Guido Davidzon

All Publications

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

  View details for Web of Science ID 000522166100252

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

  View details for Web of Science ID 000522166100274

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

  Abstract

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

  View details for DOI 10.1016/j.radcr.2019.10.022

  View details for PubMedID 31768196

• 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., Zaba, L. C., Rosenberg, J., Reddy, S. A., Nobashi, T. W., Davidzon, G., Aparici, C. M., Nguyen, J., Moradi, F., Iagaru, A., Franc, B. L. 2020

  Abstract

  The purpose of this study was to investigate the prognostic value of whole-body metabolic tumor volume (MTV) and other metabolic tumor parameters, obtained from baseline and first restaging 18F-FDG PET/CT scans in melanoma patients treated with immune checkpoint inhibitors (ICIs).Eighty-five consecutive melanoma patients (M, 57; F, 28) treated with ICIs who underwent PET/CT scans before and approximately 3 months after the start of immunotherapy were retrospectively enrolled. Metabolic tumor parameters including MTV for all melanoma lesions were measured on each scan. A Cox proportional hazards model was used for univariate and multivariate analyses of metabolic parameters combined with known clinical prognostic factors associated with overall survival (OS). Kaplan-Meier curves for patients dichotomized based on median values of imaging parameters were generated.The median OS time in all patients was 45 months (95% CI 24-45 months). Univariate analysis demonstrated that MTV obtained from first restaging PET/CT scans (MTVpost) was the strongest prognostic factor for OS among PET/CT parameters (P 

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

  View details for PubMedID 32296882

• 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., Patel, C. B., Haywood, T., Shen, B., Naya, L., Gandhi, H., Holley, D., Khalighi, M., Iagaru, A., Davidzon, G., Gambhir, S. S. 2020

  Abstract

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

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

  View details for PubMedID 31938892

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

  Abstract

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

  View details for DOI 10.2967/jnumed.119.231654

  View details for PubMedID 31628216

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

  View details for Web of Science ID 000492444402125

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

  View details for Web of Science ID 000492444405132

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

  View details for Web of Science ID 000492444400097

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

  Abstract

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

  View details for DOI 10.1148/radiol.2019190357

  View details for PubMedID 31526257

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

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

  View details for Web of Science ID 000480821000009

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

  View details for Web of Science ID 000473954100118

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

  View details for Web of Science ID 000473116801014

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

  View details for Web of Science ID 000473116801610

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

  View details for Web of Science ID 000473116801621

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

  View details for Web of Science ID 000473116801600

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

  View details for Web of Science ID 000473116801016

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

  Abstract

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

  View details for PubMedID 30854452

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

  Abstract

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

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

  View details for PubMedID 31659587

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

  View details for Web of Science ID 000466776705345

• 18F-FDG PET/MR Refines Evaluation in Newly Diagnosed Metastatic Urethral Adenocarcinoma. Nuclear medicine and molecular imaging Laudicella, R., Davidzon, G., Vasanawala, S., Baldari, S., Iagaru, A. 2019; 53 (4): 296?99

  Abstract

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

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

  View details for PubMedID 31456863

  View details for PubMedCentralID PMC6694445

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

  Abstract

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

  View details for DOI 10.1097/MNM.0000000000001088

  View details for PubMedID 31568189

• 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., Nobashi, T., Baratto, L., Duan, H., Moradi, F., Park, S., Hatami, N., Aparici, C., Davidzon, G., Iagaru, A. 2019

  Abstract

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

  View details for DOI 10.2967/jnumed.119.232504

  View details for PubMedID 31562226

• 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., Baratto, L., Nobashi, T., Park, S., Hatami, N., Davidzon, G., Kunz, P. L., Iagaru, A. 2019

  Abstract

  To evaluate the prognostic value of volumetric parameters calculated from 68Ga-1,4,7,10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-Thr3-octreotate (68Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT) in patients with well-differentiated neuroendocrine tumor (WD-NET).Ninety-two patients (44 men and 48 women, mean age of 59.5-year-old) with pathologically confirmed WD-NET (grades 1 or 2) were enrolled in a prospective expanded access protocol. Selected data was analyzed retrospectively for this project. Maximum standardized uptake value (SUVmax) in the lesion with the highest 68Ga-DOTATATE uptake was measured and recorded for each patient. In addition, two volumetric parameters, namely, somatostatin receptor expressing tumor volume (SRETV) and total lesion somatostatin receptor expression (TLSRE), were calculated in each 68Ga-DOTATATE-avid lesion. SRETV was defined as tumor volume with higher 68Ga-DOTATATE uptake than the 50% of SUVmax within the volume of interest (VOI) for each lesion. TLSRE was calculated by multiplying SRETV and mean SUV within the same VOI. Thereafter, the sum of SRETV (?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). 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

