Simultaneous measurement of RBC velocity, flux, hematocrit and shear rate in vascular networks in vivo

Abstract

Blood flow directly affects nutrient and oxygen as well drug delivery in tumors. The distribution of blood within tumor is disturbed by structural and functional abnormalities, and may be further altered by therapy. In turn, this results in heterogeneous distribution of drugs and/or oxygen, with direct effects on the efficacy of cytotoxic therapies. These heterogeneities are poorly understood because of the inability of current techniques to characterize the function of individual vessels and their local network. To address this problem, we have developed a novel methodology for simultaneously quantifying blood flow (velocity, flux, hematocrit and shear rate) in extended networks at the single capillary level. Our approach relies on deconvolution of signals produced by labeled red blood cells as they move relative to the scanning laser of a confocal or multiphoton microscope, and provides fully‐resolved three‐dimensional flow profiles within vessel networks. Using this methodology, we show that blood velocity profiles are perturbed and asymmetrical near intussusceptive tissue structures in tumors. Furthermore, we show that subpopulations of vessels, classified by functional parameters, exist in different tissue regions, and that Angiopeitin‐1 can improve tumor perfusion by inducing arteriogenesis.