Dr. Guido A. Davidzon is a physician-scientist board certified in Nuclear Medicine. He is an attending physician in Nuclear Medicine and Molecular Imaging at Stanford Health Care.
He graduated with honors from medical school in Argentina and completed an internship at Yale University New-Haven Hospital in Connecticut. He did his residency and was chief resident at Stanford Health Care. He completed a research fellowship in mitochondrial diseases at Columbia University in New York and, a U.S. National Library of Medicine Award supported, Biomedical Informatics fellowship at Massachusetts General Hospital in conjunction with a Science Masters at MIT.
Dr. Davidzon is Clinical Assistant Professor in the Department of Radiology at Stanford University. His clinical specialties include early diagnostic imaging of cancer, coronary artery disease, and dementias using molecular probes as well as the treatment of cancer for which he employs targeted radiopharmaceutical therapy.
Dr. Davidzon investigates the use of machine learning in medical imaging to improve clinical outcomes, he is involved in the professional Society of Nuclear Medicine and Molecular Imaging. He serves as a peer reviewer for multiple medical journals. Dr. Davidzon is a native of Buenos Aires, Argentina and has lived in the U.S. for over a decade. He travels to Argentina frequently, with his wife and three sons.
- Nuclear Medicine
- Molecular Imaging
- Positron Emission Tomography
- Targeted Radionuclide Therapy
Clinical Assistant Professor, Radiology - Rad/Nuclear Medicine
Alt Member, Clinical Radiation Safety Committee (2017 - Present)
Director, DXA Imaging Program (2017 - Present)
Honors & Awards
First SNMMI Emerging Leader Award, SMMMI (6/2017)
Future Leaders Academy Award, SNMMI (1/2015)
Best Abstract Award Young Professionals Competition 2nd Sino-American Conference, SNMMI/CSNM (1/2013)
Best Essay Travel Award, SNMMI/ACNM (1/2012)
Nuclear Oncology Council Young Investigator Award, SNMMI (6/2011)
Boards, Advisory Committees, Professional Organizations
Vice President, SNMMI Northern California Chapter (2018 - Present)
Secretary/Treasurer, SNMMI Northern California Chapter (2016 - 2018)
Member, Radiology Faculty Diversity Committee, Stanford University (2017 - Present)
Member, Prostate Cancer Outreach Working Group, SNMMI (2017 - Present)
Board Certification: Nuclear Medicine, American Board of Nuclear Medicine (2013)
Residency:Stanford Health Services - Fellowship/Diagnostic Radiology (2013) CA
Fellowship, Massachusetts General Hospital - LCS, Clinical Informatics (2010)
SM, Massachusetts Institute of Technology, Biomedical Informatics (2010)
Internship:Yale - New Haven Hospital (2007) CT
Fellowship, Columbia University, Mitochondrial Genetic Disorders (2006)
MD with Honors, Universidad Maimonides, Argentina, Doctor in Medicine (2003)
A Pilot Study of 68Ga PSMA 11 PET/MRI and 68Ga RM2 PET/MRI for Biopsy Guidance in Patients With Suspected Prostate Cancer
The objective of the study is to evaluate 68Ga PSMA 11 PET/MRI and 68Ga RM2 PET/MRI for biopsy guidance in patients with suspected prostate cancer.
Quantitative 13N-Ammonia Cardiac Rest/Stress Digital PET/CT
Accurate measurements from a non-invasive test like myocardial perfusion positron emission tomography/ computed tomography (PET/CT) may decrease the need for invasive procedures such as cardiac catheterization.The investigators wish to see if the measurements from cardiac catheterization can be predicted using a non-invasive 13N-NH3 digital PET/CT scan.
Study to Evaluate Immunological Response to PD-1 Inhibition in Squamous Cell Carcinoma of the Head and Neck (SCCHN)
This is a single-center cross-sectional imaging and correlative biomarker study in patients with Squamous Cell Carcinoma of the Head and Neck (SCCHN). Cohort 1 will be patients with unresectable or metastatic SCCHN cancer receiving standard of care (SOC) anti-PD-1 treatment and Cohort 2 will be neoadjuvant study participants who will receive one dose of anti-PD-1 treatment prior to tumor resection or radiation. Blood sampling and tissue biopsies will be collected from both cohorts and both cohorts will undergo two whole body PET(Positron Emission Tomography)/CT(Computed Tomography) imaging with [18F]F-AraG. First scan prior to initiating anti-PD-1 treatment and second scan post initiation of anti-PD-1 treatment in Cohort 1 and prior to tumor resection or radiation in Cohort 2
EAP 177Lu-DOTA0-Tyr3-Octreotate for Inoperable, SSR+, NETs, Progressive Under SSA Tx
Advanced Accelerator Applications is currently pursuing marketing approval for 177Lu-DOTA0-Tyr3-Octreotate (Lutathera). This expanded access therapeutic protocol aims to allow patients suffering from inoperable, somatostatin receptor positive, neuroendocrine tumors, progressive under somatostatin analogue therapy to access the investigational product, 177Lu-DOTA0-Tyr3-Octreotate (Lutathera), prior to its commercial availability.
Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.
Bone Marrow and Tumor Radiomics at 18F-FDG PET/CT: Impact on Outcome Prediction in Non-Small Cell Lung Cancer.
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 2019; 53 (4): 296–99
Non-invasive quantification of tau accumulation in dementia using simultaneous F-18-PI-2620 PET/MRI
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
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
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
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
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
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.)
2019; 5 (1): 145–53
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
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
To evaluate the prognostic value of volumetric parameters calculated from 68Ga-1,4,7,10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-Thr3-octreotate (68Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT) in patients with well-differentiated neuroendocrine tumor (WD-NET).Ninety-two patients (44 men and 48 women, mean age of 59.5-year-old) with pathologically confirmed WD-NET (grades 1 or 2) were enrolled in a prospective expanded access protocol. Selected data was analyzed retrospectively for this project. Maximum standardized uptake value (SUVmax) in the lesion with the highest 68Ga-DOTATATE uptake was measured and recorded for each patient. In addition, two volumetric parameters, namely, somatostatin receptor expressing tumor volume (SRETV) and total lesion somatostatin receptor expression (TLSRE), were calculated in each 68Ga-DOTATATE-avid lesion. SRETV was defined as tumor volume with higher 68Ga-DOTATATE uptake than the 50% of SUVmax within the volume of interest (VOI) for each lesion. TLSRE was calculated by multiplying SRETV and mean SUV within the same VOI. Thereafter, the sum of SRETV (ΣSRETV) and TLSRE (ΣTLSRE) for all detected lesions per patient were calculated. Progression-free survival (PFS) was set as primary endpoint. Kaplan-Meier survival analysis, log-rank test, and Cox's proportional hazard model were used for statistical analysis.Univariate analyses revealed significant difference of PFS for WHO tumor grade and ΣSRETV (P < 0.05), while there were no significant differences in age, sex, SUVmax, and ΣTLSRE (P > 0.05). Multivariate analysis identified WHO tumor grade and ΣSRETV as independent predictors of PFS.ΣSRETV calculated from 68Ga-DOTATATE PET/CT may have prognostic value of PFS in WD-NET patients.
View details for DOI 10.1007/s00259-019-04455-9
View details for PubMedID 31350603
18F-FDG PET/MR Refines Evaluation in Newly Diagnosed Metastatic Urethral Adenocarcinoma.
Nuclear medicine and molecular imaging
2019; 53 (4): 296–99
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
Integrated Bone Marrow and Tumor Radiomics on [18F] FDG Positron Emission Tomography (PET) Augment Stage for Outcome Prediction in Non-Small Cell Lung Cancer
AMER THORACIC SOC. 2019
View details for Web of Science ID 000466776705345
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
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
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
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
SPRINGER. 2018: S713
View details for Web of Science ID 000449266206215
- Embrace Progress JOURNAL OF NUCLEAR MEDICINE 2018; 59 (7): 1169
Initial experience with a SiPM-based PET/CT scanner: influence of acquisition time on image quality
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 295.3-429.9 MBq (mean ± SD 356.3 ± 37.4) and imaging started at 71-142 min (mean ± SD 101.41 ± 17.52) after administration of the radiopharmaceutical. The patients' BMI ranged 19.79-46.16 (mean ± SD 26.55 ± 5.53). We retrospectively reconstructed the raw TOF data at 30, 60, 90, and 120 s/bed and at the standard image acquisition time per clinical protocol (180 or 210 s/bed depending on BMI). Each reconstruction was reviewed blindly by two nuclear medicine physicians and scored 1-5 (1-poor, 5-excellent quality). The liver signal-to-noise ratio (SNR) was used as a quantitative measure of image quality.The average scores ± SD of the readers were 2.61 ± 0.83, 3.70 ± 0.92, 4.36 ± 0.82, 4.82 ± 0.39, and 4.91 ± 0.91 for the 30, 60, 90, and 120 s/bed and at standard acquisition time, respectively. Inter-reader agreement on image quality assessment was good, with a weighted kappa of 0.80 (95% CI 0.72-0.81). In the evaluation of the effects of time per bed acquisition on semi-quantitative measurements, we found that the only time point significantly different from the standard time were 30 and 60 s (both with P < 0.001). The effects of dose and BMI were not statistically significant (P = 0.195 and 0.098, respectively). There was a significant positive effect of time on SNR (P < 0.001), as well as a significant negative effect of weight (P < 0.001).Our results suggest that despite significant delays from injection to imaging (due to comparison with standard PET/CT) compared to standard clinical operations and even in a population with average BMI > 25, images can be acquired as fast as 90 s/bed using the SiPM PET/CT and still result in very good image quality (average score > 4).