  View details for Web of Science ID 000449266206241

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

  View details for Web of Science ID 000449266201099

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

  View details for Web of Science ID 000449266201100

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

  View details for Web of Science ID 000449266206215

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

  View details for DOI 10.2967/jnumed.118.212761

  View details for Web of Science ID 000437237200044

  View details for PubMedID 29700130

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

  Abstract

  A newly introduced PET/CT scanner (Discovery Meaningful Insights-DMI, GE Healthcare) includes the silicon photomultiplier (SiPM) with time-of-flight (TOF) technology first used in the GE SIGNA PET/MRI. In this study, we investigated the impact of various acquisition times on image quality using this SiPM-based PET/CT.We reviewed data from 58 participants with cancer who were scanned using the DMI PET/CT scanner. The administered dosages ranged 295.3-429.9 MBq (mean?±?SD 356.3?±?37.4) and imaging started at 71-142 min (mean?±?SD 101.41?±?17.52) after administration of the radiopharmaceutical. The patients' BMI ranged 19.79-46.16 (mean?±?SD 26.55?±?5.53). We retrospectively reconstructed the raw TOF data at 30, 60, 90, and 120 s/bed and at the standard image acquisition time per clinical protocol (180 or 210 s/bed depending on BMI). Each reconstruction was reviewed blindly by two nuclear medicine physicians and scored 1-5 (1-poor, 5-excellent quality). The liver signal-to-noise ratio (SNR) was used as a quantitative measure of image quality.The average scores?±?SD of the readers were 2.61?±?0.83, 3.70 ±?0.92, 4.36?±?0.82, 4.82?±?0.39, and 4.91?±?0.91 for the 30, 60, 90, and 120 s/bed and at standard acquisition time, respectively. Inter-reader agreement on image quality assessment was good, with a weighted kappa of 0.80 (95% CI 0.72-0.81). In the evaluation of the effects of time per bed acquisition on semi-quantitative measurements, we found that the only time point significantly different from the standard time were 30 and 60 s (both with P??25, images can be acquired as fast as 90 s/bed using the SiPM PET/CT and still result in very good image quality (average score >?4).

  View details for PubMedID 29666972

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

  Abstract

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

  View details for DOI 10.1097/RLU.0000000000001880

  View details for Web of Science ID 000418319900001

  View details for PubMedID 29076913

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

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

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

  View details for Web of Science ID 000449980305167

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

  Abstract

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

  View details for DOI 10.1371/journal.pone.0178936

  View details for PubMedID 28582472

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

  View details for DOI 10.2196/jmir.6400

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

  Abstract

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

  Abstract

  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 67±11 years, 46% were male and 67% were ever smokers. Stage I and II patients comprised 83% of the cohort and the majority had adenocarcinoma (73%). From 88 FDG PET scans available, average SUVmax and SUVmean were 8.3±6.6, and 3.7±2.4 respectively. Increasing NF-?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
• FDG-PET/CT Initial and Subsequent Therapy Evaluation: Progressing to PET/MR Imaging. PET clinics Mosci, C., Davidzon, G. A., Quon, A. 2012; 7 (4): 369-380

  Abstract

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

  View details for DOI 10.1016/j.cpet.2012.06.002

  View details for PubMedID 27157644

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

  Abstract

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

  View details for DOI 10.3390/jpm2040138

  View details for PubMedID 23766893

  View details for PubMedCentralID PMC3678286

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

  Abstract

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

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

  View details for PubMedID 22710433

• Utility of 18F FDG PET/CT in patients with advanced thymic neoplasms SNMMI Davidzon, G., Wakelee, H., Neal, J., Mittra, E., Quon, A., Iagaru, A. J Nucl Med. 2012
• Detection of bone marrow disease in lymphoma using computer aided segmentation and analysis SNMMI Davidzon, G., Peng, Z., Anand, V., Zhou, X., Quon, A. J Nucl Med. 2012
• 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

  View details for DOI 10.1260/2040-2295.2.1.97

  View details for Web of Science ID 000311668900007

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

  Abstract

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

  View details for DOI 10.1016/j.nmd.2010.04.004

  View details for Web of Science ID 000279099100005

  View details for PubMedID 20471263

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

  Abstract

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

  View details for DOI 10.1159/000209385

  View details for Web of Science ID 000268898000001

  View details for PubMedID 19321960

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

  Abstract

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

  View details for DOI 10.1016/j.jad.2007.05.016

  View details for Web of Science ID 000252905300018

  View details for PubMedID 17588675

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

  Abstract

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

  View details for Web of Science ID 000252313000017

  View details for PubMedID 18195150

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

  Abstract

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

  View details for PubMedID 18999188

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

  Abstract

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

  View details for Web of Science ID 000252313000016

  View details for PubMedID 18195149

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

  Abstract

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

  View details for DOI 10.1038/sj.ejhg.5201831

  View details for Web of Science ID 000247436300011

  View details for PubMedID 17426723

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

  Abstract

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

  View details for DOI 10.1016/j.nmd.2006.11.006

  View details for Web of Science ID 000246119600011

  View details for PubMedID 17241783

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

  Abstract

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

  View details for Web of Science ID 000239656400011

  View details for PubMedID 16908738

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

  View details for DOI 10.1093/brain/awl169

  View details for Web of Science ID 000238761200008

  View details for PubMedID 16803839

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

  Abstract

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

  View details for DOI 10.1002/ana.20831

  View details for Web of Science ID 000237164600020

  View details for PubMedID 16634032

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

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

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

  Abstract

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

  View details for DOI 10.1002/ana.20498

  View details for Web of Science ID 000229518300019

  View details for PubMedID 15929042

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

  Abstract

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

  View details for Web of Science ID 000228339400003

  View details for PubMedID 15835264

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

  Abstract

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

  View details for DOI 10.1080/07853890510007368

  View details for Web of Science ID 000229451400008

  View details for PubMedID 16019721