Integrated method for quantitative morphometry and oxygen transport modeling in striated muscle

Abstract

Identifying structural limitations in O2 transport is primarily restricted by current methods employed to characterize the nature of physiological remodeling. Inadequate resolution or breadth of available data has impaired development of routine diagnostic protocols and effective therapeutic strategies. Understanding O2 transport within striated muscle faces major challenges, most notably in quantifying how well individual fibers are supplied by the microcirculation, which has necessitated exploring tissue O2 supply using theoretical modeling of diffusive exchange. With capillary domains identified as a suitable model for the description of local O2 supply and requiring less computation than numerically calculating the trapping regions that are supplied by each capillary via biophysical transport models, we sought to design a high-throughput method for histological analysis. We present an integrated package that identifies optimal protocols for identification of important input elements, processing of digitized images with semiautomated routines, and incorporation of these data into a mathematical modeling framework with computed output visualized as the tissue partial pressure of O2 (Po2) distribution across a biopsy sample. Worked examples are provided using muscle samples from experiments involving rats and humans. NEW & NOTEWORTHY Progress in quantitative morphometry and analytical modeling has tended to develop independently. Real diagnostic power lies in harnessing both disciplines within one user-friendly package. We present a semiautomated, high-throughput tool for determining muscle phenotype from biopsy material, which also provides anatomically relevant input to quantify tissue oxygenation, in a coherent package not previously available to nonspecialist investigators.