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Introduction Inflammation plays a pivotal role in the pathogenesis of both Hodgkin and non-Hodgkin's lymphoma and it has been shown recently that disease burden is associated with arterial inflammation. This can be captured by 18F-fluorodeoxyglucose (18F-FDG) positron emission computed tomography (PET/CT), a commonly used imaging modality for staging and treatment response of patients with lymphoma, which has also been established as a reliable marker of arterial inflammation. Chemotherapy remains the cornerstone of lymphoma treatment; however, its direct effect on arterial 18F-FDG uptake is unknown. Purpose To investigate the effect of chemotherapy on arterial inflammation using 18F-FDG PET/CT imaging, in patients with lymphoma. Methods Sixty-six patients (22 male, mean age 56 years) with Hodgkin (n=34) or non-Hodgkin's lymphoma (n=32) underwent 18F-FDG PET/CT imaging at baseline, during and after completion of chemotherapy as part of their routine protocol. Arterial 18F-FDG uptake was assessed at the same time points by measuring the metabolic activity (maximum standardized uptake value (SUVmax) and the arterial target to background ratio (TBR)) of the aortic wall along the entire aorta. Patients with Hodgkin lymphoma underwent therapy with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). The interim scan was performed at 1 to 3 days prior to initiating the 3rd chemotherapy cycle. Patients with non-Hodgkin's lymphoma underwent therapy with cyclophosphamide, doxorubicin, vincristine and prednisone+rituximab (R-CHOP). Their interim scan was obtained at 2 weeks post the 4th chemotherapy cycle. All patients were re-assessed with 18F-FDG PET/CT imaging 6–8 weeks after chemotherapy completion. Results Baseline total aortic TBR was not associated with the presence of diabetes, dyslipidaemia or smoking (p=0.258, p=0.302 and p=0.452, respectively). Twelve patients were receiving statin therapy, however, there was no significant difference in baseline aortic TBR between patients on statins and patients who were not on statin therapy (p=0.265). In the whole study sample, the index vessel TBR progressively decreased by 0.17 from baseline to 6 weeks following the end of treatment (p=0.013 ANOVA with Bonferroni Correction, Figure 1). Conclusion Our findings suggest that arterial inflammation is reduced during and post chemotherapy in patients with lymphoma. In addition, they indicate a potential role of molecular imaging in cardio-oncology, providing a longitudinal evaluation of disease severity and its consequences to the arterial wall metabolic activity with a single examination. Funding Acknowledgement Type of funding sources: None.

To develop and test a model predicting 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) standardized uptake value (SUV) changes over time in the aorta and the superior vena cava (SVC). Maximum aortic SUV and mean SVC SUV were determined at two time points (T1 and T2) in the ascending (ASC), descending (DSC), abdominal (ABD) aorta, aortic arch (ARC) and SVC of patients who have undergone [18F]FDG PET/CT for clinical purposes. For SUV prediction at T2, linear and non-linear models of SUV difference for a given time change were developed in a derivation group. The results were tested in an independent validation group, whilst model reproducibility was tested in patients of the validation group who have undergone a second clinically indicated scan. Applying the linear model in the derivation group, there were no statistically significant differences in measurements obtained in the examined segments: mean differences ranged from 0 ± 0.10 in SVC to 0.01 ± 0.13 in ARC between measured and predicted SUV. In contrast, in the non-linear model, there were statistically significant differences in measurements, except in ARC, with mean differences ranging from 0.04 ± 0.14 in ARC to 0.28 ± 0.13 in ABD. In the validation group using the linear model, there were no statistically significant differences, with mean differences ranging from − 0.01 ± 0.08 in ASC to − 0.03 ± 0.11 in ABD. Regarding reproducibility, mean differences were no statistically significant, ranging from 0.004 ± 0.06 in ASC to − 0.02 ± 0.16 in ABD. We have developed a linear model allowing accurate and reproducible prediction of SUV changes over time in the aorta and SVC.

The aim of this study was to evaluate in an experimental model of aortic valve (AV) stenosis the effectiveness of zoledronate on the inhibition of calcification. Sixteen New Zealand rabbits were placed on vitamin D-enriched diet for 3 weeks. All animals underwent PET/CT at baseline and before euthanasia to assess calcification. Thereafter, the AVs of eight animals were treated with local delivery of 500 μg/l zoledronate. A placebo mixture was administered in the remaining eight animals. Standardized uptake values were corrected for blood pool activity, providing mean tissue to background ratios (TBRmean). In the zoledronate group, there was no progression of AV calcification (TBRmean 1.20 ± 0.12 vs 1.17 ± 0.78,p = 0.29), while AV calcification progressed in the placebo group (1.22 ± 0.15 vs 1.53 ± 0.23,p = 0.006). Ascending aorta (AA) calcification progressed in both zoledronate and placebo groups. Histology confirmed the results of the PET/CT. Inhibition of AV calcification by local delivery of zoledronate is feasible and effective.

