Victor Gerbaudo - Academia.edu (original) (raw)
Papers by Victor Gerbaudo
European Journal of Nuclear Medicine and Molecular Imaging, 2020
Purpose Poor liver tumor visibility after microwave ablation (MWA) limits direct tumor ablation m... more Purpose Poor liver tumor visibility after microwave ablation (MWA) limits direct tumor ablation margin assessments using contrast-enhanced CT or ultrasound (US). Positron emission tomography (PET) or PET/CT may offer improved intraprocedural assessment of liver tumor ablation margins versus current imaging techniques, as 18 F-fluorodeoxyglucose (18 F-FDG)-avid tumors remain visible on PET immediately following ablation. The purpose of this study was to assess intraprocedural 18 F-FDG PET scans before and immediately after PET/CT-guided MWA for visualization and quantification of metabolic liver tumor tissue contraction resulting from MWA. Methods This retrospective study, conducted at a large academic medical center after Institutional Review Board approval, included 36 patients (20 men; mean age 63 [range 37-85]) who underwent PET/CT-guided MWA of 42 18 F-FDG-avid liver tumors from May 2013 to March 2018. Tumor metabolic diameters (short/long axes) were measured for each tumor on pre-and post-ablation PET images. Tumor metabolic volumes were calculated using tumor diameter measurements and compared with automated volumes using an SUV threshold algorithm. A two-tailed paired t test was used for the analyses. Results Comparing intraprocedural pre-and post-ablation PET images, mean metabolic tumor short-and long-axis diameters decreased from 21.4 to 14.9 mm [− 29%, p < 0.001, standard deviation (SD) 18%] and from 24.0 to 18.0 mm (− 24%, p < 0.001, SD 16%), respectively. The mean calculated tumor metabolic volume decreased from 10.5 to 4.6 mm 3 (− 55%, p < 0.001, SD 26%). The mean automated tumor metabolic volume decreased from 10.6 to 5.8 mm 3 (− 45%, p < 0.001, SD 30%). Conclusion Intraprocedural PET images of 18 F-FDG-avid liver tumors allow visualization and quantification of MWA-induced metabolic tumor tissue contraction during 18 F-FDG PET/CT-guided procedures. The ability to visualize contracted tumor immediately post-MWA may facilitate emerging intraprocedural PET and PET/CT imaging techniques that address a clinical gap in directly assessing the ablation margin.
European Journal of Radiology Open, 2020
Background: A multidisciplinary team approach to the management of esophageal cancer patients lea... more Background: A multidisciplinary team approach to the management of esophageal cancer patients leads to better clinical decisions. Purpose: The contribution of CT, endoscopic and laparoscopic ultrasound to clinical staging and treatment selection by multidisciplinary tumor boards (MTB) in patients with esophageal cancer is well documented. However, there is a paucity of data addressing the role that FDG-PET/CT (PET/CT) plays to inform the clinical decision-making process at MTB conferences. The aim of this study was to assess the impact and contribution of PET/CT to clinical management decisions and to the plan of care for esophageal cancer patients at the MTB conferences held at our institution. Materials and methods: This IRB approved study included all the cases discussed in the esophageal MTB meetings over a year period. The information contributed by PET/CT to MTB decision making was grouped into four categories. Category I, no additional information provided for clinical management; category II, equivocal and misguiding information; category III, complementary information to other imaging modalities, and category IV, information that directly changed clinical management. The overall impact on management was assessed retrospectively from prospectively discussed clinical histories, imaging, histopathology, and the official minutes of the MTB conferences. Results: 79 patients (61 males and 18 females; median age, 61 years, range, 33-86) with esophageal cancer (53 adenocarcinomas and 26 squamous cell carcinomas) were included. The contribution of PET/CT-derived information was as follows: category I in 50 patients (63%); category II in 3 patients (4%); category III in 8 patients (10%), and category IV information in 18 patients (23%). Forty-five patients (57%) had systemic disease, and in 5 (11%) of these, metastatic disease was only detected by PET/CT. In addition, PET/CT detected previously unknown recurrence in 4 (9%) of 43 patients. In summary, PET/CT provided clinically useful information to guide management in 26 of 79 esophageal cancer patients (33%) discussed at the MTB. Conclusion: The study showed that PET/CT provided additional information and changed clinical management in 1 out of 3 (33%) esophageal cancer cases discussed at MTB conferences. These results support the inclusion whenever available, of FDG-PET/CT imaging information to augment and improve the patient management decision process in MTB conferences.
Nuclear Medicine and Molecular Imaging, 2016
The increased understanding of the molecular pathology of different malignancies, especially lung... more The increased understanding of the molecular pathology of different malignancies, especially lung cancer, has directed investigational efforts to center on the identification of different molecular targets and on the development of targeted therapies against these targets. A good representative is the epidermal growth factor receptor (EGFR); a major driver of non-small cell lung cancer tumorigenesis. Today, tumor growth inhibition is possible after treating lung tumors expressing somatic mutations of the EGFR gene with tyrosine kinase inhibitors (TKI). This opened the doors to biomarkerdirected precision or personalized treatments for lung cancer patients. The success of these targeted anticancer therapies depends in part on being able to identify biomarkers and their patho-molecular make-up in order to select patients that could respond to specific therapeutic agents. While the identification of reliable biomarkers is crucial to predict response to treatment before it begins, it is also essential to be able to monitor treatment early during therapy to avoid the toxicity and morbidity of futile treatment in non-responding patients. In this context, we share our perspective on the role of PET imagingbased phenotyping in the personalized care of lung cancer patients to non-invasively direct and monitor the treatment efficacy of TKIs in clinical practice.
Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2014
Cancer Research, 2013
Lymphangioleiomyomatosis (LAM) is a female predominant lung disease characterized by widely-distr... more Lymphangioleiomyomatosis (LAM) is a female predominant lung disease characterized by widely-distributed nodules of ‘LAM’ cells and progressive cyst formation that leads to respiratory failure. LAM cells typically have mutation or inactivation of TSC2, leading to mTORC1 activation. We previously demonstrated that estrogen promotes the survival of tuberin-deficient ELT3 cells both in vitro and in vivo, and that estrogen treatment of mice bearing ELT3 cells xenograft tumors promotes lung metastasis. This estrogen-induced cell survival and metastasis was inhibited in vivo by the MEK inhibitor CI-1040. To elucidate pro-survival events mediated by estrogen in tuberin-null cells, we compared Tsc2-null ELT3 cell xenograft tumors from estrogen or placebo-treated mice using expression profiling and proteomic analysis . Expression profiling of ELT3 cell xenograft tumors revealed that estrogen upregulates the expression of genes in lipid and amino acid metabolism pathways. Among these genes, th...
Cell death & disease, 2014
Lymphangioleiomyomatosis (LAM) is a female-predominant interstitial lung disease that can lead to... more Lymphangioleiomyomatosis (LAM) is a female-predominant interstitial lung disease that can lead to respiratory failure. LAM cells typically have inactivating TSC2 mutations, leading to mTORC1 activation. The gender specificity of LAM suggests that estradiol contributes to disease development, yet the underlying pathogenic mechanisms are not completely understood. Using metabolomic profiling, we identified an estradiol-enhanced pentose phosphate pathway signature in Tsc2-deficient cells. Estradiol increased levels of cellular NADPH, decreased levels of reactive oxygen species, and enhanced cell survival under oxidative stress. Mechanistically, estradiol reactivated Akt in TSC2-deficient cells in vitro and in vivo, induced membrane translocation of glucose transporters (GLUT1 or GLUT4), and increased glucose uptake in an Akt-dependent manner. (18)F-FDG-PET imaging demonstrated enhanced glucose uptake in xenograft tumors of Tsc2-deficient cells from estradiol-treated mice. Expression ar...
The International journal of periodontics & restorative dentistry
The aim of this study was to evaluate the effects of an osteogenic medium supplemented with plate... more The aim of this study was to evaluate the effects of an osteogenic medium supplemented with platelet-derived growth factor (PDGF) BB and osteogenic protein (OP) 1 on the proliferation and differentiation of mesenchymal stem cells (MSCs) in an anorganic bovine cancellous bone scaffold. At day 7, there was a statistically significant increase in the number of cells in the scaffolds in the group treated with the medium supplemented with both PDGF-BB and OP-1 when compared with the control groups. The highest alkaline phosphate levels, at 14 and 21 days, were recorded for the samples in medium supplemented with OP-1 alone reflecting osteogenic differentiation. The results commend OP-1, as well as PDGF-BB, for incorporation into porous mineral scaffolds for vertical ridge augmentation.
Radiology, 2012
To develop and validate an open-source informatics toolkit capable of creating a radiation exposu... more To develop and validate an open-source informatics toolkit capable of creating a radiation exposure data repository from existing nuclear medicine report archives and to demonstrate potential applications of such data for quality assurance and longitudinal patient-specific radiation dose monitoring. This study was institutional review board approved and HIPAA compliant. Informed consent was waived. An open-source toolkit designed to automate the extraction of data on radiopharmaceuticals and administered activities from nuclear medicine reports was developed. After iterative code training, manual validation was performed on 2359 nuclear medicine reports randomly selected from September 17, 1985, to February 28, 2011. Recall (sensitivity) and precision (positive predictive value) were calculated with 95% binomial confidence intervals. From the resultant institutional data repository, examples of usage in quality assurance efforts and patient-specific longitudinal radiation dose monit...
Journal of applied clinical medical physics / American College of Medical Physics, Jan 15, 2011
For PET/CT, fast CT acquisition time can lead to errors in attenuation correction, particularly a... more For PET/CT, fast CT acquisition time can lead to errors in attenuation correction, particularly at the lung/diaphragm interface. Gated 4D PET can reduce motion artifacts, though residual artifacts may persist depending on the CT dataset used for attenuation correction. We performed phantom studies to evaluate 4D PET images of targets near a density interface using three different methods for attenuation correction: a single 3D CT (3D CTAC), an averaged 4D CT (CINE CTAC), and a fully phase matched 4D CT (4D CTAC). A phantom was designed with two density regions corresponding to diaphragm and lung. An 8 mL sphere phantom loaded with 18F-FDG was used to represent a lung tumor and background FDG included at an 8:1 ratio. Motion patterns of sin(x) and sin4(x) were used for dynamic studies. Image data was acquired using a GE Discovery DVCT-PET/CT scanner. Attenuation correction methods were compared based on normalized recovery coefficient (NRC), as well as a novel quantity "fixed ac...
Journal of nuclear medicine technology, 2004
A mass casualty disaster drill involving the simulated explosion of a radiation dispersal device ... more A mass casualty disaster drill involving the simulated explosion of a radiation dispersal device (dirty bomb) was performed with the participation of multiple hospitals, emergency responders, and governmental agencies. The exercise was designed to stress trauma service capacities, communications, safety, and logistic functions. We report our experience and critique of the planning, training, and execution of the exercise, with special attention to the integrated response of the Departments of Nuclear Medicine, Health Physics, and Emergency Medicine. The Health Physics Department presented multiple training sessions to the Emergency Medicine Department, Operating Room, and ancillary staff; reviewing basics of radiation biology and risk, protection standards, and detection of radiocontamination. Competency-based simulations using Geiger-Müller detectors and sealed sources were performed. Two nuclear medicine technologists played an important role in radiation discrimination-that is, a...
