Guido A. Davidzon

All Publications

• Florbetaben amyloid PET acquisition time: Influence on Centiloids and interpretation. Alzheimer's & dementia : the journal of the Alzheimer's Association Johns, E., Vossler, H. A., Young, C. B., Carlson, M. L., Winer, J. R., Younes, K., Park, J., Rathmann-Bloch, J., Smith, V., Harrison, T. M., Landau, S., Henderson, V., Wagner, A., Sha, S. J., Zeineh, M., Zaharchuk, G., Poston, K. L., Davidzon, G. A., Mormino, E. C. 2024

  Abstract

  Amyloid positron emission tomography (PET) acquisition timing impacts quantification.In florbetaben (FBB) PET scans of 245 adults with and without cognitive impairment, we investigated the impact of post-injection acquisition time on Centiloids (CLs) across five reference regions. CL equations for FBB were derived using standard methods, using FBB data collected between 90 and 110 min with paired Pittsburgh compound B data. Linear mixed models and t-tests evaluated the impact of acquisition time on CL increases.CL values increased significantly over the scan using the whole cerebellum, cerebellar gray matter, and brainstem as reference regions, particularly in amyloid-positive individuals. In contrast, CLs based on white matter-containing reference regions decreased across the scan.The quantification of CLs in FBB PET imaging is influenced by both the overall scan acquisition time and the choice of reference region. Standardized acquisition protocols or the application of acquisition time-specific CL equations should be implemented in clinical protocols.Acquisition timing affects florbetaben positron emission tomography (PET) scan quantification, especially in amyloid-positive participants. The impact of acquisition timing on quantification varies across common reference regions. Consistent acquisitions and/or appropriate post-injection adjustments are needed to ensure comparability of PET data.

  View details for DOI 10.1002/alz.13893

  View details for PubMedID 38962867

• Prospective Comparison of 68Ga-NeoB and 68Ga-PSMA-R2 PET/MRI in Patients with Biochemically Recurrent Prostate Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Duan, H., Song, H., Davidzon, G. A., Moradi, F., Liang, T., Loening, A., Vasanawala, S., Iagaru, A. 2024

  Abstract

  Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptors are both overexpressed in prostate cancer (PC) but may provide complementary information.68Ga-PSMA-R2 and 68Ga-NeoB (DOTA-p-aminomethylaniline-diglycolic acid-DPhe-Gln-Trp-Ala-Val-Gly-His-NH-CH[CH2-CH(CH3)2]2) are novel PET radiopharmaceuticals that were developed for theranostic use. In this phase II imaging study, we assessed the feasibility, safety, and diagnostic performance of 68Ga-NeoB and 68Ga-PSMA-R2 PET/MRI for detection of biochemically recurrent PC. Methods: We prospectively enrolled 27 men with suspected biochemically recurrent PC after initial treatment but noncontributory conventional imaging results (negative or equivocal findings on MRI, CT, and/or bone scan). Participants underwent 68Ga-NeoB and 68Ga-PSMA-R2 PET/MRI within 2 wk in noncontrolled order. The SUVmax of putative PC lesions was measured and compared with a composite reference standard (histopathology, follow-up imaging, prostate-specific antigen change). The SUVmax and SUVmean of background organs were measured. Vital signs were recorded before injection of the radiopharmaceuticals and after the scans. Adverse events were recorded up to 72 h after each scan. Results: The prostate-specific antigen level at enrollment was 3.5 ± 3.9 ng/mL (range, 0.3-13.5 ng/mL). 68Ga-NeoB PET/MRI detected 31 lesions in 18 patients (66.7%), whereas 68Ga-PSMA-R2 identified 20 lesions in 15 participants (55.6%). 68Ga-NeoB PET/MRI showed higher sensitivity (85.7% vs. 71.4%), accuracy (88.9% vs. 77.8%), and negative predictive value (66.7% vs. 50.0%) than 68Ga-PSMA-R2, whereas specificity and positive predictive value were equally high (100.0% for both). In 6 patients, 68Ga-NeoB PET/MRI identified 14 lesions that were false-negative on 68Ga-PSMA-R2 PET/MRI. The mean lesion SUVmax was 6.6 ± 3.2 (range, 2.9-13.2) for 68Ga-NeoB and 4.4 ± 1.5 (range, 2.6-8.8) for 68Ga-PSMA-R2 (P = 0.019). Overall lower uptake was noted in tumors and background organs for 68Ga-PSMA-R2. There were no significant changes in vital signs before and after the scans. No adverse events were reported in the 72-h period after scans. Conclusion: 68Ga-NeoB and 68Ga-PSMA-R2 are safe for diagnostic imaging. 68Ga-NeoB PET/MRI showed better diagnostic performance than 68Ga-PSMA-R2. 68Ga-PSMA-R2 showed overall lower uptake, equally in background organs and tumors, and might therefore not be an ideal theranostic compound. Further evaluation in larger cohorts is needed to confirm our preliminary data.

  View details for DOI 10.2967/jnumed.123.267017

  View details for PubMedID 38664016

• Same-day post-therapy imaging with a new generation whole-body digital SPECT/CT in assessing treatment response to [177Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer. European journal of nuclear medicine and molecular imaging Song, H., Leonio, M. I., Ferri, V., Duan, H., Aparici, C. M., Davidzon, G., Franc, B. L., Moradi, F., Shah, J., Bergstrom, C. P., Fan, A. C., Shah, S., Khaki, A. R., Srinivas, S., Iagaru, A. 2024

  Abstract

  PURPOSE: Lutetium-177 [177Lu]Lu-PSMA-617 radioligand therapy (RLT) represents a significant advancement for metastatic castration-resistant prostate cancer (mCRPC), demonstrating improvements in radiographic progression free survival (rPFS) and overall survival (OS) with a low rate of associated side effects. Currently, most post-therapy SPECT/CT is conducted at 24h after infusion. This study examines the clinical utility of a next-generation multi-detector Cadmium-Zinc-Telluride (CZT) SPECT/CT system (StarGuide) in same-day post-infusion assessment and early treatment response to [177Lu]Lu-PSMA-617.METHODS: In this retrospective study, 68 men with progressive mCRPC treated with [177Lu]Lu-PSMA-617 at our center from June 2022 to June 2023 were evaluated. Digital whole-body SPECT/CT imaging was performed after [177Lu]Lu-PSMA-617infusion (mean±SD: 1.8±0.6h, range 1.1-4.9h). Quantitative analysis of [177Lu]Lu-PSMA-617 positive lesions was performed in patients who underwent at least 2 post-therapy SPECT/CT, using liver parenchyma uptake as reference. Metrics including [177Lu]Lu-PSMA-617 positive total tumor volume (Lu-TTV), SUVmax and SUVmean were calculated. These quantitative metrics on post-infusion SPECT/CT images after cycles 1, 2 and 3 were correlated with overall survival (OS), prostate specific antigen-progression free survival (PSA-PFS) as defined by prostate cancer working group 3 (PCWG3), and PSA decrease over 50% (PSA50) response rates.RESULTS: 56 patients (means age 76.2±8.1 years, range: 60-93) who underwent at least 2 post-therapy SPECT/CT were included in the image analysis. The whole-body SPECT/CT scans (~12min per scan) were well tolerated, with 221 same-day scans performed (89%). At a median of 10-months follow-up, 33 (58.9%) patients achieved PSA50 after [177Lu]Lu-PSMA-617 treatment and median PSA-PFS was 5.0 months (range: 1.0-15 months) while median OS was not reached. Quantitative analysis of SPECT/CT images showed that 37 patients (66%) had>30% reduction in Lu-TTV, associated with significantly improved overall survival (median not reached vs. 6 months, P=0.008) and PSA-PFS (median 6 months vs. 1 months, P<0.001). However, changes in SUVmax or SUVmean did not correlate with PSA-PFS or OS.CONCLUSION: We successfully implemented same-day post-therapy SPECT/CT after [177Lu]Lu-PSMA-617 infusions. Quantitation of 1-2h post-therapy SPECT/CT images is a promising method for assessing treatment response. However, the approach is currently limited by its suboptimal detection of small tumor lesions and the necessity of incorporating a third-cycle SPECT/CT to mitigate the effects of any potential treatment-related flare-up. Further investigation in a larger patient cohort and prospective validation is essential to confirm these findings and to explore the role of SPECT/CT as a potential adjunct to PSMA PET/CT in managing mCRPC.

  View details for DOI 10.1007/s00259-024-06718-6

  View details for PubMedID 38635050

• 68Ga-RM2 PET-MRI versus MRI alone for evaluation of patients with biochemical recurrence of prostate cancer: a single-centre, single-arm, phase 2/3 imaging trial. The Lancet. Oncology Duan, H., Moradi, F., Davidzon, G. A., Liang, T., Song, H., Loening, A. M., Vasanawala, S., Srinivas, S., Brooks, J. D., Hancock, S., Iagaru, A. 2024

  Abstract

  National Comprehensive Cancer Network guidelines include prostate-specific membrane antigen (PSMA)-targeted PET for detection of biochemical recurrence of prostate cancer. However, targeting a single tumour characteristic might not be sufficient to reflect the full extent of disease. Gastrin releasing peptide receptors (GRPR) have been shown to be overexpressed in prostate cancer. In this study, we aimed to evaluate the diagnostic performance of the GRPR-targeting radiopharmaceutical 68Ga-RM2 in patients with biochemical recurrence of prostate cancer.This single-centre, single-arm, phase 2/3 trial was done at Stanford University (USA). Adult patients (aged ≥18 years) with biochemical recurrence of prostate cancer, a Karnofsky performance status of 50 or higher, increasing prostate-specific antigen concentration 0·2 ng/mL or more after prostatectomy or 2 ng/mL or more above nadir after radiotherapy, and non-contributory conventional imaging (negative CT or MRI, and bone scan) were eligible. All participants underwent 68Ga-RM2 PET-MRI. The primary outcome was the proportion of patients with PET-positive findings on 68Ga-RM2 PET-MRI compared with MRI alone after initial therapy, at a per-patient and per-lesion level. The primary outcome would be considered met if at least 30% of patients had one or more lesions detected by 68Ga-RM2 PET-MRI and the detection by 68Ga-RM2 PET-MRI was significantly greater than for MRI. Each PET scan was interpreted by three independent masked readers using a standardised evaluation criteria. This study is registered with ClinicalTrials.gov, NCT02624518, and is complete.Between Dec 12, 2015, and July 27, 2021, 209 men were screened for eligibility, of whom 100 were included in analyses. Median follow-up was 49·3 months (IQR 36·7-59·2). The primary endpoint was met; 68Ga-RM2 PET-MRI was positive in 69 (69%) patients and MRI alone was positive in 40 (40%) patients (p<0·0001). In the per-lesion analysis 68Ga-RM2 PET-MRI showed significantly higher detection rates than MRI alone (143 vs 96 lesions; p<0·0001). No grade 1 or worse events were reported.68Ga-RM2 PET-MRI showed better diagnostic performance than MRI alone in patients with biochemical recurrence of prostate cancer. Further prospective comparative studies with PSMA-targeted PET are needed to gain a better understanding of GRPR and PSMA expression patterns in these patients.The US Department of Defense.

  View details for DOI 10.1016/S1470-2045(24)00069-X

  View details for PubMedID 38423030

• Nuclear Medicine and Molecular Imaging Applications in Gynecologic Malignancies: A Comprehensive Review. Seminars in nuclear medicine Khessib, T., Jha, P., Davidzon, G. A., Iagaru, A., Shah, J. 2024

  Abstract

  Gynecologic malignancies, consisting of endometrial, cervical, ovarian, vulvar, and vaginal cancers, pose significant diagnostic and management challenges due to their complex anatomic location and potential for rapid progression. These tumors cause substantial morbidity and mortality, often because of their delayed diagnosis and treatment. An estimated 19% of newly diagnosed cancers among women are gynecologic in origin. In recent years, there has been growing evidence supporting the integration of nuclear medicine imaging modalities in the diagnostic work-up and management of gynecologic cancers. The sensitivity of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) combined with the anatomical specificity of computed tomography (CT) and magnetic resonance imaging (MRI) allows for the hybrid evaluation of metabolic activity and structural abnormalities that has become an indispensable tool in oncologic imaging. Lymphoscintigraphy, using technetium 99m (99mTc) based radiotracers along with single photon emission computed tomography/ computed tomography (SPECT/CT), holds a vital role in the identification of sentinel lymph nodes to minimize the surgical morbidity from extensive lymph node dissections. While not yet standard for gynecologic malignancies, promising therapeutic nuclear medicine agents serve as specialized treatment options for patients with advanced or recurrent disease. This article aims to provide a comprehensive review on the nuclear medicine applications in gynecologic malignancies through the following objectives: 1) To describe the role of nuclear medicine in the initial staging, lymph node mapping, response assessment, and recurrence/surveillance imaging of common gynecologic cancers, 2) To review the limitations of 18F-FDG PET/CT and promising applications of 18F-FDG PET/MRI in gynecologic malignancy, 3) To underscore the promising theragnostic applications of nuclear medicine, 4) To highlight the current role of nuclear medicine imaging in gynecologic cancers as per the National Comprehensive Cancer Network (NCCN), European Society of Surgical Oncology (ESGO), and European Society of Medical Oncology (ESMO) guidelines.

  View details for DOI 10.1053/j.semnuclmed.2024.01.003

  View details for PubMedID 38342655

• Reply to Perera Molligoda Arachchige AS [1] CLINICAL AND TRANSLATIONAL IMAGING Laudicella, R., Davidzon, G. A., Dimos, N., Provenzano, G., Iagaru, A., Bisdas, S. 2024; 12 (1): 109-110

  View details for DOI 10.1007/s40336-023-00597-x

  View details for Web of Science ID 001151700500009

• Total and anatomically contextualized quantitative <SUP>18</SUP>F-DCFPyL PET at biochemical recurrence to predict subsequent biochemical progression-free survival in patients with prostate cancer. Song, H., Anand, A., Sjostrand, K., Ferri, V., Duan, H., Shah, J., Moradi, F., Aparici, C., Franc, B., Davidzon, G., Bergstrom, C. P., Fan, A. C., Shah, S., Khaki, A., Srinivas, S., Iagaru, A. LIPPINCOTT WILLIAMS & WILKINS. 2024: 33

  View details for DOI 10.1200/JCO.2024.42.4_suppl.33

  View details for Web of Science ID 001266676900393

• Assessing the clinical utility of rapid post-therapy whole-body digital SPECT/CT in evaluating early treatment response of <SUP>177</SUP>Lu-PSMA-617 treatment. Leonio, M., Ferri, V., Duan, H., Shah, J., Moradi, F., Mari Aparici, C., Franc, B., Davidzon, G., Bergstrom, C. P., Fan, A. C., Shah, S., Khaki, A., Srinivas, S., Iagaru, A., Iagaru, A. LIPPINCOTT WILLIAMS & WILKINS. 2024: 32

  View details for DOI 10.1200/JCO.2024.42.4_suppl.32

  View details for Web of Science ID 001266676900643

• Turning brain MRI into diagnostic PET: 15O-water PET CBF synthesis from multi-contrast MRI via attention-based encoder-decoder networks. Medical image analysis Hussein, R., Shin, D., Zhao, M. Y., Guo, J., Davidzon, G., Steinberg, G., Moseley, M., Zaharchuk, G. 2023; 93: 103072

  Abstract

  Accurate quantification of cerebral blood flow (CBF) is essential for the diagnosis and assessment of a wide range of neurological diseases. Positron emission tomography (PET) with radiolabeled water (15O-water) is the gold-standard for the measurement of CBF in humans, however, it is not widely available due to its prohibitive costs and the use of short-lived radiopharmaceutical tracers that require onsite cyclotron production. Magnetic resonance imaging (MRI), in contrast, is more accessible and does not involve ionizing radiation. This study presents a convolutional encoder-decoder network with attention mechanisms to predict the gold-standard 15O-water PET CBF from multi-contrast MRI scans, thus eliminating the need for radioactive tracers. The model was trained and validated using 5-fold cross-validation in a group of 126 subjects consisting of healthy controls and cerebrovascular disease patients, all of whom underwent simultaneous 15O-water PET/MRI. The results demonstrate that the model can successfully synthesize high-quality PET CBF measurements (with an average SSIM of 0.924 and PSNR of 38.8 dB) and is more accurate compared to concurrent and previous PET synthesis methods. We also demonstrate the clinical significance of the proposed algorithm by evaluating the agreement for identifying the vascular territories with impaired CBF. Such methods may enable more widespread and accurate CBF evaluation in larger cohorts who cannot undergo PET imaging due to radiation concerns, lack of access, or logistic challenges.

  View details for DOI 10.1016/j.media.2023.103072

  View details for PubMedID 38176356

• Early-Frame [18F]Florbetaben PET/MRI for Cerebral Blood Flow Quantification in Patients with Cognitive Impairment: Comparison to an [15O]Water Gold Standard. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Fettahoglu, A., Zhao, M., Khalighi, M., Vossler, H., Jovin, M., Davidzon, G., Zeineh, M., Boada, F., Mormino, E., Henderson, V. W., Moseley, M., Chen, K. T., Zaharchuk, G. 2023

  Abstract

  Cerebral blood flow (CBF) may be estimated from early-frame PET imaging of lipophilic tracers, such as amyloid agents, enabling measurement of this important biomarker in participants with dementia and memory decline. Although previous methods could map relative CBF, quantitative measurement in absolute units (mL/100 g/min) remained challenging and has not been evaluated against the gold standard method of [15O]water PET. The purpose of this study was to develop and validate a minimally invasive quantitative CBF imaging method combining early [18F]florbetaben (eFBB) with phase-contrast MRI using simultaneous PET/MRI. Methods: Twenty participants (11 men and 9 women; 8 cognitively normal, 9 with mild cognitive impairment, and 3 with dementia; 10 β-amyloid negative and 10 β-amyloid positive; 69 ± 9 y old) underwent [15O]water PET, phase-contract MRI, and eFBB imaging in a single session on a 3-T PET/MRI scanner. Quantitative CBF images were created from the first 2 min of brain activity after [18F]florbetaben injection combined with phase-contrast MRI measurement of total brain blood flow. These maps were compared with [15O]water CBF using concordance correlation (CC) and Bland-Altman statistics for gray matter, white matter, and individual regions derived from the automated anatomic labeling (AAL) atlas. Results: The 2 methods showed similar results in gray matter ([15O]water, 55.2 ± 14.7 mL/100 g/min; eFBB, 55.9 ± 14.2 mL/100 g/min; difference, 0.7 ± 2.4 mL/100 g/min; P = 0.2) and white matter ([15O]water, 21.4 ± 5.6 mL/100 g/min; eFBB, 21.2 ± 5.3 mL/100 g/min; difference, -0.2 ± 1.0 mL/100 g/min; P = 0.4). The intrasubject CC for AAL-derived regions was high (0.91 ± 0.04). Intersubject CC in different AAL-derived regions was similarly high, ranging from 0.86 for midfrontal regions to 0.98 for temporal regions. There were no significant differences in performance between the methods in the amyloid-positive and amyloid-negative groups as well as participants with different cognitive statuses. Conclusion: We conclude that eFBB PET/MRI can provide robust CBF measurements, highlighting the capability of simultaneous PET/MRI to provide measurements of both CBF and amyloid burden in a single imaging session in participants with memory disorders.

  View details for DOI 10.2967/jnumed.123.266273

  View details for PubMedID 38071587

• Segmenting Cervical Arteries in Phase Contrast Magnetic Resonance Imaging Using Convolutional Encoder-Decoder Networks APPLIED SCIENCES-BASEL Campbell, B., Yadav, D., Hussein, R., Jovin, M., Hoover, S., Halbert, K., Holley, D., Khalighi, M., Davidzon, G. A., Tong, E., Steinberg, G. K., Moseley, M., Zhao, M. Y., Zaharchuk, G. 2023; 13 (21)

  View details for DOI 10.3390/app132111820

  View details for Web of Science ID 001100429200001

• Reply to Perera Molligoda Arachchige AS [1] CLINICAL AND TRANSLATIONAL IMAGING Laudicella, R., Davidzon, G. A., Dimos, N., Provenzano, G., Iagaru, A., Bisdas, S. 2023

  View details for DOI 10.1007/s40336-023-00597

  View details for Web of Science ID 001067805000001

• Final Analysis of a Prospective, Single-center, Phase II/III Imaging Trial of<SUP>68</SUP>Ga-RM2 PET/MRI in Patients with Biochemical Recurrence of Prostate Cancer Duan, H., Moradi, F., Davidzon, G. A., Liang, T., Song, H., Loening, A., Vasanawala, S., Srinivas, S., Brooks, J. D., Hancock, S. L., Iagaru, A. SPRINGER. 2023: S229

  View details for Web of Science ID 001084059701047

• Modified PROMISE Criteria for Standardized Interpretation of Gastrin Releasing Peptide Receptor (GRPR)-targeted PET Duan, H., Davidzon, G. A., Moradi, F., Liang, T., Song, H., Iagaru, A. SPRINGER. 2023: S542

  View details for Web of Science ID 001084059702325

• Generative Adversarial Network-Enhanced Ultra-Low-Dose [18F]-PI-2620 tau PET/MRI in Aging and Neurodegenerative Populations. AJNR. American journal of neuroradiology Chen, K. T., Tesfay, R., Koran, M. E., Ouyang, J., Shams, S., Young, C. B., Davidzon, G., Liang, T., Khalighi, M., Mormino, E., Zaharchuk, G. 2023

  Abstract

  BACKGROUND AND PURPOSE: With the utility of hybrid tau PET/MR imaging in the screening, diagnosis, and follow-up of individuals with neurodegenerative diseases, we investigated whether deep learning techniques can be used in enhancing ultra-low-dose [18F]-PI-2620 tau PET/MR images to produce diagnostic-quality images.MATERIALS AND METHODS: Forty-four healthy aging participants and patients with neurodegenerative diseases were recruited for this study, and [18F]-PI-2620 tau PET/MR data were simultaneously acquired. A generative adversarial network was trained to enhance ultra-low-dose tau images, which were reconstructed from a random sampling of 1/20 (approximately 5% of original count level) of the original full-dose data. MR images were also used as additional input channels. Region-based analyses as well as a reader study were conducted to assess the image quality of the enhanced images compared with their full-dose counterparts.RESULTS: The enhanced ultra-low-dose tau images showed apparent noise reduction compared with the ultra-low-dose images. The regional standard uptake value ratios showed that while, in general, there is an underestimation for both image types, especially in regions with higher uptake, when focusing on the healthy-but-amyloid-positive population (with relatively lower tau uptake), this bias was reduced in the enhanced ultra-low-dose images. The radiotracer uptake patterns in the enhanced images were read accurately compared with their full-dose counterparts.CONCLUSIONS: The clinical readings of deep learning-enhanced ultra-low-dose tau PET images were consistent with those performed with full-dose imaging, suggesting the possibility of reducing the dose and enabling more frequent examinations for dementia monitoring.

