presence or absence of definite radiographic sacroiliitis was used as a reference. The performance of the neural network was evaluated by calculating areas under the receiver operating characteristic curves (AUCs) as well as sensitivity and specificity. Cohen's kappa and the absolute agreement were used to assess the agreement between the neural network and the human readers.The neural network achieved an excellent performance in the detection of definite radiographic sacroiliitis with an AUC of 0.97 and 0.94 for the validation and test datasets, respectively. Sensitivity and specificity for the cut-off weighting both measurements equally were 88% and 95% for the validation and 92% and 81% for the test set. The Cohen's kappa between the neural network and the reference judgements were 0.79 and 0.72 for the validation and test sets with an absolute agreement of 90% and 88%, respectively.Deep artificial neural networks enable the accurate detection of definite radiographic sacroiliitis relevant for the diagnosis and classification of axSpA.

    View details for DOI 10.1186/s13075-021-02484-0

    View details for Web of Science ID 000638243800002

    View details for PubMedID 33832519

    View details for PubMedCentralID PMC8028815

  • Deep learning for accurately recognizing common causes of shoulder pain on radiographs SKELETAL RADIOLOGY Grauhan, N. F., Niehues, S. M., Gaudin, R. A., Keller, S., Vahldiek, J. L., Adams, L. C., Bressem, K. K. 2022; 51 (2): 355-362

    Abstract

    Training a convolutional neural network (CNN) to detect the most common causes of shoulder pain on plain radiographs and to assess its potential value in serving as an assistive device to physicians.We used a CNN of the ResNet-50 architecture which was trained on 2700 shoulder radiographs from clinical practice of multiple institutions. All radiographs were reviewed and labeled for six findings: proximal humeral fractures, joint dislocation, periarticular calcification, osteoarthritis, osteosynthesis, and joint endoprosthesis. The trained model was then evaluated on a separate test dataset, which was previously annotated by three independent expert radiologists. Both the training and the test datasets included radiographs of highly variable image quality to reflect the clinical situation and to foster robustness of the CNN. Performance of the model was evaluated using receiver operating characteristic (ROC) curves, the thereof derived AUC as well as sensitivity and specificity.The developed CNN demonstrated a high accuracy with an area under the curve (AUC) of 0.871 for detecting fractures, 0.896 for joint dislocation, 0.945 for osteoarthritis, and 0.800 for periarticular calcifications. It also detected osteosynthesis and endoprosthesis with near perfect accuracy (AUC 0.998 and 1.0, respectively). Sensitivity and specificity were 0.75 and 0.86 for fractures, 0.95 and 0.65 for joint dislocation, 0.90 and 0.86 for osteoarthrosis, and 0.60 and 0.89 for calcification.CNNs have the potential to serve as an assistive device by providing clinicians a means to prioritize worklists or providing additional safety in situations of increased workload.

    View details for DOI 10.1007/s00256-021-03740-9

    View details for Web of Science ID 000619919600001

    View details for PubMedID 33611622

    View details for PubMedCentralID PMC8692302

  • Improving CT accuracy in the diagnosis of COVID-19 in a hospital setting CLINICAL IMAGING Erxleben, C., Adams, L. C., Albrecht, J., Petersen, A., Vahldiek, J. L., Thiess, H., Kremmin, J., Makowski, M. R., Niehues, A., Niehues, S. M., Bressem, K. K. 2021; 76: 1-5

    Abstract

    This study aimed to improve the accuracy of CT for detection of COVID-19-associated pneumonia and to identify patient subgroups who might benefit most from CT imaging.A total of 269 patients who underwent CT for suspected COVID-19 were included in this retrospective analysis. COVID-19 was confirmed by reverse-transcription-polymerase-chain-reaction. Basic demographics (age and sex) and initial vital parameters (O2-saturation, respiratory rate, and body temperature) were recorded. Generalized mixed models were used to calculate the accuracy of vital parameters for detection of COVID-19 and to evaluate the diagnostic accuracy of CT. A clinical score based on vital parameters, age, and sex was established to estimate the pretest probability of COVID-19 and used to define low, intermediate, and high risk groups. A p-value of <0.05 was considered statistically significant.The sole use of vital parameters for the prediction of COVID-19 was inferior to CT. After correction for confounders, such as age and sex, CT showed a sensitivity of 0.86, specificity of 0.78, and positive predictive value of 0.36. In the subgroup analysis based on pretest probability, positive predictive value and sensitivity increased to 0.53 and 0.89 in the high-risk group, while specificity was reduced to 0.68. In the low-risk group, sensitivity and positive predictive value decreased to 0.76 and 0.33 with a specificity of 0.83. The negative predictive value remained high (0.94 and 0.97) in both groups.The accuracy of CT for the detection of COVID-19 might be increased by selecting patients with a high-pretest probability of COVID-19.

    View details for DOI 10.1016/j.clinimag.2021.01.026

    View details for Web of Science ID 000661902100001

    View details for PubMedID 33545516

    View details for PubMedCentralID PMC7846468

  • CT diagnostics of pulmonary embolism: Does iodine delivery rate still affect image quality in iterative reconstruction? CLINICAL HEMORHEOLOGY AND MICROCIRCULATION Burdenski, T., Bressem, K. K., Adams, L. C., Grauhan, N. F., Niehues, S. M. 2021; 79 (1): 81-89

    Abstract

    Computed tomographic (CT) imaging in suspected pulmonary artery embolism represents the standard procedure. Studies without iterative reconstruction proved beneficial using increased iodine delivery rate (IDR). This study compares image quality in pulmonary arteries on iteratively reconstructed CT images of patients with suspected pulmonary embolism using different IDR.1065 patients were included in the study. Patients in group A (n = 493) received an iodine concentration of 40 g/100 ml (IDR 1.6 g/s) and patients in group B (n = 572) an iodine concentration of 35 g/100 ml (IDR 1.4 g/s) at a flow rate of 4 ml/s. A 80-detector spiral CT scanner with iterative reconstruction was used. We measured mean density values in truncus pulmonalis, both pulmonary arteries and segmental pulmonary arteries. Subjectively, the contrast of apical and basal pulmonary arteries was determined on a 4-point Likert scale.Radiodensity was significantly higher in all measured pulmonary arteries using the increased IDR (p < 0.001). TP: 483.0 HU vs. 393.4 HU; APD: 452.1 HU vs. 372.1 HU; APS: 448.2 HU vs. 374.4 HU; ASP: 443.9 vs. 374.4 HU. Subjectively assessed contrast enhancement in apical (p = 0.077) and basal (p = 0.429) lung sections showed no significant differences.Higher IDR improves objective image quality in all patients with significantly higher radiodensities by iterative reconstruction. Subjective contrast of apical and basal lung sections did not differ. The number of non-sufficient scans decreased with high IDR.

    View details for DOI 10.3233/CH-219115

    View details for Web of Science ID 000708959000009

    View details for PubMedID 34487032

  • Molecular MR Imaging of Prostate Cancer BIOMEDICINES Kader, A., Brangsch, J., Kaufmann, J. O., Zhao, J., Mangarova, D. B., Moeckel, J., Adams, L. C., Sack, I., Taupitz, M., Hamm, B., Makowski, M. R. 2021; 9 (1)

    Abstract

    This review summarizes recent developments regarding molecular imaging markers for magnetic resonance imaging (MRI) of prostate cancer (PCa). Currently, the clinical standard includes MR imaging using unspecific gadolinium-based contrast agents. Specific molecular probes for the diagnosis of PCa could improve the molecular characterization of the tumor in a non-invasive examination. Furthermore, molecular probes could enable targeted therapies to suppress tumor growth or reduce the tumor size.

    View details for DOI 10.3390/biomedicines9010001

    View details for Web of Science ID 000609837100001

    View details for PubMedID 33375045

    View details for PubMedCentralID PMC7822017

  • Value of susceptibility-weighted imaging for the assessment of angle measurements reflecting hip morphology SCIENTIFIC REPORTS Boeker, S. M., Adams, L. C., Fahlenkamp, U., Diederichs, G., Hamm, B., Makowski, M. R. 2020; 10 (1): 20899

    Abstract

    Radiographs are the clinical first line imaging modality for evaluating hip morphology and pathology. MRI offers additional information and is the method of choice to evaluate soft tissue, bone marrow and preradiographic signs of osteoarthritis. Radiographs are used to measure the most morphometric parameters. The aim of this study was to compare susceptibility weighted MRI (SWMR) with radiographs to evaluate hip morphology. 40 Patients were examined with standard MR-sequences, coronal SWMR and radiographs in anteroposterior pelvic view. Coronal maximum intensity projection (MIP) images of both hips were automatically reconstructed on SWMR and T1weighted images. Sharp´s angle, Tönnis angle, lateral center-edge angle of Wiberg and caput-collum-diaphyseal angle were measured on coronal SWMR MIP-images, T1weighted MIP-images and radiographs. Measurements were compared by linear regression analysis and Bland-Altmann Plots, using radiographs as reference standard. Additionally, a ratio between the signal intensity of muscles and bone on SWMR and T1weighted MIP-images was calculated and compared between these two sequences. SWMR enables the reliable assessment of Sharp´s angle (SWMR: R2 = 0.80; T1weighted: R2 = 0.37), Tönnis angle (SWMR: R2 = 0.86; T1weighted: not measurable), lateral center-edge angle of Wiberg (SWMR: R2 = 0.88; T1weighted: R2 = 0.40) and caput-collum-diaphyseal angle (SWMR: R2 = 0.38; T1weighted: R2 = 0.18) compared to radiographs with a higher accuracy than conventional MR imaging. The ratio between the intensity of muscles and bone was significant higher on SWMR (2.00 and 2.02) than on T1weighted MIP-images (1.6 and 1.42; p < 0.001).