White adipose tissue (WAT) thermogenic activity may play a role in whole-body energy balance and two of its main regulators are thought to be environmental temperature (Tenv) and exercise. Low Tenv may increase uncoupling protein one (UCP1; the main biomarker of thermogenic activity) in WAT to regulate body temperature. On the other hand, exercise may stimulate UCP1 in WAT, which is thought to alter body weight regulation. However, our understanding of the roles (if any) of Tenv and exercise in WAT thermogenic activity remains incomplete. Our aim was to examine the impacts of low Tenv and exercise on WAT thermogenic activity, which may alter energy homeostasis and body weight regulation. We conducted a series of four experimental studies, supported by two systematic reviews and meta-analyses. We found increased UCP1 mRNA (p = 0.03; but not protein level) in human WAT biopsy samples collected during the cold part of the year, a finding supported by a systematic review and meta-analysis (PROSPERO review protocol: CRD42019120116). Additional clinical trials (NCT04037371; NCT04037410) using Positron Emission Tomography/Computed Tomography (PET/CT) revealed no impact of low Tenv on human WAT thermogenic activity (p > 0.05). Furthermore, we found no effects of exercise on UCP1 mRNA or protein levels (p > 0.05) in WAT biopsy samples from a human randomized controlled trial (Clinical trial: NCT04039685), a finding supported by systematic review and meta-analytic data (PROSPERO review protocol: CRD42019120213). Taken together, the present experimental and meta-analytic findings of UCP1 and SUVmax, demonstrate that cold and exercise may play insignificant roles in human WAT thermogenic activity. Abbreviations: WAT:White adipose tissue; Tenv: Environmental temperature; UCP1: Uncoupling protein one; BAT: Brown adipose tissue; BMI:Body mass index; mRNA: Messenger ribonucleic acid; RCT: Randomized controlled trial; WHR: Waist-to-hip ratio; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-analyses; PET/CT: Positron Emission Tomography and Computed Tomography; REE: Resting energy expenditure; 18F-FDG: F18 fludeoxyglucose; VO2peak:Peak oxygen consumption; 1RM: One repetition maximum; SUVmax: Maximum standardized uptake value; Std: Standardized mean difference

Background Adipose tissue regulates energy balance and glucose homeostasis via the secretion of circulating molecules, termed adipokines, such as leptin and adiponectin. Excess adiposity and adipose tissue dysfunction have been involved in the pathogenesis of dyslipidemias. Positron emission tomography/computed tomography (PET/CT) with F-18-Fluorodeoxyglycose (FDG) has been used for the assessment of adiposity. Purpose To compare abdominal adipose tissue function assessed by FDG uptake with serum indices, such as plasma adipokines' levels in individuals with different subtypes of dyslipidemia and normolipidemics. Methods Seventy individuals (mean age 44±13 years, range 21–75, 43 men) with a clinical diagnosis of either heterozygous familial hypercholesterolemia (heFH) (n=38) or familial combined hyperlipidemia (FCH) (n=32), not under statins for at least one year, and 20 age and sex matched controls, were enrolled. Visceral (VAT) and subcutaneous adipose tissue metabolic activity (SAT) was assessed with FDG-PET/CT imaging and was quantified by calculating the target-to-background ratios (TBR) in consecutive axial fat images between the proximal (cephalic) end of the L1 and distal (caudal) end of the L3 vertebrae by dividing the average of the mean standard uptake value (SUV) to the mean SUV of the vena cava. Leptin and adiponectin were measured in all the subjects. Results There was no significant difference of plasma leptin values between FCH, heFH and non dyslipidemics subjects (p=0.204). FCH had reduced adiponectin values compared to heFH patients and controls [median 5.7 IQR (3.9–7.6) vs. 13.1 (9.2–23.3) vs. 10.9 (6.1–19.1) μg/mL, respectively, p Conclusions Visceral adipose tissue FDG uptake is reduced in patients with FCH compared to those with heFH and normolipidemics. In addition, serum adiponectin levels are lower in patients with FCH. These findings highlight the different pathophysiological role of visceral fat function in the two most common types of familial dyslipidemia and suggest that visceral fat could be an attractive target for the treatment of FCH.