  View details for DOI 10.3174/ajnr.A7961

  View details for PubMedID 37591771

• Modified PROMISE criteria for standardized interpretation of gastrin-releasing peptide receptor (GRPR)-targeted PET. European journal of nuclear medicine and molecular imaging Duan, H., Davidzon, G. A., Moradi, F., Liang, T., Song, H., Iagaru, A. 2023

  Abstract

  There are image interpretation criteria to standardize reporting prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET). As up to 10% of prostate cancer (PC) do not express PSMA, other targets such as gastrin-releasing peptide receptor (GRPR) are evaluated. Research on GRPR-targeted imaging has been slowly increasing in usage at staging and biochemical recurrence (BCR) of PC. We therefore propose a modification of the Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria (mPROMISE) for GRPR-targeted PET.[68 Ga]Ga-RM2 PET data from initially prospective studies performed at our institution were retrospectively reviewed: 44 patients were imaged for staging and 100 patients for BCR PC. Two nuclear medicine physicians independently evaluated PET according to the mPROMISE criteria. A third expert reader served as standard reference. Interreader reliability was computed for GRPR expression, prostate bed (T), lymph node (N), skeleton (Mb), organ (Mc) metastases, and final judgment of the scan.The interrater reliability for GRPR PET at staging was moderate for GRPR expression (0.59; 95% confidence interval [CI] 0.40, 0.78), substantial for T-stage (0.78; 95% CI 0.63, 0.94), and almost perfect for N-stage (0.97; 95% CI 0.92, 1.00) and final judgment (0.92; 95% CI 0.82, 1.00). The interreader agreement at BCR showed substantial agreement for GRPR expression (0.70; 95% CI 0.59, 0.81) and final judgment (0.65; 95% CI 0.53, 0.78), while almost perfect agreement was seen across the major categories (T, N, Mb, Mc). Acceptable performance of the mPROMISE criteria was found for all subsets when compared to the standard reference.Interpreting GRPR-targeted PET using the mPROMISE criteria showed its reliability with substantial or almost perfect interrater agreement across all major categories. The proposed modification of the PROMISE criteria will aid clinicians in decreasing the level of uncertainty, and clinical trials to achieve uniform evaluation, reporting, and comparability of GRPR-targeted PET.Clinicaltrials.gov Identifier: NCT03113617 and NCT02624518.

  View details for DOI 10.1007/s00259-023-06385-z

  View details for PubMedID 37555901

  View details for PubMedCentralID 9635676

• Total and anatomically contextualized quantitative 18F-DCFPyL PET at biochemical recurrence to predict subsequent biochemical progression free survival in patients with prostate cancer Song, H., Sjostrand, K., Duan, H., Ferri, V., Aparici, C., Davidzon, G., Franc, B., Moradi, F., Anand, A., Iagaru, A. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772002474

• Predicting FDG-PET Images From Multi-Contrast MRI Using Deep Learning in Patients With Brain Neoplasms. Journal of magnetic resonance imaging : JMRI Ouyang, J., Chen, K. T., Duarte Armindo, R., Davidzon, G. A., Hawk, K. E., Moradi, F., Rosenberg, J., Lan, E., Zhang, H., Zaharchuk, G. 2023

  Abstract

  18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is valuable for determining presence of viable tumor, but is limited by geographical restrictions, radiation exposure, and high cost.To generate diagnostic-quality PET equivalent imaging for patients with brain neoplasms by deep learning with multi-contrast MRI.Retrospective.Patients (59 studies from 51 subjects; age 56 ± 13 years; 29 males) who underwent 18 F-FDG PET and MRI for determining recurrent brain tumor.3T; 3D GRE T1, 3D GRE T1c, 3D FSE T2-FLAIR, and 3D FSE ASL, 18 F-FDG PET imaging.Convolutional neural networks were trained using four MRIs as inputs and acquired FDG PET images as output. The agreement between the acquired and synthesized PET was evaluated by quality metrics and Bland-Altman plots for standardized uptake value ratio. Three physicians scored image quality on a 5-point scale, with score ≥3 as high-quality. They assessed the lesions on a 5-point scale, which was binarized to analyze diagnostic consistency of the synthesized PET compared to the acquired PET.The agreement in ratings between the acquired and synthesized PET were tested with Gwet's AC and exact Bowker test of symmetry. Agreement of the readers was assessed by Gwet's AC. P = 0.05 was used as the cutoff for statistical significance.The synthesized PET visually resembled the acquired PET and showed significant improvement in quality metrics (+21.7% on PSNR, +22.2% on SSIM, -31.8% on RSME) compared with ASL. A total of 49.7% of the synthesized PET were considered as high-quality compared to 73.4% of the acquired PET which was statistically significant, but with distinct variability between readers. For the positive/negative lesion assessment, the synthesized PET had an accuracy of 87% but had a tendency to overcall.The proposed deep learning model has the potential of synthesizing diagnostic quality FDG PET images without the use of radiotracers.3 TECHNICAL EFFICACY: Stage 2.

  View details for DOI 10.1002/jmri.28837

  View details for PubMedID 37259967

• Rapid dynamic reconstruction using list mode data for monitoring PET image quality accurately predicts final image noise and perceived quality Moradi, F., Khalighi, M., Su, K., Zhang, X., Wollenweber, S., Spangler-Bickell, M., Bharathi, P., Franc, B., Davidzon, G., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2023

  View details for Web of Science ID 001109210200126

• A Case-Based Primer on FDG PET/CT for Imaging Cardiovascular Infections: Protocol, Interpretation, and Pitfalls. Zhou, W., Moradi, F., Davidzon, G., Song, H., Grady, E., Nguyen, J., Franc, B., Aparici, C., Iagaru, A., Shah, J. SOC NUCLEAR MEDICINE INC. 2023

  View details for Web of Science ID 001109210201036

• Total and Anatomically Contextualized Quantitative 18F-DCFPyL PET at biochemical recurrence predicts subsequent biochemical progression free survival in prostate cancer patients Song, H., Duan, H., Ferri, V., Na, S., Davidzon, G., Franc, B., Aparici, C., Moradi, F., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2023

  View details for Web of Science ID 001109210201271

• Final Analysis of a Prospective, Single-center, Phase II/III Imaging Trial of 68Ga-RM2 PET/MRI in Patients with Biochemical Recurrence of Prostate Cancer Duan, H., Moradi, F., Davidzon, G., Liang, T., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2023

  View details for Web of Science ID 001109210201177

• Modified PROMISE Criteria for Standardized Interpretation of Gastrin Releasing Peptide Receptor (GRPR)-targeted PET Duan, H., Davidzon, G., Moradi, F., Liang, T., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2023

  View details for Web of Science ID 001109210201173

• ChatGPT in nuclear medicine and radiology: lights and shadows in the AI bionetwork CLINICAL AND TRANSLATIONAL IMAGING Laudicella, R., Davidzon, G. A., Dimos, N., Provenzano, G., Iagaru, A., Bisdas, S. 2023

  View details for DOI 10.1007/s40336-023-00574-4

  View details for Web of Science ID 000995015300001

• SPECT at the speed of PET: a feasibility study of CZT-based whole-body SPECT/CT in the post 177Lu-DOTATATE and 177Lu-PSMA617 setting. European journal of nuclear medicine and molecular imaging Song, H., Ferri, V., Duan, H., Aparici, C. M., Davidzon, G., Franc, B. L., Moradi, F., Nguyen, J., Shah, J., Iagaru, A. 2023

  Abstract

  To evaluate the feasibility of using the StarGuide (General Electric Healthcare, Haifa, Israel), a new generation multi-detector cadmium-zinc-telluride (CZT)-based SPECT/CT, for whole-body imaging in the setting of post-therapy imaging of 177Lu-labeled radiopharmaceuticals.Thirty-one patients (34-89 years old; mean ± SD, 65.5 ± 12.1) who were treated with either 177Lu-DOTATATE (n=17) or 177Lu-PSMA617 (n=14) as part of standard of care were scanned post-therapy with the StarGuide; some were also scanned with the standard GE Discovery 670 Pro SPECT/CT. All patients had either 64Cu-DOTATATE or 18F-DCFPyL PET/CT prior to first cycle of therapy for eligibility check. The detection/targeting rate (lesion uptake greater than blood pool uptake) of large lesions meeting RECIST 1.1 size criteria on post-therapy StarGuide SPECT/CT was evaluated and compared to the standard design GE Discovery 670 Pro SPECT/CT (when available) and pre-therapy PET by two nuclear medicine physicians with consensus read.This retrospective analysis identified a total of 50 post-therapy scans performed with the new imaging protocol from November 2021 to August 2022. The StarGuide system acquired vertex to mid-thighs post-therapy SPECT/CT scans with 4 bed positions, 3 min/bed and a total scan time of 12 min. In comparison, the standard GE Discovery 670 Pro SPECT/CT system typically acquires images in 2 bed positions covering the chest, abdomen, and pelvis with a total scan time of 32 min. The pre-therapy 64Cu-DOTATATE PET takes 20 min with 4 bed positions on GE Discovery MI PET/CT, and 18F-DCFPyL PET takes 8-10 min with 4-5 bed positions on GE Discovery MI PET/CT. This preliminary evaluation showed that the post-therapy scans acquired with faster scanning time using StarGuide system had comparable detection/targeting rate compared to the Discovery 670 Pro SPECT/CT system and detected large lesions defined by RECIST criteria on the pre-therapy PET scans.Fast acquisition of whole-body post-therapy SPECT/CT is feasible with the new StarGuide system. Short scanning time improves the patients' clinical experience and compliance which may lead to increased adoption of post-therapy SPECT. This opens the possibility to offer imaged-based treatment response assessment and personalized dosimetry to patients referred for targeted radionuclide therapies.

  View details for DOI 10.1007/s00259-023-06176-6

  View details for PubMedID 36869177

  View details for PubMedCentralID 6667427

• Reductions in synaptic marker SV2A in early-course Schizophrenia. Journal of psychiatric research Yoon, J. H., Zhang, Z., Mormino, E., Davidzon, G., Minzenberg, M. J., Ballon, J., Kalinowski, A., Hardy, K., Naganawa, M., Carson, R. E., Khalighi, M., Park, J. H., Levinson, D. F., Chin, F. T. 2023; 161: 213-217

  Abstract

  Excess synaptic pruning during neurodevelopment has emerged as one of the leading hypotheses on the causal mechanism for schizophrenia. It proposes that excess synaptic elimination occurs during development before the formal onset of illness. Accordingly, synaptic deficits may be observable at all stages of illnesses, including in the early phases. The availability of [11C]UCB-J, the first-in-human in vivo synaptic marker, represents an opportunity for testing this hypothesis with a relatively high level of precision. The first two published [11C]UCB-J schizophrenia studies have documented significant, widespread reductions in binding in chronic patients. The present study tested the hypothesis that reductions are present in early-course patients. 18 subjects completed [11C]UCB-J PET scans, (nine with schizophrenia, average duration of illness of 3.36 years, and nine demographically-matched healthy individuals). We compared binding levels, quantified as non-displaceable specific binding (BPND), in a set of a priori-specified brain regions of interest (ROIs). Eight ROIs (left and right hippocampus, right superior temporal and Heschl's gyrus, left and right putamen, and right caudal and rostral middle frontal gyrus) showed large reductions meeting Bonferroni corrected significant levels, p<0.0036. Exploratory, atlas-wide analyses confirmed widespread reductions in schizophrenia. We also observed significant positive correlations between binding levels and cognitive performance and a negative correlation with the severity of delusions. These results largely replicate findings from chronic patients, indicating that extensive [11C]UCB-J binding deficits are reliable and reproducible. Moreover, these results add to the growing evidence that excess synaptic pruning is a major disease mechanism for schizophrenia.

  View details for DOI 10.1016/j.jpsychires.2023.02.026

  View details for PubMedID 36934603

• A Pilot Study of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for Biopsy Guidance in Patients with Suspected Prostate Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Duan, H., Ghanouni, P., Daniel, B., Rosenberg, J., Thong, A., Kunder, C., Mari Aparici, C., Davidzon, G. A., Moradi, F., Sonn, G. A., Iagaru, A. 2022

  Abstract

  Purpose: Targeting of lesions seen on multiparametric MRI (mpMRI) improves prostate cancer (PC) detection at biopsy. However, 20-65% of highly suspicious lesions on mpMRI (PI-RADS 4 or 5) are false positives (FP), while 5-10% of clinically significant PC (csPC) are missed. Prostate specific membrane antigen (PSMA) and gastrin-releasing peptide receptors (GRPR) are both overexpressed in PC. We therefore aimed to evaluate the potential of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for biopsy guidance in patients with suspected PC. Methods: A highly selective cohort of 13 men, aged 58.0±7.1 years, with suspected PC (persistently high prostate-specific antigen [PSA] and PSA density) but negative or equivocal mpMRI and/or negative biopsy were prospectively enrolled to undergo 68Ga-PSMA11 and 68Ga-RM2 PET/MRI. PET/MRI included whole-body and dedicated pelvic imaging after a delay of 20 minutes. All patients had targeted biopsy of any lesions seen on PET followed by standard 12-core biopsy. Maximum standardized uptake values (SUVmax) of suspected PC lesions were collected and compared to gold standard biopsy. Results: PSA and PSA density at enrollment were 9.8±6.0 (1.5-25.5) ng/mL and 0.20±0.18 (0.06-0.68) ng/mL2, respectively. Standardized systematic biopsy revealed a total of 14 PC in 8 participants: 7 were csPC and 7 were non-clinically significant PC (ncsPC). 68Ga-PSMA11 identified 25 lesions, of which 11 (44%) were true positive (TP) (5 csPC). 68Ga-RM2 showed 27 lesions, of which 14 (52%) were TP, identifying all 7 csPC and also 7 ncsPC. There were 17 concordant lesions in 11 patients vs. 14 discordant lesions in 7 patients between 68Ga-PSMA11 and 68Ga-RM2 PET. Incongruent lesions had the highest rate of FP (12 FP vs. 2 TP). SUVmax was significantly higher for TP than FP lesions in delayed pelvic imaging for 68Ga-PSMA11 (6.49±4.14 vs. 4.05±1.55, P = 0.023) but not for whole-body images, nor for 68Ga-RM2. Conclusion: Our results show that 68Ga-PSMA11 and 68Ga-RM2 PET/MRI are feasible for biopsy guidance in suspected PC. Both radiopharmaceuticals detected additional clinically significant cancers not seen on mpMRI in this selective cohort. 68Ga-RM2 PET/MRI identified all csPC confirmed at biopsy.

  View details for DOI 10.2967/jnumed.122.264448

  View details for PubMedID 36396456

• Performance of a fully-automated Lumipulse plasma phospho-tau181 assay for Alzheimer's disease. Alzheimer's research & therapy Wilson, E. N., Young, C. B., Ramos Benitez, J., Swarovski, M. S., Feinstein, I., Vandijck, M., Le Guen, Y., Kasireddy, N. M., Shahid, M., Corso, N. K., Wang, Q., Kennedy, G., Trelle, A. N., Lind, B., Channappa, D., Belnap, M., Ramirez, V., Skylar-Scott, I., Younes, K., Yutsis, M. V., Le Bastard, N., Quinn, J. F., van Dyck, C. H., Nairn, A., Fredericks, C. A., Tian, L., Kerchner, G. A., Montine, T. J., Sha, S. J., Davidzon, G., Henderson, V. W., Longo, F. M., Greicius, M. D., Wagner, A. D., Wyss-Coray, T., Poston, K. L., Mormino, E. C., Andreasson, K. I. 2022; 14 (1): 172

  Abstract

  BACKGROUND: The recent promise of disease-modifying therapies for Alzheimer's disease (AD) has reinforced the need for accurate biomarkers for early disease detection, diagnosis and treatment monitoring. Advances in the development of novel blood-based biomarkers for AD have revealed that plasma levels of tau phosphorylated at various residues are specific and sensitive to AD dementia. However, the currently available tests have shortcomings in access, throughput, and scalability that limit widespread implementation.METHODS: We evaluated the diagnostic and prognostic performance of a high-throughput and fully-automated Lumipulse plasma p-tau181 assay for the detection of AD. Plasma from older clinically unimpaired individuals (CU, n = 463) and patients with mild cognitive impairment (MCI, n = 107) or AD dementia (n = 78) were obtained from the longitudinal Stanford University Alzheimer's Disease Research Center (ADRC) and the Stanford Aging and Memory Study (SAMS) cohorts. We evaluated the discriminative accuracy of plasma p-tau181 for clinical AD diagnosis, association with amyloid beta peptides and p-tau181 concentrations in CSF, association with amyloid positron emission tomography (PET), and ability to predict longitudinal cognitive and functional change.RESULTS: The assay showed robust performance in differentiating AD from control participants (AUC 0.959, CI: 0.912 to 0.990), and was strongly associated with CSF p-tau181, CSF Abeta42/Abeta40 ratio, and amyloid-PET global SUVRs. Associations between plasma p-tau181 with CSF biomarkers were significant when examined separately in Abeta+ and Abeta- groups. Plasma p-tau181 significantly increased over time in CU and AD diagnostic groups. After controlling for clinical diagnosis, age, sex, and education, baseline plasma p-tau181 predicted change in MoCA overall and change in CDR Sum of Boxes in the AD group over follow-up of up to 5 years.CONCLUSIONS: This fully-automated and available blood-based biomarker assay therefore may be useful for early detection, diagnosis, prognosis, and treatment monitoring of AD.

  View details for DOI 10.1186/s13195-022-01116-2

  View details for PubMedID 36371232

• A Pilot Study of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for Evaluation of Prostate Cancer Response to High Intensity Focused Ultrasound (HIFU) Therapy. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Duan, H., Ghanouni, P., Daniel, B., Rosenberg, J., Davidzon, G. A., Mari Aparici, C., Kunder, C., Sonn, G., Iagaru, A. 2022

  Abstract

  Rationale: Focal therapy for localized prostate cancer (PC) using high intensity focused ultrasound (HIFU) is gaining in popularity as it is non-invasive and associated with fewer side effects than standard whole-gland treatments. However, better methods to evaluate response to HIFU ablation are an unmet need. Prostate specific membrane antigen (PSMA) and gastrin-releasing peptide receptors (GRPR) are both overexpressed in PC. In this study, we evaluated a novel approach of using both 68Ga-RM2 and 68Ga-PSMA11 PET/MRI in each patient before and after HIFU to assess accuracy of target tumor localization and response to treatment. Methods: Fourteen men, 64.5 ± 8.0 (range 48-78) years-old, with newly diagnosed PC were prospectively enrolled. Pre-HIFU, patients underwent prostate biopsy, multiparametric MRI (mpMRI), 68Ga-PSMA11, and 68Ga-RM2 PET/MRI. Response to treatment was assessed at a minimum of 6 months after HIFU with prostate biopsy (n = 13), as well as 68Ga-PSMA11 and 68Ga-RM2 PET/MRI (n = 14). Maximum and peak standardized uptake values (SUVmax and SUVpeak) of known or suspected PC lesions were collected. Results: Pre-HIFU biopsy revealed 18 cancers of which 14 were clinically significant (Gleason score ≥3+4). mpMRI identified 18 lesions; 14 of them were ≥PI-RADS 4. 68Ga-PSMA11 and 68Ga-RM2 PET/MRI each showed 23 positive intraprostatic lesions; 21 were congruent in 13 patients and five were incongruent in 5 patients. Pre-HIFU, 68Ga-PSMA11 identified all target tumors while 68Ga-RM2 PET/MRI missed two tumors. Post-HIFU, 68Ga-RM2 and 68Ga-PSMA11 PET/MRI both identified clinically significant residual disease in one patient. Three significant ipsilateral recurrent lesions were identified, whereas one was missed by 68Ga-PSMA11. Pre-treatment prostate specific antigen (PSA) decreased significantly after HIFU by 66%. Concordantly, pre-treatment SUVmax decreased significantly after HIFU for 68Ga-PSMA11 (P = 0.001) and 68Ga-RM2 (P = 0.005). Conclusion: The results of this pilot study show that 68Ga-PSMA11 and 68Ga-RM2 PET/MRI identified the target tumor for HIFU in 100% and 86%, respectively, and accurately verified response to treatment. PET might be a useful tool in the guidance and monitoring of treatment success in patients receiving focal therapy for PC. These preliminary findings warrant larger studies for validation.