    View details for DOI 10.1038/s41598-020-77671-1

    View details for Web of Science ID 000608975400011

    View details for PubMedID 33262372

    View details for PubMedCentralID PMC7708417

  • Molecular MR-Imaging for Noninvasive Quantification of the Anti-Inflammatory Effect of Targeting Interleukin-1 beta in a Mouse Model of Aortic Aneurysm MOLECULAR IMAGING Brangsch, J., Reimann, C., Kaufmann, J., Adams, L., Onthank, D., Thoene-Reineke, C., Robinson, S., Wilke, M., Weller, M., Buchholz, R., Karst, U., Botnar, R., Hamm, B., Makowski, M. 2020; 19: 1536012120961875

    Abstract

    Molecular-MRI is a promising imaging modality for the assessment of abdominal aortic aneurysms (AAAs). Interleukin-1β (IL-1β) represents a new therapeutic tool for AAA-treatment, since pro-inflammatory cytokines are key-mediators of inflammation. This study investigates the potential of molecular-MRI to evaluate therapeutic effects of an anti-IL-1β-therapy on AAA-formation in a mouse-model.Osmotic-minipumps were implanted in apolipoprotein-deficient-mice (N = 27). One group (Ang-II+01BSUR group, n = 9) was infused with angiotensin-II (Ang-II) for 4 weeks and received an anti-murine IL-1β-antibody (01BSUR) 3 times. One group (Ang-II-group, n = 9) was infused with Ang-II for 4 weeks but received no treatment. Control-group (n = 9) was infused with saline and received no treatment. MR-imaging was performed using an elastin-specific gadolinium-based-probe (0.2 mmol/kg).Mice of the Ang-II+01BSUR-group showed a lower aortic-diameter compared to mice of the Ang-II-group and control mice (p < 0.05). Using the elastin-specific-probe, a significant decrease in elastin-destruction was observed in mice of the Ang-II+01BSUR-group. In vivo MR-measurements correlated well with histopathology (y = 0.34x-13.81, R2 = 0.84, p < 0.05), ICP-MS (y = 0.02x+2.39; R2 = 0.81, p < 0.05) and LA-ICP-MS. Immunofluorescence and western-blotting confirmed a reduced IL-1β-expression.Molecular-MRI enables the early visualization and quantification of the anti-inflammatory-effects of an IL-1β-inhibitor in a mouse-model of AAAs. Responders and non-responders could be identified early after the initiation of the therapy using molecular-MRI.

    View details for DOI 10.1177/1536012120961875

    View details for Web of Science ID 000593576400001

    View details for PubMedID 33216687

    View details for PubMedCentralID PMC7682246

  • Is lung density associated with severity of COVID-19? POLISH JOURNAL OF RADIOLOGY Bressem, K. K., Adams, L. C., Albrecht, J., Petersen, A., Thiess, H., Niehues, A., Niehues, S. M., Vahldiek, J. L. 2020; 85: E600-E606

    Abstract

    Emphysema and chronic obstructive lung disease were previously identified as major risk factors for severe disease progression in COVID-19. Computed tomography (CT)-based lung-density analysis offers a fast, reliable, and quantitative assessment of lung density. Therefore, we aimed to assess the benefit of CT-based lung density measurements to predict possible severe disease progression in COVID-19.Thirty COVID-19-positive patients were included in this retrospective study. Lung density was quantified based on routinely acquired chest CTs. Presence of COVID-19 was confirmed by reverse transcription polymerase chain reaction (RT-PCR). Wilcoxon test was used to compare two groups of patients. A multivariate regression analysis, adjusted for age and sex, was employed to model the relative increase of risk for severe disease, depending on the measured densities.Intensive care unit (ICU) patients or patients requiring mechanical ventilation showed a lower proportion of medium- and low-density lung volume compared to patients on the normal ward, but a significantly larger volume of high-density lung volume (12.26 dl IQR 4.65 dl vs. 7.51 dl vs. IQR 5.39 dl, p = 0.039). In multivariate regression analysis, high-density lung volume was identified as a significant predictor of severe disease.The amount of high-density lung tissue showed a significant association with severe COVID-19, with odds ratios of 1.42 (95% CI: 1.09-2.00) and 1.37 (95% CI: 1.03-2.11) for requiring intensive care and mechanical ventilation, respectively. Acknowledging our small sample size as an important limitation; our study might thus suggest that high-density lung tissue could serve as a possible predictor of severe COVID-19.

    View details for DOI 10.5114/pjr.2020.100788

    View details for Web of Science ID 000588345800001

    View details for PubMedID 33204375

    View details for PubMedCentralID PMC7654311

  • Intracellular accumulation capacity of gadoxetate: initial results for a novel biomarker of liver function SCIENTIFIC REPORTS Fahlenkamp, U., Ziegeler, K., Adams, L., Boeker, S., Engel, G., Makowski, M. 2020; 10 (1): 18104

    Abstract

    Previous studies have shown gadoxetate disodium's potential to represent liver function by its retention in the hepatobiliary phase. Additionally, in cardiac imaging, quantitative characterization of altered parenchyma is established by extracellular volume (ECV) calculation with extracellular contrast agents. Therefore, the purpose of our study was to evaluate whether intracellular accumulation capacity (IAC) of gadoxetate disodium derived from ECV calculation provides added scientific value in terms of liver function compared to the established parameter reduction rate (RR). After local review board approval, 105 patients undergoing standard MR examination with gadoxetate disodium were included. Modified Look-Locker sequences were obtained before and 20 min after contrast agent administration. RR and IAC were calculated and correlated with serum albumin, as a marker of synthetic liver function. Correlation was higher between IAC and albumin, than between RR and albumin. Additionally, capacity of both RR and IAC to distinguish between patients with or without liver cirrhosis was investigated, and differed significantly in their respective means between patients with cirrhosis and those without. We concluded, that the formula to calculate ECV can be transferred to calculate IAC of gadoxetate disodium in hepatocytes, and, thereby, IAC may possibly qualify as an imaging-based parameter to estimate synthetic liver function.

    View details for DOI 10.1038/s41598-020-75145-y

    View details for Web of Science ID 000615379800097

    View details for PubMedID 33093649

    View details for PubMedCentralID PMC7582909

  • Development and Validation of an Artificial Intelligence Approach for the Detection of Radiographic Sacroiliitis Bressem, K., Vahldiek, J., Adams, L., Niehues, S., Haibel, H., Rodriguez, V., Torgutalp, M., Protopopov, M., Proft, F., Rademacher, J., Sieper, J., Rudwaleit, M., Hamm, B., Makowski, M., Hermann, K., Poddubnyy, D. WILEY. 2020
  • Native T1 Mapping Magnetic Resonance Imaging as a Quantitative Biomarker for Characterization of the Extracellular Matrix in a Rabbit Hepatic Cancer Model BIOMEDICINES Keller, S., Borde, T., Brangsch, J., Adams, L. C., Kader, A., Reimann, C., Gebert, P., Hamm, B., Makowski, M. 2020; 8 (10)

    Abstract

    To characterize the tumor extracellular matrix (ECM) using native T1 mapping magnetic resonance imaging (MRI) in an experimental hepatic cancer model, a total of 27 female New Zealand white rabbits with hepatic VX2 tumors were examined by MRI at different time points following tumor implantation (day 14, 21, 28). A steady-state precession readout single-shot MOLLI sequence was acquired in a 3 T MRI scanner in prone position using a head-neck coil. The tumors were segmented into a central, marginal, and peritumoral region in anatomical images and color-coded T1 maps. In histopathological sections, stained with H&E and Picrosirius red, the regions corresponded to central tumor necrosis and accumulation of viable cells with fibrosis in the tumor periphery. Another region of interest (ROI) was placed in healthy liver tissue. T1 times were correlated with quantitative data of collagen area staining. A two-way repeated-measures ANOVA was used to compare cohorts and tumor regions. Hepatic tumors were successfully induced in all rabbits. T1 mapping demonstrated significant differences between the different tumor regions (F(1.43,34.26) = 106.93, p < 0.001) without interaction effects between time points and regions (F(2.86,34.26) = 0.74, p = 0.53). In vivo T1 times significantly correlated with ex vivo collagen stains (area %), (center: r = 0.78, p < 0.001; margin: r = 0.84, p < 0.001; peritumoral: r = 0.73, p < 0.001). Post hoc tests using Sidak's correction revealed significant differences in T1 times between all three regions (p < 0.001). Native T1 mapping is feasible and allows the differentiation of tumor regions based on ECM composition in a longitudinal tumor study in an experimental small animal model, making it a potential quantitative biomarker of ECM remodeling and a promising technique for future treatment studies.

    View details for DOI 10.3390/biomedicines8100412

    View details for Web of Science ID 000584036500001

    View details for PubMedID 33066169

    View details for PubMedCentralID PMC7601966

  • Comparing different deep learning architectures for classification of chest radiographs SCIENTIFIC REPORTS Bressem, K. K., Adams, L. C., Erxleben, C., Hamm, B., Niehues, S. M., Vahldiek, J. L. 2020; 10 (1): 13590

    Abstract

    Chest radiographs are among the most frequently acquired images in radiology and are often the subject of computer vision research. However, most of the models used to classify chest radiographs are derived from openly available deep neural networks, trained on large image datasets. These datasets differ from chest radiographs in that they are mostly color images and have substantially more labels. Therefore, very deep convolutional neural networks (CNN) designed for ImageNet and often representing more complex relationships, might not be required for the comparably simpler task of classifying medical image data. Sixteen different architectures of CNN were compared regarding the classification performance on two openly available datasets, the CheXpert and COVID-19 Image Data Collection. Areas under the receiver operating characteristics curves (AUROC) between 0.83 and 0.89 could be achieved on the CheXpert dataset. On the COVID-19 Image Data Collection, all models showed an excellent ability to detect COVID-19 and non-COVID pneumonia with AUROC values between 0.983 and 0.998. It could be observed, that more shallow networks may achieve results comparable to their deeper and more complex counterparts with shorter training times, enabling classification performances on medical image data close to the state-of-the-art methods even when using limited hardware.

