Quantitative real-time optical imaging of the tissue metabolic rate of oxygen consumption

Abstract.

The tissue metabolic rate of oxygen consumption ( ${\mathrm{tMRO}}_2$ ) is a clinically relevant marker for a number of pathologies including cancer and arterial occlusive disease. We present and validate a noncontact method for quantitatively mapping ${\mathrm{tMRO}}_2$ over a wide, scalable field of view at $16\text{\hspace{0.17em}\hspace{0.17em}frames}/\mathrm{s}$ . We achieve this by developing a dual-wavelength, near-infrared coherent spatial frequency-domain imaging (cSFDI) system to calculate tissue optical properties (i.e., absorption, ${\mu }_a$ , and reduced scattering, ${\mu }_s^{\prime }$ , parameters) as well as the speckle flow index (SFI) at every pixel. Images of tissue oxy- and deoxyhemoglobin concentration ( $[{\mathrm{HbO}}_2]$ and [HHb]) are calculated from optical properties and combined with SFI to calculate ${\mathrm{tMRO}}_2$ . We validate the system using a series of yeast-hemoglobin tissue-simulating phantoms and conduct in vivo tests in humans using arterial occlusions that demonstrate sensitivity to tissue metabolic oxygen debt and its repayment. Finally, we image the impact of cyanide exposure and toxicity reversal in an in vivo rabbit model showing clear instances of mitochondrial uncoupling and significantly diminished ${\mathrm{tMRO}}_2$ . We conclude that dual-wavelength cSFDI provides rapid, quantitative, wide-field mapping of ${\mathrm{tMRO}}_2$ that can reveal unique spatial and temporal dynamics relevant to tissue pathology and viability.