View details for PubMedID 29666972
Comparison Between Different PET and CT-Based Imaging Interpretation Criteria at Interim Imaging in Patients With Diffuse Large B-Cell Lymphoma
CLINICAL NUCLEAR MEDICINE
2018; 43 (1): 1–8
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
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
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.
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
2016; 18 (12)
View details for DOI 10.2196/jmir.6400
Case 207: Hodgkin lymphoma with paraneoplastic hypercalcemic pancreatitis.
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 μmol/L) (normal level, <1.2 mg/dL [<106.1 μmol/L]). A follow-up PET/CT scan was performed approximately 2 months later after initial therapy.
View details for DOI 10.1148/radiol.14120419
View details for PubMedID 24956051
NF-?B protein expression associates with (18)F-FDG PET tumor uptake in non-small cell lung cancer: A radiogenomics validation study to understand tumor metabolism.
2014; 83 (2): 189-196
We previously demonstrated that NF-κB may be associated with (18)F-FDG PET uptake and patient prognosis using radiogenomics in patients with non-small cell lung cancer (NSCLC). To validate these results, we assessed NF-κB protein expression in an extended cohort of NSCLC patients.We examined NF-κBp65 by immunohistochemistry (IHC) using a Tissue Microarray. Staining intensity was assessed by qualitative ordinal scoring and compared to tumor FDG uptake (SUVmax and SUVmean), lactate dehydrogenase A (LDHA) expression (as a positive control) and outcome using ANOVA, Kaplan Meier (KM), and Cox-proportional hazards (CPH) analysis.365 tumors from 355 patients with long-term follow-up were analyzed. The average age for patients was 67±11 years, 46% were male and 67% were ever smokers. Stage I and II patients comprised 83% of the cohort and the majority had adenocarcinoma (73%). From 88 FDG PET scans available, average SUVmax and SUVmean were 8.3±6.6, and 3.7±2.4 respectively. Increasing NF-κBp65 expression, but not LDHA expression, was associated with higher SUVmax and SUVmean (p=0.03 and 0.02 respectively). Both NF-κBp65 and positive FDG uptake were significantly associated with more advanced stage, tumor histology and invasion. Higher NF-κBp65 expression was associated with death by KM analysis (p=0.06) while LDHA was strongly associated with recurrence (p=0.04). Increased levels of combined NF-κBp65 and LDHA expression were synergistic and associated with both recurrence (p=0.04) and death (p=0.03).NF-κB IHC was a modest biomarker of prognosis that associated with tumor glucose metabolism on FDG PET when compared to existing molecular correlates like LDHA, which was synergistic with NF-κB for outcome. These findings recapitulate radiogenomics profiles previously reported by our group and provide a methodology for studying tumor biology using computational approaches.
View details for DOI 10.1016/j.lungcan.2013.11.001
View details for PubMedID 24355259
- Biodistribution and kinetics of 18F FPPRGD2 in cancer patients SNMMI J Nucl Med. 2013
FDG-PET/CT Initial and Subsequent Therapy Evaluation: Progressing to PET/MR Imaging.
2012; 7 (4): 369-380
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
2012; 2 (4): 138-148
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
2012; 72 (15): 3725-3734
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 J Nucl Med. 2012
- Detection of bone marrow disease in lymphoma using computer aided segmentation and analysis SNMMI J Nucl Med. 2012
- A Clinical Database-Driven Approach to Decision Support: Predicting Mortality Among Patients with Acute Kidney Injury JOURNAL OF HEALTHCARE ENGINEERING 2011; 2 (1): 97-109
- Comparison of four different imaging response criteria in patients with Hodgkin and non-Hodgkin lymphoma using PET/CT SNMMI J Nucl Med. 2011
Neutral lipid storage disease with subclinical myopathy due to a retrotransposal insertion in the PNPLA2 gene
2010; 20 (6): 397-402
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
2009; 25 (2): 177-182
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
2008; 106 (1-2): 173-177
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
2008; 65 (1): 125-131
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
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
2008; 65 (1): 121-124
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
2007; 15 (7): 779-783
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
2007; 17 (3): 258-261
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
2006; 63 (8): 1122-1126
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 2006; 129: 1637-1639
Early-onset familial Parkinsonism due to POLG mutations
ANNALS OF NEUROLOGY
2006; 59 (5): 859-862
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
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
2005; 57 (6): 921-923
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
2005; 64 (4): 280-294
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
2005; 37 (3): 222-232
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