    View details for DOI 10.1038/s41598-020-70479-z

    View details for Web of Science ID 000563534600012

    View details for PubMedID 32788602

    View details for PubMedCentralID PMC7423963

  • Native T1 mapping for assessment of the perilesional zone in metastases and benign lesions of the liver SCIENTIFIC REPORTS Fahlenkamp, U., Ziegeler, K., Adams, L., Boeker, S., Engel, G., Makowski, M. 2020; 10 (1): 12889

    Abstract

    Adjacent to hepatic metastases, liver parenchyma is often histopathologically altered even if its visual appearance on native magnetic resonance (MR) images is blunt. Yet, relaxation properties in MR imaging may show structural changes prior to visual alteration, and therefore, the aim of this study was to investigate whether T1 relaxation times in the perilesional zone differ between metastases and benign lesions. A total of 113 patients referred for MRI were included prospectively. Images were assessed for metastases, solid benign lesions and cysts, and regions-of-interest were drawn on T1 maps including the focal lesion and a close (inner perilesional zone = IPZ) and a larger perilesional zone (outer perilesional zone = OPZ). Simple ratios between these zones, as well as a gradient ratio between the IPZ and the entire perilesional zone (EPZ) were calculated. Within the collective, 44 patients had lesions of one or two entities. For metastases, the simple ratio between IPZ and OPZ as well as the mean EPZ gradient was significantly higher than for both solid benign lesions and cysts. Lesion size was not a significant covariate. We conclude, that native T1 properties of the perilesional zones differ significantly between malignant and both solid and cystic benign lesions.

    View details for DOI 10.1038/s41598-020-69819-w

    View details for Web of Science ID 000559797100107

    View details for PubMedID 32733016

    View details for PubMedCentralID PMC7393097

  • Subregion Radiomics Analysis to Display Necrosis After Hepatic Microwave Ablation-A Proof of Concept Study INVESTIGATIVE RADIOLOGY Bressem, K. K., Adams, L. C., Vahldiek, J. L., Erxleben, C., Poch, F., Lehmann, K. S., Hamm, B., Niehues, S. M. 2020; 55 (7): 422-429

    Abstract

    The aim of this study was to improve the visualization of coagulation necrosis after computed tomography (CT)-guided microwave ablation (MWA) in routine postablational imaging.Ten MWAs were performed in 8 pigs under CT guidance. After each ablation, we obtained contrast-enhanced CT scans in venous phase. Ablations were then resected as a whole, and histologic slices were obtained orthogonally through the ablation center. Subsequently, a vital stain was applied to the sections for visualization of coagulation necrosis. Computed tomography images were reformatted to match the histologic slices. Afterwards, quantitative imaging features were extracted from the subregions of all images, and binary classifiers were used to predict the presence of coagulation necrosis for each subregion. From this, heatmaps could be created, which visually represented the extent of necrosis in each CT image. Two independent observers evaluated the extent of coagulative necrosis between the heat maps and histological sections.We applied 4 different classifiers, including a generalized linear mixed model (GLMM), a stochastic gradient boosting classifier, a random forest classifier, and a k-nearest neighbor classifier, out of which the GLMM showed the best performance to display coagulation necrosis. The GLMM resulted in an area under the curve of 0.84 and a Jaccard index of 0.6 between the generated heat map and the histologic reference standard as well as a good interobserver agreement with a Jaccard index of 0.9.Subregion radiomics analysis may improve visualization of coagulation necrosis after hepatic MWA in an in vivo porcine model.

    View details for DOI 10.1097/RLI.0000000000000653

    View details for Web of Science ID 000549981700003

    View details for PubMedID 32028297

  • Multiparametric Assessment of Changes in Renal Tissue after Kidney Transplantation with Quantitative MR Relaxometry and Diffusion-Tensor Imaging at 3 T JOURNAL OF CLINICAL MEDICINE Adams, L. C., Bressem, K. K., Scheibl, S., Nunninger, M., Gentsch, A., Fahlenkamp, U. L., Eckardt, K., Hamm, B., Makowski, M. R. 2020; 9 (5)

    Abstract

    Magnetic resonance relaxometry (MRR) offers highly reproducible pixel-wise parametric maps of T1 and T2 relaxation times, reflecting specific tissue properties, while diffusion-tensor imaging (DTI) is a promising technique for the characterization of microstructural changes, depending on the directionality of molecular motion. Both MMR and DTI may be used for non-invasive assessment of parenchymal changes caused by kidney injury or graft dysfunction.We examined 46 patients with kidney transplantation and 16 healthy controls, using T1/T2 relaxometry and DTI at 3 T. Twenty-two early transplants and 24 late transplants were included. Seven of the patients had prior renal biopsy (all of them dysfunctional allografts; 6/7 with tubular atrophy and 7/7 with interstitial fibrosis).Compared to healthy controls, T1 and T2 relaxation times in the renal parenchyma were increased after transplantation, with the highest T1/T2 values in early transplants (T1: 1700 ± 53 ms/T2: 83 ± 6 ms compared to T1: 1514 ± 29 ms/T2: 78 ± 4 ms in controls). Medullary and cortical ADC/FA values were decreased in early transplants and highest in controls, with medullary FA values showing the most pronounced difference. Cortical renal T1, mean medullary FA and corticomedullary differentiation (CMD) values correlated best with renal function as measured by eGFR (cortical T1: r = -0.63, p < 0.001; medullary FA: r = 0.67, p < 0.001; FA CMD: r = 0.62, p < 0.001). Mean medullary FA proved to be a significant predictor for tubular atrophy (p < 0.001), while cortical T1 appeared as a significant predictor of interstitial fibrosis (p = 0.003).Cortical T1, medullary FA, and FA CMD might serve as new imaging biomarkers of renal function and histopathologic microstructure.

    View details for DOI 10.3390/jcm9051551

    View details for Web of Science ID 000540223800308

    View details for PubMedID 32455558

    View details for PubMedCentralID PMC7290480

  • Noninvasive imaging of vascular permeability to predict the risk of rupture in abdominal aortic aneurysms using an album-inbinding probe SCIENTIFIC REPORTS Adams, L. C., Brangsch, J., Reimann, C., Kaufmann, J. O., Nowak, K., Buchholz, R., Karst, U., Botnar, R. M., Hamm, B., Makowski, M. R. 2020; 10 (1): 3231

    Abstract

    Abdominal aortic aneurysm (AAA) remains a fatal disease. Its development encompasses a complex interplay between hemodynamic stimuli on and changes in the arterial wall. Currently available biomarkers fail to predict the risk of AAA rupture independent of aneurysm size. Therefore, novel biomarkers for AAA characterization are needed. In this study, we used a mouse model of AAA to investigate the potential of magnetic resonance imaging (MRI) with an albumin-binding probe to assess changes in vascular permeability at different stages of aneurysm growth. Two imaging studies were performed: a longitudinal study with follow-up and death as endpoint to predict rupture risk and a week-by-week study to characterize AAA development. AAAs, which eventually ruptured, demonstrated a significantly higher in vivo MR signal enhancement from the albumin-binding probe (p = 0.047) and a smaller nonenhancing thrombus area compared to intact AAAs (p = 0.001). The ratio of albumin-binding-probe enhancement of the aneurysm wall to size of nonenhancing-thrombus-area predicted AAA rupture with high sensitivity/specificity (100%/86%). More advanced aneurysms with higher vascular permeability demonstrated an increased uptake of the albumin-binding-probe. These results indicate that MRI with an albumin-binding probe may enable noninvasive assessment of vascular permeability in murine AAAs and prediction of rupture risk.

    View details for DOI 10.1038/s41598-020-59842-2

    View details for Web of Science ID 000563268400006

    View details for PubMedID 32094414

    View details for PubMedCentralID PMC7039902

  • Dual-probe molecular MRI for the in vivo characterization of atherosclerosis in a mouse model: Simultaneous assessment of plaque inflammation and extracellular-matrix remodeling SCIENTIFIC REPORTS Reimann, C., Brangsch, J., Kaufmann, J. O., Adams, L. C., Onthank, D. C., Thoene-Reineke, C., Robinson, S. P., Hamm, B., Botnar, R. M., Makowski, M. R. 2019; 9: 13827

    Abstract

    Molecular MRI is a promising in-vivo modality to detect and quantify morphological and molecular vessel-wall changes in atherosclerosis. The combination of different molecular biomarkers may improve the risk stratification of patients. This study aimed to investigate the feasibility of simultaneous visualization and quantification of plaque-burden and inflammatory activity by dual-probe molecular MRI in a mouse-model of progressive atherosclerosis and in response-to-therapy. Homozygous apolipoprotein E knockout mice (ApoE-/-) were fed a high-fat-diet (HFD) for up to four-months prior to MRI of the brachiocephalic-artery. To assess response-to-therapy, a statin was administered for the same duration. MR imaging was performed before and after administration of an elastin-specific gadolinium-based and a macrophage-specific iron-oxide-based probe. Following in-vivo MRI, samples were analyzed using histology, immunohistochemistry, inductively-coupled-mass-spectrometry and laser-inductively-coupled-mass-spectrometry. In atherosclerotic-plaques, intraplaque expression of elastic-fibers and inflammatory activity were not directly linked. While the elastin-specific probe demonstrated the highest accumulation in advanced atherosclerotic-plaques after four-months of HFD, the iron-oxide-based probe showed highest accumulation in early atherosclerotic-plaques after two-months of HFD. In-vivo measurements for the elastin and iron-oxide-probe were in good agreement with ex-vivo histopathology (Elastica-van-Giesson stain: y = 298.2 + 5.8, R2 = 0.83, p < 0.05; Perls' Prussian-blue-stain: y = 834.1 + 0.67, R2 = 0.88, p < 0.05). Contrast-to-noise-ratio (CNR) measurements of the elastin probe were in good agreement with ICP-MS (y = 0.11x-11.3, R² = 0.73, p < 0.05). Late stage atherosclerotic-plaques displayed the strongest increase in both CNR and gadolinium concentration (p < 0.05). The gadolinium probe did not affect the visualization of the iron-oxide-probe and vice versa. This study demonstrates the feasibility of simultaneous assessment of plaque-burden and inflammatory activity by dual-probe molecular MRI of progressive atherosclerosis. The in-vivo detection and quantification of different MR biomarkers in a single scan could be useful to improve characterization of atherosclerotic-lesions.

