First-in-human assessment of the novel LAT1 targeting PET probe 18F-FIMP.

In the first-in-human PET study, we evaluated the biodistribution and tumor accumulation of the novel PET probe, (S)-2-amino-3-[3-(2-18F-fluoroethoxy)-4-iodophenyl]-2-methylpropanoic acid (18F-FIMP), which targets the tumor-related L-type amino acid transporter 1 (LAT1), and compared it with L-[methyl-11C]methionine (11C-MET) and 2-Deoxy-2-18F-fluoro-D-glucose (18F-FDG). 18F-FIMP biodistribution was revealed by whole-body and brain scans in 13 healthy controls. Tumor accumulation of 18F-FIMP was evaluated in 7 patients with a brain tumor, and compared with those of 11C-MET and 18F-FDG. None of the subjects had significant problems due to probe administration, such as adverse effects or abnormal vital signs. 18F-FIMP was rapidly excreted from the kidneys to the urinary bladder. There was no characteristic physiological accumulation in healthy controls. 18F-FIMP PET resulted in extremely clear images in patients with suspected glioblastoma compared with 11C-MET and 18F-FDG. 18F-FIMP could be a useful novel PET probe for LAT1-positive tumor imaging including glioblastoma.

Role of quantitative myocardial blood flow and 13N-ammonia washout for viability assessment in ischemic cardiomyopathy.

OBJECTIVE: Positron emission tomography (PET) integrating assessment of perfusion with 13N-ammonia (NH3) and viability with 18F-fluorodeoxyglucose (FDG) has high accuracy to identify viable, hibernating myocardium. We tested whether quantification of myocardial blood flow (MBF) and washout (k2) can predict myocardial viability using FDG as standard of reference. METHODS: In 180 consecutive patients with ischemic cardiomyopathy, myocardium was categorized on a segment-level into normal, ischemic, hibernating, and scar. From dynamic images, stress MBF, rest MBF, and k2 were derived and myocardial flow reserve (MFR) and volume of distribution (VD) were calculated. RESULTS: Across myocardial tissues, all parameters differed significantly. The area under the curve (AUC) was 0.564 (95% CI 0.527-0.601), 0.635 (0.599-0.671), 0.553 (0.516-0.591), 0.520 (0.482-0.559), and 0.560 (0.522-0.597) for stress MBF, rest MBF, MFR, k2, and VD. The generalized linear mixed model correctly classified 81% of scar as viable, hibernating myocardium. If the threshold of rest MBF to predict viability was set to 0.45 mL·min-1·g-1, sensitivity and specificity were 96% and 12%, respectively. CONCLUSION: Quantitative NH3 PET parameters have low to moderate diagnostic performance to predict viability in ischemic cardiomyopathy. However, if rest MBF falls below 0.45 mL·min-1·g-1, viability testing by FDG-PET may be safely deferred.

Functional Imaging for Therapeutic Assessment and Minimal Residual Disease Detection in Multiple Myeloma.

Serum markers and bone marrow examination are commonly used for monitoring therapy response in multiple myeloma (MM), but this fails to identify minimal residual disease (MRD), which frequently persists after therapy even in complete response patients, and extra-medullary disease escape. Positron emission tomography with computed tomography using 18F-deoxyglucose (FDG-PET/CT) is the reference imaging technique for therapeutic assessment and MRD detection in MM. To date, all large prospective cohort studies of transplant-eligible newly diagnosed MM patients have shown a strong and independent pejorative prognostic impact of not obtaining complete metabolic response by FDG-PET/CT after therapy, especially before maintenance. The FDG-PET/CT and MRD (evaluated by flow cytometry or next-generation sequencing at 10-5 and 10-6 levels, respectively) results are complementary for MRD detection outside and inside the bone marrow. For patients with at least a complete response, to reach double negativity (FDG-PET/CT and MRD) is a predictive surrogate for patient outcome. Homogenization of FDG-PET/CT interpretation after therapy, especially clarification of complete metabolic response definition, is currently underway. FDG-PET/CT does not allow MRD to be evaluated when it is negative at initial workup of symptomatic MM. New PET tracers such as CXCR4 ligands have shown high diagnostic value and could replace FDG in this setting. New sensitive functional magnetic resonance imaging (MRI) techniques such as diffusion-weighted MRI appear to be complementary to FDG-PET/CT for imaging MRD detection. The goal of this review is to examine the feasibility of functional imaging, especially FDG-PET/CT, for therapeutic assessment and MRD detection in MM.

