Utility of local capillary supply indices: Insights from computational image-based modelling

Area of Science:

• Muscle physiology and oxygen transport
• Skeletal muscle morphometrics and oxygenation
• Computational modeling in biological systems

Background:

• Muscle oxygenation is critical for function, influenced by capillary supply.
• Existing morphometric indices for capillary supply often lack validation against oxygen tension.
• Uncertainty exists regarding the physiological relevance of current indices for adaptive or pathological changes.

Purpose of the Study:

• To evaluate six local supply indices for their correlation and predictive power regarding muscle fiber oxygen tension (PO2).
• To identify the most sensitive and critical indices for assessing muscle oxygenation.
• To validate morphometric indices for research and clinical applications in muscle health.

Main Methods:

• High-throughput histological analysis of rat tibialis anterior muscle sections.
• Image-based computational modeling of oxygen transport.
• Assessment of six local supply indices: CCi, C:Fi, CFPEi, LCFRi, LCDi, and Dmax,i.
• Statistical analyses including linear correlation, distance-correlation, partial least squares, and tree-ensemble regressions.

Main Results:

• Local capillary density (LCDi) and maximum diffusion distance (Dmax,i) showed the strongest correlations with fiber PO2 (r = 0.8874 and -0.9054, respectively).
• Both LCDi and Dmax,i were identified as robust predictors of fiber oxygenation, capturing curvilinear relationships.
• These area-based indices were the most sensitive predictors, crucial for detecting early pathophysiological or adaptive responses.

Conclusions:

• LCDi and Dmax,i are theoretically validated and physiologically relevant indices for assessing muscle oxygenation.
• These indices offer improved sensitivity for detecting changes in muscle oxygenation compared to other metrics.
• Findings support the use of LCDi and Dmax,i to enhance understanding of muscle physiology and improve diagnosis of muscle pathologies.