    View details for DOI 10.1038/s41598-019-50100-8

    View details for Web of Science ID 000487586600018

    View details for PubMedID 31554825

    View details for PubMedCentralID PMC6761132

  • Use of quantitative T2 mapping for the assessment of renal cell carcinomas: first results CANCER IMAGING Adams, L. C., Bressem, K. K., Jurmeister, P., Fahlenkamp, U. L., Ralla, B., Engel, G., Hamm, B., Busch, J., Makowski, M. R. 2019; 19: 35

    Abstract

    Correct staging and grading of patients with clear cell renal cell carcinoma (cRCC) is of clinical relevance for the prediction of operability and for individualized patient management. As partial or radial resection with postoperative tumor grading currently remain the methods of choice for the classification of cRCC, non-invasive preoperative alternatives to differentiate lower grade from higher grade cRCC would be beneficial.This institutional-review-board approved cross-sectional study included twenty-seven patients (8 women, mean age ± SD, 61.3 ± 14.2) with histopathologically confirmed cRCC, graded according to the International Society of Urological Pathology (ISUP). A native, balanced steady-state free precession T2 mapping sequence (TrueFISP) was performed at 1.5 T. Quantitative T2 values were measured with circular 2D ROIs in the solid tumor portion and also in the normal renal parenchyma (cortex and medulla). To estimate the optimal cut-off T2 value for identifying lower grade cRCC, a Receiver Operating Characteristic Curve (ROC) analysis was performed and sensitivity and specificity were calculated. Students' t-tests were used to evaluate the differences in mean values for continuous variables, while intergroup differences were tested for significance with two-tailed Mann-Whitney-U tests.There were significant differences between the T2 values for lower grade (ISUP 1-2) and higher grade (ISUP 3-4) cRCC (p < 0.001), with higher T2 values for lower grade cRCC compared to higher grade cRCC. The sensitivity and specificity for the differentiation of lower grade from higher grade tumors were 83.3% (95% CI: 0.59-0.96) and 88.9% (95% CI: 0.52-1.00), respectively, using a threshold value of ≥110 ms. Intraobserver/interobserver agreement for T2 measurements was excellent/substantial.Native T2 mapping based on a balanced steady-state free precession MR sequence might support an image-based distinction between lower and higher grade cRCC in a two-tier-system and could be a helpful addition to multiparametric imaging.

    View details for DOI 10.1186/s40644-019-0222-8

    View details for Web of Science ID 000471009500002

    View details for PubMedID 31174616

    View details for PubMedCentralID PMC6555952

  • Perioperative and oncologic outcome in patients treated for renal cell carcinoma with an extended inferior vena cava tumour thrombus level II-IV. Aktuelle Urologie Ralla, B., Adams, L., Maxeiner, A., Mang, J., Krimphove, M., Dushe, S., Makowski, M., Miller, K., Fuller, F., Busch, J. 2019

    Abstract

     Surgical treatment of patients with renal cell carcinoma (RCC) and an extended tumour thrombus (TT) in the inferior vena cava (IVC) is challenging and often requires a multidisciplinary approach. The aim of this study was to analyse results in the real-world management of RCC patients with an extended IVC TT (level II-IV according to the Mayo classification of macroscopic venous invasion in RCC) in terms of pre-, peri- and postoperative outcome, complications and oncologic outcome. We investigated 61 patients with evidence of RCC and an extended TT in the IVC undergoing radical nephrectomy and tumour thrombectomy at our tertiary referral centre. Patients and operative characteristics were recorded and complications were analysed using the Clavien-Dindo classification. Follow-up data were retrieved by contacting the treating outpatient urologists, general practitioners and patients. The TT level was II in 36, III in 8 and IV in 17 patients. Complications grade IIIb and higher according to the Clavien-Dindo classification occurred in n = 3 (8.4 %), n = 2 (25.0 %) and n = 5 (29.5 %) patients with level II, III and IV TT, respectively. The overall survival of patients with TT level II, III and IV at 24 months (60 months) was 66.9 % (41.6 %), 83.3 % (83.3 %) and 64.1 % (51.3 %). Presence of primary metastatic disease was the only significant independent predictor for OS.  CONCLUSIONS:  Radical nephrectomy with tumour thrombectomy appears to be a feasible and effective treatment option in the management of patients with RCC and an extended IVC TT.

    View details for DOI 10.1055/a-0919-4043

    View details for PubMedID 31163462

  • Evaluation of osseous cervical foraminal stenosis in spinal radiculopathy using susceptibility-weighted magnetic resonance imaging EUROPEAN RADIOLOGY Engel, G., Bender, Y. Y., Adams, L. C., Boker, S. M., Fahlenkamp, U. L., Wagner, M., Diederichs, G., Hamm, B., Makowski, M. R. 2019; 29 (4): 1855-1862

    Abstract

    The aim of this study was to evaluate the diagnostic performance of susceptibility-weighted magnetic resonance imaging (SW-MRI) for the evaluation of osseous foraminal stenosis (FS) of the cervical spine compared to conventional MRI-sequences, using computed tomography (CT) as a reference standard.Twenty-one patients with suspected radiculopathy of the cervical spine were prospectively included. CT and MRI data sets were available for all patients. As standard of reference, 280 neuroforamina of the cervical spine, including 58 foraminal stenosis, were identified on sagittal CT images. T1-, T2-, and SW-MRI of the cervical spine were performed. The presence of foraminal stenosis was assessed on sagittal views in all sequences. Sensitivity and specificity were calculated and differences in detection rate and severity scoring of foraminal stenosis between the different sequences were tested. CT was used as reference standard for all analysis.Fifty-six of 58 osseous foraminal stenosis could be correctly identified on SW-MR magnitude images. SW-MRI achieved a sensitivity of 96.6% and specificity of 99.5% for the identification of foraminal stenosis. In comparison, conventional T1-weighted MRI sequences achieved a sensitivity and specificity of 43.1% and 100% respectively. T2-weighted MRI sequences achieved a sensitivity and specificity of 65.5% and 99.1%, respectively. The overall detection rate was significantly (p < 0.05) higher on SW-MRI and there was no significant difference (p > 0.05) in severity scoring compared to CT. T1- and T2-weighted MRI underestimated the degree of foraminal stenosis. Intermodality and interobserver agreements were highest for SW-MRI.SW-MRI enables the reliable detection of osseous foraminal stenosis of the cervical spine in patients with spinal radiculopathy with a higher sensitivity compared to conventional T1- and T2-MRI sequences, with CT as a reference standard.• Susceptibility-weighted magnetic resonance imaging enables the reliable detection of osseous foraminal stenosis of the cervical spine with CT as a reference standard. • This could be relevant for younger patients in order to prevent unnecessary radiation exposure. • This may also facilitate a one-stop-shop approach and speed up diagnostic work-up.

    View details for DOI 10.1007/s00330-018-5769-4

    View details for Web of Science ID 000461329400026

    View details for PubMedID 30324384

  • Improved visualisation of hepatic metastases in gadoxetate disodium-enhanced MRI: Potential of contrast-optimised (phase-sensitive) inversion recovery imaging PLOS ONE Fahlenkamp, U., Engel, G., Adams, L., Boeker, S., Minh Huynh Anh, Wagner, M., Hamm, B., Makowski, M. 2019; 14 (3): e0213408

    Abstract

    Detection of metastases can have a significant impact on therapy. Nevertheless, even in gadoxetate disodium-enhanced MR scans, very small hepatic metastases may be difficult to see.To investigate the potential of a contrast-optimised (phase-sensitive) inversion recovery MR sequence in gadoxetate disodium-enhanced scans for detection of hepatic metastases.With institutional review board approval and after written informed consent, 40 patients (18 male, 22 female) with suspected or known hepatic metastases were examined on a 1.5 T MR system. A T1-weighted gradient-echo volumetric-interpolated-breath-hold (VIBE) sequence was acquired as part of the standard imaging protocol 20 minutes after administration of gadoxetate disodium. Additionally, an IR sequence was acquired with an inversion time to suppress native signal from metastases. Overall image quality and delineation of lesions were assessed on VIBE as well as on magnitude-reconstructed (MAG) and phase-sensitive IR (PSIR) sequences. Lesion-to-liver contrast (LLC) was compared between VIBE and MAG images.Overall image quality was high in both VIBE and MAG IR sequences (VIBE 4.275; MAG 4.313), yet significantly lower in PSIR (4.038). Subjective delineation of lesions was higher on MAG and PSIR images compared to VIBE in all size groups with an overall statistically significant difference for VIBE vs. MAG vs. PSIR (p < .001) in the variance analysis. Mean LLC was 0.35±0.01 for VIBE sequences, and 0.73±0.01 for MAG.Contrast-optimised PSIR seems to improve imaging characteristics of hepatic metastases in gadoxetate disodium-enhanced scans compared to T1 gradient-echo VIBE sequences.