Assessment of the Prognostic Value of Radiomic Features in 18F-FMISO PET Imaging of Hypoxia in Postsurgery Brain Cancer Patients: Secondary Analysis of Imaging Data from a Single-Center Study and the Multicenter ACRIN 6684 Trial.

Hypoxia is associated with resistance to radiotherapy and chemotherapy in malignant gliomas, and it can be imaged by positron emission tomography with 18F-fluoromisonidazole (18F-FMISO). Previous results for patients with brain cancer imaged with 18F-FMISO at a single center before conventional chemoradiotherapy showed that tumor uptake via T/Bmax (tissue SUVmax/blood SUV) and hypoxic volume (HV) was associated with poor survival. However, in a multicenter clinical trial (ACRIN 6684), traditional uptake parameters were not found to be prognostically significant, but tumor SUVpeak did predict survival at 1 year. The present analysis considered both study cohorts to reconcile key differences and examine the potential utility of adding radiomic features as prognostic variables for outcome prediction on the combined cohort of 72 patients with brain cancer (30 University of Washington and 42 ACRIN 6684). We used both 18F-FMISO intensity metrics (T/Bmax, HV, SUV, SUVmax, SUVpeak) and assessed radiomic measures that determined first-order (histogram), second-order, and higher-order radiomic features of 18F-FMISO uptake distributions. A multivariate model was developed that included age, HV, and the intensity of 18F-FMISO uptake. HV and SUVpeak were both independent predictors of outcome for the combined data set (P < .001) and were also found significant in multivariate prognostic models (P < .002 and P < .001, respectively). Further model selection that included radiomic features showed the additional prognostic value for overall survival of specific higher order texture features, leading to an increase in relative risk prediction performance by a further 5%, when added to the multivariate clinical model..

Twelve weeks of exenatide treatment increases [18F]fluorodeoxyglucose uptake by brown adipose tissue without affecting oxidative resting energy expenditure in nondiabetic males.

AIMS/HYPOTHESIS: Brown adipose tissue (BAT) improves energy metabolism by combusting glucose and lipids into heat. Agonism of the glucagon-like peptide-1 receptor (GLP-1R) within the central nervous system activates BAT in mice. Moreover, in patients with type 2 diabetes, GLP-1R agonism lowers body weight and improves glucose and lipid levels, possibly involving BAT activation. Interestingly, people from South Asian descent are prone to develop cardiometabolic disease. We studied the effect of GLP-1R agonism on BAT in humans, specifically in South Asians and Europids without obesity or type 2 diabetes. METHODS: Twelve Dutch South Asian and 12 age- and BMI-matched Europid nondiabetic men received 12 weeks extended-release exenatide (Bydureon) in this single-arm prospective study. Before and after treatment, BAT was visualized by a cold-induced [18F]FDG-PET/CT scan and a thermoneutral MRI scan, and resting energy expenditure (REE), substrate oxidation, body composition and fasting plasma glucose and serum lipids were determined. Appetite was rated using a visual analogue scale. RESULTS: Since the effect of exenatide on metabolic parameters did not evidently differ between ethnicities, data of all participants were pooled. Exenatide decreased body weight (-1.5 ±â€¯0.4 kg, p < 0.01), without affecting REE or substrate oxidation, and transiently decreased appetite ratings during the first weeks. Exenatide also lowered triglycerides (-15%, p < 0.05) and total cholesterol (-5%, p < 0.05), and tended to lower glucose levels. Notably, exenatide increased BAT metabolic volume (+28%, p < 0.05) and mean standardized uptake value (+11%, p < 0.05) ([18F]FDG-PET/CT), without affecting supraclavicular adipose tissue fat fraction (MRI). CONCLUSIONS/INTERPRETATION: We show for the first time that GLP-1R agonism increases [18F]FDG uptake by BAT in South Asian and Europid men without obesity or type 2 diabetes. TRIAL REGISTRY: Clinicaltrials.gov NCT03002675.

Clinical significance of quantitative assessment of glucose utilization in patients with ischemic cardiomyopathy.

