Utility of local capillary supply indices: insights from computational image‐based modelling

Journal article

Muscle oxygenation critically depends on capillary number and distribution within atissue. Despite the development of numerous morphometric indices to quantify these attributes,many lack sensitivity or validation against local oxygen tension (PO2) in muscle fibres, leadingto uncertainty about their physiological relevance and utility for gauging adaptive changes. Weassessed six local supply indices to determine which best correlated with and predicted calculatedfibre PO2 , using high-throughput histological analysis and image-based computational modellingof oxygen transport on digitised rat tibialis anterior sections: capillary contacts (CCi), individualcapillary-to-fibre ratio (C:Fi), capillary-to-fibre perimeter exchange (CFPEi), local capillary-to-fibreratio (LCFRi), local capillary density (LCDi) and a novel index, Dmax,i, which averages themaximum diffusion distances from capillary domains that overlap a fibre. LCDi and Dmax,i exhibitedthe strongest correlations with fibre PO 2 (linear correlation: 0.8874 and −0.9054, respectively;P < 0.0001). Distance-correlation analysis confirmed both indices as robust predictors of fibreoxygenation (distance correlation: 0.85 and 0.79, respectively; P < 0.0001), demonstrating theirability to capture a curvilinear relationship that plateaus as mean fibre PO 2 approaches the capillarysource PO 2 (P < 0.0001). Partial least squares and tree-ensemble regressions further identified bothindices as the most sensitive and critical predictors of fibre PO 2 (P < 0.001), suggesting they areless likely to miss early pathophysiological or adaptive responses. These findings support the useof theoretically validated morphometric indices in research and clinical applications, to enhanceunderstanding of fundamental muscle physiology and improve the diagnosis and treatment ofmuscle-related pathology.

Authors: Al‐Shammari, AA; Kissane, RWP; Ashkanani, A; Madhoun, AA; Al‐Mulla, F

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Journal of Physiology
• Publication date: 2025-12-05
• Acceptance date: 2025-11-17
• DOI: 10.1113/jp288043
• EISSN: 1469-7793
• ISSN: 0022-3751
• Language: English
• Keywords: computational modelling; microvascular geometry; oxygen delivery; morphometric indices; skeletal muscle; capillary supply