    View details for DOI 10.1371/journal.pone.0213408

    View details for Web of Science ID 000460372100083

    View details for PubMedID 30840710

    View details for PubMedCentralID PMC6402670

  • Concurrent Molecular Magnetic Resonance Imaging of Inflammatory Activity and Extracellular Matrix Degradation for the Prediction of Aneurysm Rupture CIRCULATION-CARDIOVASCULAR IMAGING Brangsch, J., Reimann, C., Kaufmann, J. O., Adams, L. C., Onthank, D. C., Thone-Reineke, C., Robinson, S. P., Buchholz, R., Karst, U., Botnar, R. M., Hamm, B., Makowski, M. R. 2019; 12 (3): e008707

    Abstract

    Molecular magnetic resonance imaging is a promising modality for the characterization of abdominal aortic aneurysms (AAAs). The combination of different molecular imaging biomarkers may improve the assessment of the risk of rupture. This study investigates the feasibility of imaging inflammatory activity and extracellular matrix degradation by concurrent dual-probe molecular magnetic resonance imaging in an AAA mouse model.Osmotic minipumps with a continuous infusion of Ang II (angiotensin II; 1000 ng/[kg·min]) to induce AAAs were implanted in apolipoprotein-deficient mice (N=58). Animals were assigned to 2 groups. In group 1 (longitudinal group, n=13), imaging was performed once after 1 week with a clinical dose of a macrophage-specific iron oxide-based probe (ferumoxytol, 4 mgFe/kg, surrogate marker for inflammatory activity) and an elastin-specific gadolinium-based probe (0.2 mmol/kg, surrogate marker for extracellular matrix degradation). Animals were then monitored with death as end point. In group 2 (week-by-week-group), imaging with both probes was performed after 1, 2, 3, and 4 weeks (n=9 per group). Both probes were evaluated in 1 magnetic resonance session.The combined assessment of inflammatory activity and extracellular matrix degradation was the strongest predictor of AAA rupture (sensitivity 100%; specificity 89%; area under the curve, 0.99). Information from each single probe alone resulted in lower predictive accuracy. In vivo measurements for the elastin- and iron oxide-probe were in good agreement with ex vivo histopathology (Prussian blue-stain: R2=0.96, P<0.001; Elastica van Giesson stain: R2=0.79, P<0.001). Contrast-to-noise ratio measurements for the iron oxide and elastin-probe were in good agreement with inductively coupled mass spectroscopy ( R2=0.88, R2=0.75, P<0.001) and laser ablation coupled to inductively coupled plasma-mass spectrometry.This study demonstrates the potential of the concurrent assessment of inflammatory activity and extracellular matrix degradation by dual-probe molecular magnetic resonance imaging in an AAA mouse model. Based on the combined information from both molecular probes, the rupture of AAAs could reliably be predicted.

    View details for DOI 10.1161/CIRCIMAGING.118.008707

    View details for Web of Science ID 000469315100009

    View details for PubMedID 30871334

  • Differentiation of Predominantly Osteoblastic and Osteolytic Spine Metastases by Using Susceptibility-weighted MRI RADIOLOGY Boeker, S. M., Adams, L. C., Bender, Y. Y., Fahlenkamp, U. L., Wagner, M., Hamm, B., Makowski, M. R. 2019; 290 (1): 146-154

    Abstract

    Purpose To evaluate the use of susceptibility-weighted MRI for the differentiation of predominantly osteoblastic and osteolytic spine metastases. Materials and Methods For this prospective study, 53 study participants (mean age, 54.5 years ± 14.3 [range, 22-88 years]; 27 men with a mean age of 55.3 years ± 12.7 [range, 22-72 years] and 26 women with a mean age of 53.8 years ± 15.7 [range, 23-88 years]) with clinically suspected spine metastases underwent imaging with standard MRI sequences, susceptibility-weighted MRI, and CT. Sensitivities and specificities of MRI sequences for the detection of predominantly osteoblastic and osteolytic metastases were determined by using CT as the reference standard. The metastases-to-vertebral body signal intensity ratio (MVR) was calculated to compare modalities. Phantom measurements were obtained to correlate bone densities between MRI sequences and CT. Results A total of 64 metastases (38 predominantly osteoblastic, 26 predominantly osteolytic) were detected. Susceptibility-weighted MRI achieved a sensitivity of 100% (38 of 38) and specificity of 96% (25 of 26) for predominantly osteoblastic metastases and a sensitivity of 96% (25 of 26) and specificity of 100% (38 of 38) for predominantly osteolytic metastases. Standard MRI sequences achieved a sensitivity of 89% (34 of 38) and specificity of 73% (19 of 26) for predominantly osteoblastic metastases and a sensitivity of 73% (19 of 26) and specificity of 92% (35 of 38) for predominantly osteolytic metastases. MVR measurements obtained with susceptibility-weighted MRI demonstrated a strong correlation with those obtained with CT (R2 = 0.75), whereas those obtained with T1-weighted MRI, T2-weighted MRI, and turbo inversion-recovery magnitude MRI showed a weak to moderate correlation (R2 = 0.00, R2 = 0.35, and R2 = 0.39, respectively). Susceptibility-weighted MRI showed a strong correlation with CT with regard to metastases size (R2 = 0.91). In phantom measurements, susceptibility-weighted MRI enabled the reliable differentiation of different degrees of mineralization (R2 = 0.92 compared with CT). Conclusion Susceptibility-weighted MRI enables the reliable differentiation between predominantly osteoblastic and osteolytic spine metastases with a higher accuracy than standard MRI sequences. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Schweitzer in this issue.

    View details for DOI 10.1148/radiol.2018172727

    View details for Web of Science ID 000453784400028

    View details for PubMedID 30375926

  • MR Angiography of the Head/Neck Vascular System in Mice on a Clinical MRI System CONTRAST MEDIA & MOLECULAR IMAGING Reimann, C., Brangsch, J., Adams, L., Thoene-Reineke, C., Hamm, B., Makowski, M. 2019: 5461809

    Abstract

    Magnetic resonance angiography (MRA) represents a clinical reference standard for the in vivo assessment of the vasculature. In this study, the potential of non-contrast-enhanced and contrast-enhanced angiography of the head/neck vasculature in mice on a clinical MR imaging system was tested.All in vivo magnetic resonance imaging was performed with a 3T clinical system (Siemens). Non-contrast-enhanced (time-of-flight, TOF) and contrast-enhanced angiography (gadofosveset-trisodium, GdT) were performed in C57BL/6J mouse strain. Lumen-to-muscle ratios (LMRs) and area measurements were assessed. Histology was performed as reference standard of all relevant vascular structures.A close correlation between TOF (R 2 = 0.79; p < 0.05) and contrast-enhanced (GdT) angiography (R 2 = 0.92; p < 0.05) with histological area measurements was found. LMRs were comparable between both sequences. Regarding interobserver reproducibility, contrast-enhanced (GdT) angiography yielded a smaller 95% confidence interval and a closer interreader correlation compared to non-contrast-enhanced (TOF) measurements (-0.73-0.89; R 2 = 0.81 vs. -0.55-0.56; R 2 = 0.94).This study demonstrates that non-contrast-enhanced and contrast-enhanced angiographies of the head/neck vasculature of small animals can reliably performed on a clinical 3T MR scanner. Contrast-enhanced angiography enables the visualization of vascular structures with higher intravascular contrast and higher reproducibility.

    View details for DOI 10.1155/2019/5461809

    View details for Web of Science ID 000471006500001

    View details for PubMedID 31275084

    View details for PubMedCentralID PMC6560327

  • Non-alcoholic fatty liver disease in underweight patients with inflammatory bowel disease: A case-control study PLOS ONE Adams, L. C., Luebbe, F., Bressem, K., Wagner, M., Hamm, B., Makowski, M. R. 2018; 13 (11): e0206450

    Abstract

    Non-alcoholic fatty liver disease (NAFLD) was shown to also occur in lean and underweight patients. So far, the prevalence of NAFLD in underweight individuals with and without inflammatory bowel disease (IBD) is insufficiently enlightened. In this cross-sectional age, gender and disease-matched case-control study, underweight patients (BMI<18.5 kg/m2) with inflammatory bowel disease (IBD), who underwent abdominal MRI at 1.5 T/3 T with fat-saturated fast-spin-echo imaging from 10/2005-07/2018 were analysed (control-to-case-ratio 1:1, n = 130). All patients were additionally investigated for duration, history of surgery, medical treatment, laboratory values, liver and spleen diameters. On MRI, liver fat was quantified by two observers based on the relative signal loss on T2-weighted fast spin-echo MR images with fat saturation compared to images without fat saturation. The prevalence of NAFLD/liver steatosis, defined as a measured intrahepatic fat content of at least 5%, was significantly higher in underweight IBD patients than in normal weight patients (87.6% versus 21.5%, p<0.001). Compared to the cases, the liver fat content of the controls was reduced by -0.19 units on average (-19%; 95%Cl: -0.20; -0.14). Similar results were obtained for the subgroup of non-IBD individuals (n = 12; -0.25 units on average (-25%); 95%Cl: -0.35; -0.14). Patients with extremely low body weight (BMI <17.5 kg/m2) showed the highest liver fat content (+0.15 units on average (+15%) compared to underweight patients with a BMI of 17.5-18.5 kg/m2 (p<0.05)). Furthermore, underweight patients showed slightly increased liver enzymes and liver diameters. There were no indications of significant differences in disease duration, type of medications or surgery between cases and controls and also, there were no significant differences between observers or field strengths (p>0.05). The prevalence of liver steatosis was higher among underweight IBD and non-IBD patients compared to normal weight controls. Also, underweight patients showed slightly increased liver enzymes and liver diameters, hinting at initial metabolic disturbances.

    View details for DOI 10.1371/journal.pone.0206450

    View details for Web of Science ID 000450138500053

    View details for PubMedID 30427909

    View details for PubMedCentralID PMC6241122

  • Quantitative susceptibility mapping across two clinical field strengths: Contrast-to-noise ratio enhancement at 1.5T JOURNAL OF MAGNETIC RESONANCE IMAGING Ippoliti, M., Adams, L. C., Winfried, B., Hamm, B., Spincemaille, P., Wang, Y., Makowski, M. R. 2018; 48 (5): 1410-1420

    Abstract

    Quantitative susceptibility mapping (QSM) is an MRI postprocessing technique that allows quantification of the spatial distribution of tissue magnetic susceptibility in vivo. Contributing sources include iron, blood products, calcium, myelin, and lipid content.To evaluate the reproducibility and consistency of QSM across clinical field strengths of 1.5T and 3T and to optimize the contrast-to-noise ratio (CNR) at 1.5T through bandwidth tuning.Prospective.Sixteen healthy volunteers (10 men, 6 women; age range 24-37; mean age 27.8 ± 3.2 years).1.5T and 3T systems from the same vendor. Four spoiled gradient echo (SPGR) sequences were designed with different acquisition bandwidths.QSM reconstruction was achieved through a nonlinear morphology-enabled dipole inversion (MEDI) algorithm employing L1 regularization. CNR was calculated in seven regions of interest (ROIs), while reproducibility and consistency of QSM measurements were evaluated through voxel-based and region-specific linear correlation analyses and Bland-Altman plots.Interclass correlation, Wilcoxon rank sum test, linear regression analysis, Bland-Altman analysis, Welch's t-test.CNR analysis showed a statistically significant (P < 0.05) increase in four out of seven ROIs for the lowest bandwidth employed with respect to the highest (25.18% increase in CNR of caudate nucleus). All sequences reported an excellent correlation across field strength and bandwidth variation (R ≥ 0.96, widest limits of agreement from -18.7 to 25.8 ppb) in the ROI-based analysis, while the correlation was found to be good for the voxel-based analysis of averaged maps (R ≥ 0.90, widest limits of agreement from -9.3 to 9.1 ppb).CNR of QSM images reconstructed from 1.5T acquisitions can be enhanced through bandwidth tuning. MEDI-based QSM reconstruction demonstrated to be reproducible and consistent both across field strengths (1.5T and 3T) and bandwidth variation.1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1410-1420.

