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Context and objectives: Recent studies have shown the potential benefits of using 177Lu-based Peptide Receptor Radionuclide Therapy (PRRT) in neuroendocrine tumors. For 177Lu-based and other radionuclide therapies, it appears that a robust Monte Carlo-based internal dosimetry framework is highly desirable. Gafchromic EBT3 films can potentially contribute to the validation of such a dosimetry framework, but require an appropriate calibration procedure to account for their energy dependence. Monte Carlo simulations were used to investigate this dependence with 177Lu, and to develop a film calibration procedure with an orthovoltage beam having a quality (Q) and a similar energy dependence. Methods: The physical quantity evaluated in this work was the film equivalent absorbed dose to water f(Q). This was obtained with Geant4 simulations as the ratio of the absorbed dose in water to the absorbed dose in the film displacing a water volume. f(Q) was calculated with different orthovoltage beams and with a 177Lu source placed in a water filled Jaszczak phantom. X-ray beam qualities ranging from 2.24 to 3.22 mm Cu (HVL) were tested, corresponding to peak voltages of [220–300] kVp and effective energies of [115–142] keV. The simulation input spectra were obtained with the SpeckCalc software. 177Lu disintegrations were simulated with Geant4 RadioactiveDecay5.1.1 data. Results: A minimal difference of 0.4% in f(Q) was obtained between 177Lu and an orthovoltage beam quality of 3.07 mm Cu (HVL) having an effective energy of 138 keV (300 kVp). For beams with effective energies ranging from 136 to 142 keV, this difference was <1%. Discussion and conclusion: The optimal orthovoltage beam quality for the calibration of EBT3 film to use with 177Lu was found. The f(Q) does not show a strong kVp dependence in the range explored, and calibration can be performed with a beam having an effective energy of approximately 140 keV and a quality of 3 mm Cu (HVL). This represents the first step towards the validation of a fast GPU-based, in-house Monte Carlo code dedicated to accurate internal dosimetry in nuclear medicine. [ABSTRACT FROM AUTHOR]

GPUMCD, a fast GPU-based Monte Carlo transport code, was initially developed and validated for photon and electron dose calculations in radiation oncology. In this work, the code was adapted to rapidly simulate realistic X-ray Cone-Beam Computed Tomography (CBCT) projections, and in particular to estimate the scatter component of the signal. This estimate is thereafter filtered and used for scatter correction, which is especially important in a CBCT geometry. The signal generated by scattered photons on a 1028 × 768 detector was estimated with GPUMCD. The simulation geometry was derived from actual CBCT reconstructions (pelvis, thorax), with density and materials assigned to each voxel with a HU-electronic density calibration curve. Simulations were conducted on a NVIDIA GTX970m GPU with either 10 7 or 10 9 photons per projection. Recursive Gaussian filtering in projections with 10 7 photons was performed to assess the potential of faster simulations conducted with fewer photons. A simple Gaussian filter was used for the projection of 10 9 photons. The primary signal was obtained with deterministic ray-tracing, and normalized by the primary signal computed derived from the Monte Carlo simulation. Simulated projections with 10 7 photons were obtained in 3.5 s while the primary signal estimation took 0.2s. Recursive Gaussian filtering of projections was shown to be an effective way to reduce the simulation time by a factor 100 and preserve more complex scatter patterns. The simulation times reported here let envision a Monte Carlo-based scatter correction strategies in CBCT reconstruction. [ABSTRACT FROM AUTHOR]

GPUMCD, a fast GPU-based Monte Carlo transport code, was initially developed and validated for photon and electron dose calculations in radiation oncology. In this work, the code was adapted to X-ray medical imaging applications, notably to simulate Cone-Beam Computed Tomography (CBCT) projections. The photon interaction processes in GPUMCD, initially validated for the therapeutic (megavoltage) energy range, were revisited with imaging and therefore lower energies in mind. Comparisons with physics models available in Geant4 were conducted for the photoelectric effect, Compton and Rayleigh scattering. For Compton scattering, four Geant4 models were used: two from the Geant4 standard physics (G4KleinNishinaModel and G4KleinNishinaCompton), one from Livermore physics (G4LivermoreComptonModel) and one from Penelope physics (G4PenelopeCompton). Three out of the four models consider atomic shells and the energy of the recoil electron. This correction is not considered in G4KleinNishinaCompton and GPUMCD. Tracking of electron was turned off in GPUMCD and Geant4. The photoelectric and Rayleigh scattering algorithms yielded consistent results in GPUMCD and Geant4. However, significant differences were identified between GPUMCD and Geant4 for Compton scattering. More specifically, differences of up to 15% in energy fluence in simulated projections were observed between simulations with and without atomic shell corrections, consistent with the known overestimation of forward scatter in the plain Klein-Nishina model. Implementing shell correction in GPUMCD would significantly increase computation times but appears necessary for imaging applications. [ABSTRACT FROM AUTHOR]