Annals of Clinical and Translational Neurology, 2014
ObjectiveCancer patients may experience neurologic adverse effects, such as alterations in neuroc... more ObjectiveCancer patients may experience neurologic adverse effects, such as alterations in neurocognitive function, as a consequence of chemotherapy. The mechanisms underlying such neurotoxic syndromes remain poorly understood. We here describe the temporal and regional effects of systemically administered platinum‐based chemotherapy on glucose metabolism in the brain of cancer patients.MethodsUsing sequential FDG‐PET/CT imaging prior to and after administration of chemotherapy, we retrospectively characterized the effects of intravenously administered chemotherapy on brain glucose metabolism in a total of 24 brain regions in a homogenous cohort of 10 patients with newly diagnosed non‐small‐cell lung cancer.ResultsSignificant alterations of glucose metabolism were found in response to chemotherapy in all gray matter structures, including cortical structures, deep nuclei, hippocampi, and cerebellum. Metabolic changes were also notable in frontotemporal white matter (WM) network syste...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2002
Malignant pleural mesothelioma is an aggressive primary neoplasm for which early detection and ac... more Malignant pleural mesothelioma is an aggressive primary neoplasm for which early detection and accurate staging are known diagnostic challenges. The role of (18)F-FDG dual-head gamma-camera coincidence imaging ((18)F-FDG-CI) is yet to be defined. The purpose of this study was to evaluate the usefulness of (18)F-FDG-CI in the assessment of malignant pleural mesothelioma using histopathology as the gold standard. Fifteen consecutive patients with CT scan evidence of pleural thickening, fluid, plaques, or calcification underwent (18)F-FDG imaging 1.5 h after the intravenous administration of 370 MBq (18)F-FDG. Imaging was performed with a dual-head gamma camera equipped with 2.54-cm-thick NaI crystals operating in coincidence mode. Using an iterative algorithm, whole-body images were reconstructed as transaxial, sagittal, and coronal images. No attenuation correction was applied. The results of (18)F-FDG-CI scans were compared with CT and with histopathologic diagnosis. Eleven of 15 pa...
Clinical Radiology, 2014
AIM-To investigate radiological and clinical characteristics of pathologically proven cases of in... more AIM-To investigate radiological and clinical characteristics of pathologically proven cases of intrathymic cysts. MATERIALS AND METHODS-The study population consisted of 18 patients (five males, 13 females; median age 56 years) with pathologically confirmed intrathymic cysts who underwent thymectomy and had preoperative chest computed tomography (CT) available for review. The patient demographics, clinical presentation, and preoperative radiological diagnoses were reviewed. CT images were evaluated for shape, contour, location of the cysts and the presence of
Academic Radiology, 2014
Objective: Determine the intra-and interobserver variability of thymic measurements on computed t... more Objective: Determine the intra-and interobserver variability of thymic measurements on computed tomography (CT) in patients with pathological diagnosis of thymic hyperplasia or normal thymus. Materials and Methods: Thirty-three patients with pathological diagnosis of thymic hyperplasia (n=25) or normal thymus (n=8) who had identifiable thymus gland on CT were retrospectively studied. Two radiologists independently measured thymic size and CT attenuation. Concordance correlation coefficients (CCCs) and Bland-Altman plots were used to assess intraand interobserver agreements. Results: The intra-and interobserver agreements of thymic diameters and the lobe length were moderate, with CCCs ranging 0.73-0.89 and 0.72-0.81, respectively. Higher agreement was noted among patients whose measurements were performed on the same CT image in two independent measurements, with intraobserver CCC ≥0.95 for diameters and length. After providing readers with an instruction for consistent selection of CT image for measurements, the intra-and interobserver agreement improved, resulting in CCCs ranging 0.81-0.92 and 0.77-0.85 for diameters and length, respectively. Thymic lobe thickness had the least agreement. CT attenuation measurements were highly reproducible, with CCCs ranging 0.88-0.97. In patients with thymic CT attenuation >30HU, the attenuation measurements were more reproducible with narrower 95% limits of agreement.
American journal of nuclear medicine and molecular imaging, 2015
To evaluate (18)F-labeled-fluorodeoxyglucose ((18)F-FDG-) and (18)F-labeled-sodium fluoride ((18)... more To evaluate (18)F-labeled-fluorodeoxyglucose ((18)F-FDG-) and (18)F-labeled-sodium fluoride ((18)F-NaF-) positron emission tomography/computed tomography (PET/CT) as biomarkers in metastatic castrate-resistant prostate cancer (mCRPC). Nine men (53-75 years) in a phase 1 trial of abiraterone and cabozantinib had (18)F-FDG-PET/CT, (18)F-NaF-PET/CT and standard imaging ((99m)Tc-labeled-methylene-diphosphonate ((99m)Tc-MDP) bone scan and abdominal/pelvic CT) at baseline and after 8 weeks of therapy. Baseline disease was classified as widespread (18)F-FDG-avid, oligometastatic (18)F-FDG-avid (1 site), or non-(18)F-FDG-avid. Metabolic response was classified using European Organisation for Research and Treatment of Cancer (EORTC) criteria. Treatment response using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, Prostate Cancer Working Group 2 (PCWG2) guidelines and days on trial (DOT) were recorded. All men were followed for 1 year or until progression. Four men had (18)F-FDG-a...
