Investigation of microvascular morphological measures for skeletal muscle tissue oxygenation by image-based modelling in three dimensions

Abstract

The supply of oxygen in sufficient quantity is vital for the correct functioning of all organs in the human body, especially for skeletal muscle during exercise. Traditionally, microvascular oxygen supply capability is assessed by the analysis of morphological measures on transverse cross-sections of muscle, e.g. capillary density or capillary-to-fibre ratio. In this work, we investigate the relationship between microvascular structure and muscle tissue oxygenation in mice. Phase contrast imaging was performed using synchrotron radiation computed tomography (SR CT) to visualize red blood cells (RBCs) within the microvasculature in mouse soleus muscle. Image-based mathematical modelling of the oxygen diffusion from the RBCs into the muscle tissue was subsequently performed, as well as a morphometric analysis of the microvasculature. The mean tissue oxygenation was then compared with the morphological measures of the microvasculature. RBC volume fraction and spacing (mean distance of any point in tissue to the closest RBC) emerged as the best predictors for muscle tissue oxygenation, followed by length density (summed RBC length over muscle volume). The two-dimensional measures of capillary density and capillary-to-fibre ratio ranked last. We, therefore, conclude that, in order to assess the states of health of muscle tissue, it is advisable to rely on three-dimensional morphological measures rather than on the traditional two-dimensional measures.