BACKGROUND: Familial dyslipidemias of either heterozygous (heFH) or combined (FCH) type lead to accelerated atherogenesis and increased cardiovascular risk. OBJECTIVE: The aim of this study was to investigate in statin-naïve adult patients with familial dyslipidemias whether inflammatory activation and liver, spleen and bone marrow metabolic activity differ compared with normolipidemic subjects and between dyslipidemic groups. METHODS: Fourteen patients with FCH, 14 with heFH, and 14 normolipidemic individuals were enrolled. Serum lipids, high-sensitivity C-reactive protein, and fibrinogen levels were measured, followed by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography imaging. Radiotracer uptake in the aortic wall, spleen, bone marrow, and liver was quantified as tissue-to-background ratio (TBR). RESULTS: Patients with heFH had significantly higher low-density lipoprotein levels compared with those with FCH and controls (P CONCLUSIONS: Systemic, as well as vascular inflammation and spleen, bone marrow, and hepatic metabolic activity are increased in patients with FCH despite lower levels of low-density lipoprotein.

Familial combined hyperlipidaemia (FCH) phenotype is associated with increased prevalence of non-alcoholic fatty liver disease and obesity. No data exists regarding the impact of heterozygous familial hypercholesterolaemia (heFH), another type of familial dyslipidaemia, on liver function and

The purpose of this study was to determine whether image characteristics could be used to predict the outcome of ROC studies in PET/CT imaging. Patients suspected for recurrent thyroid cancer underwent a standard whole body (WB) examination and an additional high-resolution head-and-neck (HN) F18-FDG PET/CT scan. The value of the latter was determined with an ROC study, the results of which showed that the WB+HN combination was better than WB alone for thyroid cancer detection and diagnosis. Following the ROC experiment, the WB and HN images of confirmed benign or malignant thyroid disease were analyzed and first and second order textural features were determined. Features included minimum, mean, and maximum intensity, as well as contrast in regions of interest encircling the thyroid lesions. Lesion size and standard uptake values (SUV) were also determined. Bivariate analysis was applied to determine relationships between WB and HN features and between observer ROC responses and the various feature values. The two sets showed significant associations in the values of SUV, contrast, and lesion size. They were completely different when the intensities were considered; no relationship was found between the WB minimum, maximum, and mean ROI values and their HN counterparts. SUV and contrast were the strongest predictors of ROC performance on PET/CT examinations of thyroid cancer. The high resolution HN images seem to enhance these relationships but without a single dramatic effect as was projected from the ROC results. A combination of features from both WB and HN datasets may possibly be a more robust predictor of ROC performance.

Patients with surgically repaired coarctation of aorta (RCoA) are at increased cardiovascular mortality risk. Inflammation is an important element in RCoA.1,2 Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) is the gold-standard imaging modality to noninvasively assess vascular inflammation in vivo. In this pilot study, we explore the value of 18F-FDG PET/CT imaging in assessing aortic wall inflammation in RCoA subjects. A total of 15 patients with successful RCoA and 15 age- and sex-matched control subjects who have undergone treatment for lymphoma—a potentially high cardiovascular risk group—but were disease-free at the time of enrollment underwent 18F-FDG PET/CT to evaluate aortic wall inflammation. RCoA patients also underwent measurement of arterial elastic properties (augmentation index and carotid–femoral pulse wave velocity) by SphygmoCor (AtCor Medical, Sydney, Australia). The central arterial blood pressure was derived from the use of a generalized transfer function. Plasma levels of IL-6 (interleukin-6), TGF-β (transforming growth factor-β), and macrophage colony-stimulating factor were determined as markers of systemic inflammation and aortic wall remodeling. Patients with hypercholesterolemia or diabetes mellitus were excluded. To test the hypothesis that aortic coarctation is associated with increased aortic wall inflammation even in the absence of adverse hemodynamic burden to the aorta, patients with recoarctation were also …

Over the past few years, positron emission tomography/computed tomography (PET/CT) imaging for computer-aided diagnosis has received increasing attention. Supervised deep learning architectures are usually employed for the detection of abnormalities, with anatomical localization, especially in the case of CT scans. However, the main limitations of the supervised learning paradigm include (i) large amounts of data required for model training, and (ii) the assumption of fixed network weights upon training completion, implying that the performance of the model cannot be further improved after training. In order to overcome these limitations, we apply a few-shot learning (FSL) scheme. Contrary to traditional deep learning practices, in FSL the model is provided with less data during training. The model then utilizes end-user feedback after training to constantly improve its performance. We integrate FSL in a U-Net architecture for lung cancer lesion segmentation on PET/CT scans, allowing for dynamic model weight fine-tuning and resulting in an online supervised learning scheme. Constant online readjustments of the model weights according to the users’ feedback, increase the detection and classification accuracy, especially in cases where low detection performance is encountered. Our proposed method is validated on the Lung-PET-CT-DX TCIA database. PET/CT scans from 87 patients were included in the dataset and were acquired 60 minutes after intravenous 18F-FDG injection. Experimental results indicate the superiority of our approach compared to other state-of-the-art methods.