In vivo preclinical photoacoustic imaging of tumor vasculature development and therapy

TLDR

A novel all‑optical photoacoustic scanner is introduced to image tumor vasculature development and its response to a vascular‑disrupting agent. The scanner uses a Fabry‑Perot polymer‑film ultrasound sensor and attenuation‑compensated acoustic time‑reversal reconstruction to noninvasively image colorectal tumor xenografts in mice, enabling visualization of vascular features and monitoring of vascular‑disrupting agent effects. Label‑free 3‑D in vivo imaging achieved sub‑100‑µm resolution to ~10 mm depth, revealing the destruction and recovery phases of OXi4503 and demonstrating the scanner’s potential for preclinical and clinical vascular studies.

Abstract

The use of a novel all-optical photoacoustic scanner for imaging the development of tumor vasculature and its response to a therapeutic vascular disrupting agent is described. The scanner employs a Fabry-Perot polymer film ultrasound sensor for mapping the photoacoustic waves and an image reconstruction algorithm based upon attenuation-compensated acoustic time reversal. The system was used to noninvasively image human colorectal tumor xenografts implanted subcutaneously in mice. Label-free three-dimensional in vivo images of whole tumors to depths of almost 10 mm with sub-100-micron spatial resolution were acquired in a longitudinal manner. This enabled the development of tumor-related vascular features, such as vessel tortuosity, feeding vessel recruitment, and necrosis to be visualized over time. The system was also used to study the temporal evolution of the response of the tumor vasculature following the administration of a therapeutic vascular disrupting agent (OXi4503). This revealed the well-known destruction and recovery phases associated with this agent. These studies illustrate the broader potential of this technology as an imaging tool for the preclinical and clinical study of tumors and other pathologies characterized by changes in the vasculature.