Three-dimensional optoacoustic mesoscopy of the tumor heterogeneity in vivo using high depth-to-resolution multispectral optoacoustic tomography

Multispectral optoacoustic mesoscopy (MSOM) has been recently introduced for cancer imaging, it has the potential for high resolution imaging of cancer development in vivo, at depths beyond the diffusion limit. Based on spectral features, optoacoustic imaging is capable of visualizing angiogenesis and imaging cancer heterogeneity of malignant tumors through endogenous hemoglobin. However, high-resolution structural and functional imaging of whole tumor mass is limited by modest penetration and image quality, due to the insufficient capability of ultrasound detectors and the twodimensional scan geometry. In this study, we introduce a novel multi-spectral optoacoustic mesoscopy (MSOM) for imaging subcutaneous or orthotopic tumors implanted in lab mice, with the high-frequency ultrasound linear array and a conical scanning geometry. Detailed volumetric images of vasculature and oxygen saturation of tissue in the entire tumors are obtained in vivo, at depths up to 10 mm with the desirable spatial resolutions approaching 70μm. This unprecedented performance enables the visualization of vasculature morphology and hypoxia conditions has been verified with ex vivo studies. These findings demonstrate the potential of MSOM for preclinical oncological studies in deep solid tumors to facilitate the characterization of tumor's angiogenesis and the evaluation of treatment strategies.