  View details for DOI 10.2967/jnumed.122.264783

  View details for PubMedID 36328488

• Modified PROMISE Criteria for Standardized Interpretation of GRPR-targeted PET Duan, H., Davidzon, G. A., Moradi, F., Liang, T., Iagaru, A. SPRINGER. 2022: S288

  View details for Web of Science ID 000857046600603

• Head-to-head Comparison of a Conventional or CZT-based SPECT/CT with a Next Generation Multidetector CZT-based SPECT/CT System Duan, H., Ferri, V., Castaneda, P., Visser, T., Luong, K., Davidzon, G. A., Aparici, C., Iagaru, A. SPRINGER. 2022: S263

  View details for Web of Science ID 000857046600550

• A Pilot Study of Ga-68-PSMA11 and 68Ga-RM2 PET/MRI for Biopsy Guidance in Patients with Suspected Prostate Cancer Duan, H., Ghanouni, P., Daniel, B., Rosenberg, J., Thong, A., Sonn, G. A., Kunder, C., Davidzon, G. A., Aparici, C., Moradi, F., Iagaru, A. SPRINGER. 2022: S484

  View details for Web of Science ID 000857046602091

• A Pilot Study of Ga-68-PSMA11 and Ga-68-RM2 PET/MRI for Evaluation of Prostate Cancer Response to High Intensity Focused Ultrasound (HIFU) Therapy Duan, H., Ghanouni, P., Daniel, B., Rosenberg, J., Davidzon, G. A., Aparici, C., Thong, A., Sonn, G. A., Kunder, C., Iagaru, A. SPRINGER. 2022: S497-S498

  View details for Web of Science ID 000857046602123

• Hong Song, Heying Duan, Caitlyn Harrison, Kip Guja, Negin Hatami, Judy Nguyen, Benjamin Franc, Farshad Moradi, Carina Mari Aparici, Guido Davidzon, Sandy Srinivas and Andrei lagaru Song, H., Duan, H., Harrison, C., Guja, K., Hatami, N., Nguyen, J., Franc, B., Moradi, F., Aparici, C., Davidzon, G., Srinivas, S., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2022

  View details for Web of Science ID 000893739700240

• Results of First Interim Analysis of 68Ga-NeoB and 68Ga-PSMA R2 PET/MRI in Patients with Biochemically Recurrent Prostate Cancer Duan, H., Song, H., Davidzon, G., Moradi, F., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2022

  View details for Web of Science ID 000893739700242

• Correlation of 68Ga-RM2 PET with Post-Surgery Histopathology Findings in Patients with Newly Diagnosed Intermediate- or High-Risk Prostate Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Duan, H., Baratto, L., Fan, R. E., Soerensen, S. J., Liang, T., Chung, B. I., Thong, A. E., Gill, H., Kunder, C., Stoyanova, T., Rusu, M., Loening, A. M., Ghanouni, P., Davidzon, G. A., Moradi, F., Sonn, G. A., Iagaru, A. 2022

  Abstract

  Rationale: 68Ga-RM2 targets gastrin-releasing peptide receptors (GRPR), which are overexpressed in prostate cancer (PC). Here, we compared pre-operative 68Ga-RM2 PET to post-surgery histopathology in patients with newly diagnosed intermediate- or high-risk PC. Methods: Forty-one men, 64.0+/-6.7-year-old, were prospectively enrolled. PET images were acquired 42 - 72 (median+/-SD 52.5+/-6.5) minutes after injection of 118.4 - 247.9 (median+/-SD 138.0+/-22.2)MBq of 68Ga-RM2. PET findings were compared to pre-operative mpMRI (n = 36) and 68Ga-PSMA11 PET (n = 17) and correlated to post-prostatectomy whole-mount histopathology (n = 32) and time to biochemical recurrence. Nine participants decided to undergo radiation therapy after study enrollment. Results: All participants had intermediate (n = 17) or high-risk (n = 24) PC and were scheduled for prostatectomy. Prostate specific antigen (PSA) was 8.8+/-77.4 (range 2.5 - 504) ng/mL, and 7.6+/-5.3 (range 2.5 - 28.0) ng/mL when excluding participants who ultimately underwent radiation treatment. Pre-operative 68Ga-RM2 PET identified 70 intraprostatic foci of uptake in 40/41 patients. Post-prostatectomy histopathology was available in 32 patients in which 68Ga-RM2 PET identified 50/54 intraprostatic lesions (detection rate = 93%). 68Ga-RM2 uptake was recorded in 19 non-enlarged pelvic lymph nodes in 6 patients. Pathology confirmed lymph node metastases in 16 lesions, and follow-up imaging confirmed nodal metastases in 2 lesions. 68Ga-PSMA11 and 68Ga-RM2 PET identified 27 and 26 intraprostatic lesions, respectively, and 5 pelvic lymph nodes each in 17 patients. Concordance between 68Ga-RM2 and 68Ga-PSMA11 PET was found in 18 prostatic lesions in 11 patients, and 4 lymph nodes in 2 patients. Non-congruent findings were observed in 6 patients (intraprostatic lesions in 4 patients and nodal lesions in 2 patients). Both 68Ga-RM2 and 68Ga-PSMA11 had higher sensitivity and accuracy rates with 98%, 89%, and 95%, 89%, respectively, compared to mpMRI at 77% and 77%. Specificity was highest for mpMRI with 75% followed by 68Ga-PSMA11 (67%), and 68Ga-RM2 (65%). Conclusion: 68Ga-RM2 PET accurately detects intermediate- and high-risk primary PC with a detection rate of 93%. In addition, it showed significantly higher specificity and accuracy compared to mpMRI and similar performance to 68Ga-PSMA11 PET. These findings need to be confirmed in larger studies to identify which patients will benefit from one or the other or both radiopharmaceuticals.

  View details for DOI 10.2967/jnumed.122.263971

  View details for PubMedID 35552245

• 68Ga-PSMA-11 PET/MRI in patients with newly diagnosed intermediate or high-risk prostate adenocarcinoma: PET findings correlate with outcomes after definitive treatment. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Moradi, F., Duan, H., Song, H., Davidzon, G. A., Chung, B. I., Thong, A. E., Loening, A. M., Ghanouni, P., Sonn, G., Iagaru, A. 2022

  Abstract

  Prostate-specific membrane antigen (PSMA) PET offers superior accuracy to other imaging modalities in initial staging of prostate cancer and is more likely to affect management. We examined the prognostic value of 68Ga-PSMA-11 uptake in primary lesion and presence of metastatic disease on PET in newly diagnosed prostate cancer patients prior to initial therapy. Methods: In a prospective study from April 2016 to December 2020, 68Ga-PSMA-11 PET/MRI was done in men with new diagnosis of intermediate or high-grade prostate cancer who were candidates for prostatectomy. Patients were followed up after initial therapy for up to 5 years. We examined the Kendall correlation between PET (intense uptake in primary lesion and presence of metastatic disease) and clinical and pathologic findings (grade group, extraprostatic extension, nodal involvement) relevant for risk stratification, and examined the relationship between PET findings and outcome using Kaplan-Meier analysis. Results: Seventy-three men, 64.0±6.3 years of age were imaged. Seventy-two had focal uptake in prostate and in 20 (27%), PSMA-avid metastatic disease was identified. Uptake correlated with grade group and prostate-specific antigen (PSA). Presence of PSMA metastasis correlated with grade group and pathologic nodal stage. PSMA PET had higher per-patients positivity than nodal dissection in patients with only 5-15 nodes removed (8/41 vs. 3/41) but lower positivity if more than 15 nodes were removed (13/21 vs. 10/21). High uptake in primary (SUVmax>12.5, P = .008) and presence of PSMA metastasis (P = .013) were associated with biochemical failure, and corresponding hazard ratios for recurrence within 2-years (4.93 and 3.95, respectively) were similar or higher than other clinicopathologic prognostic factors. Conclusions: 68Ga-PSMA-11 PET can risk stratify patients with intermediate or high-grade prostate cancer prior to prostatectomy based on degree of uptake in prostate and presence of metastatic disease.

  View details for DOI 10.2967/jnumed.122.263897

  View details for PubMedID 35512996

• Evaluation of Liver and Renal Toxicity in Peptide Receptor Radionuclide Therapy for Somatostatin Receptor Expressing Tumors: A 2-Year Follow-Up. The oncologist Duan, H., Ferri, V., Fisher, G. A., Shaheen, S., Davidzon, G. A., Iagaru, A., Mari Aparici, C. 2022

  Abstract

  Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin receptor (SSR) analogs is now an established systemic treatment for neuroendocrine tumors (NET). However, more short- and long-term data about renal and hepatotoxicity is needed. Here we present our experience in this clinical scenario.Eighty-six patients with progressive SSR-expressing malignancies underwent PRRT with Lu-177 Dotatate and were followed up for up to 2 years. Laboratory tests were done 1 week before each cycle and every 2 months at follow-up. Hepatic and renal toxicity was determined based on NCI CTCAE V5.0.55/86 (64%) patients completed all 4 cycles of PRRT; 18/86 (20.9%) are currently being treated; 13/86 (15.1%) had to discontinue PRRT: 4/13 (31%) due to hematologic toxicity, 9/13 (69%) due to non-PRRT-related comorbidities. Out of the patients who finished treatment, only transient grade 2 toxicities were observed during PRRT: hypoalbuminemia in 5.5% (3/55), and renal toxicity (serum creatinine and estimated glomerular filtration rate) in 1.8% (1/55). No grade 3 or 4 liver and renal toxicity occurred. Patients presenting with impaired liver or renal function prior to PRRT, either improved or had stable findings. No deterioration was observed.Peptide receptor radionuclide therapy does not have a negative impact on liver and renal function, even in patients with pre-existing impaired parameters. No grade 3 or 4 hepatic or renal toxicity was identified. Only transient grade 2 hypoalbuminemia in 5.5% and nephrotoxicity in 1.8% of patients were seen during PRRT.

  View details for DOI 10.1093/oncolo/oyab072

  View details for PubMedID 35641196

• Evaluation of Liver and Renal Toxicity in Peptide Receptor Radionuclide Therapy for Somatostatin Receptor Expressing Tumors: A 2-Year Follow-Up ONCOLOGIST Duan, H., Ferri, V., Fisher, G., Shaheen, S., Davidzon, G., Iagaru, A., Aparici, C. 2022

  View details for DOI 10.1093/oncolo/oyab072

  View details for Web of Science ID 000769640100001

• Peptide Receptor Radionuclide Therapy (PRRT) in Advanced Pheochromocytoma and Paraganglioma From a Single Institution Experience Duan, H., Ferri, V., Fisher, G. A., Shaheen, S., Davidzon, G. A., Moradi, F., Nguyen, J., Franc, B. L., Iagaru, A., Aparici, C. LIPPINCOTT WILLIAMS & WILKINS. 2022: E42-E43

  View details for Web of Science ID 000819123700057

• Evaluation of interim Dotatate-PET after two cycles of Peptide Receptor Radionuclide Therapy (PRRT) in neuroendocrine tumors (NET) Duan, H., Song, H., Ferri, Fisher, G., Shaheen, S., Shah, J., Nguyen, J., Moradi, F., Davidzon, G., Franc, B., Iagaru, A., Mari, A. C. WILEY. 2022: 141

  View details for Web of Science ID 000779149500128

• Phenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders. Biomedicines Napolioni, V., Fredericks, C. A., Kim, Y., Channappa, D., Khan, R. R., Kim, L. H., Zafar, F., Couthouis, J., Davidzon, G. A., Mormino, E. C., Gitler, A. D., Montine, T. J., Schule, B., Greicius, M. D. 1800; 10 (1)

  Abstract

  We describe the clinical and neuropathologic features of patients with Lewy body spectrum disorder (LBSD) carrying a nonsense variant, c.604C>T; p.R202X, in the glucocerebrosidase 1 (GBA) gene. While this GBA variant is causative for Gaucher's disease, the pathogenic role of this mutation in LBSD is unclear. Detailed neuropathologic evaluation was performed for one index case and a structured literature review of other GBA p.R202X carriers was conducted. Through the systematic literature search, we identified three additional reported subjects carrying the same GBA mutation, including one Parkinson's disease (PD) patient with early disease onset, one case with neuropathologically-verified LBSD, and one unaffected relative of a Gaucher's disease patient. Among the affected subjects carrying the GBA p.R202X, all males were diagnosed with Lewy body dementia, while the two females presented as PD. The clinical penetrance of GBA p.R202X in LBSD patients and families argues strongly for a pathogenic role for this variant, although presenting with a striking phenotypic heterogeneity of clinical and pathological features.

  View details for DOI 10.3390/biomedicines10010160

  View details for PubMedID 35052839

• Multi-tracer PET Imaging Using Deep Learning: Applications in Patients with High-Grade Gliomas Wardak, M., Hooper, S. M., Schiepers, C., Chen, W., Aparici, C., Davidzon, G. A., Vermesh, O., Cloughesy, T. F., Huang, S., Gambhir, S., Rekik, Adeli, E., Park, S. H., Cintas, C. SPRINGER INTERNATIONAL PUBLISHING AG. 2022: 24-35

  View details for DOI 10.1007/978-3-031-16919-9_3

  View details for Web of Science ID 000867616800003

• Multi-task Deep Learning for Cerebrovascular Disease Classification and MRI-to-PET Translation Hussein, R., Zhao, M. Y., Shin, D., Guo, J., Chen, K. T., Armindo, R. D., Davidzon, G., Moseley, M., Zaharchuk, G., IEEE IEEE. 2022: 4306-4312

  View details for DOI 10.1109/ICPR56361.2022.9956549

  View details for Web of Science ID 000897707604044

• 68Ga-PSMA11 PET/CT for biochemically recurrent prostate cancer: Influence of dual-time and PMT- vs SiPM-based detectors. Translational oncology Duan, H., Baratto, L., Hatami, N., Liang, T., Mari Aparici, C., Davidzon, G. A., Iagaru, A. 2021; 15 (1): 101293

  Abstract

  OBJECTIVES: 68Ga-PSMA11 PET/CT is excellent for evaluating biochemically recurrent prostate cancer (BCR PC). Here, we compared the positivity rates of dual-time point imaging using a PET/CT scanner (DMI) with silicon photomultiplier (SiPM) detectors and a PET/CT scanner (D690) with photomultiplier tubes (PMT), in patients with BCR PC.METHODS: Fifty-eight patients were prospectively recruited and randomized to receive scans on DMI followed by D690 or vice-versa. Images from DMI were reconstructed using the block sequential regularized expectation maximization (BSREM) algorithm and images from D690 were reconstructed using ordered subset expectation maximization (OSEM), according to the vendor's recommendations. Two readers independently reviewed all images in randomized order, recorded the number and location of lesions, as well as standardized uptake value (SUV) measurements.RESULTS: Twenty-eight patients (group A) had DMI as first scanner followed by D690, while 30 patients (group B) underwent scans in reversed order. Mean PSA was 30±112.9 (range 0.3-600.66)ng/mL for group A and 41.5±213.2 (range 0.21-1170) ng/mL for group B (P=0.796). The positivity rate in group A was 78.6% (22/28 patients) vs. 73.3% (22/30 patients) in group B. Although the performance of the two scanners was equivalent on a per-patient basis, DMI identified 5 additional sites of suspected recurrent disease when used as first scanner. The second scan time point did not reveal additional abnormal uptake.CONCLUSIONS: The delayed time point in 68Ga-PSMA11 PET/CT did not show a higher positivity rate. SiPM-based PET/CT identified additional lesions. Further studies with larger cohorts are needed to confirm these results.

  View details for DOI 10.1016/j.tranon.2021.101293

  View details for PubMedID 34823095

• Six Recurrent Amyloid-Related Imaging Abnormality Episodes in a Patient Treated With Aducanumab. JAMA neurology Hall, J. N., Mormino, E., Ng, A., Boumis, A., Gaudioso, J. L., Davidzon, G. A., Sha, S. J. 2021

  View details for DOI 10.1001/jamaneurol.2021.3933

  View details for PubMedID 34747986

• Author Correction: Low-count whole-body PET with deep learning in a multicenter and externally validated study. NPJ digital medicine Chaudhari, A. S., Mittra, E., Davidzon, G. A., Gulaka, P., Gandhi, H., Brown, A., Zhang, T., Srinivas, S., Gong, E., Zaharchuk, G., Jadvar, H. 2021; 4 (1): 139

  View details for DOI 10.1038/s41746-021-00512-6

  View details for PubMedID 34521985

• A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2 Induced Glycolytic Reprogramming in Glioblastoma. Clinical cancer research : an official journal of the American Association for Cancer Research Beinat, C., Patel, C. B., Haywood, T., Murty, S., Naya, L., Castillo, J. B., Reyes, S. T., Phillips, M., Buccino, P., Shen, B., Park, J. H., Koran, M. E., Alam, I. S., James, M. L., Holley, D., Halbert, K., Gandhi, H., He, J. Q., Granucci, M., Johnson, E., Liu, D. D., Uchida, N., Sinha, R., Chu, P., Born, D. E., Warnock, G. I., Weissman, I., Hayden Gephart, M., Khalighi, M. M., Massoud, T. F., Iagaru, A., Davidzon, G., Thomas, R., Nagpal, S., Recht, L. D., Gambhir, S. S. 2021

  Abstract

  PURPOSE: Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key process of cancer metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in healthy brain. We describe the development, validation, and translation of a novel positron emission tomography (PET) tracer to study PKM2 in GBM. We evaluated 1-((2-fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in cell culture, mouse models of GBM, healthy human volunteers, and GBM patients.EXPERIMENTAL DESIGN: [18F]DASA-23 was synthesized with a molar activity of 100.47 {plus minus} 29.58 GBq/mol and radiochemical purity >95%. We performed initial testing of [18F]DASA-23 in GBM cell culture and human GBM xenografts implanted orthotopically into mice. Next we produced [18F]DASA-23 under FDA oversight, and evaluated it in healthy volunteers, and a pilot cohort of glioma patients.RESULTS: In mouse imaging studies, [18F]DASA-23 clearly delineated the U87 GBM from surrounding healthy brain tissue and had a tumor-to-brain ratio (TBR) of 3.6 {plus minus} 0.5. In human volunteers, [18F]DASA-23 crossed the intact blood-brain barrier and was rapidly cleared. In GBM patients, [18F]DASA-23 successfully outlined tumors visible on contrast-enhanced magnetic resonance imaging (MRI). The uptake of [18F]DASA-23 was markedly elevated in GBMs compared to normal brain, and it identified a metabolic non-responder within 1-week of treatment initiation.CONCLUSIONS: We developed and translated [18F]DASA-23 as a new tracer that demonstrated the visualization of aberrantly expressed PKM2 for the first time in human subjects. These results warrant further clinical evaluation of [18F]DASA-23 to assess its utility for imaging therapy-induced normalization of aberrant cancer metabolism.

  View details for DOI 10.1158/1078-0432.CCR-21-0544

  View details for PubMedID 34475101

• A Pilot Study of Ga-68-PSMA11 and Ga-68-RM2 PET/MRI for Evaluation of Prostate Cancer Response to High Intensity Focused Ultrasound (HIFU) Therapy Duan, H., Ghanouni, P., Hatami, N., Davidzon, G. A., Aparici, C., Thong, A., Sonn, G. A., Iagaru, A. SPRINGER. 2021: S205-S206

  View details for Web of Science ID 000709355000336

• PROSPECTIVE EVALUATION OF F-18-DCFPYL PET/CT IN BIOCHEMICALLY RECURRENT PROSTATE CANCER: ANALYSIS OF F-18-DCFPYL UPTAKE IN POSSIBLE EXTRA-PELVIC OLIGOMETASTASES Song, H., Nguyen, J., Moradi, F., Aparici, C., Franc, B., Davidzon, G., Iagaru, A. LIPPINCOTT WILLIAMS & WILKINS. 2021: E1177-E1178

  View details for Web of Science ID 000693689000847

• PROSPECTIVE STUDY OF (68)GA-RM2 PET/MRI IN PATIENTS WITH BIOCHEMICALLY RECURRENT PROSTATE CANCER AND NEGATIVE CONVENTIONAL IMAGING Baratto, L., Song, H., Duan, H., Moradi, F., Davidzon, G., Iagaru, A. LIPPINCOTT WILLIAMS & WILKINS. 2021: E1178

  View details for Web of Science ID 000693689000848

• A Pilot Study of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for Biopsy Guidance in Patients with Suspected Prostate Cancer Duan, H., Ferri, V., Ghanouni, P., Daniel, B., Hatami, N., Davidzon, G. A., Aparici, C., Thong, A., Sonn, G. A., Iagaru, A. SPRINGER. 2021: S204

  View details for Web of Science ID 000709355000333

• Low-count whole-body PET with deep learning in a multicenter and externally validated study. NPJ digital medicine Chaudhari, A. S., Mittra, E., Davidzon, G. A., Gulaka, P., Gandhi, H., Brown, A., Zhang, T., Srinivas, S., Gong, E., Zaharchuk, G., Jadvar, H. 2021; 4 (1): 127

  Abstract

  More widespread use of positron emission tomography (PET) imaging is limited by its high cost and radiation dose. Reductions in PET scan time or radiotracer dosage typically degrade diagnostic image quality (DIQ). Deep-learning-based reconstruction may improve DIQ, but such methods have not been clinically evaluated in a realistic multicenter, multivendor environment. In this study, we evaluated the performance and generalizability of a deep-learning-based image-quality enhancement algorithm applied to fourfold reduced-count whole-body PET in a realistic clinical oncologic imaging environment with multiple blinded readers, institutions, and scanner types. We demonstrate that the low-count-enhanced scans were noninferior to the standard scans in DIQ (p<0.05) and overall diagnostic confidence (p<0.001) independent of the underlying PET scanner used. Lesion detection for the low-count-enhanced scans had a high patient-level sensitivity of 0.94 (0.83-0.99) and specificity of 0.98 (0.95-0.99). Interscan kappa agreement of 0.85 was comparable to intrareader (0.88) and pairwise inter-reader agreements (maximum of 0.72). SUV quantification was comparable in the reference regions and lesions (lowest p-value=0.59) and had high correlation (lowest CCC=0.94). Thus, we demonstrated that deep learning can be used to restore diagnostic image quality and maintain SUV accuracy for fourfold reduced-count PET scans, with interscan variations in lesion depiction, lower than intra- and interreader variations. This method generalized to an external validation set of clinical patients from multiple institutions and scanner types. Overall, this method may enable either dose or exam-duration reduction, increasing safety and lowering the cost of PET imaging.