BACKGROUND: The aim of this study was to prospectively quantify the rate of myocardial glucose uptake (MRGlu) in myocardium with different perfusion-metabolism patterns and determine its prognostic value in patients with ischemic cardiomyopathy. METHODS AND RESULTS: 79 patients with ischemic cardiomyopathy were prospectively enrolled for dynamic cardiac FDG PET, and then followed for at least 6 months. Perfusion-metabolism patterns were determined based on visual score analysis of 201Tl SPECT and FDG PET. MRGlu was analyzed using the Patlak kinetic model. The primary end-point was cardiovascular mortality. Significantly higher MRGlu was observed in viable compared with non-viable areas. Negative correlations were found between MRGlu in transmural match and a history of hyperlipidemia, statin usage, and triglyceride levels. Diabetic patients receiving dipeptidyl peptidase-4 inhibitors (DPP4i) had a significantly lower MRGlu in transmural match, mismatch, and reverse mismatch. Patients with MRGlu in transmural match ≥ 23.40 or reverse mismatch ≥ 36.90 had a worse outcome. CONCLUSIONS: Myocardial glucose utilization was influenced by substrates and medications, including statins and DPP4i. MRGlu could discriminate between viable and non-viable myocardium, and MRGlu in transmural match and reverse mismatch may be prognostic predictors of cardiovascular death in patients with ischemic cardiomyopathy.

Multiparametric assessment of left atrial remodeling using 18F-FDG PET/CT cardiac imaging: A pilot study.

BACKGROUND: Left atrial (LA) remodeling is associated with structural, electric, and metabolic LA changes. Integrated evaluation of these features in vivo is lacking. METHODS: Patients undergoing 18F-fluorodeoxyglucose (FDG) PET-CT during a hyperinsulinemic-euglycemic clamp were classified into sinus rhythm (SR), paroxysmal AF (PAF), and persistent AF (PerAF). The LA was semiautomatically segmented, and global FDG uptake was quantified using standardized uptake values (SUVmax and SUVmean) in gated, attenuation-corrected images and normalized to LA blood pool activity. Regression was used to relate FDG data to AF burden and critical patient factors. Continuous variables were compared using t-tests or Mann-Whitney tests. RESULTS: 117 patients were included (76% men, age 66.4 ± 11.0, ejection fraction (EF) 25[22-35]%) including those with SR (n = 48), PAF (n = 55), and PerAF (n = 14). Patients with any AF had increased SUVmean (2.3[1.5-2.4] vs 2.0[1.5-2.5], P = 0.006), SUVmax (4.4[2.8-6.7] vs 3.2[2.3-4.3], P < 0.001), uptake coefficient of variation (CoV) 0.28[0.22-0.40] vs 0.25[0.2-0.33], P < 0.001), and hypometabolic scar (32%[14%-53%] vs 16.5%[0%-38.5%], P = 0.01). AF burden correlated with increased SUVmean, SUVmax, CoV, and scar independent of age, gender, EF, or LA size (P < 0.03 for all). CONCLUSIONS: LA structure and metabolism can be assessed using FDG PET/CT. Greater AF burden correlates with the increased LA metabolism and scar.

Whole body FDG-PET/CT for the assessment of bone marrow infiltration in patients with newly diagnosed lymphoma.

BACKGROUND: Positron emission tomography-computed tomography (PET-CT) and bone marrow biopsy are currently the common clinical examination of lymphoma infiltration. The aim of this research is to evaluate the value of PET-CT in diagnosis of bone marrow infiltration, clinical staging and pathological typing of lymphoma. METHODS: 153 cases were analyzed retrospectively to compare the consistency of PET-CT and bone marrow biopsy. We analyzed the sensitivity, accuracy and specificity of PET-CT in different clinical pathology of lymphoma. RESULTS: The PET-CT sensitivity in detecting bone marrow infiltration is 54.3% with a specificity of 80.5% and accuracy of 74.5%. In aggressive B-cell lymphoma (DLBCL, HG-BL) and MZL, PET-CT results of bone marrow infiltration showed high accuracy of 88.1% and 83.3% respectively. The median value of SUVmax in the patients detected to have bone marrow infiltration by BMB was significantly higher than patients with BMB negative results among subgroups of aggressive B-cell lymphoma, MZL and T-NHL (p<.05). CONCLUSION: PET-CT is significant in detecting bone marrow infiltration in certain pathological types of lymphoma. However pathological inconsistencies still exist between bone marrow biopsy and PET-CT, thus PET-CT cannot completely replace biopsy.

Aortic valve stenosis-multimodality assessment with PET/CT and PET/MRI.

