SLIME: robust, high-speed 3D microvascular mapping

Abstract

Three dimensional (3D) microvascular imaging of cubic millimeter to centimeter size volumes often requires much time and expensive instruments. By combining optical clearing with a novel scatter-based optical coherence tomography (OCT) contrast agent, we have greatly extended OCT imaging depth in excised tissues while maintaining a simple and low cost approach that does not require in-depth OCT knowledge. The new method enables fast 3D microvascular mapping in large tissue volumes, providing a promising tool for investigating organ level microvascular abnormalities in large cohorts.

Three-dimensional alignment of microvasculature and cardiomyocytes in the developing ventricle

“…The spatial organization of the developing coronaries had not been quantified, with previous studies conducted in turkeys, chickens, mice and humans focusing on capillary density 8,[10][11][12][13]44,45 . Our recent study in quails 23 uncovered highly aligned coronary microvessels at the newly septate embryonic heart surface instead of a plexus of coronaries as in preceding stages 49,50 . This strong alignment disappeared when the embryos were dosed with ethanol in a model of prenatal alcohol exposure, but the vessel alignment in neither the healthy nor the diseased hearts were quantified.…”

“…Cardiomyocyte disarray has been observed in the mouse embryo as a precursor to hypertrophic cardiomyopathy 32 and could contribute to a disorganized vasculature by affecting the maturation of the vascular plexus. In a previous study, we observed abnormal coronary microvascular alignment in the ventricular wall in a model of fetal alcohol spectrum disorders 23 . These abnormalities included chaotic microvasculature patterns and regions of missing vasculature.…”

“…The development of the large coronaries and congenital anomalies has also been a major research focus because of its clinical significance 44 – 46 . In contrast the intermediary stages when the ventricular walls rapidly thicken and the microvasculature develops within the myocardium has been addressed in few studies 23 , 47 , 48 , leaving many fundamental questions unanswered. These stages were the focus of this study.…”

“…Is cardiomyocyte disarray associated with disorganized vasculature? In our group's previous study, coronary microvascular disarray was observed in a quail model of prenatal alcohol exposure 23 , but this was not quantified. Disorganization of the coronary microvasculature and cardiomyocytes early in development could lead to improper oxygenation and abnormal cardiac function, which are associated with further dysmorphology and dysfunction 38 .…”

“…Thus, we are likely underestimating the coronary microvasculature's impact in various diseases. In research studies, there have been several strategies to visualize the microvasculature including genetically engineered markers [16][17][18] , antibodies to endothelial-specific markers [19][20][21] , and contrast agents perfused into the vasculature 17,[22][23][24][25][26] . However, most studies yielded qualitative results and either did not visualize the entire vasculature of the developing heart or provided limited opportunity for quantification.…”