Rationnel L'accumulation de tissu adipeux (TA) viscéral est fortement associée au diabète de type 2 et aux facteurs de risque cardiovasculaire. Il a été suggéré qu'au-delà de son volume, la densité du TA (atténuation mesurée par tomodensitométrie (TDM)) pourrait aussi influencer le profil de risque cardiométabolique (CM). L'objectif de cette étude est d'examiner si l'atténuation du TA viscéral, marqueur de sa densité, est associée aux facteurs de risque cm, indépendamment du volume de TA viscéral. Patients et Méthodes Une analyse transversale a été réalisée chez 2 061 hommes et 1 842 femmes de l'étude INSPIRE ME IAA (INternational Study of Prediction of Intra-abdominal adiposity and its RElationship with cardioMEtabolic risk/Intra-Abdominal Adiposity). La surface (cm 2 ) et l'atténuation (HU) du TA viscéral, évaluées par TDM au niveau L4-L5, ainsi que plusieurs facteurs de risque cm (diabète de type 2, maladies cardiovasculaires, hypertension, glycémie, insulinémie, HOMA, triglycérides (TG), HDL-Cholestérol (HDL-C), apolipoprotéine A1 (ApoA1), apolipoprotéine B (ApoB), protéine C-réactive (CRP), plasminogen activator inhibitor 1 et adiponectine) ont été mesurées. Les relations entre paramètres d'intérêt ont été étudiées par analyses de variance (tertiles de surface TA viscéral) et modèles de régression multivariée. Résultats L'atténuation du TA viscéral, marqueur de sa densité, diminue inversement avec la surface de TA viscéral ( p < 0,0001). Indépendamment de la surface de TA viscéral, l'atténuation du TA viscéral est significativement associée aux facteurs de risque cm. Une interaction significative entre surface et atténuation du TA viscéral a été identifiée pour les niveaux de TG, HDL-C, ApoA1 (femmes), ApoB (hommes), adiponectine et HOMA, avec un impact plus important de l'atténuation pour les niveaux d'adiposité viscérale les plus faibles. Conclusions La densité du TA viscéral est associée de manière significative et indépendante au profil cm, et ce, plus particulièrement à des niveaux d'adiposité plus faible. L'atténuation du TA mesuré par TDM peut donc permettre de caractériser plus précisément la qualité du TA viscéral et son impact sur le profil cardiométabolique, au-delà de la quantité de TA viscéral. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Relative contributions of abdominal versus epicardial adipose tissues to the cardiometabolic profile of young and healthy adults are unknown. We investigated the associations between subcutaneous abdominal adipose tissue (SAT), visceral abdominal adipose tissue (VAT) and epicardial adipose tissue (EAT) with markers of the cardiometabolic profile in young and apparently healthy males and females.METHOD AND RESULTS: Two hundred and eighty young and apparently healthy subjects (48% (134 of 280) male; age 18 to 35 years; BMI <30 kg/m2) underwent magnetic resonance imaging after voluntary recruitment in the community. We quantified SAT, VAT and EAT. Plasma cardiometabolic risk profile was assessed for each subject (blood pressure, lipid profile, fasting glucose). Associations with markers of the cardiometabolic profile were stronger for VAT and EAT than for SAT. In multivariable regression analyses including all three adipose tissues and taking into account gender and age, only VAT maintained significant associations to systolic and diastolic blood pressure, and plasma low-density lipoprotein cholesterol, total/high-density lipoprotein cholesterol ratio, triglycerides and apolipoproteins B/A1 ratio. In an effort to identify the strongest office-based predictor of visceral adiposity in this young and apparently healthy young adult sample, we determined that while BMI, waist circumference (WC) and waist-to-hip ratio were all associated to VAT in univariable analyses (p<0.05 for all), only WC remained independently associated to VAT in multivariable analysis (p<0.001). Concurrently, WC was also an independent predictor of EAT in multivariable analysis (p<0.001).CONCLUSION - Because visceral adipose tissues - EAT, and to a greater extent VAT - are more strongly and widely associated with the cardiometabolic profile than is SAT, we believe that assessing visceral adiposity is relevant in young and apparently healthy adults. Beyond simply measuring BMI, the addition of WC measurement in young and apparently healthy adults improves the prediction of visceral adiposity. [ABSTRACT FROM AUTHOR]

