Fractal Analysis of Right Ventricular Trabeculae in Pulmonary Hypertension.

Purpose To measure right ventricular (RV) trabecular complexity by its fractal dimension (FD) in healthy subjects and patients with pulmonary hypertension (PH) and to assess its relationship with hemodynamic and functional parameters and future cardiovascular events. Materials and Methods This retrospective study used data acquired from May 2004 to October 2013 in 256 patients with newly diagnosed PH who underwent cardiac MRI, right-sided heart catheterization, and 6-minute walk distance testing, with median follow-up of 4.0 years. A total of 256 healthy control subjects underwent cardiac MRI only. Biventricular FD, volumes, and function were assessed on short-axis cine images. Reproducibility was assessed with the intraclass correlation coefficient, correlation between variables was assessed with the Pearson correlation test, and mortality prediction was compared by using uni- and multivariable Cox regression analyses. Results RV FD reproducibility had an intraclass correlation coefficient of 0.97 (95% confidence interval [CI]: 0.96, 0.98). RV FD was higher in patients with PH (median, 1.310; interquartile range [IQR], 1.281-1.341) than in healthy subjects (median, 1.264; IQR, 1.242-1.295; P < .001), with the greatest difference near the apex. RV FD was associated with pulmonary vascular resistance (r = 0.30, P < .001). At univariable Cox regression analysis, RV FD was a significant predictor of death (hazard ratio [HR], 1.256; 95% CI: 1.011, 1.560; P = .04); however, at multivariable analysis, RV FD did not enable prediction of survival independently of conventional parameters of RV remodeling (HR, 1.179; 95% CI: 0.871, 1.596; P = .29). Conclusion Fractal analysis of RV trabecular complexity is a highly reproducible measure of remodeling in patients with PH that is associated with afterload, although the gain in survival prediction over traditional markers is not significant. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Systematic and detailed analysis of behavioural tests in the rat middle cerebral artery occlusion model of stroke: Tests for long-term assessment.

In order to test therapeutics, functional assessments are required. In pre-clinical stroke research, there is little consensus regarding the most appropriate behavioural tasks to assess deficits, especially when testing over extended times in milder models with short occlusion times and small lesion volumes. In this study, we comprehensively assessed 16 different behavioural tests, with the aim of identifying those that show robust, reliable and stable deficits for up to two months. These tasks are regularly used in stroke research, as well as being useful for examining striatal dysfunction in models of Huntington's and Parkinson's disease. Two cohorts of male Wistar rats underwent the intraluminal filament model of middle cerebral artery occlusion (30 min) and were imaged 24 h later. This resulted in primarily subcortical infarcts, with a small amount of cortical damage. Animals were tested, along with sham and naïve groups at 24 h, seven days, and one and two months. Following behavioural testing, brains were processed and striatal neuronal counts were performed alongside measurements of total brain and white matter atrophy. The staircase, adjusting steps, rotarod and apomorphine-induced rotations were the most reliable for assessing long-term deficits in the 30 min transient middle cerebral artery occlusion model of stroke.

Ex vivo magnetic resonance imaging of crystalline lens dimensions in chicken.

PURPOSE: A reduction in the power of the crystalline lens during childhood is thought to be important in the emmetropization of the maturing eye. However, in humans and model organisms, little is known about the factors that determine the dimensions of the crystalline lens and in particular whether these different parameters (axial thickness, surface curvatures, equatorial diameter, and volume) are under a common source of control or regulated independently of other aspects of eye size and shape. METHODS: Using chickens from a broiler-layer experimental cross as a model system, three-dimensional magnetic resonance imaging (MRI) scans were obtained at 115-microm isotropic resolution for one eye of 501 individuals aged 3-weeks old. After fixation with paraformaldehyde, the excised eyes were scanned overnight (16 h) in groups of 16 arranged in a 2x2x4 array. Lens dimensions were calculated from each image by fitting a three-dimensional mesh model to the lens, using the semi-automated analysis program mri3dX. The lens dimensions were compared to measures of eye and body size obtained in vivo using techniques that included keratometry and A-scan ultrasonography. RESULTS: A striking finding was that axial lens thickness measured using ex vivo MRI was only weakly correlated with lens thickness measured in vivo by ultrasonography (r=0.19, p<0.001). In addition, the MRI lens thickness estimates had a lower mean value and much higher variance. Indeed, about one-third of crystalline lenses showed a kidney-shaped appearance instead of the typical biconvex shape. Since repeat MRI scans of the same eye showed a high degree of reproducibility for the scanning and mri3dX analysis steps (the correlation in repeat lens thickness measurements was r=0.95, p<0.001) and a recent report has shown that paraformaldehyde fixation induces a loss of water from the human crystalline lens, it is likely that the tissue fixation step caused a variable degree of shrinkage and a change in shape to the lenses examined here. Despite this serious source of imprecision, we found significant correlations between lens volume and eye/body size (p<0.001) and between lens equatorial diameter and eye/body size (p<0.001) in these chickens. CONCLUSIONS: Our results suggest that certain aspects of lens size (specifically, lens volume and equatorial diameter) are controlled by factors that also regulate the size of the eye and body (presumably, predominantly genetic factors). However, since it has been shown previously that axial lens thickness is regulated almost independently of eye and body size, these results suggest that different systems might operate to control lens volume/diameter and lens thickness in normal chickens.

Ghrelin induces abdominal obesity via GHS-R-dependent lipid retention.

Circulating ghrelin elevates abdominal adiposity by a mechanism independent of its central orexigenic activity. In this study we tested the hypothesis that peripheral ghrelin induces a depot-specific increase in white adipose tissue (WAT) mass in vivo by GH secretagogue receptor (GHS-R(1a))-mediated lipolysis. Chronic iv infusion of acylated ghrelin increased retroperitoneal and inguinal WAT volume in rats without elevating superficial sc fat, food intake, or circulating lipids and glucose. Increased retroperitoneal WAT mass resulted from adipocyte enlargement probably due to reduced lipid export (ATP-binding cassette transporter G1 mRNA expression and circulating free fatty acids were halved by ghrelin infusion). In contrast, ghrelin treatment did not up-regulate biomarkers of adipogenesis (peroxisome proliferator-activated receptor-gamma2 or CCAAT/enhancer binding protein-alpha) or substrate uptake (glucose transporter 4, lipoprotein lipase, or CD36) and although ghrelin elevated sterol-regulatory element-binding protein 1c expression, WAT-specific mediators of lipogenesis (liver X receptor-alpha and fatty acid synthase) were unchanged. Adiposity was unaffected by infusion of unacylated ghrelin, and the effects of acylated ghrelin were abolished by transcriptional blockade of GHS-R(1a), but GHS-R(1a) mRNA expression was similar in responsive and unresponsive WAT. Microarray analysis suggested that depot-specific sensitivity to ghrelin may arise from differential fine tuning of signal transduction and/or lipid-handling mechanisms. Acylated ghrelin also induced hepatic steatosis, increasing lipid droplet number and triacylglycerol content by a GHS-R(1a)-dependent mechanism. Our data imply that, during periods of energy insufficiency, exposure to acylated ghrelin may limit energy utilization in specific WAT depots by GHS-R(1a)-dependent lipid retention.