    View details for DOI 10.1002/jmri.26045

    View details for Web of Science ID 000448081300027

    View details for PubMedID 29659131

  • Feasibility of gadoxetate disodium enhanced 3D T1 MR cholangiography (MRC) with a specific inversion recovery prepulse for the assessment of the hepatobiliary system PLOS ONE Fahlenkamp, U., Adams, L., Boeker, S., Engel, G., Minh Huynh Anh, Wagner, M., Hamm, B., Makowski, M. 2018; 13 (9): e0203476

    Abstract

    To compare the potential of a gadoxetate disodium enhanced navigator-triggered 3D T1 magnetic-resonance cholangiography (MRC) sequence with a specific inversion recovery prepulse to T2-weighted MRCP for assessment of the hepatobiliary system.30 patients (12 male, 18 female) prospectively underwent conventional navigator-triggered 3D turbo spin-echo T2-weighted MRCP and 3D T1 MRC with a specific inversion pulse to minimise signal from the liver 30 minutes after administration of gadoxetate disodium on a 1.5 T MRI system. For qualitative evaluation, biliary duct depiction was assessed segmentally following a 5-point Likert scale. Visualisation of hilar structures as well as image quality was recorded. Additionally, the extrahepatic bile ducts were assessed quantitatively by calculation of signal-to-noise ratios (SNR).The advantages of T1 3D MRC include reduced affection of image quality by bowel movement and robust depiction of the relative position of the extrahepatic bile ducts in relation to the portal vein and the duodenum compared to T2 MRCP. However, overall T1 3D MRC did not significantly (p > 0.05) improve the biliary duct depiction compared to T2 MRCP in all segments: Common bile duct 4.1 vs. 4.4, right hepatic duct 3.6 vs. 4.2, left hepatic duct 3.5 vs. 4.1. Image quality did not differ significantly (p > 0.05) between both sequences (3.6 vs. 3.5). SNR measurements for the hepatobiliary system did not differ significantly (p > 0.05) between navigator-triggered T1 3D MRC and T2 MRCP.This preliminary study demonstrates that T1 3D MRC of a specific inversion recovery prepulse has potential to complement T2 MRCP, especially for the evaluation of liver structures close to the hilum in the diagnostic work-up of the biliary system in patients receiving gadoxetate disodium.

    View details for DOI 10.1371/journal.pone.0203476

    View details for Web of Science ID 000443789900064

    View details for PubMedID 30183778

    View details for PubMedCentralID PMC6124795

  • Assessing venous thrombus in renal cell carcinoma: preliminary results for unenhanced 3D-SSFP MRI CLINICAL RADIOLOGY Adams, L. C., Ralla, B., Engel, G., Diederichs, G., Hamm, B., Busch, J., Fuller, F., Makowski, M. R. 2018; 73 (8): 757.e9-757.e19

    Abstract

    To test the potential of unenhanced cardiac- and respiratory-motion-corrected three-dimensional steady-state free precession (3D-SSFP) magnetic resonance imaging (MRI) for the assessment of inferior vena cava (IVC) thrombus in patients with clear-cell renal cell carcinoma (cRCC), compared to standard contrast-enhanced (CE)-MRI and CE-computed tomography (CT).Eighteen patients with cRCC and IVC thrombus, who received CE-MRI and 3D-SSFP at 1.5 T between June 2015 and December 2017, were included. The diagnostic performance of 3D-SSFP in determining the level of thrombus extension, contrast-to-noise ratio (CNR), and image quality were compared with standard MRI/CT and validated against intraoperative and histopathology results.There was 100% agreement between 3D-SSFP, 83.3% agreement between CE-MRI, and 71.4% agreement between CE-CT and surgical findings regarding the level of IVC thrombus. In addition, 3D-SSFP showed a slightly superior estimate of pathological IVC volume. 3D-SSFP reached a significantly higher CNR in the supra- and infrarenal IVC compared to the morphological sequence T2-weighted half-Fourier axial single-shot fast spin-echo (T2-HASTE) and all phases of CE-MRI. More specifically, 3D-SSFP showed a significantly higher CNR in the infrarenal IVC (mean CNR of 10.09±5.74 versus 4.21±2.33 in the delayed phase, p≤0.001) and in the suprarenal IVC (mean CNR of 9.22±4.11 versus 4.84±5.74 in the late arterial phase, p=0.015). CE-CT also was significantly inferior to 3D-SSFP (p≤0.01) and slightly inferior to CE-MRI (p>0.05). The thrombus delineation score for 3D-SSFP (4.38±0.67) was higher compared to CE-MRI (3.76±0.56, p=0.005).This preliminary study indicates that 3D-SSFP can achieve an accurate assessment of IVC thrombus in cRCC patients without the need for contrast medium administration, being superior to standard MRI and CT.

    View details for DOI 10.1016/j.crad.2018.04.003

    View details for Web of Science ID 000437001000015

    View details for PubMedID 29779758

  • Renal cell carcinoma with venous extension: prediction of inferior vena cava wall invasion by MRI CANCER IMAGING Adams, L. C., Ralla, B., Bender, Y. Y., Bressem, K., Hamm, B., Busch, J., Fuller, F., Makowski, M. R. 2018; 18: 17

    Abstract

    Renal cell carcinoma (RCC) are accompanied by inferior vena cava (IVC) thrombus in up to 10% of the cases, with surgical resection remaining the only curative option. In case of IVC wall invasion, the operative procedure is more challenging and may even require IVC resection. This study aims to determine the diagnostic performance of contrast-enhanced magnetic resonance imaging (MRI) for the assessment of wall invasion by IVC thrombus in patients with RCC, validated with intraoperative findings.Data were collected on 81 patients with RCC and IVC thrombus, who received a radical nephrectomy and vena cava thrombectomy between February 2008 and November 2017. Forty eight patients met the inclusion criteria. Sensitivity and specificity as well as the positive and negative predictive values were calculated for preoperative MRI, based on the assessments of the two readers for visual wall invasion. Furthermore, a logistic regression model was used to determine if there was an association between intraoperative wall adherence and IVC diameter.Complete occlusion of the IVC lumen or vessel breach could reliably assess IVC wall invasion with a sensitivity of 92.3% (95%-CI: 0.75-0.99) and a specificity of 86.4% (95%-CI: 0.65-0.97) (Fisher-test: p-value< 0.001). The positive predictive value (PPV) was 88.9% (95%-CI: 0.71-0.98) and the negative predictive value reached 90.5% (95%-CI: 0.70-0.99). There was an excellent interobserver agreement for determining IVC wall invasion with a kappa coefficient of 0.90 (95%CI: 0.79-1.00).The present study indicates that standard preoperative MR imaging can be used to reliably assess IVC wall invasion, evaluating morphologic features such as the complete occlusion of the IVC lumen or vessel breach. Increases in IVC diameter are associated with a higher probability of IVC wall invasion.

    View details for DOI 10.1186/s40644-018-0150-z

    View details for Web of Science ID 000431822700001

    View details for PubMedID 29724245

    View details for PubMedCentralID PMC5934829

  • Evaluation of vertebral body fractures using susceptibility-weighted magnetic resonance imaging EUROPEAN RADIOLOGY Boeker, S. M., Adams, L. C., Bender, Y. Y., Wagner, M., Diekhoff, T., Fallenberg, E., Hamm, B., Makowski, M. R. 2018; 28 (5): 2228-2235

    Abstract

    To test the diagnostic performance of susceptibility-weighted MRI (sMRI) for the evaluation of vertebral body fractures versus standard MRI-sequences, using CT as reference standard.In this prospective study 88 vertebral fractures (45 healed, 43 non-healed) were detected in 39 patients who underwent T1/T2/TIRM MRI-sequences and sMRI. All fractures were evaluated with CT as reference standard. In all modalities/sequences, displacement and height of the posterior vertebral body cortex and visibility of fracture lines and cortical breaks were assessed. Sensitivity, specificity and inter-reader agreement between MRI and CT were calculated.sMRI demonstrated highest diagnostic accuracy for detection of posterior vertebral body cortex involvement (sensitivity: 98 %/specificity: 100 %), fracture lines (86 %/99 %) and cortical breaks (93 %/100 %) versus T1/T2/TIRM sequences. Regarding evaluation of posterior vertebral body cortex displacement and height, sMRI demonstrated the closest intermodality agreement (R2=0.96; 95 % CI -0.92-0.89/R2=0.97; 95 % CI -1.67-1.23) with CT and the closest interobserver agreement (R2=0.97; 95 % CI -0.71-1.01).sMRI allows reliable evaluation of vertebral body fractures with regard to posterior vertebral body cortex displacement and height, cortical breaks and fracture lines with higher accuracy versus standard MRI, especially in patients with non-healed vertebral body fractures.• sMRI allows a reliable evaluation of vertebral body fractures. • sMRI has higher accuracy than standard-MRI for evaluation of vertebral body fractures. • sMRI is especially useful in patients with non-healed vertebral body fractures.

