Label-free oxygen-metabolic photoacoustic microscopy in vivo

TLDR

Abnormal oxygen metabolism underlies many diseases, and accurate measurement of the metabolic rate of oxygen (MRO2) is valuable for pathophysiological studies and early diagnosis, yet existing techniques either lack high resolution or depend on exogenous contrast. The study proposes label‑free metabolic photoacoustic microscopy (mPAM) to noninvasively quantify MRO2 in vivo at small‑vessel resolution. mPAM achieves this by simultaneously imaging tissue volume, vessel cross‑section, hemoglobin concentration, hemoglobin oxygen saturation, and blood flow speed. Longitudinal in‑vivo imaging of hyperthermia, cryotherapy, melanoma, and glioblastoma revealed that elevated MRO2 does not always lead to hypoxia or increased oxygen extraction, and early‑stage cancers can be hyperoxic despite hypermetabolism.

Abstract

Almost all diseases, especially cancer and diabetes, manifest abnormal oxygen metabolism. Accurately measuring the metabolic rate of oxygen (MRO2) can be helpful for fundamental pathophysiological studies, and even early diagnosis and treatment of disease. Current techniques either lack high resolution or rely on exogenous contrast. Here, we propose label-free metabolic photoacoustic microscopy (mPAM) with small vessel resolution to noninvasively quantify MRO2 in vivo in absolute units. mPAM is the unique modality for simultaneously imaging all five anatomical, chemical, and fluid-dynamic parameters required for such quantification: tissue volume, vessel cross-section, concentration of hemoglobin, oxygen saturation of hemoglobin, and blood flow speed. Hyperthermia, cryotherapy, melanoma, and glioblastoma were longitudinally imaged in vivo. Counterintuitively, increased MRO2 does not necessarily cause hypoxia or increase oxygen extraction. In fact, early-stage cancer was found to be hyperoxic despite hypermetabolism.