Semi-automated analysis of cerebral capillary red blood cell velocities allows modeling of transit time distribution after experimental subarachnoid hemorrhage in mice.

Abstract

Significance: Microvascular dysfunction stems from the origin of various neurological diseases. Among these, delayed cerebral ischemia following subarachnoid hemorrhage (SAH) is a major complication. Even though pathogenesis remains poorly understood, hypotheses converge toward early and persistent microvascular dysfunction. In this context, mathematical models have been developed to study oxygen delivery using theoretical distributions of capillary flux. However, these distributions lack experimental validation.

Aim: We propose experimental recording of capillary red blood cell (RBC) velocities in a superficial cortical microvascular network in a mouse model of SAH, testing theoretical transit time distributions and their implications on tissue oxygenation.

Approach: We performed optical recording of RBC velocities. We propose a complete software, available on GitHub, for velocity semi-automated measurement. Experimental data were fitted with Gamma and Cauchy probability distribution functions (PDFs). Corresponding maximal oxygen metabolic rates ( ${\mathrm{CMRO}}_2^{\max }$ ) were computed.

Results: Data showed that transit time distributions changed after SAH, such that they followed a Cauchy distribution. Corresponding ${\mathrm{CMRO}}_2^{\max }$ maps showed a malignant capillary heterogeneity state.

Conclusions: We provide distributions of transit times in an SAH mouse model, allowing us to discuss PDF implications for maximal oxygen consumption.