Thorax, 2003
Background: Malignant pleural mesothelioma is an aggressive neoplasm with a highly variable cours... more Background: Malignant pleural mesothelioma is an aggressive neoplasm with a highly variable course. This pilot study evaluated the significance of the pattern, intensity and kinetics of 18 F-FDG uptake in mesothelioma in the context of histopathology and surgical staging. Methods: Sixteen consecutive patients with pleural disease on CT scan underwent 18 F-FDG imaging. Imaging was performed with a dual detector gamma camera operating in coincidence mode. Semiquantitative image analysis was performed by obtaining lesion-to-background ratios (18 F-FDG uptake index) and calculating the increment of 18 F-FDG lesion uptake over time (malignant metabolic potential index (MMPi)). Results: Twelve patients had histologically proven malignant mesotheliomas (10 epithelial, two sarcomatoid). Thirty two lesions were positive for tumour. Patterns of uptake matched the extent of pleural and parenchymal involvement observed on CT scanning and surgery. Mean (SD) 18 F-FDG uptake index for malignant lesions was 3.99 (1.92), range 1.5-9.46. Extrathoracic spread and metastases had higher 18 F-FDG uptake indices (5.17 (2)) than primary (3.42 (1.52)) or nodal lesions (2.99 (1)). No correlation was found between histological grade and stage. The intensity of lesion uptake had poor correlation with histological grade but good correlation with surgical stage. 18 F-FDG lesion uptake increased over time at a higher rate in patients with more advanced disease. The MMPi was a better predictor of disease aggressiveness than the histological grade. Conclusions: This pilot study suggests that the pattern, intensity, and kinetics of 18 F-FDG uptake in mesothelioma are good indicators of tumour aggressiveness and are superior to the histological grade in this regard.
Physics in Medicine and Biology, 2008
Journal of Vascular and Interventional Radiology, 2011
To develop a technique for guiding percutaneous biopsies of abdominal masses in a positron emissi... more To develop a technique for guiding percutaneous biopsies of abdominal masses in a positron emission tomography (PET)/computed tomography (CT) scanner, and test its feasibility and safety in patients. Materials and Methods: The authors conducted a prospective study in 12 patients who were in need of both a diagnostic 18 F-fluoro-deoxy-D-glucose (FDG) PET/CT scan and a percutaneous biopsy of an abdominal mass, located in the liver (n ϭ 7), presacral soft tissue (n ϭ 2), lymph node (n ϭ 2), and kidney (n ϭ 1). After completion of the PET/CT scan, with the patient remaining on the table, a one-table-position PET/CT scan was obtained with a radiopaque grid in place, and the biopsy procedure was planned. Then, a biopsy needle was placed into the mass using one-table-position CT scan registered to the planning PET scan. Masses were sampled after confirming accurate positioning of the needle tips with a final one-table-position PET/CT scan. Negative results were confirmed independently with follow-up imaging. Results: All biopsy procedures yielded diagnostic results; nine were positive for malignancy, and three were negative (fibrosis, steatosis, and Escherichia coli infection). One non-FDG-avid mass biopsy yielded a malignant result. Seven masses were either invisible or poorly depicted with unenhanced CT scan, and two masses contained FDG avidity in only a portion of the mass. There were no complications. Conclusions: Although our data are preliminary, this initial experience suggests that abdominal masses can undergo successful biopsy in a PET/CT scanner. PET/CT guidance may be helpful when performing biopsy on FDG-avid masses that are either not visible with unenhanced CT or are FDG avid in only a portion. ABBREVIATIONS FDG ϭ 18 F-fluoro-deoxy-D-glucose, PET ϭ positron emission tomography, RF ϭ radiofrequency, SUV ϭ standard uptake value
Journal of Nuclear Medicine Technology, 2012
Handling and administration of radiopharmaceuticals are a key contributor to staff radiation dose... more Handling and administration of radiopharmaceuticals are a key contributor to staff radiation dose. Shielded automated infusion devices potentially standardize and reduce radiation exposure during procedures. However, loading the devices adds incremental radiation exposure, which may mitigate dose savings. We measured radiation doses from the loading and use of an automated infusion device and compared these with those from manual injection of 18 F radiotracers. Methods: Adult patients were administered 18 F-FDG or 18 F-FLT before 3-dimensional PET whole-body or brain imaging, respectively. Radioactivity amounts from manual injections performed with protective syringe shields and vial holders were measured by a standard dose calibrator before and after injection. Automated infusions were performed using the shielded infusion device. Staff wore electronic dosimeters at the wrist and trunk. Electronic dosimeters were also worn while multidose 18 F-FDG vials were loaded and unloaded. For each task, background radiation was determined and subtracted from the electronic dosimeter values. Results: Twenty-seven manually injected unit doses yielded a mean administered dose to patients of 480.7 6 66.2 MBq (12.99 6 1.79 mCi), compared with 431.9 6 22.7 MBq (11.67 6 0.61 mCi) in 34 automated injections. The mean difference was statistically significant. To control for this difference, results were expressed as a standardized dose per unit of activity. With the automated infusion device, the mean extremity dose per injection was 0.003 6 0.002 mSv/MBq, compared with 0.026 6 0.017 mSv/MBq with manual injections. Mean body dose per procedure with automated infusion was 0.001 mSv/MBq, versus 0.011 mSv/MBq with manual injection (P , 0.001). The changing of bulk 18 F-FDG vials in 37 procedures added a mean dose per vial change of 0.89 6 1.3 mSv to the extremities and 0.47 6 2.0 mSv to the body. Conclusion: The use of a shielded automatic infusion device in a clinical PET setting resulted in an approximately 10-fold decrease in staff extremity and body doses during the administration of 18 F-labeled radiopharmaceuticals. Loading and unloading bulk vials of radiotracer did not significantly offset these dose savings.
