Label-free oxygen-metabolic photoacoustic microscopy <em>in vivo</em>
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 MRO2in 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.
Acknowledgments
The authors thank Christopher Favazza, Kim Chulhong, Song Hu, Lidai Wang, Dakang Yao, and Arie Krumholz for helpful discussions; Li Li for experimental assistance; and Professor James Ballard for manuscript editing. This research was supported by the National Institutes of Health Grants Nos. R01 EB000712, R01 EB008085, R01 CA134539, U54 {"type":"entrez-nucleotide","attrs":{"text":"CA136398","term_id":"35025352","term_text":"CA136398"}}CA136398, R01 EB010049, and 5P60 DK02057933.