  View details for DOI 10.1038/s41746-021-00497-2

  View details for PubMedID 34426629

• Results of a Prospective Trial to Compare 68Ga-DOTA-TATE with SiPM-Based PET/CT vs. Conventional PET/CT in Patients with Neuroendocrine Tumors. Diagnostics (Basel, Switzerland) Baratto, L., Toriihara, A., Hatami, N., Aparici, C. M., Davidzon, G., Levin, C. S., Iagaru, A. 2021; 11 (6)

  Abstract

  We prospectively enrolled patients with neuroendocrine tumors (NETs). They underwent a single 68Ga-DOTA-TATE injection followed by dual imaging and were randomly scanned using first either the conventional or the silicon photomultiplier (SiPM) positron emission tomography/computed tomography (PET/CT), followed by imaging using the other system. A total of 94 patients, 44 men and 50 women, between 35 and 91 years old (mean ± SD: 63 ± 11.2), were enrolled. Fifty-two out of ninety-four participants underwent SiPM PET/CT first and a total of 162 lesions were detected using both scanners. Forty-two out of ninety-four participants underwent conventional PET/CT first and a total of 108 lesions were detected using both scanners. Regardless of whether SiPM-based PET/CT was used first or second, maximum standardized uptake value (SUVmax) of lesions measured on SiPM was on average 20% higher when comparing two scanners with all enrolled patients, and the difference was statistically significant. SiPM-based PET/CT detected 19 more lesions in 13 patients compared with conventional PET/CT. No lesions were only identified by conventional PET/CT. In conclusion, we observed higher SUVmax for lesions measured from SiPM PET/CT compared with conventional PET/CT regardless of the order of the scans. SiPM PET/CT allowed for identification of more lesions than conventional PET/CT. While delayed imaging can lead to higher SUVmax in cancer lesions, in the series of lesions identified when SiPM PET/CT was used first, this was not the case; therefore, the data suggest superior performance of the SiPM PET/CT scanner in visualizing and quantifying lesions.

  View details for DOI 10.3390/diagnostics11060992

  View details for PubMedID 34070751

• Initial Clinical Evaluation of [F-18]DASA-23, a PET Imaging Tracer for Evaluation of Aberrantly Expressed Pyruvate Kinase M2 in Glioblastoma Beinat, C., Patel, C., Haywood, T., Naya, L., Castillo, J., Shen, B., Massoud, T., Iagaru, A., Davidzon, G., Recht, L., Gambhir, S. SOC NUCLEAR MEDICINE INC. 2021

  View details for Web of Science ID 000713713600098

• Perfusion Only Scans with and without SPECT/CT in the Era of COVID-19 Zhang, R., Moradi, F., Aparici, C., Davidzon, G., Nguyen, J., Iagaru, A., Franc, B. SOC NUCLEAR MEDICINE INC. 2021

  View details for Web of Science ID 000713713600506

• A Pilot Study of68Ga-PSMA11 PET/MRI and68GaRM2 PET/MRI for Biopsy Guidance in Patients with Suspected Prostate Cancer Duan, H., Ferri, V., Ghanouni, P., Daniel, B., Hatami, N., Davidzon, G., Aparici, C., Moradi, F., Thong, A., Sonn, G., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2021

  View details for Web of Science ID 000713713600481

• PSMA- and GRPR-targeted PET: Results from 50 Patients with Biochemically Recurrent Prostate Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Baratto, L., Song, H., Duan, H., Hatami, N., Bagshaw, H., Buyyounouski, M., Hancock, S., Shah, S. A., Srinivas, S., Swift, P., Moradi, F., Davidzon, G. A., Iagaru, A. 2021

  Abstract

  Rationale: Novel radiopharmaceuticals for positron emission tomography (PET) are evaluated for the diagnosis of biochemically recurrent prostate cancer (BCR PC). Here, we compare the gastrin releasing peptide receptors (GRPR) - targeting 68Ga-RM2 with the prostate specific membrane antigen (PSMA) - targeting 68Ga-PSMA11 and 18F-DCFPyL. Methods: Fifty patients had both 68Ga-RM2 PET/MRI and 68Ga-PSMA11 PET/CT (n = 23) or 18F-DCFPyL PET/CT (n = 27) at an interval ranging from 1 to 60 days (mean±SD: 15.8±17.7). Maximum standardized uptake values (SUVmax) were collected for all lesions. Results: RM2 PET was positive in 35 and negative in 15 of the 50 patients. PSMA PET was positive in 37 and negative in 13 of the 50 patients. Both scans detected 70 lesions in 32 patients. Forty-three lesions in 18 patients were identified only on one scan: 68Ga-RM2 detected 7 more lesions in 4 patients, while PSMA detected 36 more lesions in 13 patients. Conclusion: 68Ga-RM2 remains a valuable radiopharmaceutical even when compared with the more widely used 68Ga-PSMA11/18F-DCFPyL in the evaluation of BCR PC. Larger studies are needed to verify that identifying patients for whom these two classes of radiopharmaceuticals are complementary may ultimately allow for personalized medicine.

  View details for DOI 10.2967/jnumed.120.259630

  View details for PubMedID 33674398

• Artificial Intelligence for Optimization and Interpretation of PET/CT and PET/MR Images. Seminars in nuclear medicine Zaharchuk, G., Davidzon, G. 2021; 51 (2): 134–42

  Abstract

  Artificial intelligence (AI) has recently attracted much attention for its potential use in healthcare applications. The use of AI to improve and extract more information out of medical images, given their parallels with natural images and the immense progress in the area of computer vision, has been at the forefront of these advances. This is due to a convergence of factors, including the increasing numbers of scans performed, the availability of open source AI tools, and decreases in the costs of hardware required to implement these technologies. In this article, we review the progress in the use of AI toward optimizing PET/CT and PET/MRI studies. These two methods, which combine molecular information with structural and (in the case of MRI) functional imaging, are extremely valuable for a wide range of clinical indications. They are also tremendously data-rich modalities and as such are highly amenable to data-driven technologies such as AI. The first half of the article will focus on methods to improve PET reconstruction and image quality, which has multiple benefits including faster image acquisition, image reconstruction, and lower or even "zero" radiation dose imaging. It will also address the value of AI-driven methods to perform MR-based attenuation correction. The second half will address how some of these advances can be used to perform to optimize diagnosis from the acquired images, with examples given for whole-body oncology, cardiology, and neurology indications. Overall, it is likely that the use of AI will markedly improve both the quality and safety of PET/CT and PET/MRI as well as enhance our ability to interpret the scans and follow lesions over time. This will hopefully lead to expanded clinical use cases for these valuable technologies leading to better patient care.

  View details for DOI 10.1053/j.semnuclmed.2020.10.001

  View details for PubMedID 33509370

• Single Institution Experience With Peptide Receptor Radionuclide Therapy (PRRT) in Neuroendocrine Tumors (NET) Duan, H., Ferri, V., Kunz, P., Davidzon, G., Nguyen, J., Moradi, F., Franc, B., Iagaru, A., Aparici, C. LIPPINCOTT WILLIAMS & WILKINS. 2021: 456

  View details for Web of Science ID 000655285500090

• Renal and Hepatotoxicity of Peptide Receptor Radionuclide Therapy (PRRT) - A Single Institution Experience Duan, H., Ferri, V., Kunz, P., Davidzon, G., Nguyen, J., Moradi, F., Franc, B., Iagaru, A., Aparici, C. LIPPINCOTT WILLIAMS & WILKINS. 2021: 456-457

  View details for Web of Science ID 000655285500093

• Hematotoxicity of Peptide Receptor Radionuclide Therapy (PRRT) - A Single Institution Experience Duan, H., Ferri, V., Kunz, P., Davidzon, G., Moradi, F., Nguyen, J., Franc, B., Iagaru, A., Aparici, C. LIPPINCOTT WILLIAMS & WILKINS. 2021: 456

  View details for Web of Science ID 000655285500092

• Hematotoxicity of Peptide Receptor Radionuclide Therapy (PRRT) - A Single Institution Experience Duan, H., Ferri, V., Kunz, P., Davidzon, G., Moradi, F., Nguyen, J., Franc, B., Iagaru, A., Aparici, C. LIPPINCOTT WILLIAMS & WILKINS. 2021: 456

  View details for Web of Science ID 000639230600092

• Single Institution Experience With Peptide Receptor Radionuclide Therapy (PRRT) in Neuroendocrine Tumors (NET) Duan, H., Ferri, V., Kunz, P., Davidzon, G., Nguyen, J., Moradi, F., Franc, B., Iagaru, A., Aparici, C. LIPPINCOTT WILLIAMS & WILKINS. 2021: 456

  View details for Web of Science ID 000639230600090

• Renal and Hepatotoxicity of Peptide Receptor Radionuclide Therapy (PRRT) - A Single Institution Experience Duan, H., Ferri, V., Kunz, P., Davidzon, G., Nguyen, J., Moradi, F., Franc, B., Iagaru, A., Aparici, C. LIPPINCOTT WILLIAMS & WILKINS. 2021: 456-457

  View details for Web of Science ID 000639230600093

• Diagnostic Performance of 18F-DCFPyL-PET/CT in Men with Biochemically Recurrent Prostate Cancer: Results from the CONDOR Phase 3, Multicenter Study. Clinical cancer research : an official journal of the American Association for Cancer Research Morris, M. J., Rowe, S. P., Gorin, M. A., Saperstein, L., Pouliot, F., Josephson, D. Y., Wong, J. Y., Pantel, A. R., Cho, S. Y., Gage, K. L., Piert, M. R., Iagaru, A., Pollard, J. H., Wong, V., Jensen, J., Lin, T., Stambler, N., Carroll, P., Siegel, B. A., Wibmer, A. G., Durack, J. C., Solomon, S. B., Harb, R., Pucar, D., Sprenkle, P., Beauregard, J., Beaulieu, A., Buteau, F., Yamauchi, D., Glaser, S., Dorff, T. B., Narayan, V., Fillare, M. A., Schubert, E., Cooley, G., Morris, Z. S., Langeland, M., Pow-Sang, J. M., Yamoah, K., Alva, A. S., Reichert, Z., Spratt, D., Davidzon, G., Mari Aparici, C., Moradi, F., Tracy, C., Behr, S., Nguyen, H. G., Simko, J. P., Jennings, J. W., Michalski, J. M., Pachynski, R. K. 2021

  Abstract

  PURPOSE: Current FDA-approved imaging modalities are inadequate for localizing prostate cancer biochemical recurrence (BCR). 18F-DCFPyL is a highly selective, small-molecule PSMA-targeted PET radiotracer. CONDOR was a prospective study designed to determine the performance of 18F-DCFPyL-PET/CT in patients with BCR and uninformative standard imaging.METHODS: Men with rising PSA {greater than or equal to}0.2 ng/mL after prostatectomy or {greater than or equal to}2 ng/mL above nadir after radiation therapy were eligible. The primary endpoint was correct localization rate (CLR) defined as positive predictive value with an additional requirement of anatomic lesion co-localization between 18F-DCFPyL-PET/CT and a composite standard of truth (SOT). The SOT consisted of, in descending priority: 1) histopathology, 2) subsequent correlative imaging findings, or 3) post-radiation PSA response. The trial was considered a success if the lower bound of the 95% confidence interval for CLR exceeded 20% for 2 of 3 18F‑DCFPyL-PET/CT readers. Secondary endpoints included change in intended management and safety.RESULTS: 208 men with a median baseline PSA of 0.8 ng/mL (range: 0.2-98.4 ng/mL) underwent 18F-DCFPyL-PET/CT. The CLR was 84.8%-87.0% (lower bound of 95% CI: 77.8%-80.4%). 63.9% of evaluable patients had a change in intended management after 18F-DCFPyL-PET/CT. The disease detection rate was 59% to 66% (at least one lesion detected per patient by 18F-DCFPyL-PET/CT by central readers).CONCLUSION: Performance of 18F-DCFPyL-PET/CT achieved the study's primary endpoint, demonstrating disease localization in the setting of negative standard imaging and providing clinically meaningful and actionable information. These data further support the utility of 18F-DCFPyL-PET/CT to localize disease in men with recurrent prostate cancer.

  View details for DOI 10.1158/1078-0432.CCR-20-4573

  View details for PubMedID 33622706

• Prognostic value of bone marrow metabolism on pretreatment 18F-FDG PET/CT in patients with metastatic melanoma treated with anti-PD-1 therapy. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Nakamoto, R., Zaba, L. C., Liang, T., Reddy, S. A., Davidzon, G., Aparici, C. M., Nguyen, J., Moradi, F., Iagaru, A., Franc, B. L. 2021

  Abstract

  Purpose: To investigate the prognostic value of 18F-FDG PET/CT parameters in melanoma patients before beginning anti-PD-1 therapy. Methods: Imaging parameters including SUVmax, metabolic tumor volume (MTV), and bone marrow to liver SUVmean ratio (BLR) were measured from baseline PET/CT in 92 patients before the start of anti-PD-1 therapy. Association with survival and imaging parameters combined with clinical factors was evaluated. Clinical and laboratory data between high (> median) and low (≤ median) BLR groups were compared. Results: Multivariate analyses demonstrated that BLR was an independent prognostic factor for PFS and OS (P = 0.017, P = 0.011, respectively). The high BLR group had higher levels of white blood cell count/neutrophil count and C-Reactive Protein than the low BLR group (P < 0.05). Conclusion: Patients with high BLR were associated with poor PFS and OS, potentially explained by evidence of systemic inflammation known to be associated with immunosuppression.

  View details for DOI 10.2967/jnumed.120.254482

  View details for PubMedID 33547210

• A single institution experience with peptide receptor radionuclide therapy (PRRT) in non-midgut neuroendocrine tumors (NETs) Duan, H., Ferri, Fisher, G., Shaheen, S., Davidzon, G., Moradi, F., Nguyen, J., Franc, B., Iagaru, A., Mari, A. C. WILEY. 2021: 181

  View details for Web of Science ID 000620738200168

• A single institution experience with peptide receptor radionuclide therapy (PRRT) in advanced pheochromocytoma and paraganglioma Duan, H., Ferri, Fisher, G., Shaheen, S., Davidzon, G., Moradi, F., Nguyen, J., Franc, B., Iagaru, A., Mari, A. C. WILEY. 2021: 180

  View details for Web of Science ID 000620738200167

• Multi-task weak supervision enables anatomically-resolved abnormality detection in whole-body FDG-PET/CT. Nature communications Eyuboglu, S., Angus, G., Patel, B. N., Pareek, A., Davidzon, G., Long, J., Dunnmon, J., Lungren, M. P. 2021; 12 (1): 1880

  Abstract

  Computational decision support systems could provide clinical value in whole-body FDG-PET/CT workflows. However, limited availability of labeled data combined with the large size of PET/CT imaging exams make it challenging to apply existing supervised machine learning systems. Leveraging recent advancements in natural language processing, we describe a weak supervision framework that extracts imperfect, yet highly granular, regional abnormality labels from free-text radiology reports. Our framework automatically labels each region in a custom ontology of anatomical regions, providing a structured profile of the pathologies in each imaging exam. Using these generated labels, we then train an attention-based, multi-task CNN architecture to detect and estimate the location of abnormalities in whole-body scans. We demonstrate empirically that our multi-task representation is critical for strong performance on rare abnormalities with limited training data. The representation also contributes to more accurate mortality prediction from imaging data, suggesting the potential utility of our framework beyond abnormality detection and location estimation.

  View details for DOI 10.1038/s41467-021-22018-1

  View details for PubMedID 33767174

• Increasing Diversity in Radiology and Molecular Imaging: Current Challenges. Molecular imaging and biology Fite, B. Z., Hinostroza, V. n., States, L. n., Hicks-Nelson, A. n., Baratto, L. n., Kallianos, K. n., Codari, M. n., Yu, B. n., Jha, P. n., Shams, M. n., Stoyanova, T. n., Chapelin, F. F., Liu, A. n., Rashidi, A. n., Soto, F. n., Quintana, Y. n., Davidzon, G. A., Marycz, K. n., Gibbs, I. C., Chonde, D. B., Patel, C. B., Daldrup-Link, H. E. 2021

  Abstract

  This paper summarizes the 2020 Diversity in Radiology and Molecular Imaging: What We Need to Know Conference, a three-day virtual conference held September 9-11, 2020. The World Molecular Imaging Society (WMIS) and Stanford University jointly organized this event to provide a forum for WMIS members and affiliates worldwide to openly discuss issues pertaining to diversity in science, technology, engineering, and mathematics (STEM). The participants discussed three main conference themes, "racial diversity in STEM," "women in STEM," and "global health," which were discussed through seven plenary lectures, twelve scientific presentations, and nine roundtable discussions, respectively. Breakout sessions were designed to flip the classroom and seek input from attendees on important topics such as increasing the representation of underrepresented minority (URM) members and women in STEM, generating pipeline programs in the fields of molecular imaging, supporting existing URM and women members in their career pursuits, developing mechanisms to effectively address microaggressions, providing leadership opportunities for URM and women STEM members, improving global health research, and developing strategies to advance culturally competent healthcare.

  View details for DOI 10.1007/s11307-021-01610-3

  View details for PubMedID 33903986

• True ultra-low-dose amyloid PET/MRI enhanced with deep learning for clinical interpretation. European journal of nuclear medicine and molecular imaging Chen, K. T., Toueg, T. N., Koran, M. E., Davidzon, G. n., Zeineh, M. n., Holley, D. n., Gandhi, H. n., Halbert, K. n., Boumis, A. n., Kennedy, G. n., Mormino, E. n., Khalighi, M. n., Zaharchuk, G. n. 2021

  Abstract

  While sampled or short-frame realizations have shown the potential power of deep learning to reduce radiation dose for PET images, evidence in true injected ultra-low-dose cases is lacking. Therefore, we evaluated deep learning enhancement using a significantly reduced injected radiotracer protocol for amyloid PET/MRI.Eighteen participants underwent two separate 18F-florbetaben PET/MRI studies in which an ultra-low-dose (6.64 ± 3.57 MBq, 2.2 ± 1.3% of standard) or a standard-dose (300 ± 14 MBq) was injected. The PET counts from the standard-dose list-mode data were also undersampled to approximate an ultra-low-dose session. A pre-trained convolutional neural network was fine-tuned using MR images and either the injected or sampled ultra-low-dose PET as inputs. Image quality of the enhanced images was evaluated using three metrics (peak signal-to-noise ratio, structural similarity, and root mean square error), as well as the coefficient of variation (CV) for regional standard uptake value ratios (SUVRs). Mean cerebral uptake was correlated across image types to assess the validity of the sampled realizations. To judge clinical performance, four trained readers scored image quality on a five-point scale (using 15% non-inferiority limits for proportion of studies rated 3 or better) and classified cases into amyloid-positive and negative studies.The deep learning-enhanced PET images showed marked improvement on all quality metrics compared with the low-dose images as well as having generally similar regional CVs as the standard-dose. All enhanced images were non-inferior to their standard-dose counterparts. Accuracy for amyloid status was high (97.2% and 91.7% for images enhanced from injected and sampled ultra-low-dose data, respectively) which was similar to intra-reader reproducibility of standard-dose images (98.6%).Deep learning methods can synthesize diagnostic-quality PET images from ultra-low injected dose simultaneous PET/MRI data, demonstrating the general validity of sampled realizations and the potential to reduce dose significantly for amyloid imaging.

  View details for DOI 10.1007/s00259-020-05151-9

  View details for PubMedID 33416955

• Association of CSF Biomarkers with Hippocampal-dependent Memory in Preclinical Alzheimer Disease. Neurology Trelle, A. N., Carr, V. A., Wilson, E. N., Swarovski, M. S., Hunt, M. P., Toueg, T. N., Tran, T. T., Channappa, D. n., Corso, N. K., Thieu, M. K., Jayakumar, M. n., Nadiadwala, A. n., Guo, W. n., Tanner, N. J., Bernstein, J. D., Litovsky, C. P., Guerin, S. A., Khazenzon, A. M., Harrison, M. B., Rutt, B. K., Deutsch, G. K., Chin, F. T., Davidzon, G. A., Hall, J. N., Sha, S. J., Fredericks, C. A., Andreasson, K. I., Kerchner, G. A., Wagner, A. D., Mormino, E. C. 2021

  Abstract

  To determine if memory tasks with demonstrated sensitivity to hippocampal function can detect variance related to preclinical Alzheimer's disease (AD) biomarkers, we examined associations between performance in three memory tasks and CSF Aβ42/Aβ40 and p-tau181 in cognitively unimpaired older adults (CU).CU enrolled in the Stanford Aging and Memory Study (N=153; age 68.78 ± 5.81 yrs; 94 female) completed a lumbar puncture and memory assessments. CSF Aβ42, Aβ40, and phosopho-tau181 (p-tau181) were measured with the automated Lumipulse G system in a single-batch analysis. Episodic memory was assayed using a standardized delayed recall composite, paired associate (word-picture) cued recall, and a mnemonic discrimination task that involves discrimination between studied 'target' objects, novel 'foil' objects, and perceptually similar 'lure' objects. Analyses examined cross-sectional relationships between memory performance, age, and CSF measures, controlling for sex and education.Age and lower Aβ42/Aβ40 were independently associated with elevated p-tau181. Age, Aβ42/Aβ40, and p-tau181 were each associated with a) poorer associative memory and b) diminished improvement in mnemonic discrimination performance across levels of decreased task difficulty (i.e., target-lure similarity). P-tau mediated the effect of Aβ42/Aβ40 on memory. Relationships between CSF proteins and delayed recall were similar but non-significant. CSF Aβ42 was not significantly associated with p-tau181 or memory.Tests designed to tax hippocampal function are sensitive to subtle individual differences in memory among CU, and correlate with early AD-associated biomarker changes in CSF. These tests may offer utility for identifying cognitively unimpaired older adults with preclinical AD pathology.