Aortic valve disease is the most common form of heart valve disease in developed countries and a growing healthcare burden with an ageing population. Transthoracic and transoesophageal echocardiography remains central to the diagnosis and surveillance of patients with aortic stenosis, providing gold standard assessments of valve haemodynamics and myocardial performance. However, other multimodality imaging techniques are being explored for the assessment of aortic stenosis, including combined PET/CT and PET/MR. Both approaches provide unique information with respect to disease activity in the valve alongside more conventional anatomic assessments of the valve and myocardium in this condition. This review investigates the emerging use of PET/CT and PET/MR to assess patients with aortic stenosis, examining how the complementary data provided by each modality may be used for research applications and potentially in future clinical practice.

Correlation analysis of 18F-FDG PET/CT for the staging and treatment effect assessment of breast cancer.

OBJECTIVE: Since cancer treatment and outcome differ among the patients diagnosed with breast cancer at different stages, this study aims to elucidate the factors associated with PET/CT staging, treatment effect, and maximal standardized uptake value (SUVmax) in breast cancer patients. METHODS: Twenty-eight patients who underwent two PET/CT examinations with the complete pathological and immunohistochemical data were retrospectively reviewed. Pearson and Spearman correlation analyses were performed to investigate the relationships of patient PET/CT staging (first round PET/CT), treatment effect (comparison between the results of two rounds of PET/CT), and tumor SUVmax, with respect to patient age, tumor location, tumor long diameter, short diameter, time of first round PET/CT examination, histological type and grade, axillary lymph node metastasis rate, interval between the two PET/CT examinations, treatment method, and the expression of the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), P53, and Ki67. RESULTS: PET/CT staging (first round PET/CT) relates to HER2 and Ki67 expression with the correlation coefficients of 0.432 and 0.552, and P-values of 0.022 and 0.002, respectively. The treatment effect (comparison between the results of two rounds of PET/CT) associates with tumor site and P53 expression in which the correlation coefficients are - 0.412 and 0.845, and P-values are 0.029 and 0.000, respectively. The measured SUVmax correlates well with the tumor long diameter, short diameter, and treatment effect in which the correlation coefficients are 0.943, 0.886, and 0.878, and P-values are 0.005, 0.019, and 0.02, respectively. CONCLUSIONS: Study results indicate that PET/CT staging and treatment effect associate well with SUVmax and immunohistochemical results of tumor, while SUVmax of tumor associates well with tumor size.

In vivo assessment of neuroinflammation in progressive multiple sclerosis: a proof of concept study with [18F]DPA714 PET.

BACKGROUND: Over the past decades, positron emission tomography (PET) imaging has become an increasingly useful research modality in the field of multiple sclerosis (MS) research, as PET can visualise molecular processes, such as neuroinflammation, in vivo. The second generation PET radioligand [18F]DPA714 binds with high affinity to the 18-kDa translocator-protein (TSPO), which is mainly expressed on activated microglia. The aim of this proof of concept study was to evaluate this in vivo marker of neuroinflammation in primary and secondary progressive MS. METHODS: All subjects were genotyped for the rs6971 polymorphism within the TSPO gene, and low-affinity binders were excluded from participation in this study. Eight patients with progressive MS and seven age and genetic binding status matched healthy controls underwent a 60 min dynamic PET scan using [18F]DPA714, including both continuous on-line and manual arterial blood sampling to obtain metabolite-corrected arterial plasma input functions. RESULTS: The optimal model for quantification of [18F]DPA714 kinetics was a reversible two-tissue compartment model with additional blood volume parameter. For genetic high-affinity binders, a clear increase in binding potential was observed in patients with MS compared with age-matched controls. For both high and medium affinity binders, a further increase in binding potential was observed in T2 white matter lesions compared with non-lesional white matter. Volume of distribution, however, did not differentiate patients from healthy controls, as the large non-displaceable compartment of [18F]DPA714 masks its relatively small specific signal. CONCLUSION: The TSPO radioligand [18F]DPA714 can reliably identify increased focal and diffuse neuroinflammation in progressive MS when using plasma input-derived binding potential, but observed differences were predominantly visible in high-affinity binders.

CT-guided percutaneous core biopsy for assessment of morphologically normal adrenal glands showing high FDG uptake in patients with lung cancer.