European Journal of Nuclear Medicine and Molecular Imaging, 2020
Purpose Poor liver tumor visibility after microwave ablation (MWA) limits direct tumor ablation m... more Purpose Poor liver tumor visibility after microwave ablation (MWA) limits direct tumor ablation margin assessments using contrast-enhanced CT or ultrasound (US). Positron emission tomography (PET) or PET/CT may offer improved intraprocedural assessment of liver tumor ablation margins versus current imaging techniques, as 18 F-fluorodeoxyglucose (18 F-FDG)-avid tumors remain visible on PET immediately following ablation. The purpose of this study was to assess intraprocedural 18 F-FDG PET scans before and immediately after PET/CT-guided MWA for visualization and quantification of metabolic liver tumor tissue contraction resulting from MWA. Methods This retrospective study, conducted at a large academic medical center after Institutional Review Board approval, included 36 patients (20 men; mean age 63 [range 37-85]) who underwent PET/CT-guided MWA of 42 18 F-FDG-avid liver tumors from May 2013 to March 2018. Tumor metabolic diameters (short/long axes) were measured for each tumor on pre-and post-ablation PET images. Tumor metabolic volumes were calculated using tumor diameter measurements and compared with automated volumes using an SUV threshold algorithm. A two-tailed paired t test was used for the analyses. Results Comparing intraprocedural pre-and post-ablation PET images, mean metabolic tumor short-and long-axis diameters decreased from 21.4 to 14.9 mm [− 29%, p < 0.001, standard deviation (SD) 18%] and from 24.0 to 18.0 mm (− 24%, p < 0.001, SD 16%), respectively. The mean calculated tumor metabolic volume decreased from 10.5 to 4.6 mm 3 (− 55%, p < 0.001, SD 26%). The mean automated tumor metabolic volume decreased from 10.6 to 5.8 mm 3 (− 45%, p < 0.001, SD 30%). Conclusion Intraprocedural PET images of 18 F-FDG-avid liver tumors allow visualization and quantification of MWA-induced metabolic tumor tissue contraction during 18 F-FDG PET/CT-guided procedures. The ability to visualize contracted tumor immediately post-MWA may facilitate emerging intraprocedural PET and PET/CT imaging techniques that address a clinical gap in directly assessing the ablation margin.
European Journal of Radiology Open, 2020
Background: A multidisciplinary team approach to the management of esophageal cancer patients lea... more Background: A multidisciplinary team approach to the management of esophageal cancer patients leads to better clinical decisions. Purpose: The contribution of CT, endoscopic and laparoscopic ultrasound to clinical staging and treatment selection by multidisciplinary tumor boards (MTB) in patients with esophageal cancer is well documented. However, there is a paucity of data addressing the role that FDG-PET/CT (PET/CT) plays to inform the clinical decision-making process at MTB conferences. The aim of this study was to assess the impact and contribution of PET/CT to clinical management decisions and to the plan of care for esophageal cancer patients at the MTB conferences held at our institution. Materials and methods: This IRB approved study included all the cases discussed in the esophageal MTB meetings over a year period. The information contributed by PET/CT to MTB decision making was grouped into four categories. Category I, no additional information provided for clinical management; category II, equivocal and misguiding information; category III, complementary information to other imaging modalities, and category IV, information that directly changed clinical management. The overall impact on management was assessed retrospectively from prospectively discussed clinical histories, imaging, histopathology, and the official minutes of the MTB conferences. Results: 79 patients (61 males and 18 females; median age, 61 years, range, 33-86) with esophageal cancer (53 adenocarcinomas and 26 squamous cell carcinomas) were included. The contribution of PET/CT-derived information was as follows: category I in 50 patients (63%); category II in 3 patients (4%); category III in 8 patients (10%), and category IV information in 18 patients (23%). Forty-five patients (57%) had systemic disease, and in 5 (11%) of these, metastatic disease was only detected by PET/CT. In addition, PET/CT detected previously unknown recurrence in 4 (9%) of 43 patients. In summary, PET/CT provided clinically useful information to guide management in 26 of 79 esophageal cancer patients (33%) discussed at the MTB. Conclusion: The study showed that PET/CT provided additional information and changed clinical management in 1 out of 3 (33%) esophageal cancer cases discussed at MTB conferences. These results support the inclusion whenever available, of FDG-PET/CT imaging information to augment and improve the patient management decision process in MTB conferences.
Nuclear Medicine and Molecular Imaging, 2016
The increased understanding of the molecular pathology of different malignancies, especially lung... more The increased understanding of the molecular pathology of different malignancies, especially lung cancer, has directed investigational efforts to center on the identification of different molecular targets and on the development of targeted therapies against these targets. A good representative is the epidermal growth factor receptor (EGFR); a major driver of non-small cell lung cancer tumorigenesis. Today, tumor growth inhibition is possible after treating lung tumors expressing somatic mutations of the EGFR gene with tyrosine kinase inhibitors (TKI). This opened the doors to biomarkerdirected precision or personalized treatments for lung cancer patients. The success of these targeted anticancer therapies depends in part on being able to identify biomarkers and their patho-molecular make-up in order to select patients that could respond to specific therapeutic agents. While the identification of reliable biomarkers is crucial to predict response to treatment before it begins, it is also essential to be able to monitor treatment early during therapy to avoid the toxicity and morbidity of futile treatment in non-responding patients. In this context, we share our perspective on the role of PET imagingbased phenotyping in the personalized care of lung cancer patients to non-invasively direct and monitor the treatment efficacy of TKIs in clinical practice.
Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2014
Cancer Research, 2013
Lymphangioleiomyomatosis (LAM) is a female predominant lung disease characterized by widely-distr... more Lymphangioleiomyomatosis (LAM) is a female predominant lung disease characterized by widely-distributed nodules of ‘LAM’ cells and progressive cyst formation that leads to respiratory failure. LAM cells typically have mutation or inactivation of TSC2, leading to mTORC1 activation. We previously demonstrated that estrogen promotes the survival of tuberin-deficient ELT3 cells both in vitro and in vivo, and that estrogen treatment of mice bearing ELT3 cells xenograft tumors promotes lung metastasis. This estrogen-induced cell survival and metastasis was inhibited in vivo by the MEK inhibitor CI-1040. To elucidate pro-survival events mediated by estrogen in tuberin-null cells, we compared Tsc2-null ELT3 cell xenograft tumors from estrogen or placebo-treated mice using expression profiling and proteomic analysis . Expression profiling of ELT3 cell xenograft tumors revealed that estrogen upregulates the expression of genes in lipid and amino acid metabolism pathways. Among these genes, th...
Cell death & disease, 2014
Lymphangioleiomyomatosis (LAM) is a female-predominant interstitial lung disease that can lead to... more Lymphangioleiomyomatosis (LAM) is a female-predominant interstitial lung disease that can lead to respiratory failure. LAM cells typically have inactivating TSC2 mutations, leading to mTORC1 activation. The gender specificity of LAM suggests that estradiol contributes to disease development, yet the underlying pathogenic mechanisms are not completely understood. Using metabolomic profiling, we identified an estradiol-enhanced pentose phosphate pathway signature in Tsc2-deficient cells. Estradiol increased levels of cellular NADPH, decreased levels of reactive oxygen species, and enhanced cell survival under oxidative stress. Mechanistically, estradiol reactivated Akt in TSC2-deficient cells in vitro and in vivo, induced membrane translocation of glucose transporters (GLUT1 or GLUT4), and increased glucose uptake in an Akt-dependent manner. (18)F-FDG-PET imaging demonstrated enhanced glucose uptake in xenograft tumors of Tsc2-deficient cells from estradiol-treated mice. Expression ar...
The International journal of periodontics & restorative dentistry
The aim of this study was to evaluate the effects of an osteogenic medium supplemented with plate... more The aim of this study was to evaluate the effects of an osteogenic medium supplemented with platelet-derived growth factor (PDGF) BB and osteogenic protein (OP) 1 on the proliferation and differentiation of mesenchymal stem cells (MSCs) in an anorganic bovine cancellous bone scaffold. At day 7, there was a statistically significant increase in the number of cells in the scaffolds in the group treated with the medium supplemented with both PDGF-BB and OP-1 when compared with the control groups. The highest alkaline phosphate levels, at 14 and 21 days, were recorded for the samples in medium supplemented with OP-1 alone reflecting osteogenic differentiation. The results commend OP-1, as well as PDGF-BB, for incorporation into porous mineral scaffolds for vertical ridge augmentation.
Radiology, 2012
To develop and validate an open-source informatics toolkit capable of creating a radiation exposu... more To develop and validate an open-source informatics toolkit capable of creating a radiation exposure data repository from existing nuclear medicine report archives and to demonstrate potential applications of such data for quality assurance and longitudinal patient-specific radiation dose monitoring. This study was institutional review board approved and HIPAA compliant. Informed consent was waived. An open-source toolkit designed to automate the extraction of data on radiopharmaceuticals and administered activities from nuclear medicine reports was developed. After iterative code training, manual validation was performed on 2359 nuclear medicine reports randomly selected from September 17, 1985, to February 28, 2011. Recall (sensitivity) and precision (positive predictive value) were calculated with 95% binomial confidence intervals. From the resultant institutional data repository, examples of usage in quality assurance efforts and patient-specific longitudinal radiation dose monit...
Journal of applied clinical medical physics / American College of Medical Physics, Jan 15, 2011
For PET/CT, fast CT acquisition time can lead to errors in attenuation correction, particularly a... more For PET/CT, fast CT acquisition time can lead to errors in attenuation correction, particularly at the lung/diaphragm interface. Gated 4D PET can reduce motion artifacts, though residual artifacts may persist depending on the CT dataset used for attenuation correction. We performed phantom studies to evaluate 4D PET images of targets near a density interface using three different methods for attenuation correction: a single 3D CT (3D CTAC), an averaged 4D CT (CINE CTAC), and a fully phase matched 4D CT (4D CTAC). A phantom was designed with two density regions corresponding to diaphragm and lung. An 8 mL sphere phantom loaded with 18F-FDG was used to represent a lung tumor and background FDG included at an 8:1 ratio. Motion patterns of sin(x) and sin4(x) were used for dynamic studies. Image data was acquired using a GE Discovery DVCT-PET/CT scanner. Attenuation correction methods were compared based on normalized recovery coefficient (NRC), as well as a novel quantity "fixed ac...
Journal of nuclear medicine technology, 2004
A mass casualty disaster drill involving the simulated explosion of a radiation dispersal device ... more A mass casualty disaster drill involving the simulated explosion of a radiation dispersal device (dirty bomb) was performed with the participation of multiple hospitals, emergency responders, and governmental agencies. The exercise was designed to stress trauma service capacities, communications, safety, and logistic functions. We report our experience and critique of the planning, training, and execution of the exercise, with special attention to the integrated response of the Departments of Nuclear Medicine, Health Physics, and Emergency Medicine. The Health Physics Department presented multiple training sessions to the Emergency Medicine Department, Operating Room, and ancillary staff; reviewing basics of radiation biology and risk, protection standards, and detection of radiocontamination. Competency-based simulations using Geiger-Müller detectors and sealed sources were performed. Two nuclear medicine technologists played an important role in radiation discrimination-that is, a...
