High-resolution optoacoustic imaging of tissue responses to vascular-targeted therapies

The monitoring of vascular-targeted therapies via magnetic resonance imaging, computed omography or ultrasound is limited by their insufficient spatial resolution. By taking advantage of the intrinsic optical properties of haemoglobin, here we show that raster-scanning optoacoustic mesoscopy (RSOM) provides high-resolution images of the tumour vasculature and of the surrounding tissue, and that the detection of a wide range of ultrasound bandwidths enables the distinction of vessels of differing size, allowing for detailed insights into vascular responses to vascular-targeted therapy. By using RSOM to examine the responses to vascular-targeted photodynamic therapy in mice with subcutaneous xenografts, we observed a significant and immediate occlusion of the tumour vessels, followed by haemorrhage within the tissue and the eventual collapse of the entire vasculature. By using dual-wavelength RSOM, which distinguishes oxyhaemoglobin from deoxyhaemoglobin, we observed an increase in oxygenation of the entire tumour volume immediately after the application of the therapy, and a second wave of oxygen reperfusion approximately 24 h thereafter. We also show that RSOM allows for the quantification of differences in neo-angiogenesis that predict treatment efficacy.