  View details for DOI 10.1212/WNL.0000000000011477

  View details for PubMedID 33408146

• The Clinical Utility of 18F-Fluciclovine PET/CT in Biochemically Recurrent Prostate Cancer: an Academic Center Experience Post FDA Approval. Molecular imaging and biology Nakamoto, R. n., Harrison, C. n., Song, H. n., Guja, K. E., Hatami, N. n., Nguyen, J. n., Moradi, F. n., Franc, B. L., Aparici, C. M., Davidzon, G. n., Iagaru, A. n. 2021

  Abstract

  To evaluate the diagnostic performance and clinical utility of 18F-fluciclovine PET/CT in patients with biochemical recurrence (BCR) of prostate cancer (PC).18F-Fluciclovine scans of 165 consecutive men with BCR after primary definitive treatment with prostatectomy (n = 102) or radiotherapy (n = 63) were retrospectively evaluated. Seventy patients had concurrent imaging with at least one other conventional modality (CT (n = 31), MRI (n = 31), or bone scan (n = 26)). Findings from 18F-fluciclovine PET were compared with those from conventional imaging modalities. The positivity rate and impact of 18F-fluciclovine PET on patient management were recorded. In 33 patients who underwent at least one other PET imaging (18F-NaF PET/CT (n = 12), 68Ga-PSMA11 PET/CT (n = 5), 18F-DCFPyL PET/CT (n = 20), and 68Ga-RM2 PET/MRI (n = 5)), additional findings were evaluated.The overall positivity rate of 18F-fluciclovine PET was 67 %, which, as expected, increased with higher prostate-specific antigen (PSA) levels (ng/ml): 15 % (PSA < 0.5), 50 % (0.5 ≤ PSA < 1), 56 % (1 ≤ PSA < 2), 68 % (2 ≤ PSA < 5), and 94 % (PSA ≥ 5), respectively. One hundred and two patients (62 %) had changes in clinical management based on 18F-fluciclovine PET findings. Twelve of these patients (12 %) had lesion localization on 18F-fluciclovine PET, despite negative conventional imaging. Treatment plans of 14 patients with negative 18F-fluciclovine PET were changed based on additional PET imaging with a different radiopharmaceutical.18F-Fluciclovine PET/CT remains a useful diagnostic tool in the workup of patients with BCR PC, changing clinical management in 62 % of participants in our cohort.

  View details for DOI 10.1007/s11307-021-01583-3

  View details for PubMedID 33469884

• Obituary for Sanjiv Sam Gambhir, MD, PhD. Clinical nuclear medicine Davidzon, G., Franc, B., Mari Aparici, C., Moradi, F., Nguyen, J., Iagaru, A. 2020

  View details for DOI 10.1097/RLU.0000000000003284

  View details for PubMedID 32956118

• Peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors (NET): A single institution experience in the USA Duan, H., Ferri, V., Kunz, P. L., Fisher, G. A., Moradi, F., Davidzon, G. A., Franc, B. L., Iagaru, A. H., Mari, C. SPRINGER. 2020: S468–S469

  View details for Web of Science ID 000577424101134

• Prospective Single Institution Study of F18-DCFPyL PET/CT in Biochemically Recurrent Prostate Cancer: An Analysis of Lesions Detection and Localization Iagaru, A., Song, H., Duan, H., Harrison, C., Guja, K., Hatami, N., Franc, B., Nguyen, J., Moradi, F., Mari, C., Davidzon, G. SPRINGER. 2020: S171

  View details for Web of Science ID 000577424100299

• Evaluation of toxicity in peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors (NET) Duan, H., Ferri, V., Kunz, P. L., Fisher, G. A., Moradi, F., Davidzon, G. A., Franc, B. L., Iagaru, A. H., Mari, C. SPRINGER. 2020: S471–S472

  View details for Web of Science ID 000577424101140

• Imaging Characteristics and Diagnostic Performance of 2-deoxy-2-[18F]fluoro-D-Glucose PET/CT for Melanoma Patients Who Demonstrate Hyperprogressive Disease When Treated with Immunotherapy. Molecular imaging and biology Nakamoto, R., C Zaba, L., Rosenberg, J., Arani Reddy, S., W Nobashi, T., Ferri, V., Davidzon, G., Mari Aparici, C., Nguyen, J., Moradi, F., Iagaru, A., Lewis Franc, B. 2020

  Abstract

  PURPOSE: We investigated the ability of baseline 2-deoxy-2-[18F]fluoro-D-glucose PET/CT parameters, acquired before the start of immunotherapy, to predict development of hyperprogressive disease (HPD) in melanoma patients. We also evaluated the diagnostic performances of ratios of baseline and first restaging PET/CT parameters to diagnose HPD without information of the tumor growth kinetic ratio (TGKR) that requires pre-baseline imaging before baseline imaging (3 timepoint imaging).PROCEDURES: Seventy-six patients who underwent PET/CT before and approximately 3months following initiation of immunotherapy were included. PET/CT parameters, including metabolic tumor volume (MTV) for all melanoma lesions and total measured tumor burden (TMTB) based on irRECIST, were measured from baseline PET/CT (MTVbase and TMTBbase) and first restaging PET/CT (MTVpost and TMTBpost). The ratios of MTV (MTVpost/MTVbase, MTVr) and TMTB (TMTBpost/TMTBbase, TMTBr) were calculated.RESULTS: MTVbase of HPD patients (n=9, TGKR ≥2) was larger than that of non-HPD (n=67, TGKR <2) patients (P<0.05), and HPD patients demonstrated shorter median overall survival (7 vs. more than 60months, P<0.05). The area under the curve (AUC) of MTVbase (≥155.5ml) to predict the risk of HPD was 0.703, with a sensitivity of 66.7% and specificity of 81.2%. The AUCs of MTVr (≥1.25) and TMTBr (≥1.27) to diagnose HPD without information of TGKR were 0.875 and 0.977 with both sensitivities of 100%, and specificities of 79% and 83.9%, respectively.CONCLUSIONS: Patients at high risk of developing HPD could not be accurately identified based on baseline PET/CT parameters. The ratios of baseline and first restaging PET/CT parameters may be helpful to diagnose HPD, when patients do not undergo pre-baseline imaging.

  View details for DOI 10.1007/s11307-020-01526-4

  View details for PubMedID 32789649

• Application of Deep Learning to Predict Standardized Uptake Value Ratio and Amyloid Status on 18F-Florbetapir PET Using ADNI Data. AJNR. American journal of neuroradiology Reith, F., Koran, M. E., Davidzon, G., Zaharchuk, G., Alzheimers Disease Neuroimaging Initiative 2020

  Abstract

  BACKGROUND AND PURPOSE: Cortical amyloid quantification on PET by using the standardized uptake value ratio is valuable for research studies and clinical trials in Alzheimer disease. However, it is resource intensive, requiring co-registered MR imaging data and specialized segmentation software. We investigated the use of deep learning to automatically quantify standardized uptake value ratio and used this for classification.MATERIALS AND METHODS: Using the Alzheimer's Disease Neuroimaging Initiative dataset, we identified 2582 18F-florbetapir PET scans, which were separated into positive and negative cases by using a standardized uptake value ratio threshold of 1.1. We trained convolutional neural networks (ResNet-50 and ResNet-152) to predict standardized uptake value ratio and classify amyloid status. We assessed performance based on network depth, number of PET input slices, and use of ImageNet pretraining. We also assessed human performance with 3 readers in a subset of 100 randomly selected cases.RESULTS: We have found that 48% of cases were amyloid positive. The best performance was seen for ResNet-50 by using regression before classification, 3 input PET slices, and pretraining, with a standardized uptake value ratio root-mean-square error of 0.054, corresponding to 95.1% correct amyloid status prediction. Using more than 3 slices did not improve performance, but ImageNet initialization did. The best trained network was more accurate than humans (96% versus a mean of 88%, respectively).CONCLUSIONS: Deep learning algorithms can estimate standardized uptake value ratio and use this to classify 18F-florbetapir PET scans. Such methods have promise to automate this laborious calculation, enabling quantitative measurements rapidly and in settings without extensive image processing manpower and expertise.

  View details for DOI 10.3174/ajnr.A6573

  View details for PubMedID 32499247

• A prospective study of Ga-68-RM2 PET/MRI in patients with biochemically recurrent prostate cancer and negative conventional imaging. Baratto, L., Song, H., Duan, H., Aparici, C., Davidzon, G., Moradi, F., Srinivas, S., Iagaru, A. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000560368306300

• Prospective evaluation of F-18-DCFPyL PET/CT in biochemically recurrent prostate cancer: Analysis of lesion localization and distribution. Song, H., Duan, H., Harrison, C., Guja, K., Hatami, N., Franc, B., Moradi, F., Aparici, C., Davidzon, G., Srinivas, S., Iagaru, A. AMER SOC CLINICAL ONCOLOGY. 2020

  View details for Web of Science ID 000560368302399

• Visual Read Protocols for Clinicians Analyzing 18F-PI-2620 tau PET/MRI Images Koran, M., Shams, S., Adams, P., Toueg, T., Azevedo, C., Hall, J., Corso, N., Sha, S., Fredericks, C., Greicius, M., Wagner, A., Zaharchuk, G., Davidzon, G., Chin, F., Mormino, E. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290501466

• Toxicity identification and evaluation of peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors (NETs) Duan, H., Girod, B., Ninatti, G., Ferri, V., Kunz, P., Fisher, G., Moradi, F., Davidzon, G., Franc, B., Iagaru, A., Aparici, C. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290501378

• Extrahepatic Ga-68-DOTATATE-Avid Tumor Volume and serum Chromogranin A Predict Short-Term Outcome of Lu-177-DOTATATE in Late-Stage Metastatic Gastroenteropancreatic Neuroendocrine Tumors Song, H., Kunz, P., Franc, B., Moradi, F., Fisher, G., Aparici, C., Iagaru, A., Davidzon, G. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290500275

• A pilot study of F-18-FSPG SiPM-based PET/CT in patients referred for exclusion of active cardiac sarcoidosis and negative or non-diagnostic F-18-FDG PET/CT Duan, H., Hatami, N., Baratto, L., Davidzon, G., Aparici, C., Gambhir, S., Koglin, N., Witteles, R., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290501539

• Ga-68-RM2 PET/CT in Patients with Newly Diagnosed Intermediate- or High-Risk Prostate Cancer Baratto, L., Duan, H., Hatami, N., Aparici, C., Davidzon, G., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290501196

• Ga-68-PSMA-11 PET/MR Imaging before prostatectomy: correlation with surgical pathology and two-year follow up Moradi, F., Baratto, L., Duan, H., Hatami, N., Davidzon, G., Sonn, G., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290500168

• PSMA-and GRPR-targeted PET: Preliminary Results in Patients with Biochemically Recurrent Prostate Cancer Baratto, L., Duan, H., Hatami, N., Song, H., Davidzon, G., Franc, B., Aparici, C., Moradi, F., Nguyen, J., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290501184

• Prognostic value of volumetric PET parameters at early response evaluation in melanoma patients treated with immunotherapy Nakamoto, R., Zaba, L., Rosenberg, J., Reddy, S., Nobashi, T., Davidzon, G., Aparici, C., Nguyen, J., Moradi, F., Iagaru, A., Franc, B. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290500428

• Imaging characteristics and diagnostic performance of F-18-FDG PET/CT for melanoma patients who demonstrate hyperprogressive disease when treated with immunotherapy Nakamoto, R., Zaba, L., Rosenberg, J., Reddy, S., Nobashi, T., Davidzon, G., Aparici, C., Nguyen, J., Moradi, F., Iagaru, A., Franc, B. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290500424

• INTERIM ANALYSIS RESULTS OF A PROSPECTIVE STUDY OF (68)GA-RM2 PET/MRI IN PATIENTS WITH BIOCHEMICALLY RECURRENT PROSTATE CANCER AND NEGATIVE CONVENTIONAL IMAGING Baratto, L., Song, H., Duan, H., Aparici, C., Hatami, N., Davidzon, G., Moradi, F., Iagaru, A. LIPPINCOTT WILLIAMS & WILKINS. 2020: E1118

  View details for Web of Science ID 000527010300463

• Evaluation of Toxicity in Peptide Receptor Radionuclide Therapy (PRRT) for Neuroendocrine Tumors (NET) Duan, H., Girod, B., Ninatti, G., Ferri, Kunz, P., Fisher, G., Moradi, F., Davidzon, G., Franc, B., Lagaru, A., Aparici, M. C. KARGER. 2020: 252

  View details for Web of Science ID 000522166100252

• Extrahepatic 68Ga-DOTATATE-Avid Tumor Volume and Serum Chromogranin A Predict Short-Term Outcome of 177Lu-DOTATATE in Late-Stage Metastatic Gastroenteropancreatic Neuroendocrine Tumors Song, H., Kunz, P., Franc, B., Moradi, F., Fisher, G., Aparici, M. C., Lagaru, A., Davidzon, G. KARGER. 2020: 274

  View details for Web of Science ID 000522166100274

• Fungal endocarditis resembling primary cardiac malignancy in a patient with B-cell ALL with culture confirmation. Radiology case reports Girod, B. J., Guja, K. E., Davidzon, G., Chan, F., Zucker, E., Franc, B. L., Moradi, F., Iagaru, A., Aparici, C. M. 2020; 15 (2): 117–19

  Abstract

  Fungal endocarditis is a rare subtype of infective endocarditis that often presents with nonspecific symptoms in patients with complex medical histories, making diagnosis challenging. Patients with a history of ALL may present with congestive heart failure, chemo-induced cardiomyopathy, acute coronary syndrome, cardiac lymphomatous metastasis, or infections. We present the case of a patient with a history of ALL who presented with acute coronary syndrome and imaging concerning for primary cardiac lymphoma, when in fact the patient ended up suffering from culture proven fungal endocarditis.

  View details for DOI 10.1016/j.radcr.2019.10.022

  View details for PubMedID 31768196

• Single institution experience with peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors (NET) Duan, H., Ninatti, G., Girod, B., Ferri, V., Kunz, P. L., Fisher, G. A., Moradi, F., Davidzon, G., Franc, B., Iagaru, A., Mari, C. AMER SOC CLINICAL ONCOLOGY. 2020

  View details for Web of Science ID 000530922700601

• Deep learning detection of prostate cancer recurrence with 18F-FACBC (fluciclovine, Axumin®) positron emission tomography. European journal of nuclear medicine and molecular imaging Lee, J. J., Yang, H. n., Franc, B. L., Iagaru, A. n., Davidzon, G. A. 2020

  Abstract

  To evaluate the performance of deep learning (DL) classifiers in discriminating normal and abnormal 18F-FACBC (fluciclovine, Axumin®) PET scans based on the presence of tumor recurrence and/or metastases in patients with prostate cancer (PC) and biochemical recurrence (BCR).A total of 251 consecutive 18F-fluciclovine PET scans were acquired between September 2017 and June 2019 in 233 PC patients with BCR (18 patients had 2 scans). PET images were labeled as normal or abnormal using clinical reports as the ground truth. Convolutional neural network (CNN) models were trained using two different architectures, a 2D-CNN (ResNet-50) using single slices (slice-based approach) and the same 2D-CNN and a 3D-CNN (ResNet-14) using a hundred slices per PET image (case-based approach). Models' performances were evaluated on independent test datasets.For the 2D-CNN slice-based approach, 6800 and 536 slices were used for training and test datasets, respectively. The sensitivity and specificity of this model were 90.7% and 95.1%, and the area under the curve (AUC) of receiver operating characteristic curve was 0.971 (p < 0.001). For the case-based approaches using both 2D-CNN and 3D-CNN architectures, a training dataset of 100 images and a test dataset of 28 images were randomly allocated. The sensitivity, specificity, and AUC to discriminate abnormal images by the 2D-CNN and 3D-CNN case-based approaches were 85.7%, 71.4%, and 0.750 (p = 0.013) and 71.4%, 71.4%, and 0.699 (p = 0.053), respectively.DL accurately classifies abnormal 18F-fluciclovine PET images of the pelvis in patients with BCR of PC. A DL classifier using single slice prediction had superior performance over case-based prediction.

  View details for DOI 10.1007/s00259-020-04912-w

  View details for PubMedID 32556481

• Generalization of deep learning models for ultra-low-count amyloid PET/MRI using transfer learning. European journal of nuclear medicine and molecular imaging Chen, K. T., Schürer, M. n., Ouyang, J. n., Koran, M. E., Davidzon, G. n., Mormino, E. n., Tiepolt, S. n., Hoffmann, K. T., Sabri, O. n., Zaharchuk, G. n., Barthel, H. n. 2020

  Abstract

  We aimed to evaluate the performance of deep learning-based generalization of ultra-low-count amyloid PET/MRI enhancement when applied to studies acquired with different scanning hardware and protocols.Eighty simultaneous [18F]florbetaben PET/MRI studies were acquired, split equally between two sites (site 1: Signa PET/MRI, GE Healthcare, 39 participants, 67 ± 8 years, 23 females; site 2: mMR, Siemens Healthineers, 64 ± 11 years, 23 females) with different MRI protocols. Twenty minutes of list-mode PET data (90-110 min post-injection) were reconstructed as ground-truth. Ultra-low-count data obtained from undersampling by a factor of 100 (site 1) or the first minute of PET acquisition (site 2) were reconstructed for ultra-low-dose/ultra-short-time (1% dose and 5% time, respectively) PET images. A deep convolution neural network was pre-trained with site 1 data and either (A) directly applied or (B) trained further on site 2 data using transfer learning. Networks were also trained from scratch based on (C) site 2 data or (D) all data. Certified physicians determined amyloid uptake (+/-) status for accuracy and scored the image quality. The peak signal-to-noise ratio, structural similarity, and root-mean-squared error were calculated between images and their ground-truth counterparts. Mean regional standardized uptake value ratios (SUVR, reference region: cerebellar cortex) from 37 successful site 2 FreeSurfer segmentations were analyzed.All network-synthesized images had reduced noise than their ultra-low-count reconstructions. Quantitatively, image metrics improved the most using method B, where SUVRs had the least variability from the ground-truth and the highest effect size to differentiate between positive and negative images. Method A images had lower accuracy and image quality than other methods; images synthesized from methods B-D scored similarly or better than the ground-truth images.Deep learning can successfully produce diagnostic amyloid PET images from short frame reconstructions. Data bias should be considered when applying pre-trained deep ultra-low-count amyloid PET/MRI networks for generalization.

  View details for DOI 10.1007/s00259-020-04897-6

  View details for PubMedID 32535655

• Human biodistribution and radiation dosimetry of [18F]DASA-23, a PET probe targeting pyruvate kinase M2. European journal of nuclear medicine and molecular imaging Beinat, C. n., Patel, C. B., Haywood, T. n., Shen, B. n., Naya, L. n., Gandhi, H. n., Holley, D. n., Khalighi, M. n., Iagaru, A. n., Davidzon, G. n., Gambhir, S. S. 2020

  Abstract

  To assess the safety, biodistribution, and radiation dosimetry of the novel positron emission tomography (PET) radiopharmaceutical 1-((2-fluoro-6-[[18F]]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in healthy volunteers.We recruited 5 healthy volunteers who provided a written informed consent. Volunteers were injected with 295.0 ± 8.2 MBq of [18F]DASA-23 intravenously. Immediately following injection, a dynamic scan of the brain was acquired for 15 min. This was followed by serial whole-body PET/MRI scans acquired up to 3 h post-injection. Blood samples were collected at regular intervals, and vital signs monitored pre- and post-radiotracer administration. Regions of interest were drawn around multiple organs, time-activity curves were calculated, and organ uptake and dosimetry were estimated with OLINDA/EXM (version 1.1) software.All subjects tolerated the PET/MRI examination, without adverse reactions to [18F]DASA-23. [18F]DASA-23 passively crossed the blood-brain barrier, followed by rapid clearance from the brain. High accumulation of [18F]DASA-23 was noted in organs such as the gallbladder, liver, small intestine, and urinary bladder, suggesting hepatobiliary and urinary clearance. The effective dose of [18F]DASA-23 was 23.5 ± 5.8 μSv/MBq.We successfully completed a pilot first-in-human study of [18F]DASA-23. Our results indicate that [18F]DASA-23 can be used safely in humans to evaluate pyruvate kinase M2 levels. Ongoing studies are evaluating the ability of [18F]DASA-23 to visualize intracranial malignancies, NCT03539731.ClinicalTrials.gov, NCT03539731 (registered 28 May 2018).

  View details for DOI 10.1007/s00259-020-04687-0

  View details for PubMedID 31938892

• An unusual presentation of recurrent T cell lymphoma: angiocentric pattern of cutaneous uptake on [18F]FDG PET/CT. European journal of nuclear medicine and molecular imaging Guja, K. E., Brown, R. n., Girod, B. n., Song, H. n., Harrison, C. n., Franc, B. L., Moradi, F. n., Davidzon, G. n., Iagaru, A. n., Aparici, C. M. 2020

  View details for DOI 10.1007/s00259-020-05026-z

  View details for PubMedID 32918110

• Prognostic value of volumetric PET parameters at early response evaluation in melanoma patients treated with immunotherapy. European journal of nuclear medicine and molecular imaging Nakamoto, R. n., Zaba, L. C., Rosenberg, J. n., Reddy, S. A., Nobashi, T. W., Davidzon, G. n., Aparici, C. M., Nguyen, J. n., Moradi, F. n., Iagaru, A. n., Franc, B. L. 2020

  Abstract

  The purpose of this study was to investigate the prognostic value of whole-body metabolic tumor volume (MTV) and other metabolic tumor parameters, obtained from baseline and first restaging 18F-FDG PET/CT scans in melanoma patients treated with immune checkpoint inhibitors (ICIs).Eighty-five consecutive melanoma patients (M, 57; F, 28) treated with ICIs who underwent PET/CT scans before and approximately 3 months after the start of immunotherapy were retrospectively enrolled. Metabolic tumor parameters including MTV for all melanoma lesions were measured on each scan. A Cox proportional hazards model was used for univariate and multivariate analyses of metabolic parameters combined with known clinical prognostic factors associated with overall survival (OS). Kaplan-Meier curves for patients dichotomized based on median values of imaging parameters were generated.The median OS time in all patients was 45 months (95% CI 24-45 months). Univariate analysis demonstrated that MTV obtained from first restaging PET/CT scans (MTVpost) was the strongest prognostic factor for OS among PET/CT parameters (P < 0.0001). The median OS in patients with high MTVpost (≥ 23.44) was 16 months (95% CI 12-32 months) as compared with more than 60 months in patients with low MTVpost (< 23.44) (P = 0.0003). A multivariate model including PET/CT parameters and known clinical prognostic factors revealed that MTVpost and the presence of central nervous system lesions were independent prognostic factors for OS (P = 0.0004, 0.0167, respectively). One pseudoprogression case (1.2%) was seen in this population and classified into the high MTVpost group.Whole-body metabolic tumor volume from PET scan acquired approximately 3 months following initiation of immunotherapy (MTVpost) is a strong prognostic indicator of OS in melanoma patients. Although the possibility of pseudoprogression must be considered whenever evaluating first restaging PET imaging, it only occurred in 1 patient in our cohort.