Annals of Clinical and Translational Neurology, 2014
ObjectiveCancer patients may experience neurologic adverse effects, such as alterations in neuroc... more ObjectiveCancer patients may experience neurologic adverse effects, such as alterations in neurocognitive function, as a consequence of chemotherapy. The mechanisms underlying such neurotoxic syndromes remain poorly understood. We here describe the temporal and regional effects of systemically administered platinum‐based chemotherapy on glucose metabolism in the brain of cancer patients.MethodsUsing sequential FDG‐PET/CT imaging prior to and after administration of chemotherapy, we retrospectively characterized the effects of intravenously administered chemotherapy on brain glucose metabolism in a total of 24 brain regions in a homogenous cohort of 10 patients with newly diagnosed non‐small‐cell lung cancer.ResultsSignificant alterations of glucose metabolism were found in response to chemotherapy in all gray matter structures, including cortical structures, deep nuclei, hippocampi, and cerebellum. Metabolic changes were also notable in frontotemporal white matter (WM) network syste...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2002
Malignant pleural mesothelioma is an aggressive primary neoplasm for which early detection and ac... more Malignant pleural mesothelioma is an aggressive primary neoplasm for which early detection and accurate staging are known diagnostic challenges. The role of (18)F-FDG dual-head gamma-camera coincidence imaging ((18)F-FDG-CI) is yet to be defined. The purpose of this study was to evaluate the usefulness of (18)F-FDG-CI in the assessment of malignant pleural mesothelioma using histopathology as the gold standard. Fifteen consecutive patients with CT scan evidence of pleural thickening, fluid, plaques, or calcification underwent (18)F-FDG imaging 1.5 h after the intravenous administration of 370 MBq (18)F-FDG. Imaging was performed with a dual-head gamma camera equipped with 2.54-cm-thick NaI crystals operating in coincidence mode. Using an iterative algorithm, whole-body images were reconstructed as transaxial, sagittal, and coronal images. No attenuation correction was applied. The results of (18)F-FDG-CI scans were compared with CT and with histopathologic diagnosis. Eleven of 15 pa...
Clinical Radiology, 2014
AIM-To investigate radiological and clinical characteristics of pathologically proven cases of in... more AIM-To investigate radiological and clinical characteristics of pathologically proven cases of intrathymic cysts. MATERIALS AND METHODS-The study population consisted of 18 patients (five males, 13 females; median age 56 years) with pathologically confirmed intrathymic cysts who underwent thymectomy and had preoperative chest computed tomography (CT) available for review. The patient demographics, clinical presentation, and preoperative radiological diagnoses were reviewed. CT images were evaluated for shape, contour, location of the cysts and the presence of
Academic Radiology, 2014
Objective: Determine the intra-and interobserver variability of thymic measurements on computed t... more Objective: Determine the intra-and interobserver variability of thymic measurements on computed tomography (CT) in patients with pathological diagnosis of thymic hyperplasia or normal thymus. Materials and Methods: Thirty-three patients with pathological diagnosis of thymic hyperplasia (n=25) or normal thymus (n=8) who had identifiable thymus gland on CT were retrospectively studied. Two radiologists independently measured thymic size and CT attenuation. Concordance correlation coefficients (CCCs) and Bland-Altman plots were used to assess intraand interobserver agreements. Results: The intra-and interobserver agreements of thymic diameters and the lobe length were moderate, with CCCs ranging 0.73-0.89 and 0.72-0.81, respectively. Higher agreement was noted among patients whose measurements were performed on the same CT image in two independent measurements, with intraobserver CCC ≥0.95 for diameters and length. After providing readers with an instruction for consistent selection of CT image for measurements, the intra-and interobserver agreement improved, resulting in CCCs ranging 0.81-0.92 and 0.77-0.85 for diameters and length, respectively. Thymic lobe thickness had the least agreement. CT attenuation measurements were highly reproducible, with CCCs ranging 0.88-0.97. In patients with thymic CT attenuation >30HU, the attenuation measurements were more reproducible with narrower 95% limits of agreement.
American journal of nuclear medicine and molecular imaging, 2015
To evaluate (18)F-labeled-fluorodeoxyglucose ((18)F-FDG-) and (18)F-labeled-sodium fluoride ((18)... more To evaluate (18)F-labeled-fluorodeoxyglucose ((18)F-FDG-) and (18)F-labeled-sodium fluoride ((18)F-NaF-) positron emission tomography/computed tomography (PET/CT) as biomarkers in metastatic castrate-resistant prostate cancer (mCRPC). Nine men (53-75 years) in a phase 1 trial of abiraterone and cabozantinib had (18)F-FDG-PET/CT, (18)F-NaF-PET/CT and standard imaging ((99m)Tc-labeled-methylene-diphosphonate ((99m)Tc-MDP) bone scan and abdominal/pelvic CT) at baseline and after 8 weeks of therapy. Baseline disease was classified as widespread (18)F-FDG-avid, oligometastatic (18)F-FDG-avid (1 site), or non-(18)F-FDG-avid. Metabolic response was classified using European Organisation for Research and Treatment of Cancer (EORTC) criteria. Treatment response using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, Prostate Cancer Working Group 2 (PCWG2) guidelines and days on trial (DOT) were recorded. All men were followed for 1 year or until progression. Four men had (18)F-FDG-a...