Objectif: L’excès de graisse viscérale est associé à une lipolyse accrue en dépit d’une élévation des taux d’insuline qui conduit à une augmentation des acides gras libres (AGL) plasmatiques. L’objectif de cette étude fut de mesurer le changement des AGL plasmatiques après une année d’intervention visant à améliorer les habitudes de vie de patients présentant une obésité abdominale. Patients et méthodes: 144 hommes (âge 48±9 ans, IMC 30,9±3,1kg/m2) sélectionnés sur un tour de taille élevé (90cm) et une dyslipidémie (HDL-cholestérol < 1,03mmol/L et/ou triglycérides = 1,69mmol/L) participèrent à un programme de restriction calorique modérée et d’augmentation de l’activité physique. Les AGL plasmatiques furent mesurés à jeun puis au cours d’une hyperglycémie provoquée orale (HGPO) et dans les huit heures suivant un repas riche en lipides (60 %). Les marqueurs d’homéostasie glucidique, le profil lipidique, la composition corporelle (DEXA et mesure TDM de la graisse abdominale) et la réponse cardio-respiratoire à l’exercice furent également mesurés. Résultats: Après un an, les 117 hommes ayant poursuivi l’intervention perdirent 26,1±17,7 % de leur graisse viscérale. Leur réponse cardio-respiratoire à l’exercice s’améliora de 19,9±20,6 %. Les AGL à jeun baissèrent de 0,46±0,12 à 0,42±0,14pmol/L (tous, p<0,0001). L’élévation des AGL fut moindre à partir de la 6e heure suivant le repas riche en lipide, (p=0,011) et leur baisse fut plus marquée au cours de l’HGPO (p<0,0001). Pour mesurer indirectement la sensibilité de la lipolyse à l’insuline, nous avons calculé un index à jeun (FFA-RI) et un autre au cours de l’HGPO (ISI-FFA) qui s’améliorèrent significativement après l’intervention. Leur amélioration fut corrélée à celle des marqueurs de risque cardiométabolique indépendamment des changements des indices d’homéostasie glucidique (HOMA-RI et ISI-Matsuda). Conclusion: Une année d’intervention chez des hommes présentant une obésité abdominale améliore l’inhibition de la lipolyse par l’insuline, mesurée par des marqueurs plasmatiques. Cette sensibilité accrue est corrélée à l’amélioration du profil de risque cardiométabolique. [Copyright &y& Elsevier]

Summary: With an evolving landscape of a growing number of obese and/or type 2 diabetic patients in our affluent population, the metabolic syndrome has become a major issue because of its impact on cardiovascular disease risk. In this regard, although it is appropriate to aim at a better glycaemic control in type 2 diabetic patients, hyperglycaemia does not appear to be the main culprit responsible for the markedly increased cardiovascular disease risk in this population. Rather, studies have suggested that a cluster of metabolic abnormalities, which includes an atherogenic dyslipidaemic state, an impaired glucose/insulin homeostasis, and a pro-thrombotic and inflammatory profile, substantially increases the risk of coronary heart disease in type 2 diabetic patients in a manner which is partly independent of glycaemic control. These results imply that in order to reduce the risk of atherosclerotic macrovascular disease in type 2 diabetic patients, physicians need not only to focus on a better glycaemic control but also to improve the features of the metabolic syndrome. As a consequence, in order to evaluate the clinical benefits of pharmacotherapy in type 2 diabetic patients, we need to quantify the impact of any pharmacological intervention beyond glucose control. In this context, metformin has been shown to not only contribute to a better glycaemic control but also to induce some weight loss (especially in the visceral depot) which may contribute to the improvement of the features of the metabolic syndrome. Thus, metformin treatment may represent a relevant element of an integrated lifestyle modification-pharmacotherapy to prevent not only type 2 diabetes but also cardiovascular disease. [Copyright &y& Elsevier]