    View details for DOI 10.1007/s00330-017-5195-z

    View details for Web of Science ID 000429104200049

    View details for PubMedID 29260364

  • Magnetic resonance imaging in heart failure, including coronary imaging: numbers, facts, and challenges ESC HEART FAILURE Adams, L., Noutsias, M., Bigalke, B., Makowski, M. R. 2018; 5 (1): 3-8

    Abstract

    Coronary artery disease (CAD) is a major risk factor for the incidence and progression of heart failure (HF). HF is characterized by a substantial morbidity and mortality and its lifetime risk is estimated at approximately 20% for men and women. As patients are in most cases identified only after developing overt clinical symptoms, detecting early stages of CAD and HF is of paramount importance. Due to its non-invasiveness, excellent soft-tissue contrast, high spatial resolution, and multiparametric nature, cardiovascular magnetic resonance (CMR) imaging has emerged as a promising radiation-free technique to assess a wide range of cardiovascular diseases such as CAD or HF, enabling a comprehensive evaluation of myocardial anatomy, regional and global function, and viability with the additional benefit of in vivo tissue characterization. CMR has the potential to enhance our understanding of coronary atherosclerosis and the aetiology of HF on functional and biological levels, to identify patients at risk for CAD or HF, and to enable individualized patient management and improved outcomes. Even though larger-scale studies on the different applications of CMR for the assessment of heart failure are scarce, recent research highlighted new possible clinical applications for CMR in the evaluation of CAD and HF.

    View details for DOI 10.1002/ehf2.12236

    View details for Web of Science ID 000423809200001

    View details for PubMedID 29160621

    View details for PubMedCentralID PMC5793958

  • Sclerotic bone lesions as a potential imaging biomarker for the diagnosis of tuberous sclerosis complex SCIENTIFIC REPORTS Brakemeier, S., Vogt, L., Adams, L. C., Zukunft, B., Diederichs, G., Hamm, B., Budde, K., Eckardt, K., Makowski, M. R. 2018; 8: 953

    Abstract

    Tuberous-sclerosis-complex (TSC) is associated with a high lifetime risk of severe complications. Clinical manifestations are largely variable and diagnosis is often missed. Sclerotic-bone-lesions (SBL) could represent a potential imaging biomarker for the diagnosis of TSC. In this study, computed tomography (CT) data sets of 49 TSC patients (31 females) were included and compared to an age/sex matched control group. Imaging features of SBLs included frequency, size and location pattern. Sensitivities, specificities and cutoff values for the diagnosis of TSC were established for the skull, thorax, and abdomen/pelvis. In TSC patients, 3439 SBLs were detected, including 665 skull SBLs, 1426 thoracal SBLs and 1348 abdominal/pelvic SBLs. In the matched control-collective, 157 SBLs could be found. The frequency of SBLs enabled a reliable differentiation between TSC patients and the control collective with the following sensitivities and specificities. Skull: ≥5 SBLs, 0.783, 1; thorax: ≥4 SBLs, 0.967, 0.967; abdomen/pelvis: ≥5 SBLs: 0.938, 0.906. SBL size was significantly larger compared to controls (p < 0.05). Based on the frequency, size and location pattern of SBLs TSC can be suspected. SBLs may serve as a potential imaging biomarker in the workup of TSC patients.

    View details for DOI 10.1038/s41598-018-19399-7

    View details for Web of Science ID 000422716900087

    View details for PubMedID 29343816

    View details for PubMedCentralID PMC5772483

  • Contrast-Enhanced Magnetic Resonance Angiography Using a Novel Elastin-Specific Molecular Probe in an Experimental Animal Model CONTRAST MEDIA & MOLECULAR IMAGING Reimann, C., Brangsch, J., Kaufmann, J., Adams, L. C., Onthank, D. C., Robinson, S. P., Botnar, R. M., Collettini, F., Makowski, M. R. 2018: 9217456

    Abstract

    The aim of this study was to test the potential of a new elastin-specific molecular agent for the performance of contrast-enhanced first-pass and 3D magnetic resonance angiography (MRA), compared to a clinically used extravascular contrast agent (gadobutrol) and based on clinical MR sequences.Eight C57BL/6J mice (BL6, male, aged 10 weeks) underwent a contrast-enhanced first-pass and 3D MR angiography (MRA) of the aorta and its main branches. All examinations were on a clinical 3 Tesla MR system (Siemens Healthcare, Erlangen, Germany). The clinical dose of 0.1 mmol/kg was administered in both probes. First, a time-resolved MRA (TWIST) was acquired during the first-pass to assess the arrival and washout of the contrast agent bolus. Subsequently, a high-resolution 3D MRA sequence (3D T1 FLASH) was acquired. Signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) were calculated for all sequences.The elastin-specific MR probe and the extravascular imaging agent (gadobutrol) enable high-quality MR angiograms in all animals. During the first-pass, the probes demonstrated a comparable peak enhancement (300.6 ± 32.9 vs. 288.5 ± 33.1, p > 0.05). Following the bolus phase, both agents showed a comparable intravascular enhancement (SNR: 106.7 ± 11 vs. 102.3 ± 5.3; CNR 64.5 ± 7.4 vs. 61.1 ± 7.2, p > 0.05). Both agents resulted in a high image quality with no statistical difference (p > 0.05).The novel elastin-specific molecular probe enables the performance of first-pass and late 3D MR angiography with an intravascular contrast enhancement and image quality comparable to a clinically used extravascular contrast agent.

    View details for DOI 10.1155/2018/9217456

    View details for Web of Science ID 000449206800001

    View details for PubMedID 30425609

    View details for PubMedCentralID PMC6218789

  • Treatment effect of mTOR-inhibition on tissue composition of renal angiomyolipomas in tuberous sclerosis complex (TSC) PLOS ONE Brakemeier, S., Vogt, L., Adams, L., Zukunft, B., Diederichs, G., Hamm, B., Budde, K., Makowski, M. R. 2017; 12 (12): e0189132

    Abstract

    Tuberous sclerosis complex (TSC)-associated renal angiomyolipoma (AML) have a high lifetime risk of acute bleeding. MTOR-inhibitors are a promising novel treatment for TSC-AML, however adequate response to therapy can be difficult to assess. Early changes in MRI signal may serve as a novel early indicator for a satisfactory response to mTOR-inhibitor therapy of AML.Thirty-eight patients with the definite diagnosis of tuberous sclerosis receiving everolimus therapy and n = 19 patients without specific therapy were included. 1.5 Tesla MRI was performed including sequences with a selective fat suppression. Patients were investigated prior to the initiation of therapy (baseline) and after <3 months (n = 21 patients), 3 to 6 months (n = 32) and 18 to 24 months (n = 28). Signal and size changes of renal AMLs were assessed at all different timepoints. Signal-to-noise-ratio (SNR), contrast-to-noise-ratio (CNR) and size of angiomyolipomas were evaluated.Signal changes in 273 AMLs were evaluated. A significant and strong decrease of the CNR of AMLs following the initiation of therapy was measured in the fat-suppressed MR sequence at all time points, compared to the baseline: From 7.41±6.98 to 3.84±6.25 (p ≤ 0.05p = 0.002), 3.36±6.93 (p<0.0001), and 2.50±6.68 (p<0.0001) after less than 3 months, 3-6 months or 18-24 months of everolimus treatment, respectively. Also, a significant, however less pronounced, reduction of angiomyolipoma size in the different groups was measured (from baseline 2022.2±2657.7 mm2 to 1854.4±1670.9 mm2 (p = 0.009), 1875.5±3190.1 mm2 (p<0.001), and 1365.8 ± 1628.8 mm2 (p<0.0001) after less than 3 months, 3-6 months or 18-24 months of everolimus treatment, respectively). No significant changes in CNR (p>0.05) and size (p>0.05) were measured in the control group.mTOR inhibitor therapy in TSC patients results in an early and pronounced fatty transformation of AMLs on MRI. Fatty transformation could represent a novel early indicator of response to therapy in this patient collective.

    View details for DOI 10.1371/journal.pone.0189132

    View details for Web of Science ID 000417698200022

    View details for PubMedID 29232371

    View details for PubMedCentralID PMC5726644

  • IN VIVO HIGH-FREQUENCY ULTRASOUND FOR THE CHARACTERIZATION OF THROMBI ASSOCIATED WITH AORTIC ANEURYSMS IN AN EXPERIMENTAL MOUSE MODEL ULTRASOUND IN MEDICINE AND BIOLOGY Jansen, C. P., Brangsch, J., Reimann, C., Adams, L., Hamm, B., Botnar, R. M., Makowski, M. R. 2017; 43 (12): 2882-2890

    Abstract

    The development of abdominal aortic aneurysm (AAA) associated thrombi plays an important role during the onset and progression of AAAs. The aim of this study was to evaluate the potential of high-frequency ultrasound for characterization of AAA associated thrombi in an apolipoprotein-E-deficient mouse-model. Ultrasound measurements were performed using a high-resolution ultrasound system (Vevo770, FUJIFILM VisualSonics, Inc., Toronto, ON, Canada) with a 30 MHz linear-array transducer (RMV707 B). Magnetic resonance imaging with a 3 Tesla scanner (Achieva MR system, Philips Healthcare, Best, The Netherlands) and a single-loop microscopy coil was performed as a reference standard. All stages of aneurysm development were evaluated by histologic analyses. The "signal-thrombus-matrix" to "signal-blood" ratio on high-frequency ultrasound measurements showed a strong correlation (R2 = 0.81, p <0.05) with the state of extracellular matrix remodeling. Furthermore, size measurements derived from the high-frequency ultrasound correlated well with magnetic resonance imaging and histology. This study demonstrated that high-frequency ultrasound enables the reliable in vivo quantification of extracellular matrix remodeling at various stages of thrombus development, based on the thrombus echogenicity.