OBJECTIVE:: Increased fludeoxyglucose (FDG) uptake in morphologically normal adrenal glands on positron emission tomography-CT (PET-CT) is a diagnostic challenge with major implications on treatment. The purpose of this retrospective study was to report our experience of CT-guided percutaneous core biopsy of morphologically normal adrenal glands showing increased FDG uptake in a context of lung cancer. METHODS:: Biopsies for non-enlarged adrenal glands showing increased FDG uptake in lung cancer patients performed at our institution from December 2014 to December 2016 were retrospectively analyzed. Six biopsies were performed in five patients during the study period. All procedures were performed with the patients in the prone position, using a posterior approach and coaxial 17-gauge needles with 18-gauge automated cutting needles. Patient characteristics, procedural details and final pathological diagnosis were analyzed, as well as the duration of hospitalization. RESULTS:: Five of the six biopsies (83.3%) confirmed adrenal metastasis from the primary lung cancer. No complications were reported and the patients were discharged the day after the procedure. CONCLUSION:: The high confirmation rate of metastasis and lack of complications support performing CT-guided percutaneous biopsy of non-enlarged adrenal glands showing increased FDG uptake, for optimal management in lung cancer patients. ADVANCES IN KNOWLEDGE:: Morphologically normal adrenal glands showing high FDG uptake in patients with lung cancer are metastasis. This manuscript shows that CT-guided percutaneous biopsy should be proposed. Increased FDG uptake in morphologically normal adrenal glands may indicate metastasis.

Capsinoids activate brown adipose tissue (BAT) with increased energy expenditure associated with subthreshold 18-fluorine fluorodeoxyglucose uptake in BAT-positive humans confirmed by positron emission tomography scan.

Background: Capsinoids are reported to increase energy expenditure (EE) via brown adipose tissue (BAT) stimulation. However, imaging of BAT activation by capsinoids remains limited. Because BAT activation is a potential therapeutic strategy for obesity and related metabolic disorders, we sought to prove that capsinoid-induced BAT activation can be visualized by 18-fluorine fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). Objective: We compared capsinoids and cold exposure on BAT activation and whole-body EE. Design: Twenty healthy participants (8 men, 12 women) with a mean age of 26 y (range: 21-35 y) and a body mass index (kg/m2) of 21.7 (range: 18.5-26.0) underwent 18F-FDG PET and whole-body calorimetry after ingestion of 12 mg capsinoids or ≤2 h of cold exposure (∼14.5°C) in a crossover design. Mean standardized uptake values (SUVs) of the region of interest and BAT volumes were calculated. Blood metabolites were measured before and 2 h after each treatment. Results: All of the participants showed negligible 18F-FDG uptake post-capsinoid ingestion. Upon cold exposure, 12 participants showed avid 18F-FDG uptake into supraclavicular and lateral neck adipose tissues (BAT-positive group), whereas the remaining 8 participants (BAT-negative group) showed undetectable uptake. Capsinoids and cold exposure increased EE, although cold induced a 2-fold increase in whole-body EE and higher fat oxidation, insulin sensitivity, and HDL cholesterol compared with capsinoids. Conclusions: Capsinoids only increased EE in BAT-positive participants, which suggests that BAT mediates EE evoked by capsinoids. This implies that capsinoids stimulate BAT to a lesser degree than cold exposure as evidenced by 18F-FDG uptake below the presently accepted SUV thresholds defining BAT activation. This trial was registered at www.clinicaltrials.gov as NCT02964442.

Assessment of alteration in liver 18F-FDG uptake due to steatosis in lymphoma patients and its impact on the Deauville score.

