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Guido Davidzon, MD

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Nuclear Medicine

Work and Education

Professional Education

Universidad Maimonides, Buenos Aires, Argentina, 3/15/2003


Yale - New Haven Hospital, New Haven, CT, 6/30/2007


Stanford Health Services - Fellowship/Diagnostic Radiology, Stanford, CA, 6/30/2013

Board Certifications

Nuclear Medicine, American Board of Nuclear Medicine



All Publications

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


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 (meanSD: 15.817.7). 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): 13442


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

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


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 18FDCFPyL-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


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
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
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


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% (0.5PSA<1), 56% (1PSA<2), 68% (2PSA<5), and 94% (PSA5), 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

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


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

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


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

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


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


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 A42/A40 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 A42, A40, 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 A42/A40 were independently associated with elevated p-tau181. Age, A42/A40, 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 A42/A40 on memory. Relationships between CSF proteins and delayed recall were similar but non-significant. CSF A42 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

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: S468S469
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
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: S471S472
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


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


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
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
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
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
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
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
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
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
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
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
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
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
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
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): 11719


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
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


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., Schrer, 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


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, 678years, 23 females; site 2: mMR, Siemens Healthineers, 6411years, 23 females) with different MRI protocols. Twenty minutes of list-mode PET data (90-110min 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


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 295.08.2MBq of [18F]DASA-23 intravenously. Immediately following injection, a dynamic scan of the brain was acquired for 15min. This was followed by serial whole-body PET/MRI scans acquired up to 3h 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 23.55.8Sv/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 (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


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 3months 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 45months (95% CI 24-45months). 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 16months (95% CI 12-32months) as compared with more than 60months 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 3months 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


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+ (A+) 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 90min 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 A+ 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


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, meanSD: 71.57.2) 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% (0.5PSA<1), 100% (1PSA<2), 91% (2PSA<5) and 96% (PSA5), 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: S277S278
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
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: S65S66
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


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): 29699
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: 11011
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
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
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
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
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
[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): 14553


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

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


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

18F-FDG PET/MR Refines Evaluation in Newly Diagnosed Metastatic Urethral Adenocarcinoma. Nuclear medicine and molecular imaging Laudicella, R. n., Davidzon, G. n., Vasanawala, S. n., Baldari, S. n., Iagaru, A. n. 2019; 53 (4): 29699


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

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


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

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


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

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
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


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 (SRETV) and TLSRE (TLSRE) 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 SRETV (P<0.05), while there were no significant differences in age, sex, SUVmax, and TLSRE (P>0.05). Multivariate analysis identified WHO tumor grade and SRETV as independent predictors of PFS.SRETV 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

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
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
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: S151S152
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
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

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


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 295.3-429.9MBq (meanSD 356.337.4) and imaging started at 71-142min (meanSD 101.4117.52) after administration of the radiopharmaceutical. The patients' BMI ranged 19.79-46.16 (meanSD 26.555.53). We retrospectively reconstructed the raw TOF data at 30, 60, 90, and 120s/bed and at the standard image acquisition time per clinical protocol (180 or 210s/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 scoresSD of the readers were 2.610.83, 3.700.92, 4.360.82, 4.820.39, and 4.910.91 for the 30, 60, 90, and 120s/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 60s (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 90s/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): 18


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

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
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
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)


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


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 mol/L) (normal level, <1.2 mg/dL [<106.1 mol/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


We previously demonstrated that NF-B 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-B protein expression in an extended cohort of NSCLC patients.We examined NF-Bp65 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 6711 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 8.36.6, and 3.72.4 respectively. Increasing NF-Bp65 expression, but not LDHA expression, was associated with higher SUVmax and SUVmean (p=0.03 and 0.02 respectively). Both NF-Bp65 and positive FDG uptake were significantly associated with more advanced stage, tumor histology and invasion. Higher NF-Bp65 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-Bp65 and LDHA expression were synergistic and associated with both recurrence (p=0.04) and death (p=0.03).NF-B 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-B 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

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


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

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


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

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


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

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
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


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

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


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

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


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

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


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

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


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

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


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

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


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

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


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

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-?


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

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

View details for DOI 10.1093/brain/awl169

View details for Web of Science ID 000238761200008

View details for PubMedID 16803839

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


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

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
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


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

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


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

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


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

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