Thorax, 2003
Background: Malignant pleural mesothelioma is an aggressive neoplasm with a highly variable cours... more Background: Malignant pleural mesothelioma is an aggressive neoplasm with a highly variable course. This pilot study evaluated the significance of the pattern, intensity and kinetics of 18 F-FDG uptake in mesothelioma in the context of histopathology and surgical staging. Methods: Sixteen consecutive patients with pleural disease on CT scan underwent 18 F-FDG imaging. Imaging was performed with a dual detector gamma camera operating in coincidence mode. Semiquantitative image analysis was performed by obtaining lesion-to-background ratios (18 F-FDG uptake index) and calculating the increment of 18 F-FDG lesion uptake over time (malignant metabolic potential index (MMPi)). Results: Twelve patients had histologically proven malignant mesotheliomas (10 epithelial, two sarcomatoid). Thirty two lesions were positive for tumour. Patterns of uptake matched the extent of pleural and parenchymal involvement observed on CT scanning and surgery. Mean (SD) 18 F-FDG uptake index for malignant lesions was 3.99 (1.92), range 1.5-9.46. Extrathoracic spread and metastases had higher 18 F-FDG uptake indices (5.17 (2)) than primary (3.42 (1.52)) or nodal lesions (2.99 (1)). No correlation was found between histological grade and stage. The intensity of lesion uptake had poor correlation with histological grade but good correlation with surgical stage. 18 F-FDG lesion uptake increased over time at a higher rate in patients with more advanced disease. The MMPi was a better predictor of disease aggressiveness than the histological grade. Conclusions: This pilot study suggests that the pattern, intensity, and kinetics of 18 F-FDG uptake in mesothelioma are good indicators of tumour aggressiveness and are superior to the histological grade in this regard.
Physics in Medicine and Biology, 2008
Journal of Vascular and Interventional Radiology, 2011
To develop a technique for guiding percutaneous biopsies of abdominal masses in a positron emissi... more To develop a technique for guiding percutaneous biopsies of abdominal masses in a positron emission tomography (PET)/computed tomography (CT) scanner, and test its feasibility and safety in patients. Materials and Methods: The authors conducted a prospective study in 12 patients who were in need of both a diagnostic 18 F-fluoro-deoxy-D-glucose (FDG) PET/CT scan and a percutaneous biopsy of an abdominal mass, located in the liver (n ϭ 7), presacral soft tissue (n ϭ 2), lymph node (n ϭ 2), and kidney (n ϭ 1). After completion of the PET/CT scan, with the patient remaining on the table, a one-table-position PET/CT scan was obtained with a radiopaque grid in place, and the biopsy procedure was planned. Then, a biopsy needle was placed into the mass using one-table-position CT scan registered to the planning PET scan. Masses were sampled after confirming accurate positioning of the needle tips with a final one-table-position PET/CT scan. Negative results were confirmed independently with follow-up imaging. Results: All biopsy procedures yielded diagnostic results; nine were positive for malignancy, and three were negative (fibrosis, steatosis, and Escherichia coli infection). One non-FDG-avid mass biopsy yielded a malignant result. Seven masses were either invisible or poorly depicted with unenhanced CT scan, and two masses contained FDG avidity in only a portion of the mass. There were no complications. Conclusions: Although our data are preliminary, this initial experience suggests that abdominal masses can undergo successful biopsy in a PET/CT scanner. PET/CT guidance may be helpful when performing biopsy on FDG-avid masses that are either not visible with unenhanced CT or are FDG avid in only a portion. ABBREVIATIONS FDG ϭ 18 F-fluoro-deoxy-D-glucose, PET ϭ positron emission tomography, RF ϭ radiofrequency, SUV ϭ standard uptake value
Journal of Nuclear Medicine Technology, 2012
Handling and administration of radiopharmaceuticals are a key contributor to staff radiation dose... more Handling and administration of radiopharmaceuticals are a key contributor to staff radiation dose. Shielded automated infusion devices potentially standardize and reduce radiation exposure during procedures. However, loading the devices adds incremental radiation exposure, which may mitigate dose savings. We measured radiation doses from the loading and use of an automated infusion device and compared these with those from manual injection of 18 F radiotracers. Methods: Adult patients were administered 18 F-FDG or 18 F-FLT before 3-dimensional PET whole-body or brain imaging, respectively. Radioactivity amounts from manual injections performed with protective syringe shields and vial holders were measured by a standard dose calibrator before and after injection. Automated infusions were performed using the shielded infusion device. Staff wore electronic dosimeters at the wrist and trunk. Electronic dosimeters were also worn while multidose 18 F-FDG vials were loaded and unloaded. For each task, background radiation was determined and subtracted from the electronic dosimeter values. Results: Twenty-seven manually injected unit doses yielded a mean administered dose to patients of 480.7 6 66.2 MBq (12.99 6 1.79 mCi), compared with 431.9 6 22.7 MBq (11.67 6 0.61 mCi) in 34 automated injections. The mean difference was statistically significant. To control for this difference, results were expressed as a standardized dose per unit of activity. With the automated infusion device, the mean extremity dose per injection was 0.003 6 0.002 mSv/MBq, compared with 0.026 6 0.017 mSv/MBq with manual injections. Mean body dose per procedure with automated infusion was 0.001 mSv/MBq, versus 0.011 mSv/MBq with manual injection (P , 0.001). The changing of bulk 18 F-FDG vials in 37 procedures added a mean dose per vial change of 0.89 6 1.3 mSv to the extremities and 0.47 6 2.0 mSv to the body. Conclusion: The use of a shielded automatic infusion device in a clinical PET setting resulted in an approximately 10-fold decrease in staff extremity and body doses during the administration of 18 F-labeled radiopharmaceuticals. Loading and unloading bulk vials of radiotracer did not significantly offset these dose savings.