AIM: Our aim was (1) to evaluate the prevalence of steatosis in lymphoma patients and its evolution during treatment; (2) to evaluate the impact of hepatic steatosis on 18F-FDG liver uptake; and (3) to study how hepatic steatosis affects the Deauville score (DS) for discriminating between responders and non-responders. METHODS: Over a 1-year period, 358 PET scans from 227 patients [122 diffuse large B cell lymphoma (DLBCL), 57 Hodgkin lymphoma (HL) and 48 Follicular lymphoma (FL)] referred for baseline (n = 143), interim (n = 79) and end-of-treatment (EoT, n = 136) PET scans were reviewed. Steatosis was diagnosed on the unenhanced CT part of PET/CT examinations using a cut-off value of 42 Hounsfield units (HU). EARL-compliant SULmax were recorded on the liver and the tumour target lesion. DS were then computed. RESULTS: Prevalence of steatosis at baseline, interim and EoT PET was 15/143 (10.5%), 6/79 (7.6%) and 16/136 (11.8%), respectively (p = 0.62).Ten out of 27 steatotic patients (37.0%) displayed a steatotic liver on all examinations. Six patients (22.2%) had a disappearance of hepatic steatosis during their time-course of treatment. Only one patient developed steatosis during his course of treatment. Liver SULmax values were significantly lower in the steatosis versus non-steatotic groups of patients for interim (1.66 ± 0.36 versus 2.15 ± 0.27) and EoT (1.67 ± 0.29 versus 2.17 ± 0.30) PET. CT density was found to be an independent factor that correlated with liver SULmax, while BMI, blood glucose level and the type of chemotherapy regimen were not. Using a method based on this correlation to correct liver SULmax, all DS4 steatotic patients on interim (n = 1) and EoT (n = 2) PET moved to DS3. CONCLUSIONS: Steatosis is actually a theoretical but not practical issue in most patients but should be recognised and corrected in appropriate cases, namely, for those patients scored DS4 with a percentage difference between the target lesion and the liver background lower than 30%.

Semiquantitative Assessment of 18F-FDG Uptake in the Normal Skeleton: Comparison Between PET/CT and Time-of-Flight Simultaneous PET/MRI.

OBJECTIVE: Differences in the attenuation correction methods used in PET/CT scanners versus the newly introduced whole-body simultaneous PET/MRI reportedly result in differences in standardized uptake values (SUVs) in the normal skeleton. The aim of the study was to compare the semiquantitative FDG uptake in the normal skeleton using time-of-flight (TOF) PET/MRI versus PET/CT with and without TOF. SUBJECTS AND METHODS: Participants received a single FDG injection and underwent non-TOF and TOF PET/CT (n = 23) or non-TOF PET/CT and TOF PET/MRI (n = 50). Mean SUV (SUVmean) and maximum SUV (SUVmax) were measured from all PET scans for nine normal regions of the skeleton. Pearson correlation coefficients (r) were used to evaluate the SUVmax and SUVmean of normal skeleton between non-TOF and TOF PET/CT, as well as between non-TOF PET/CT and TOF PET/MRI. In addition, percentage differences in SUVmax and SUVmean of the normal skeleton between non-TOF and TOF PET/CT and between non-TOF PET/CT and TOF PET/MRI were evaluated. RESULTS: The SUVmax and SUVmean in the normal skeleton significantly increased between non-TOF and TOF PET/CT, but they significantly decreased between non-TOF PET/CT and TOF PET/MRI. The SUVmax and SUVmean in normal skeleton showed good correlation between non-TOF PET/CT and TOF PET/MRI (SUVmax, r = 0.88; SUVmean, r = 0.91) and showed a similar trend between non-TOF and TOF PET/CT (SUVmax, r = 0.88; SUVmean, r = 0.94). CONCLUSION: In the normal skeleton, SUVmax and SUVmean showed high correlations between PET/MRI and PET/CT. The MRI attenuation correction used in TOF PET/MRI provides reliable semiquantitative measurements in the normal skeleton.

Hibernating substrate of ventricular tachycardia: a three-dimensional metabolic and electro-anatomic assessment.

PURPOSE: Hibernating myocardium (HM) is associated with sudden cardiac death (SCD). Little is known about the electrophysiological properties of HM and the basis of its association with SCD. We aimed to electrophysiologically characterize HM in patients with ventricular tachycardia (VT). METHODS: Endocardial voltage mapping, metabolic 18FDG-positron emission tomography (PET) and perfusion 82Rb, 201Tl, or 99mTc scans were performed in 61 ischemic heart disease patients with VT. Hibernating areas were identified which was followed by three-dimensional PET reconstructions and integration with voltage maps to allow hybrid metabolic-electro-anatomic assessment of the arrhythmogenic substrate. RESULTS: Of 61 patients with ischemic heart disease and refractory VT, 7 were found to have hibernating myocardium (13%). A total of 303 voltage points were obtained within hibernating myocardium (8.2 points per 10 cm2) and displayed abnormal voltage in 48.5 and 78.3% of bipolar and unipolar recordings, respectively, with significant heterogeneity of bipolar (p < 0.0001) and unipolar voltage measurements (p = 0.0004). Hibernating areas in 6 of 7 patients contained all three categories of bipolar voltage-defined scar (<0.5 mV), border zone (0.5-1.5 mV), and normal myocardium (>1.5 mV). The characteristics of local electrograms were also assessed and found abnormal in most recordings (76.6, 10.2% fractionated, 5.3% isolated potentials). Exit sites of clinical VTs were determined in 6 patients, of which 3 were located within hibernating myocardium. CONCLUSIONS: Hibernating myocardium displays abnormal and heterogeneous electrical properties and seems to contribute to the substrate of VT. These observations may underlie the vulnerability to reentry and SCD in patients with hypoperfused yet viable myocardium.