    View details for DOI 10.1016/j.ultrasmedbio.2017.08.007

    View details for Web of Science ID 000415604700014

    View details for PubMedID 28965722

  • Diagnostic performance of susceptibility-weighted magnetic resonance imaging for the detection of calcifications: A systematic review and meta-analysis SCIENTIFIC REPORTS Adams, L. C., Bressem, K., Boeker, S., Bender, Y., Noerenberg, D., Hamm, B., Makowski, M. R. 2017; 7: 15506

    Abstract

    Since its introduction, susceptibility-weighted-magnetic resonance imaging (SW-MRI) has shown the potential to overcome the insensitivity of MRI to calcification. Previous studies reporting the diagnostic performance of SW-MRI and magnetic resonance imaging (MRI) for the detection of calcifications are inconsistent and based on single-institution designs. To our knowledge, this is the first meta-analysis on SW-MRI, determining the potential of SW-MRI to detect calcifications. Two independent investigators searched MEDLINE, EMBASE and Web of Science for eligible diagnostic accuracy studies, which were published until March 24, 2017 and investigated the accuracy of SW-MRI to detect calcifications, using computed tomography (CT) as a reference. The QUADAS-2 tool was used to assess study quality and methods for analysis were based on PRISMA. A bivariate diagnostic random-effects model was applied to obtain pooled sensitivities and specificities. Out of the 4629 studies retrieved by systematic literature search, 12 clinical studies with 962 patients and a total of 1,032 calcifications were included. Pooled sensitivity was 86.5% (95%-confidence interval (CI): 73.6-93.7%) for SW-MRI and 36.7% (95%-CI:29.2-44.8%) for standard MRI. Pooled specificities of SW-MRI (90.8%; 95%-CI:81.0-95.8%) and standard MRI (94.2; 95%-CI:88.9-96.7%) were comparable. Results of the present meta-analysis suggest, that SW-MRI is a reliable method for detecting calcifications in soft tissues.

    View details for DOI 10.1038/s41598-017-15860-1

    View details for Web of Science ID 000415166000002

    View details for PubMedID 29138506

    View details for PubMedCentralID PMC5686169

  • Assessment of Intracranial Meningioma-Associated Calcifications Using Susceptibility-Weighted MRI JOURNAL OF MAGNETIC RESONANCE IMAGING Adams, L. C., Boeker, S. M., Bender, Y. Y., Fallenberg, E. M., Wagner, M., Buchert, R., Hamm, B., Makowski, M. R. 2017; 46 (4): 1177-1186

    Abstract

    To determine the diagnostic accuracy of susceptibility-weighted MRI (SW-MRI) for the detection of intracranial meningioma-associated calcifications compared with standard MR sequences, using computed tomography (CT) as a reference standard.354 patients, who had received both a CT and a 1.5 Tesla clinical brain MRI with SW-MRI sequences between January 2014 and July 2016, were retrospectively evaluated and 316 patients were included. Calcification diameter was used to assess correlation between imaging modalities. Sensitivity and specificity as well as intra- and interobserver agreement were calculated for SW-MRI and standard MRI sequences when compared with reference standard CT.Fifty patients had positive findings for intracranial meningioma-associated calcifications on CT scans. SW-MRI reached a sensitivity of 94% (95% confidence interval [CI]: 83-99%) and a specificity of 95% (95% CI: 92-98%) for the detection of meningioma-associated calcifications, while standard MRI yielded a sensitivity of 64% (95% CI: 49-77%) and a specificity of 94% (95% CI: 90-96%). Diameter measurements between SW-MRI and CT showed a close correlation (R2  = 0.99; P < 0.001) with a slight overestimation of size, which, however, did not reach significance level (SW-MRI: 8.2 mm ± 7.1; CT: 6.8 mm ± 6.4; P = 0.29). Compared with standard MRI, SW-MRI showed a better interobserver agreement for size measurements of calcifications.SW-MRI enables a reliable detection of intracranial meningioma-associated calcifications by using CT as a reference and offers a higher diagnostic accuracy than standard MRI.3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1177-1186.

    View details for DOI 10.1002/jmri.25614

    View details for Web of Science ID 000410309300024

    View details for PubMedID 28106942

  • Detection of vessel wall calcifications in vertebral arteries using susceptibility weighted imaging NEURORADIOLOGY Adams, L. C., Boeker, S. M., Bender, Y. Y., Fallenberg, E. M., Wagner, M., Liebig, T., Hamm, B., Makowski, M. R. 2017; 59 (9): 861-872

    Abstract

    Calcification of the brain supplying arteries has been linked to an increased risk for cerebrovascular disease. The purpose of this study was to test the potential of susceptibility weighted MR imaging (SWMR) for the detection of vertebral artery calcifications, based on CT as a reference standard.Four hundred seventy-four patients, who had received head CT and 1.5 T MR scans with SWMR, including the distal vertebral artery, between January 2014 and December 2016, were retrospectively evaluated and 389 patients were included. Sensitivity and specificity for the detection of focal calcifications and intra- and interobserver agreement were calculated for SWMR and standard MRI, using CT as a standard of reference. The diameter of vertebral artery calcifications was used to assess correlations between imaging modalities. Furthermore, the degree of vessel stenosis was determined in 30 patients, who had received an additional angiography.On CT scans, 40 patients showed a total of 52 vertebral artery calcifications. While SWMR reached a sensitivity of 94% (95% CI 84-99%) and a specificity of 97% (95% CI 94-98%), standard MRI yielded a sensitivity of 33% (95% CI 20-46%), and a specificity of 93% (95% CI 90-96%). Linear regression analysis of size measurements confirmed a close correlation between SWMR and CT measurements (R 2 = 0.74, p < 0.001). Compared to standard MRI (ICC = 0.52; CI 0.45-0.59), SWMR showed a higher interobserver agreement for calcification measurements (ICC = 0.84; CI 0.81-0.87).For detection of distal vertebral artery calcifications, SWMR demonstrates a performance comparable to CT and considerably higher than conventional MRI.

    View details for DOI 10.1007/s00234-017-1878-z

    View details for Web of Science ID 000407825500006

    View details for PubMedID 28730268

  • Diagnostic accuracy of susceptibility-weighted magnetic resonance imaging for the evaluation of pineal gland calcification PLOS ONE Adams, L. C., Boeker, S. M., Bender, Y. Y., Diederichs, G., Fallenberg, E. M., Wagner, M., Hamm, B., Makowski, M. R. 2017; 12 (3): e0172764

    Abstract

    To determine the diagnostic performance of susceptibility-weighted magnetic resonance imaging (SWMR) for the detection of pineal gland calcifications (PGC) compared to conventional magnetic resonance imaging (MRI) sequences, using computed tomography (CT) as a reference standard.384 patients who received a 1.5 Tesla MRI scan including SWMR sequences and a CT scan of the brain between January 2014 and October 2016 were retrospectively evaluated. 346 patients were included in the analysis, of which 214 showed PGC on CT scans. To assess correlation between imaging modalities, the maximum calcification diameter was used. Sensitivity and specificity and intra- and interobserver reliability were calculated for SWMR and conventional MRI sequences.SWMR reached a sensitivity of 95% (95% CI: 91%-97%) and a specificity of 96% (95% CI: 91%-99%) for the detection of PGC, whereas conventional MRI achieved a sensitivity of 43% (95% CI: 36%-50%) and a specificity of 96% (95% CI: 91%-99%). Detection rates for calcifications in SWMR and conventional MRI differed significantly (95% versus 43%, p<0.001). Diameter measurements between SWMR and CT showed a close correlation (R2 = 0.85, p<0.001) with a slight but not significant overestimation of size (SWMR: 6.5 mm ± 2.5; CT: 5.9 mm ± 2.4, p = 0.02). Interobserver-agreement for diameter measurements was excellent on SWMR (ICC = 0.984, p < 0.0001).Combining SWMR magnitude and phase information enables the accurate detection of PGC and offers a better diagnostic performance than conventional MRI with CT as a reference standard.

    View details for DOI 10.1371/journal.pone.0172764

    View details for Web of Science ID 000396087900128

    View details for PubMedID 28278291

    View details for PubMedCentralID PMC5344338

  • Evaluation of sclerosis in Modic changes of the spine using susceptibility-weighted magnetic resonance imaging EUROPEAN JOURNAL OF RADIOLOGY Boeker, S. M., Bender, Y. Y., Adams, L. C., Fallenberg, E. M., Wagner, M., Hamm, B., Makowski, M. R. 2017; 88: 148-154

    Abstract

    To evaluate the diagnostic performance of susceptibility-weighted magnetic resonance imaging (SWMR) for the differentiation of sclerotic and non-sclerotic Modic changes (MC) of the spine compared to computed tomography (CT) and radiographs.The Institutional Ethics-Review-Board approved this prospective study in advance. Written consent was obtained from all subjects. SWMR and standard T1/T2 MR of the cervical (n=21) and/or lumbar spine (n=34) were performed in 54 patients. 21 patients served as control. 18 patients were evaluated with CT; in all other patients radiographs were available. 67 Modic changes were identified on T1/T2 MR. On SWMR changes were classified as sclerotic and non-sclerotic based on signal intensity measurements. The sensitivity and specificity of SWMR and T1/T2 MR for differentiating between sclerotic and non-sclerotic Modic changes were determined with CT and radiographs as reference standard.On SWMR, signal measurements between sclerotic and non-sclerotic Modic changes differed significantly (p<0.01). On T1- and T2-weighted MR no significant difference (p>0.05) was measured. On SWMR, a reliable differentiation between sclerotic and non-sclerotic Modic changes could be achieved, with a sensitivity of 100% and specificity of 95%. In contrast, the combination of T1-/T2-weighted MR yielded a significantly lower sensitivity to detect sclerosis (20%).SWMR allows a reliable detection of sclerosis in Modic changes with a higher accuracy compared to standard spine MR sequences, using radiographs and CT as reference standard.

    View details for DOI 10.1016/j.ejrad.2016.12.024

    View details for Web of Science ID 000397269600022

    View details for PubMedID 28189200