Single capillary oximetry and tissue ultrastructural sensing by dual-band dual-scan inverse spectroscopic optical...

Measuring capillary oxygenation and the surrounding ultrastructure can allow one to monitor a microvascular niche and better understand crucial biological mechanisms. However, capillary oximetry and pericapillary ultrastructure are challenging to measure in vivo. Here we demonstrate a novel optical imaging system, dual-band dual-scan inverse spectroscopic optical coherence tomography (D2-ISOCT), that, for the first time, can simultaneously obtain the following metrics in vivo using endogenous contrast: (1) capillary-level oxygen saturation and arteriolar-level blood flow rates, oxygen delivery rates, and oxygen metabolic rates; (2) spatial characteristics of tissue structures at length scales down to 30 nm; and (3) morphological images up to 2 mm in depth. To illustrate the capabilities of D2-ISOCT, we monitored alterations to capillaries and the surrounding pericapillary tissue (tissue between the capillaries) in the healing response of a mouse ear wound model. The obtained microvascular and ultrastructural metrics corroborated well with each other, showing the promise of D2-ISOCT for becoming a powerful new non-invasive imaging tool.