Lung Nodule with Increasing Fluorodeoxyglucose Uptake in a Patient with a History of Lung Carcinoma and Talc Pleurodesis Evaluated by EBUS-TBNA On-Site Assessment.

BACKGROUND: Fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan is an indicator of potential malignancy or infection. Patients with a history of talc pleurodesis can develop pleural or lung parenchymal nodules/talcomas. In these patients, talc-associated (non-malignancy-related) FDG uptake may occur over years. CASE REPORT: A 66-year-old female presented with a past medical history significant for resected non-small-cell lung cancer and was treated with chemotherapy/radiation. The referring physician indicated that she subsequently developed benign pleural effusions and had talc pleurodesis to limit recurrence. The patient was referred to our institution for endobronchial ultrasound-guided transbronchial fine-needle aspiration (EBUS-TBNA) due to a new left upper lobe nodule with increasing FDG uptake on follow-up interval PET performed at the referring institution. On-site cytologic evaluation showed no evidence of malignancy, but found refractile foreign material, consistent with the presence of talc particles. CONCLUSION: This case presents the importance of cytologic recognition of talc particles during on-site evaluation and discusses the phenomenon of increasing PET-FDG uptake associated with talc pleurodesis.

The roles of 18F-FDG-PET/CT and US-guided FNAC in assessment of axillary nodal metastases in breast cancer patients.

BACKGROUND: There is a need for less invasive techniques for preoperative identification of axillary lymph node (ALN) metastases. METHOD: Patients underwent ultrasonography (US) and 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT), and then US-guided fine needle aspiration cytology (FNAC) and/or sentinel lymph node (SLN) biopsy were performed based on the US findings of the ALNs. Subsequently, patients with positive FNAC as well as those with positive SLN underwent axillary lymph node dissection (ALND). Postoperatively, removed SLNs and ALNs were examined histologically. RESULTS: Fifty (85 %) of 59 patients with positive 18F-FDG uptake in the axilla had axillary metastases, but 18F-FDG uptake results were false-positive in 9 (15 %) cases. On the other hand, 29 patients with positive FNAC underwent ALND without the need for SLN biopsy, while the remaining 20 patients with negative FNAC as well as 249 patients with negative US findings underwent SLN biopsy. Subsequently, 68 patients with positive SLN underwent ALND. CONCLUSIONS: Positive FDG uptake in the axilla does not always indicate axillary metastasis. US-guided FNAC is useful to avoid unnecessary ALND in patients with positive 18F-FDG uptake. However, SLN biopsy is needed in patients with negative US findings of the ALNs and those with negative FNAC.

Noninvasive measurement of radiopharmaceutical time-activity data using external thermoluminescent dosimeters (TLDs).

In this study, we present a new method for estimating the time-activity data using serial timely measurements of thermoluminescent dosimeters (TLDs). The approach is based on the combination of the measurement of surface dose using TLD and Monte Carlo (MC) simulation to estimate the radiopharmaceutical time-activity data. It involves four steps: (1) identify the source organs and outline their contours in computed tomography images; (2) compute the S values on the body surface for each source organ using a MC code; (3) obtain a serial measurement of the dose with numerous TLDs placed on the body surface; (4) solve the dose-activity equation to generate organ cumulative activity for each period of measurement. The activity of each organ at the time of measurement is simply the cumulative activity divided by the timespan between measurements. The usefulness of this method was studied using a MC simulation based on an Oak Ridge National Laboratory mathematical phantom with 18F-FDG filled in six source organs. Numerous TLDs were placed on different locations of the surface and were repeatedly read and replaced. The time-activity curves (TACs) of all organs were successfully reconstructed. Experiments on a physical phantom were also performed. Preliminary results indicate that it is an effective, robust, and simple method for assessing the TAC. The proposed method holds great potential for a range of applications in areas such as targeted radionuclide therapy, pharmaceutical research, and patient-specific dose estimation.