Combined PET/DCE-MRI in a Rabbit Model of Atherosclerosis: Integrated Quantification of Plaque Inflammation, Permeability, and Burden During Treatment With a Leukotriene A4 Hydrolase Inhibitor.

OBJECTIVES: The authors sought to develop combined positron emission tomography (PET) dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to quantify plaque inflammation, permeability, and burden to evaluate the efficacy of a leukotriene A4 hydrolase (LTA4H) inhibitor in a rabbit model of atherosclerosis. BACKGROUND: Multimodality PET/MRI allows combining the quantification of atherosclerotic plaque inflammation, neovascularization, permeability, and burden by combined 18F-fluorodeoxyglucose (18F-FDG) PET, DCE-MRI, and morphological MRI. The authors describe a novel, integrated PET-DCE/MRI protocol to noninvasively quantify these parameters in aortic plaques of a rabbit model of atherosclerosis. As proof-of-concept, the authors apply this protocol to assess the efficacy of the novel LTA4H inhibitor BI691751. METHODS: New Zealand White male rabbits (N = 49) were imaged with integrated PET-DCE/MRI after atherosclerosis induction and 1 and 3 months after randomization into 3 groups: 1) placebo; 2) high-dose BI691751; and 3) low-dose BI691751. All animals were euthanized at the end of the study. RESULTS: Among the several metrics that were quantified, only maximum standardized uptake value and target-to-background ratio by 18F-FDG PET showed a modest, but significant, reduction in plaque inflammation in rabbits treated with low-dose BI691751 (p = 0.03), whereas no difference was detected in the high-fat diet and in the high-dose BI691751 groups. No differences in vessel wall area by MRI and area under the curve by DCE-MRI were detected in any of the groups. No differences in neovessel and macrophage density were found at the end of study among groups. CONCLUSIONS: The authors present a comprehensive, integrated 18F-FDG PET and DCE-MRI imaging protocol to noninvasively quantify plaque inflammation, neovasculature, permeability, and burden in a rabbit model of atherosclerosis on a simultaneous PET/MRI scanner. A modest reduction was found in plaque inflammation by 18F-FDG PET in the group treated with a low dose of the LTA4H inhibitor BI691751.

Intravascular ultrasound guided directional atherectomy versus directional atherectomy guided by angiography for the treatment of femoropopliteal in-stent restenosis.

BACKGROUND: The aim of this study was to compare 1-year outcomes for patients with femoropopliteal in-stent restenosis using directional atherectomy guided by intravascular ultrasound (IVUS) versus directional atherectomy guided by angiography. METHODS AND RESULTS: This was a retrospective analysis for patients with femoropopliteal in-stent restenosis treated with IVUS-guided directional atherectomy versus directional atherectomy guided by angiography from a single center between March 2012 and February 2016. Clinically driven target lesion revascularization was the primary endpoint and was evaluated through medical chart review as well as phone call follow up. CONCLUSIONS: Directional atherectomy guided by IVUS reduces clinically driven target lesion revascularization for patients with femoropopliteal in-stent restenosis.

Long-term in vivo resistin overexpression induces myocardial dysfunction and remodeling in rats.

We have previously reported that resistin induces hypertrophy and impairs contractility in isolated rat cardiomyocytes. To examine the long-term cardiovascular effects of resistin, we induced in vivo overexpression of resistin using adeno-associated virus serotype 9 injected by tail vein in rats and compared to control animals. Ten weeks after viral injection, overexpression of resistin was associated with increased ratio of left ventricular (LV) weight/body weight, increased end-systolic LV volume and significant decrease in LV contractility, measured by the end-systolic pressure volume relationship slope in LV pressure volume loops, compared to controls. At the molecular level, mRNA expression of ANF and ß-MHC, and protein levels of phospholamban were increased in the resistin group without a change in the level of SERCA2a protein expression. Increased fibrosis by histology, associated with increased mRNA levels of collagen, fibronectin and connective tissue growth factor were observed in the resistin-overexpressing hearts. Resistin overexpression was also associated with increased apoptosis in vivo, along with an apoptotic molecular phenotype in vivo and in vitro. Resistin-overexpressing LV tissue had higher levels of TNF-α receptor 1 and iNOS, and reduced levels of eNOS. Cardiomyocytes overexpressing resistin in vitro produced larger amounts of TNFα in the medium, had increased phosphorylation of IκBα and displayed increased intracellular reactive oxygen species (ROS) content with increased expression and activity of ROS-producing NADPH oxidases compared to controls. Long-term resistin overexpression is associated with a complex phenotype of oxidative stress, inflammation, fibrosis, apoptosis and myocardial remodeling and dysfunction in rats. This phenotype recapitulates key features of diabetic cardiomyopathy. This article is part of Special Issue Item Group entitled "Possible Editorial".