  View details for DOI 10.1007/s00259-020-04792-0

  View details for PubMedID 32296882

• Tau PET imaging with 18F-PI-2620 in aging and neurodegenerative diseases. European journal of nuclear medicine and molecular imaging Mormino, E. C., Toueg, T. N., Azevedo, C. n., Castillo, J. B., Guo, W. n., Nadiadwala, A. n., Corso, N. K., Hall, J. N., Fan, A. n., Trelle, A. N., Harrison, M. B., Hunt, M. P., Sha, S. J., Deutsch, G. n., James, M. n., Fredericks, C. A., Koran, M. E., Zeineh, M. n., Poston, K. n., Greicius, M. D., Khalighi, M. n., Davidzon, G. A., Shen, B. n., Zaharchuk, G. n., Wagner, A. D., Chin, F. T. 2020

  Abstract

  In vivo measurement of the spatial distribution of neurofibrillary tangle pathology is critical for early diagnosis and disease monitoring of Alzheimer's disease (AD).Forty-nine participants were scanned with 18F-PI-2620 PET to examine the distribution of this novel PET ligand throughout the course of AD: 36 older healthy controls (HC) (age range 61 to 86), 11 beta-amyloid+ (Aβ+) participants with cognitive impairment (CI; clinical diagnosis of either mild cognitive impairment or AD dementia, age range 57 to 86), and 2 participants with semantic variant primary progressive aphasia (svPPA, age 66 and 78). Group differences in brain regions relevant in AD (medial temporal lobe, posterior cingulate cortex, and lateral parietal cortex) were examined using standardized uptake value ratios (SUVRs) normalized to the inferior gray matter of the cerebellum.SUVRs in target regions were relatively stable 60 to 90 min post-injection, with the exception of very high binders who continued to show increases over time. Robust elevations in 18F-PI-2620 were observed between HC and Aβ+ CI across all AD regions. Within the HC group, older age was associated with subtle elevations in target regions. Mildly elevated focal uptake was observed in the anterior temporal pole in one svPPA patient.Preliminary results suggest strong differences in the medial temporal lobe and cortical regions known to be impacted in AD using 18F-PI-2620 in patients along the AD trajectory. This work confirms that 18F-PI-2620 holds promise as a tool to visualize tau aggregations in AD.

  View details for DOI 10.1007/s00259-020-04923-7

  View details for PubMedID 32572562

• Prospective Evaluation in an Academic Center of 18F-DCFPyL PET/CT in Biochemically Recurrent Prostate Cancer: A Focus on Localizing Disease and Changes in Management. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Song, H., Harrison, C., Duan, H., Guja, K., Hatami, N., Franc, B., Moradi, F., Mari Aparici, C., Davidzon, G., Iagaru, A. 2019

  Abstract

  18F-DCFPyL is a promising PET radiopharmaceutical targeting prostate specific membrane antigen (PSMA). We present our experience in this single academic center prospective study evaluating the positivity rate of 18F-DCFPyL PET/CT in patients with biochemical recurrence (BCR) of prostate cancer (PC). Methods: We prospectively enrolled 72 men (52-91 years old, mean±SD: 71.5±7.2) with BCR after primary definitive treatment with prostatectomy (n = 42) or radiotherapy (n = 30). The presence of lesions compatible with PC was evaluated by two independent readers. Fifty-nine patients had concurrent scans with at least one other conventional scan: bone scan (24), CT (21), MR (20), 18F-Fluciclovine PET/CT (18) and/or 18F-NaF PET (14). Findings from 18F-DCFPyL PET/CT were compared with those from other modalities. Impact on patient management based on 18F-DCFPyL PET/CT was recorded from clinical chart review. Results: 18F-DCFPyL PET/CT had an overall positivity rate of 85%, which increased with higher prostate specific antigen (PSA) levels (ng/mL): 50% (PSA<0.5), 69% (0.5≤PSA<1), 100% (1≤PSA<2), 91% (2≤PSA<5) and 96% (PSA≥5), respectively. 18F-DCFPyL PET detected more lesions than conventional imaging. For anatomic imaging, 20/41 (49%) CT/MRI had congruent findings with 18F-DCFPyL, while 18F-DCFPyL PET was positive in 17/41 (41%) cases with negative CT/MRI. For bone imaging, 26/38 (68%) bone scan/18F-NaF PET were congruent with 18F-DCFPyL PET, while 18F-DCFPyL PET localized bone lesions in 8/38 (21%) patients with negative bone scan/18F-NaF PET. In 8/18 (44%) patients, 18F-Fluciclovine PET had located the same lesions as the 18F-DCFPyL PET, while 5/18 (28%) patients with negative 18F-Fluciclovine had positive 18F-DCFPyL PET findings and 1/18 (6%) patient with negative 18F-DCFPyL had uptake in the prostate bed on 18F-Fluciclovine PET. In the remaining 4/18 (22%) patients, 18F-DCFPyL and 18F-Fluciclovine scans showed different lesions. Lastly, 43/72 (60%) patients had treatment changes after 18F-DCFPyL PET and, most noticeably, 17 of these patients (24% total) had lesion localization only on 18F-DCFPyL PET, despite negative conventional imaging. Conclusion: 18F-DCFPyL PET/CT is a promising diagnostic tool in the work-up of biochemically recurrent prostate cancer given the high positivity rate as compared to FDA-approved currently available imaging modalities and its impact on clinical management in 60% of patients.

  View details for DOI 10.2967/jnumed.119.231654

  View details for PubMedID 31628216

• Ga-68-RM2 PET/CT in Patients with Newly Diagnosed Intermediate- or High-Risk Prostate Cancer Iagaru, A., Baratto, L., Duan, H., Hatami, N., Mari, C., Davidzon, G. SPRINGER. 2019: S277–S278

  View details for Web of Science ID 000492444402125

• Prospective evaluation of F-18-DCFPyL in Patients with Biochemically Recurrent Prostate Cancer Iagaru, A., Duan, H., Song, H., Harrison, C., Guja, K., Franc, B., Moradi, F., Davidzon, G. SPRINGER. 2019: S593

  View details for Web of Science ID 000492444405132

• Machine Learning to Detect Prostate Cancer Recurrence using F-18-Fluciclovine PET Davidzon, G. A., Lee, J., Yang, H., Song, H., Harrison, C., Iagaru, A. SPRINGER. 2019: S65–S66

  View details for Web of Science ID 000492444400097

• Bone Marrow and Tumor Radiomics at 18F-FDG PET/CT: Impact on Outcome Prediction in Non-Small Cell Lung Cancer. Radiology Mattonen, S. A., Davidzon, G. A., Benson, J., Leung, A. N., Vasanawala, M., Horng, G., Shrager, J. B., Napel, S., Nair, V. S. 2019: 190357

  Abstract

  Background Primary tumor maximum standardized uptake value is a prognostic marker for non-small cell lung cancer. In the setting of malignancy, bone marrow activity from fluorine 18-fluorodeoxyglucose (FDG) PET may be informative for clinical risk stratification. Purpose To determine whether integrating FDG PET radiomic features of the primary tumor, tumor penumbra, and bone marrow identifies lung cancer disease-free survival more accurately than clinical features alone. Materials and Methods Patients were retrospectively analyzed from two distinct cohorts collected between 2008 and 2016. Each tumor, its surrounding penumbra, and bone marrow from the L3-L5 vertebral bodies was contoured on pretreatment FDG PET/CT images. There were 156 bone marrow and 512 tumor and penumbra radiomic features computed from the PET series. Randomized sparse Cox regression by least absolute shrinkage and selection operator identified features that predicted disease-free survival in the training cohort. Cox proportional hazards models were built and locked in the training cohort, then evaluated in an independent cohort for temporal validation. Results There were 227 patients analyzed; 136 for training (mean age, 69 years ± 9 [standard deviation]; 101 men) and 91 for temporal validation (mean age, 72 years ± 10; 91 men). The top clinical model included stage; adding tumor region features alone improved outcome prediction (log likelihood, -158 vs -152; P = .007). Adding bone marrow features continued to improve performance (log likelihood, -158 vs -145; P = .001). The top model integrated stage, two bone marrow texture features, one tumor with penumbra texture feature, and two penumbra texture features (concordance, 0.78; 95% confidence interval: 0.70, 0.85; P < .001). This fully integrated model was a predictor of poor outcome in the independent cohort (concordance, 0.72; 95% confidence interval: 0.64, 0.80; P < .001) and a binary score stratified patients into high and low risk of poor outcome (P < .001). Conclusion A model that includes pretreatment fluorine 18-fluorodeoxyglucose PET texture features from the primary tumor, tumor penumbra, and bone marrow predicts disease-free survival of patients with non-small cell lung cancer more accurately than clinical features alone. © RSNA, 2019 Online supplemental material is available for this article.

  View details for DOI 10.1148/radiol.2019190357

  View details for PubMedID 31526257

• F-18-FDG PET/MR Refines Evaluation in Newly Diagnosed Metastatic Urethral Adenocarcinoma NUCLEAR MEDICINE AND MOLECULAR IMAGING Laudicella, R., Davidzon, G., Vasanawala, S., Baldari, S., Iagaru, A. 2019; 53 (4): 296–99

  View details for DOI 10.1007/s13139-019-00597-8

  View details for Web of Science ID 000480821000009

• 18F-FDG PET/MR Refines Evaluation in Newly Diagnosed Metastatic Urethral Adenocarcinoma. Nuclear medicine and molecular imaging Laudicella, R., Davidzon, G., Vasanawala, S., Baldari, S., Iagaru, A. 2019; 53 (4): 296-299

  Abstract

  We described the clinical impact of 18F-FDG PET/MR in refining the evaluation of a 39-year-old female with newly diagnosed metastatic urethral adenocarcinoma. We detailed the diagnostic imaging workup focusing our attention on the CT, MR, and 18F-FDG PET/MR different findings. In this case, 18F-FDG PET/MR imaging evaluation resulted not only effective but also altered staging and spared additional invasive procedures in the assessment of a metastatic urethral adenocarcinoma. Combining a highly sensitive PET with the increase tissue resolution of MR (PET/MR) may improve abdominal and pelvic lesion detection outperforming PET/CT for this indication.

  View details for DOI 10.1007/s13139-019-00597-8

  View details for PubMedID 31456863

  View details for PubMedCentralID PMC6694445

• Non-invasive quantification of tau accumulation in dementia using simultaneous F-18-PI-2620 PET/MRI Fan, A. P., Chen, K. T., Nadiadwala, A., Toueg, T., Sha, S., Greicius, M. D., Davidzon, G. A., Chin, F. T., Zaharchuk, G., Mormino, E. C. SAGE PUBLICATIONS INC. 2019: 110–11

  View details for Web of Science ID 000473954100118

• Preliminary Results of a Prospective Study of Ga-68-RM2 PET/MRI for Detection of Recurrent Prostate Cancer in Patients with Negative Conventional Imaging Baratto, L., Duan, H., Harrison, C., Hatami, N., Aparici, C., Davidzon, G., Yohannan, T., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2019

  View details for Web of Science ID 000473116801014

• Prospective evaluation of F-18- DCFPyL in Patients with Biochemically Recurrent Prostate Cancer: Positivity Rate and Correlation with PSA levels Harrison, C., Song, H., Franc, B. L., Guja, K., Moradi, F., Davidzon, G., Aparici, C., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2019

  View details for Web of Science ID 000473116801610

• Prospective Comparison of F-18-DCFPyL PET/CT with F-18-NaF PET/CT for Detection of Skeletal Metastases in Biochemically Recurrent Prostate Cancer Duan, H., Song, H., Baratto, L., Khalaf, M., Hatami, N., Franc, B., Moradi, F., Davidzon, G., Aparici, C., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2019

  View details for Web of Science ID 000473116801621

• Comparison of three interpretation criteria of Ga-68-PS A PET based on in er and intra-reader agreement Toriihara, A., Nobashi, T., Baratto, L., Park, S., Hatami, N., Duan, H., Aparici, C., Davidzon, G., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2019

  View details for Web of Science ID 000473116801600

• Prospective Evaluation of F-18-DCFPyL PET/CT and Conventional Imaging in Patients with Biochemically Recurrent Prostate Cancer Song, H., Harrison, C., Guja, K., Franc, B., Moradi, F., Davidzon, G., Aparici, C., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2019

  View details for Web of Science ID 000473116801016

• [18F] FDG Positron Emission Tomography (PET) Tumor and Penumbra Imaging Features Predict Recurrence in Non-Small Cell Lung Cancer. Tomography (Ann Arbor, Mich.) Mattonen, S. A., Davidzon, G. A., Bakr, S., Echegaray, S., Leung, A. N., Vasanawala, M., Horng, G., Napel, S., Nair, V. S. 2019; 5 (1): 145–53

  Abstract

  We identified computational imaging features on 18F-fluorodeoxyglucose positron emission tomography (PET) that predict recurrence/progression in non-small cell lung cancer (NSCLC). We retrospectively identified 291 patients with NSCLC from 2 prospectively acquired cohorts (training, n = 145; validation, n = 146). We contoured the metabolic tumor volume (MTV) on all pretreatment PET images and added a 3-dimensional penumbra region that extended outward 1 cm from the tumor surface. We generated 512 radiomics features, selected 435 features based on robustness to contour variations, and then applied randomized sparse regression (LASSO) to identify features that predicted time to recurrence in the training cohort. We built Cox proportional hazards models in the training cohort and independently evaluated the models in the validation cohort. Two features including stage and a MTV plus penumbra texture feature were selected by LASSO. Both features were significant univariate predictors, with stage being the best predictor (hazard ratio [HR] = 2.15 [95% confidence interval (CI): 1.56-2.95], P < .001). However, adding the MTV plus penumbra texture feature to stage significantly improved prediction (P = .006). This multivariate model was a significant predictor of time to recurrence in the training cohort (concordance = 0.74 [95% CI: 0.66-0.81], P < .001) that was validated in a separate validation cohort (concordance = 0.74 [95% CI: 0.67-0.81], P < .001). A combined radiomics and clinical model improved NSCLC recurrence prediction. FDG PET radiomic features may be useful biomarkers for lung cancer prognosis and add clinical utility for risk stratification.

  View details for PubMedID 30854452

• [18F] FDG Positron Emission Tomography (PET) Tumor and Penumbra Imaging Features Predict Recurrence in Non-Small Cell Lung Cancer TOMOGRAPHY Mattonen, S. A., Davidzon, G. A., Bakr, S., Echegaray, S., Leung, A. C., Vasanawala, M., Horng, G., Napel, S., Nair, V. S. 2019; 5 (1): 145–53

  View details for DOI 10.18383/j.tom.2018.00026

  View details for Web of Science ID 000460943000018

• Comparison of three interpretation criteria of 68Ga-PSMA11 PET based on inter- and intra-reader agreement. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Toriihara, A. n., Nobashi, T. n., Baratto, L. n., Duan, H. n., Moradi, F. n., Park, S. n., Hatami, N. n., Aparici, C. n., Davidzon, G. n., Iagaru, A. n. 2019

  Abstract

  Positron emission tomography (PET) using radiolabeled prostate specific membrane antigen (PSMA) is now more and more widely adopted as a valuable tool to evaluate patients with prostate cancer (PC). Recently, three different criteria for interpretation of PSMA PET were published: European Association of Nuclear Medicine (EANM) criteria, prostate cancer molecular imaging standardized evaluation (PROMISE) criteria, and PSMA-reporting and data system (PSMA-RADS). We compared these three criteria in terms of inter-reader, intra-reader, and inter-criteria agreement. Methods: Data from 104 patients prospectively enrolled in research protocols at our institution were retrospectively reviewed. The cohort consisted of two groups: 47 patients (mean age: 64.2 years old) who underwent Glu-NH-CO-NH-Lys-(Ahx)-[68Ga(HBED-CC)] (68Ga-PSMA11) PET/magnetic resonance imaging (MRI) for initial staging of biopsy-proven intermediate- or high-risk PC, and 57 patients (mean age: 70.5 years old) who underwent 68Ga-PSMA11 PET/computed tomography (CT) due to biochemically recurrent (BCR) PC. Three nuclear medicine physicians independently evaluated all 68Ga-PSMA11 PET/MRI and PET/CT studies according to the three interpretation criteria. Two of them reevaluated all studies 6 months later in the same manner and blinded to the initial reading. Gwet's AC was calculated to evaluate inter- and intra-reader, and inter-criteria agreement based on the following sites: local lesion (primary tumor or prostate bed after radical prostatectomy), lymph node metastases, and other metastases. Results: In the PET/MRI group, inter-reader, intra-reader, and inter-criteria agreements were substantial to almost perfect in any sites according to all of the three criteria. In the PET/CT group, inter-reader agreement was substantial to almost perfect except judgement of distant metastases based on PSMA-RADS (Gwet's AC = 0.57, moderate agreement), in which the most frequent cause of disagreement was lung nodules. Intra-reader agreements were substantial to almost perfect in any sites according to all of the three criteria. Inter-criteria agreements of each site were also substantial to almost perfect. Conclusion: Although the three published criteria have good inter-reader and intra-reader reproducibility in evaluating 68Ga-PSMA11 PET, there are factors bringing inter-reader disagreement. This indicates that further work is needed to address the issue.

  View details for DOI 10.2967/jnumed.119.232504

  View details for PubMedID 31562226

• Initial experience with a PET/computed tomography system using silicon photomultiplier detectors. Nuclear medicine communications Park, S. Y., Barrato, L. n., Hatami, N. n., Davidzon, G. n., Gambhir, S. S., Iagaru, A. n. 2019

  Abstract

  A PET/computed tomography (CT) that uses silicon photomultiplier (SiPM) technology was installed at our institution. Here, we report the initial use of the new scanner and evaluate the image quality in comparison to standard PET/CT scanners.Seventy-two patients were scanned first using standard PET/CT followed immediately by the new PET/CT system. Images from the new PET/CT system were reconstructed using a conventional [non time-of-flight (TOF)] algorithm, TOF alone and TOF in combination with BSREM. Images from standard PET/CT were reconstructed using clinical standard-of-care settings. Three blinded readers randomly reviewed four datasets (standard, non-TOF, TOF alone, TOF+BSREM) per patient for image quality using a five-point Likert scale. SUV measurements for the single most avid lesion on each dataset were also recorded.Datasets from the new scanner had higher image quality (P < 0.001) and SUV measurements (P < 0.001) compared with the standard scanners, and scores further improved when TOF and BSREM algorithms were added (mean scores for standard, non-TOF, TOF alone and TOF+BSREM were 3.1, 3.9, 4.3 and 5.0, respectively; mean SUVmax for hottest lesion were 8.8, 10.3, 10.7 and 13.3, respectively).The SiPM-based PET/CT system outperforms two standard Bismuth germanium oxide- and Lutetium-yttrium oxyorthosilicate-based scanners in terms of image quality, with further benefits added using TOF and BSREM. This may be beneficial for detecting small lesions and more accurate disease staging.

  View details for DOI 10.1097/MNM.0000000000001088

  View details for PubMedID 31568189

• Integrated Bone Marrow and Tumor Radiomics on [18F] FDG Positron Emission Tomography (PET) Augment Stage for Outcome Prediction in Non-Small Cell Lung Cancer Mattonen, S. A., Davidzon, G. A., Benson, J. A., Vasanawala, M., Leung, A. C., Horng, G. S., Shrager, J. B., Napel, S., Nair, V. S. AMER THORACIC SOC. 2019

  View details for Web of Science ID 000466776705345

• Prognostic value of somatostatin receptor expressing tumor volume calculated from 68Ga-DOTATATE PET/CT in patients with well-differentiated neuroendocrine tumors. European journal of nuclear medicine and molecular imaging Toriihara, A. n., Baratto, L. n., Nobashi, T. n., Park, S. n., Hatami, N. n., Davidzon, G. n., Kunz, P. L., Iagaru, A. n. 2019

  Abstract

  To evaluate the prognostic value of volumetric parameters calculated from 68Ga-1,4,7,10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-Thr3-octreotate (68Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT) in patients with well-differentiated neuroendocrine tumor (WD-NET).Ninety-two patients (44 men and 48 women, mean age of 59.5-year-old) with pathologically confirmed WD-NET (grades 1 or 2) were enrolled in a prospective expanded access protocol. Selected data was analyzed retrospectively for this project. Maximum standardized uptake value (SUVmax) in the lesion with the highest 68Ga-DOTATATE uptake was measured and recorded for each patient. In addition, two volumetric parameters, namely, somatostatin receptor expressing tumor volume (SRETV) and total lesion somatostatin receptor expression (TLSRE), were calculated in each 68Ga-DOTATATE-avid lesion. SRETV was defined as tumor volume with higher 68Ga-DOTATATE uptake than the 50% of SUVmax within the volume of interest (VOI) for each lesion. TLSRE was calculated by multiplying SRETV and mean SUV within the same VOI. Thereafter, the sum of SRETV (ΣSRETV) and TLSRE (ΣTLSRE) for all detected lesions per patient were calculated. Progression-free survival (PFS) was set as primary endpoint. Kaplan-Meier survival analysis, log-rank test, and Cox's proportional hazard model were used for statistical analysis.Univariate analyses revealed significant difference of PFS for WHO tumor grade and ΣSRETV (P < 0.05), while there were no significant differences in age, sex, SUVmax, and ΣTLSRE (P > 0.05). Multivariate analysis identified WHO tumor grade and ΣSRETV as independent predictors of PFS.ΣSRETV calculated from 68Ga-DOTATATE PET/CT may have prognostic value of PFS in WD-NET patients.

  View details for DOI 10.1007/s00259-019-04455-9

  View details for PubMedID 31350603

• Performance Comparison of Individual and Ensemble CNN Models for the Classification of Brain 18F-FDG-PET Scans. Journal of digital imaging Nobashi, T. n., Zacharias, C. n., Ellis, J. K., Ferri, V. n., Koran, M. E., Franc, B. L., Iagaru, A. n., Davidzon, G. A. 2019

  Abstract

  The high-background glucose metabolism of normal gray matter on [18F]-fluoro-2-D-deoxyglucose (FDG) positron emission tomography (PET) of the brain results in a low signal-to-background ratio, potentially increasing the possibility of missing important findings in patients with intracranial malignancies. To explore the strategy of using a deep learning classifier to aid in distinguishing normal versus abnormal findings on PET brain images, this study evaluated the performance of a two-dimensional convolutional neural network (2D-CNN) to classify FDG PET brain scans as normal (N) or abnormal (A).Two hundred eighty-nine brain FDG-PET scans (N; n = 150, A; n = 139) resulting in a total of 68,260 images were included. Nine individual 2D-CNN models with three different window settings for axial, coronal, and sagittal axes were trained and validated. The performance of these individual and ensemble models was evaluated and compared using a test dataset. Odds ratio, Akaike's information criterion (AIC), and area under curve (AUC) on receiver-operative-characteristic curve, accuracy, and standard deviation (SD) were calculated.An optimal window setting to classify normal and abnormal scans was different for each axis of the individual models. An ensembled model using different axes with an optimized window setting (window-triad) showed better performance than ensembled models using the same axis and different windows settings (axis-triad). Increase in odds ratio and decrease in SD were observed in both axis-triad and window-triad models compared with individual models, whereas improvements of AUC and AIC were seen in window-triad models. An overall model averaging the probabilities of all individual models showed the best accuracy of 82.0%.Data ensemble using different window settings and axes was effective to improve 2D-CNN performance parameters for the classification of brain FDG-PET scans. If prospectively validated with a larger cohort of patients, similar models could provide decision support in a clinical setting.

  View details for DOI 10.1007/s10278-019-00289-x

  View details for PubMedID 31659587

• Dual-Time Ga-68-RM2 Imaging for Staging Patients with Newly Diagnosed Intermediate or High Risk Prostate Cancer Using PMT and SiPM-Based Detectors PET/CT Baratto, L., Duan, H., Hatami, N., Yohannan, T., Mari, C., Davidzon, G., Iagaru, A. SPRINGER. 2018: S724

  View details for Web of Science ID 000449266206241

• Ga-68-RM2 PET vs. Ga-68-PSMA-11 PET: Prospective Comparison in Patients with Biochemical Recurrence of Prostate Cancer Baratto, L., Duan, H., Minamimoto, R., Mari, C., Yohannan, T., Davidzon, G., Iagaru, A. SPRINGER. 2018: S151

  View details for Web of Science ID 000449266201099

• Ga-68-RM2 PET/MRI Detection of Recurrent Prostate Cancer in Patients with Negative Conventional Imaging Baratto, L., Duan, H., Harrison, C., Mari, C., Davidzon, G., Yohannan, T., Iagaru, A. SPRINGER. 2018: S151–S152

  View details for Web of Science ID 000449266201100

• Ga-68-PSMA-11 Imaging for Biochemical Relapse of Prostate Cancer Using Dual-Time LYSO and SiPM-Based Detectors PET/CT Duan, H., Park, S., Baratto, L., Hatami, N., Khalaf, M. H., Yohannan, T. K., Davidzon, G. A., Iagaru, A. H. SPRINGER. 2018: S713

  View details for Web of Science ID 000449266206215

• Embrace Progress JOURNAL OF NUCLEAR MEDICINE Bradley, K. M., McGowan, D. R., Gleeson, F. V., Johnson, G. B., Young, J. R., Levin, C. S., Davidzon, G. A., Iagaru, A. H. 2018; 59 (7): 1169

  View details for DOI 10.2967/jnumed.118.212761

  View details for Web of Science ID 000437237200044

  View details for PubMedID 29700130

• Prognostic value of volumetric parameters calculated from Ga-68-DOTATATE PET/CT in patients with well-differentiated neuroendocrine tumors Toriihara, A., Baratto, L., Nobashi, T., Park, S., Hatami, N., Davidzon, G., Kunz, P., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2018

  View details for Web of Science ID 000467489900042

• Dual-Time Ga-68-PSMA-11 Imaging for Biochemically Recurrent Prostate Cancer Using LYSO and SiPM-Based Detectors PET/CT Park, S., Hatami, N., Baratto, L., Yohannan, T., Davidzon, G., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2018

  View details for Web of Science ID 000467489900431

• SiPM-based vs LYSO-based Ga-68-DOTA-TATE PET/CT: Comparison of Semi-Quantitative Measurements in Normal Tissues and Lesions Baratto, L., Toriihara, A., Hatami, N., Davidzon, G., Srinivas, S., Gambhir, S., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2018

  View details for Web of Science ID 000467489900430

• Ga-68-RM2 PET/MRI Detection of Recurrent Prostate Cancer in Patients with Negative Conventional Imaging Baratto, L., Harrison, C., Davidzon, G., Yohannan, T., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2018

  View details for Web of Science ID 000467489900453

• Initial experience with a SiPM-based PET/CT scanner: influence of acquisition time on image quality EJNMMI PHYSICS Sonni, I., Baratto, L., Park, S., Hatami, N., Srinivas, S., Davidzon, G., Gambhir, S., Iagaru, A. 2018; 5: 9

  Abstract

  A newly introduced PET/CT scanner (Discovery Meaningful Insights-DMI, GE Healthcare) includes the silicon photomultiplier (SiPM) with time-of-flight (TOF) technology first used in the GE SIGNA PET/MRI. In this study, we investigated the impact of various acquisition times on image quality using this SiPM-based PET/CT.We reviewed data from 58 participants with cancer who were scanned using the DMI PET/CT scanner. The administered dosages ranged 295.3-429.9 MBq (mean ± SD 356.3 ± 37.4) and imaging started at 71-142 min (mean ± SD 101.41 ± 17.52) after administration of the radiopharmaceutical. The patients' BMI ranged 19.79-46.16 (mean ± SD 26.55 ± 5.53). We retrospectively reconstructed the raw TOF data at 30, 60, 90, and 120 s/bed and at the standard image acquisition time per clinical protocol (180 or 210 s/bed depending on BMI). Each reconstruction was reviewed blindly by two nuclear medicine physicians and scored 1-5 (1-poor, 5-excellent quality). The liver signal-to-noise ratio (SNR) was used as a quantitative measure of image quality.The average scores ± SD of the readers were 2.61 ± 0.83, 3.70 ± 0.92, 4.36 ± 0.82, 4.82 ± 0.39, and 4.91 ± 0.91 for the 30, 60, 90, and 120 s/bed and at standard acquisition time, respectively. Inter-reader agreement on image quality assessment was good, with a weighted kappa of 0.80 (95% CI 0.72-0.81). In the evaluation of the effects of time per bed acquisition on semi-quantitative measurements, we found that the only time point significantly different from the standard time were 30 and 60 s (both with P < 0.001). The effects of dose and BMI were not statistically significant (P = 0.195 and 0.098, respectively). There was a significant positive effect of time on SNR (P < 0.001), as well as a significant negative effect of weight (P < 0.001).Our results suggest that despite significant delays from injection to imaging (due to comparison with standard PET/CT) compared to standard clinical operations and even in a population with average BMI > 25, images can be acquired as fast as 90 s/bed using the SiPM PET/CT and still result in very good image quality (average score > 4).

  View details for PubMedID 29666972

• Comparison Between Different PET and CT-Based Imaging Interpretation Criteria at Interim Imaging in Patients With Diffuse Large B-Cell Lymphoma CLINICAL NUCLEAR MEDICINE Baratto, L., Davidzon, G. A., Moghbel, M., Hatami, N., Iagaru, A., Mittra, E. S. 2018; 43 (1): 1–8

  Abstract

  To evaluate the predictive value of interim PET (iPET) in diffuse large B-cell lymphoma (DLBCL) using 5 different imaging interpretation criteria: Deauville 5-point scale criteria, International Harmonization Project (IHP) criteria, Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, European Organization for Research and Treatment of Cancer, and PET Response Criteria in Solid Tumors (PERCIST) 1.0.We retrospectively reviewed records from 38 patients with DLBCL who underwent baseline and iPET at our institution. Imaging was interpreted according to the previously mentioned criteria. Results were correlated with end-of-treatment response, based on reports at the end of treatment radiological examinations, overall survival (OS), and progression-free survival (PFS) to assess and compare the predictive value of iPET according to each criterion. We also evaluated the concordance between different criteria.The Deauville and PERCIST criteria were the most reliable for predicting end-of-treatment response, reporting an accuracy of 81.6%. They also correlated with OS and PFS (P = 0.0004 and P = 0.0001, and P = 0.0007 and P = 0.0002, for Deauville and PERCIST, respectively). Interim PET according to European Organization for Research and Treatment of Cancer also predicted the end-of-treatment response with an accuracy of 73.7% and had a significant correlation with OS (P = 0.007) and PFS (P = 0.007). In contrast, the IHP criteria and RECIST did not predict outcomes: the accuracy for end-of-treatment response was 34.2% and 36.8%, respectively, with no significant correlation with OS or PFS (P = 0.182 and P = 0.357, and P = 0.341 and P = 0.215, for OS and PFS, respectively).The predictive value of iPET in DLBCL patients is most reliable using the Deauville and PERCIST criteria. Criteria that rely on anatomical characteristics, namely, RECIST and IHP criteria, are less accurate in predicting patient outcomes in DLBCL.

  View details for DOI 10.1097/RLU.0000000000001880

  View details for Web of Science ID 000418319900001

  View details for PubMedID 29076913

• Positron Emission Tomography (PET) Tumor Penumbra Imaging Features Predict Outcome in Non-Small Cell Lung Cancer Mattonen, S., Davidzon, G. A., Bakr, S., Vasanawala, M., Horng, G. S., Napel, S., Nair, V. S. AMER THORACIC SOC. 2018

  View details for Web of Science ID 000449980305167

• Initial Experience with a New PET/CT System Using SiPM Detectors Park, S., Baratto, L., Hatami, N., Davidzon, G., Srinivas, S., Gambhir, S., Iagaru, A. SPRINGER. 2017: S426

  View details for Web of Science ID 000455019401212

• Improved Pulmonary Nodule Detection Using a Next Generation F-18-FDG PET Imaging System Park, S., Baratto, L., Hatami, N., Davidzon, G., Srinivas, S., Nair, V., Iagaru, A. SPRINGER. 2017: S311-S312

  View details for Web of Science ID 000455019400373

• SiPM PET/CT vs. Standard PET/CT: A Pilot Study Comparing Semi-Quantitative Measurements in Normal Tissues and Lesions Baratto, L., Park, S., Hatami, N., Davidzon, G., Srinivas, S., Gambhir, S. S., Iagaru, A. SPRINGER. 2017: S431

  View details for Web of Science ID 000455019401222

• First Experience with Fast Imaging Using Discovery MI PET/CT Sonni, I., Park, S., Baratto, L., Hatami, N., Davidzon, G., Srinivas, S., Gambhir, S., Iagaru, A. H. SPRINGER. 2017: S304

  View details for Web of Science ID 000455019400360

• Initial Experience with a SiPM-based PET/CT Scanner: Influence of Acquisition Time on Image Quality Sonni, I., Park, S., Baratto, L., Hatami, N., Davidzon, G., Srinivas, S., Gambhir, S., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2017

  View details for Web of Science ID 000404949906160

• SiPM PET/CT vs. Standard PET/CT: A Pilot Study Comparing Semi-Quantitative Measurements in Normal Tissues and Lesions Baratto, L., Park, S., Hatami, N., Davidzon, G., Srinivas, S., Gambhir, S., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2017

  View details for Web of Science ID 000404949902041

• Initial Experience with a New PET/CT System Using SiPM Detectors: Image Quality Comparison with Standard PET/CT Park, S., Baratto, L., Hatami, N., Davidzon, G., Srinivas, S., Gambhir, S., Lagaru, A. SOC NUCLEAR MEDICINE INC. 2017

  View details for Web of Science ID 000404949906122

• 18F-FDG silicon photomultiplier PET/CT: A pilot study comparing semi-quantitative measurements with standard PET/CT. PloS one Baratto, L., Park, S. Y., Hatami, N., Davidzon, G., Srinivas, S., Gambhir, S. S., Iagaru, A. 2017; 12 (6)

  Abstract

  To evaluate if the new Discovery Molecular Insights (DMI) PET/CT scanner provides equivalent results compared to the standard of care PET/CT scanners (GE Discovery 600 or GE Discovery 690) used in our clinic and to explore any possible differences in semi-quantitative measurements.The local Institutional Review Board approved the protocol and written informed consent was obtained from each patient. Between September and November 2016, 50 patients underwent a single 18F-FDG injection and two scans: the clinical standard PET/CT followed immediately by the DMI PET/CT scan. We measured SUVmax and SUVmean of different background organs and up to four lesions per patient from data acquired using both scanners.DMI PET/CT identified all the 107 lesions detected by standard PET/CT scanners, as well as additional 37 areas of focal increased 18F-FDG uptake. The SUVmax values for all 107 lesions ranged 1.2 to 14.6 (mean ± SD: 2.8 ± 2.8), higher on DMI PET/CT compared with standard of care PET/CT. The mean lesion:aortic arch SUVmax ratio and mean lesion:liver SUVmax ratio were 0.2-15.2 (mean ± SD: 3.2 ± 2.6) and 0.2-8.5 (mean ± SD: 1.9 ± 1.4) respectively, higher on DMI PET/CT than standard PET/CT. These differences were statistically significant (P value < 0.0001) and not correlated to the delay in acquisition of DMI PET data (P < 0.0001).Our study shows high performance of the new DMI PET/CT scanner. This may have a significant role in diagnosing and staging disease, as well as for assessing and monitoring responses to therapies.

  View details for DOI 10.1371/journal.pone.0178936

  View details for PubMedID 28582472

• Bridging the Health Data Divide Journal of Medical Internet Research Celi, L. A., Davidzon, G., et al 2016; 18 (12)

  View details for DOI 10.2196/jmir.6400

• Case 207: Hodgkin lymphoma with paraneoplastic hypercalcemic pancreatitis. Radiology Mittra, E. S., Davidzon, G. 2014; 272 (1): 296-300

  Abstract

  A 15-year-old girl presented with a 2-month history of 30-lb (13.6 kg) weight loss, chest and abdominal pain, nausea, bilious emesis, cough, and shortness of breath. Initial blood count (performed at an outside hospital) showed elevated white blood cell and platelet counts but low hemoglobin and hematocrit levels. On examination, she had adenopathy in the left axillary and supraclavicular regions, fullness in the left chest, and abdominal guarding. Ultrasonography (US)-guided fine-needle aspiration biopsy of the left anterior chest wall mass was nondiagnostic, and lumbar puncture and bone marrow biopsies were negative. At that time, the patient underwent several imaging studies-including chest radiography; bone scanning; contrast material-enhanced computed tomography (CT) of the chest, abdomen, and pelvis; and fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT-all performed within 1 week of each other. Pertinent serum laboratory values at the time of these tests were as follows: calcium level, 17 mg/dL (4.25 mmol/L) (normal range, 8.5-10.5 mg/dL [2.1-2.6 mmol/L]); ionized calcium level, 2.3 mmol/L (normal range, 1.1-1.3 mmol/L); lipase level, 2423 U/L (normal level, <300 U/L); amylase level, 1435 U/L (normal level, <140 U/L); lactate dehydrogenase level, 253 U/L (normal level, <240 U/L), albumin level, 2.6 g/dL (26 g/L) (normal level, 3.5-5.0 g/dL [35-50 g/L]), and creatinine level, 1.7 mg/dL (150.3 μmol/L) (normal level, <1.2 mg/dL [<106.1 μmol/L]). A follow-up PET/CT scan was performed approximately 2 months later after initial therapy.

  View details for DOI 10.1148/radiol.14120419

  View details for PubMedID 24956051

• NF-?B protein expression associates with (18)F-FDG PET tumor uptake in non-small cell lung cancer: A radiogenomics validation study to understand tumor metabolism. Lung cancer Nair, V. S., Gevaert, O., Davidzon, G., Plevritis, S. K., West, R. 2014; 83 (2): 189-196

  Abstract

  We previously demonstrated that NF-κB may be associated with (18)F-FDG PET uptake and patient prognosis using radiogenomics in patients with non-small cell lung cancer (NSCLC). To validate these results, we assessed NF-κB protein expression in an extended cohort of NSCLC patients.We examined NF-κBp65 by immunohistochemistry (IHC) using a Tissue Microarray. Staining intensity was assessed by qualitative ordinal scoring and compared to tumor FDG uptake (SUVmax and SUVmean), lactate dehydrogenase A (LDHA) expression (as a positive control) and outcome using ANOVA, Kaplan Meier (KM), and Cox-proportional hazards (CPH) analysis.365 tumors from 355 patients with long-term follow-up were analyzed. The average age for patients was 67±11 years, 46% were male and 67% were ever smokers. Stage I and II patients comprised 83% of the cohort and the majority had adenocarcinoma (73%). From 88 FDG PET scans available, average SUVmax and SUVmean were 8.3±6.6, and 3.7±2.4 respectively. Increasing NF-κBp65 expression, but not LDHA expression, was associated with higher SUVmax and SUVmean (p=0.03 and 0.02 respectively). Both NF-κBp65 and positive FDG uptake were significantly associated with more advanced stage, tumor histology and invasion. Higher NF-κBp65 expression was associated with death by KM analysis (p=0.06) while LDHA was strongly associated with recurrence (p=0.04). Increased levels of combined NF-κBp65 and LDHA expression were synergistic and associated with both recurrence (p=0.04) and death (p=0.03).NF-κB IHC was a modest biomarker of prognosis that associated with tumor glucose metabolism on FDG PET when compared to existing molecular correlates like LDHA, which was synergistic with NF-κB for outcome. These findings recapitulate radiogenomics profiles previously reported by our group and provide a methodology for studying tumor biology using computational approaches.

  View details for DOI 10.1016/j.lungcan.2013.11.001

  View details for PubMedID 24355259

• Lung Fdg Uptake On Pet-CT Is Decreased In Patients With COPD Nair, V. S., Guo, H., Davidzon, G., Zirlinger, A., Chooljian, D. M., Mittra, E., Rubin, D. AMER THORACIC SOC. 2014

  View details for Web of Science ID 000209838203701

• Pilot Prospective Evaluation of Early Response to Bevacizumab Treatment Using the Novel PET/CT Radiopharmaceutical 18F FPPRGD2 Iagaru, A., Mosci, C., Davidzon, G., Kumar, M., Shen, B., Chin, F., Gambhir, S. S. SPRINGER. 2013: S185

  View details for Web of Science ID 000325853400290

• Biodistribution and kinetics of 18F FPPRGD2 in cancer patients Davidzon, G., Mosci, C., Mittra, E., Shen, B., Chin, F., Gambhir, S., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2013

  View details for Web of Science ID 000209478700012

• Biodistribution and kinetics of 18F FPPRGD2 in cancer patients SNMMI Davidzon, G., Mosci, C., MIttra, E., Shen, B., Chin, F., Gambhir, S., Iagaru, A. J Nucl Med. 2013
• FDG-PET/CT Initial and Subsequent Therapy Evaluation: Progressing to PET/MR Imaging. PET clinics Mosci, C., Davidzon, G. A., Quon, A. 2012; 7 (4): 369-380

  Abstract

  Diagnostic imaging plays an important role in the staging, restaging, and treatment monitoring in head and neck cancer (HNC). MR imaging and computed tomography (CT) are the primary imaging modalities for the assessment of this type of tumor; however, they have been proved to be ineffective in some cases. (18)F-2-fluoro-2-deoxy-D-glucose (FDG) PET/CT and more recently PET/MR imaging are increasingly becoming a standard part of the management of HNC. The purpose of this article is to discuss the indications and benefits of (18)F-FDG PET/CT and PET/MR imaging in the management of patients with HNC.

  View details for DOI 10.1016/j.cpet.2012.06.002

  View details for PubMedID 27157644

• A Database-driven Decision Support System: Customized Mortality Prediction. Journal of personalized medicine Celi, L. A., Galvin, S., Davidzon, G., Lee, J., Scott, D., Mark, R. 2012; 2 (4): 138-148

  Abstract

  We hypothesize that local customized modeling will provide more accurate mortality prediction than the current standard approach using existing scoring systems. Mortality prediction models were developed for two subsets of patients in Multi-parameter Intelligent Monitoring for Intensive Care (MIMIC), a public de-identified ICU database, and for the subset of patients ≥80 years old in a cardiac surgical patient registry. Logistic regression (LR), Bayesian network (BN) and artificial neural network (ANN) were employed. The best-fitted models were tested on the remaining unseen data and compared to either the Simplified Acute Physiology Score (SAPS) for the ICU patients, or the EuroSCORE for the cardiac surgery patients. Local customized mortality prediction models performed better as compared to the corresponding current standard severity scoring system for all three subsets of patients: patients with acute kidney injury (AUC = 0.875 for ANN, vs. SAPS, AUC = 0.642), patients with subarachnoid hemorrhage (AUC = 0.958 for BN, vs. SAPS, AUC = 0.84), and elderly patients undergoing open heart surgery (AUC = 0.94 for ANN, vs. EuroSCORE, AUC = 0.648). Rather than developing models with good external validity by including a heterogeneous patient population, an alternative approach would be to build models for specific patient subsets using one's local database.

  View details for DOI 10.3390/jpm2040138

  View details for PubMedID 23766893

  View details for PubMedCentralID PMC3678286

• Prognostic PET F-18-FDG Uptake Imaging Features Are Associated with Major Oncogenomic Alterations in Patients with Resected Non-Small Cell Lung Cancer CANCER RESEARCH Nair, V. S., Gevaert, O., Davidzon, G., Napel, S., Graves, E. E., Hoang, C. D., Shrager, J. B., Quon, A., Rubin, D. L., Plevritis, S. K. 2012; 72 (15): 3725-3734

  Abstract

  Although 2[18F]fluoro-2-deoxy-d-glucose (FDG) uptake during positron emission tomography (PET) predicts post-surgical outcome in patients with non-small cell lung cancer (NSCLC), the biologic basis for this observation is not fully understood. Here, we analyzed 25 tumors from patients with NSCLCs to identify tumor PET-FDG uptake features associated with gene expression signatures and survival. Fourteen quantitative PET imaging features describing FDG uptake were correlated with gene expression for single genes and coexpressed gene clusters (metagenes). For each FDG uptake feature, an associated metagene signature was derived, and a prognostic model was identified in an external cohort and then tested in a validation cohort of patients with NSCLC. Four of eight single genes associated with FDG uptake (LY6E, RNF149, MCM6, and FAP) were also associated with survival. The most prognostic metagene signature was associated with a multivariate FDG uptake feature [maximum standard uptake value (SUV(max)), SUV(variance), and SUV(PCA2)], each highly associated with survival in the external [HR, 5.87; confidence interval (CI), 2.49-13.8] and validation (HR, 6.12; CI, 1.08-34.8) cohorts, respectively. Cell-cycle, proliferation, death, and self-recognition pathways were altered in this radiogenomic profile. Together, our findings suggest that leveraging tumor genomics with an expanded collection of PET-FDG imaging features may enhance our understanding of FDG uptake as an imaging biomarker beyond its association with glycolysis.

  View details for DOI 10.1158/0008-5472.CAN-11-3943

  View details for PubMedID 22710433

• Detection of bone marrow disease in lymphoma using computer aided segmentation and analysis Davidzon, G., Peng, Z., Anand, V., Zhou, X., Quon, A. SOC NUCLEAR MEDICINE INC. 2012

  View details for Web of Science ID 000443680202233

• Utility of 18F FDG PET/CT in patients with advanced thymic neoplasms Davidzon, G., Wakelee, H., Neal, J., Mittra, E., Quon, A., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2012

  View details for Web of Science ID 000443680202308

• Utility of 18F FDG PET/CT in patients with advanced thymic neoplasms SNMMI Davidzon, G., Wakelee, H., Neal, J., Mittra, E., Quon, A., Iagaru, A. J Nucl Med. 2012
• Detection of bone marrow disease in lymphoma using computer aided segmentation and analysis SNMMI Davidzon, G., Peng, Z., Anand, V., Zhou, X., Quon, A. J Nucl Med. 2012
• Comparison of four different imaging response criteria in patients with Hodgkin and non-Hodgkin lymphoma using PET/CT Davidzon, G., Mittra, E. SOC NUCLEAR MEDICINE INC. 2011

  View details for Web of Science ID 000443798900034

• A Clinical Database-Driven Approach to Decision Support: Predicting Mortality Among Patients with Acute Kidney Injury JOURNAL OF HEALTHCARE ENGINEERING Celi, L. A., Tang, R. J., Villarroel, M. C., Davidzon, G. A., Lester, W. T., Chueh, H. C. 2011; 2 (1): 97-109

  Abstract

  In exploring an approach to decision support based on information extracted from a clinical database, we developed mortality prediction models of intensive care unit (ICU) patients who had acute kidney injury (AKI) and compared them against the Simplified Acute Physiology Score (SAPS). We used MIMIC, a public de-identified database of ICU patients admitted to Beth Israel Deaconess Medical Center, and identified 1400 patients with an ICD9 diagnosis of AKI and who had an ICU stay > 3 days. Multivariate regression models were built using the SAPS variables from the first 72 hours of ICU admission. All the models developed on the training set performed better than SAPS (AUC = 0.64, Hosmer-Lemeshow p < 0.001) on an unseen test set; the best model had an AUC = 0.74 and Hosmer-Lemeshow p = 0.53. These findings suggest that local customized modeling might provide more accurate predictions. This could be the first step towards an envisioned individualized point-of-care probabilistic modeling using one's clinical database.

  View details for DOI 10.1260/2040-2295.2.1.97

  View details for Web of Science ID 000311668900007

  View details for PubMedCentralID PMC3404157

• Comparison of four different imaging response criteria in patients with Hodgkin and non-Hodgkin lymphoma using PET/CT SNMMI Davidzon, G., Mittra, E. J Nucl Med. 2011
• Neutral lipid storage disease with subclinical myopathy due to a retrotransposal insertion in the PNPLA2 gene NEUROMUSCULAR DISORDERS Akman, H. O., Davidzon, G., Tanji, K., MacDermott, E. J., Larsen, L., Davidson, M. M., Haller, R. G., Szczepaniak, L. S., Lehman, T. J., Hirano, M., DiMauro, S. 2010; 20 (6): 397-402

  Abstract

  An 18-year-old girl referred to a rheumatologist with malar flush and Gottran papules was found to have a markedly elevated serum CK. She was a good student and an avid ballet dancer. A muscle biopsy showed massive triglyceride storage, which was also found in peripheral blood granulocytes (Jordan anomaly) and cultured skin fibroblasts. Assessment using computerized dynamometry and cycle ergometry showed normal strength and muscle energetics, but proton spectroscopy revealed severe triglyceride accumulation in both skeletal and cardiac muscle. Sequencing of PNPLA2, the gene responsible for neutral lipid storage disease with myopathy (NLSDM), revealed a retrotransposal insertion of about 1.8kb in exon 3 that abrogates transcription of PNPLA2. The sequences of CGI-58, the gene responsible for Chanarin-Dorfman syndrome (CDS), another multisystem triglyceride storage disease, and of two genes encoding lipid droplets-associated proteins, perilipin A and adipophilin, were normal. This case shows that NLSDM can be a transposon-associated disease and that massive lipid storage in muscle can present as asymptomatic hyperCKemia.

  View details for DOI 10.1016/j.nmd.2010.04.004

  View details for Web of Science ID 000279099100005

  View details for PubMedID 20471263

• Intracerebral Periventricular Pseudocysts in a Fetus with Mitochondrial Depletion Syndrome: An Association or Coincidence FETAL DIAGNOSIS AND THERAPY Rohrbach, M., Chitayat, D., Maegawa, G., Shanske, S., Davidzon, G., Chong, K., Clarke, J. T., Toi, A., Tarnopolsky, M., Robinson, B., Blaser, S. 2009; 25 (2): 177-182

  Abstract

  We report the prenatal ultrasound and magnetic resonance imaging finding of periventricular, large subependymal pseudocysts (SEPCs) in a patient who was later diagnosed as having mitochondrial depletion syndrome (MDS). To our knowledge, this is the first report of fetal SEPCs in a patient with MDS. These findings may provide an important diagnostic tool for prenatal diagnosis of MDS in at risk pregnancies when the gene mutation causing the condition has not been delineated. It may also direct the neonatologist in the postnatal care of the newborn detected prenatally with SEPCs in view of the association of this finding with infection, chromosome abnormalities, metabolic disorders and other abnormalities, when such findings are identified serendipitously. Further research is needed to find if the SEPCs detected in our patient is an association or a coincidental finding.

  View details for DOI 10.1159/000209385

  View details for Web of Science ID 000268898000001

  View details for PubMedID 19321960

• Autosomal dominant psychiatric disorders and mitochondrial DNA multiple deletions: Report of a family JOURNAL OF AFFECTIVE DISORDERS Mancuso, M., Ricci, G., Choub, A., Filosto, M., DiMauro, S., Davidzon, G., Tessa, A., Santorelli, F. M., Murri, L., Siciliano, G. 2008; 106 (1-2): 173-177

  Abstract

  Psychiatric problems, including bipolar affective disorder (BD) and schizophrenia, are common in mitochondrial diseases (MD) and frequently precede the diagnosis of mitochondrial dysfunction. However, they are rarely the only persistent manifestation of a MD and they are usually associated with other neurological or non-neurological features.Here, we describe an Italian family with multiple deletions of mtDNA in muscle, in which BD, schizophrenia, and depression recurred over several generations in the absence of other major signs of mitochondrial dysfunction.In patients with positive family history of psychiatric problems, the possibility of MD should be kept in mind, even in absence of other canonical features of mitochondrial encephalomyopathies.

  View details for DOI 10.1016/j.jad.2007.05.016

  View details for Web of Science ID 000252905300018

  View details for PubMedID 17588675

• Progressive external ophthalmoplegia and vision and hearing loss in a patient with mutations in POLG2 and OPA1 ARCHIVES OF NEUROLOGY Ferraris, S., Clark, S., Garelli, E., Davidzon, G., Moore, S. A., Kardon, R. H., Bienstock, R. J., Longley, M. J., Mancuso, M., Rios, P. G., Hirano, M., Copeland, W. C., DiMauro, S. 2008; 65 (1): 125-131

  Abstract

  To describe the clinical features, muscle pathological characteristics, and molecular studies of a patient with a mutation in the gene encoding the accessory subunit (p55) of polymerase gamma (POLG2) and a mutation in the OPA1 gene.Clinical examination and morphological, biochemical, and molecular analyses.Tertiary care university hospitals and molecular genetics and scientific computing laboratory.A 42-year-old man experienced hearing loss, progressive external ophthalmoplegia (PEO), loss of central vision, macrocytic anemia, and hypogonadism. His family history was negative for neurological disease, and his serum lactate level was normal.A muscle biopsy specimen showed scattered intensely succinate dehydrogenase-positive and cytochrome-c oxidase-negative fibers. Southern blot of muscle mitochondrial DNA showed multiple deletions. The results of screening for mutations in the nuclear genes associated with PEO and multiple mitochondrial DNA deletions, including those in POLG (polymerase gamma gene), ANT1 (gene encoding adenine nucleotide translocator 1), and PEO1, were negative, but sequencing of POLG2 revealed a G1247C mutation in exon 7, resulting in the substitution of a highly conserved glycine with an alanine at codon 416 (G416A). Because biochemical analysis of the mutant protein showed no alteration in chromatographic properties and normal ability to protect the catalytic subunit from N-ethylmaleimide, we also sequenced the OPA1 gene and identified a novel heterozygous mutation (Y582C).Although we initially focused on the mutation in POLG2, the mutation in OPA1 is more likely to explain the late-onset PEO and multisystem disorder in this patient.

  View details for Web of Science ID 000252313000017

  View details for PubMedID 18195150

  View details for PubMedCentralID PMC2364721

• SemanticDx: a prototype to facilitate use of biostatistics at the point-of-care. AMIA ... Annual Symposium proceedings / AMIA Symposium. AMIA Symposium Davidzon, G., Pankey, E., Loudon, T., Schmid, P., Berger, B., Berkowicz, D. 2008: 921-?

  Abstract

  SemanticDx is a web based clinical decision support system (CDSS) that uses a semantic web framework to integrate a knowledge base, DXplain, with a diagnostic tests sensitivity and specificity and patient demographic data to provide patient-specific positive and negative predictive values at the point of care.

  View details for PubMedID 18999188

• Juvenile Alpers disease ARCHIVES OF NEUROLOGY Wiltshire, E., Davidzon, G., DiMauro, S., Akman, H. O., Sadleir, L., Haas, L., Zuccollo, J., McEwen, A., Thorburn, D. R. 2008; 65 (1): 121-124

  Abstract

  Alpers disease is commonly associated with polymerase gamma deficiency and usually affects infants or young children.To report a juvenile case of Alpers disease due to mutations in the polymerase gamma gene (POLG1).Clinical, pathologic, biochemical, and molecular analysis.Tertiary care university hospital and academic institutions.A 17-year-old adolescent girl with intractable epilepsy and liver disease.Clinical course and pathologic, biochemical, and molecular features.Biochemical and pathologic evidence suggested a respiratory chain defect, which was confirmed by enzyme analysis of the liver. Mutational analysis of POLG1 showed 2 novel mutations: T851A and R1047W.The POLG1 mutations can cause juvenile and childhood Alpers disease.

  View details for Web of Science ID 000252313000016

  View details for PubMedID 18195149

• Abundance of the POLG disease mutations in Europe, Australia, New Zealand, and the United States explained by single ancient European founders EUROPEAN JOURNAL OF HUMAN GENETICS Hakonen, A. H., Davidzon, G., Salemi, R., Bindoff, L. A., Van Goethem, G., DiMauro, S., Thorburn, D. R., Suomalainen, A. 2007; 15 (7): 779-783

  Abstract

  We reported previously that the DNA polymerase gamma (POLG) W748S mutation, a common cause of mitochondrial recessive ataxia syndrome (MIRAS), has a common ancient founder for all the disease chromosomes in Finland, Norway, United Kingdom, and Belgium. Here, we present results showing that the same ancestral chromosome underlies MIRAS and Alpers syndrome in Australia and New Zealand. Furthermore, we show that a second common POLG mutation, A467T, also shows common European ancestry: patients from Australia, New Zealand, and the United States share a common haplotype with the previously reported European patients. These data of ancestral haplotypes indicate that the POLG locus is quite stable and that the recessive W748S and A467T mutations, and probably also G848S, have occurred once in history. They have effectively spread to populations of European descent with carrier frequencies up to 1% in several populations. Our data predict that these mutations are common causes of ataxia and Alpers disease in the Western world.

  View details for DOI 10.1038/sj.ejhg.5201831

  View details for Web of Science ID 000247436300011

  View details for PubMedID 17426723

• Severe encephalomyopathy in a patient with homoplasmic A5814G point mutation in mitochondrial tRNA(Cys) gene NEUROMUSCULAR DISORDERS Scuderi, C., Borgione, E., Musumeci, S., Elia, M., Castello, F., Fichera, M., Davidzon, G., DiMauro, S. 2007; 17 (3): 258-261

  Abstract

  We report a patient with severe encephalomyopathy and homoplasmic A5814G point mutation in the mitochondrial DNA tRNA gene for cysteine. This mutation had been reported in heteroplasmic condition in patients with different clinical phenotypes. Our results confirm the pathogenicity of the mutation and support the concept that homoplasmic mutations in tRNA genes can be responsible for mitochondrial disorders with variable penetrance. This report also extends the clinical spectrum associated with the A5814G mutation.

  View details for DOI 10.1016/j.nmd.2006.11.006

  View details for Web of Science ID 000246119600011

  View details for PubMedID 17241783

• Clinical spectrum of mitochondrial DNA depletion due to mutations in the thymidine kinase 2 gene ARCHIVES OF NEUROLOGY Oskoui, M., Davidzon, G., Pascual, J., Erazo, R., Gurgel-Giannetti, J., Krishna, S., Bonilla, E., De Vivo, D. C., Shanske, S., DiMauro, S. 2006; 63 (8): 1122-1126

  Abstract

  Mitochondrial DNA depletion syndrome is an autosomal recessive disorder characterized by decreased mitochondrial DNA copy numbers in affected tissues. It has been linked to 4 genes involved in deoxyribonucleotide triphosphate metabolism: thymidine kinase 2 (TK2), deoxyguanosine kinase (DGUOK), polymerase gamma (POLG), and SUCLA2, the gene encoding the beta-subunit of the adenosine diphosphate-forming succinyl coenzyme A synthetase ligase.To highlight the variability in the clinical spectrum of TK2-related mitochondrial DNA depletion syndrome.Review of patients and the literature.Tertiary care university.Four patients with mitochondrial DNA depletion syndrome and mutations in the TK2 gene.Definition of clinical variability.Patient 1 had evidence of lower motoneuron disease and was initially diagnosed as having spinal muscular atrophy type 3. Patient 2, who is alive and ambulatory at age 9 years, presented at age 2 years with a slowly progressive mitochondrial myopathy. Patient 3 had a more severe myopathy, with onset in infancy and death at age 6 years of respiratory failure. Patient 4 had a rapidly progressive congenital myopathy with rigid spine syndrome and he died at age 19 months.The clinical spectrum of TK2 mutations is not limited to severe infantile myopathy with motor regression and early death but includes spinal muscular atrophy type 3-like presentation, rigid spine syndrome, and subacute myopathy without motor regression and with longer survival.

  View details for Web of Science ID 000239656400011

  View details for PubMedID 16908738

• A polymorphic polymerase BRAIN DiMauro, S., Davidzon, G., Hirano, M. 2006; 129: 1637-1639

  View details for DOI 10.1093/brain/awl169

  View details for Web of Science ID 000238761200008

  View details for PubMedID 16803839

• Early-onset familial Parkinsonism due to POLG mutations ANNALS OF NEUROLOGY Davidzon, G., Greene, P., Mancuso, M., Klos, K. J., Ahlskog, J. E., Hirano, M., DiMauro, S. 2006; 59 (5): 859-862

  Abstract

  To define the molecular etiology of early-onset parkinsonism and peripheral neuropathy.Two sisters had early-onset parkinsonism (dystonic toe curling, action tremor, masked face, bradykinesia, stooped posture, and rigidity), together with clinical and electrophysiological signs of sensorimotor axonal peripheral neuropathy.No mutations were found in the genes for parkin or PINK1. Muscle biopsies showed ragged-red and cytochrome c oxidase-negative fibers, and biochemistry showed decreased activities of respiratory chain complexes containing mitochondrial DNA-encoded subunits. Multiple mitochondrial DNA deletions were seen by long polymerase chain reaction, and sequencing of the POLG gene showed that the patients were compound heterozygous for two patogenic mutations.POLG mutations can cause early-onset parkinsonism in the absence of progressive external ophthalmoplegia.

  View details for DOI 10.1002/ana.20831

  View details for Web of Science ID 000237164600020

  View details for PubMedID 16634032

• L/I-13 Donor hepatectomy morbidity based on the Clavien scale Clinical Transplantation Kinkhabwala, M., Davidzon, G., Lapointe, R., Brown, R., Emond, J. 2006; 20: 31-32

  View details for DOI 10.1111/j.1399-0012.2006.00577_3_13.x

• POLG mutations and Alpers syndrome ANNALS OF NEUROLOGY Davidzon, G., Mancuso, M., Ferraris, S., Quinzii, C., Hirano, M., Peters, H. L., Kirby, D., Thorburn, D. R., DiMauro, S. 2005; 57 (6): 921-923

  Abstract

  Alpers-Huttenlocher syndrome (AHS) an autosomal recessive hepatocerebral syndrome of early onset, has been associated with mitochondrial DNA (mtDNA) depletion and mutations in polymerase gamma gene (POLG). We have identified POLG mutations in four patients with hepatocerebral syndrome and mtDNA depletion in liver, who fulfilled criteria for AHS. All were compound heterozygous for the G848S and W748S mutations, previously reported in patients with progressive external ophtalmoplegia or ataxia. We conclude that AHS should be included in the clinical spectrum of mtDNA depletion and is often associated with POLG mutations, which can cause either multiple mtDNA deletions or mtDNA depletion.

  View details for DOI 10.1002/ana.20498

  View details for Web of Science ID 000229518300019

  View details for PubMedID 15929042

• Hereditary ferritinopathy: A novel mutation, its cellular pathology, and pathogenetic insights JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY Mancuso, M., Davidzon, G., Kurlan, R. M., Tawil, R., Bonilla, E., Di Mauro, S., Powers, J. M. 2005; 64 (4): 280-294

  Abstract

  We report a family of French Canadian and Dutch ancestry with hereditary ferritinopathy (neuroferritinopathy) and a novel mutation (C insertion at nt646-647 in exon 4) in the ferritin light chain gene, resulting in a longer than normal protein. Our failure to immunostain most of the abnormal ferritin deposits in the proband with a conformation-dependent monoclonal antibody to ferritin light chain supported a previously postulated conformational change of ferritin light chain in this disease. The posterior putamen and cerebellum were the primary pathologic loci in our proband, but asymptomatic hepatocytic intranuclear accumulations of iron and ferritin also were present. Both neurons and glia displayed highly distinctive, if not pathognomonic, swollen to vacuolated nuclei containing ferritin and iron. Hyaline deposits, again staining for both ferritin and iron, were additional morphologic features that may be unique to the ferritinopathies. The iron, at least in putamen where there was a nearly 40-fold increase, appeared to be both in the ferrous (Fe2+) and ferric (Fe3+) form; it was the most likely cause of the observed neuronal and glial apoptosis. We found morphologic evidence of both lipid peroxidation and abnormal nitration of proteins in putaminal neurons and glia, confirming the expected oxidative stress due to this excessive iron. Biochemical and immunohistochemical abnormalities in mitochondria also were demonstrated, probably due to an imbalance in iron homeostasis that had a deleterious effect on the respiratory chain.

  View details for Web of Science ID 000228339400003

  View details for PubMedID 15835264

• Mitochondrial DNA and disease ANNALS OF MEDICINE DiMauro, S., Davidzon, G. 2005; 37 (3): 222-232

  Abstract

  The small circle of mitochondrial DNA (mtDNA) present in all human cells has proven to be a veritable Pandora's box of pathogenic mutations and rearrangements. In this review, we summarize the distinctive rules of mitochondrial genetics (maternal inheritance, mitotic segregation, heteroplasmy and threshold effect), stress the relatively high prevalence of mtDNA-related diseases, and consider recent additions to the already long list of pathogenic mutations (especially mutations affecting protein-coding genes). We then discuss more controversial issues, including the functional or pathological role of mtDNA haplotypes, the pathogenicity of homoplasmic mutations and the still largely obscure pathophysiology of mtDNA mutations.

  View details for DOI 10.1080/07853890510007368

  View details for Web of Science ID 000229451400008

  View details for PubMedID 16019721

• A study to evaluate immunological response to PD-1 inhibition in squamous cell carcinoma of the head and neck (SCCHN) using novel PET imaging with [18F] F-AraG Colevas, D. A., Davidzon, G. A., Sunwoo, J. B., et al 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.6050