Photoacoustic Imaging for Monitoring Vascular Disrupting Agents
Abstract
The tumour vasculature supplies the tumour with oxygen and nutrition that are vital for the survival and growth of cancer cells. Vascular disrupting agents (VDAs) are a category of cancer therapeutic drugs that target the endothelial cells lining the vessels and damage tumour vasculature. Photoacoustic (PA) imaging has high sensitivity in detecting vascular changes due to the high optical absorption of hemoglobin. PA quantitative analysis can be used to further extract structural and biochemical changes of hemoglobin through ultrasound spectral analysis and multi-spectral PA imaging. I proposed the use of simulations, in-vitro, and in-vivo PA imaging to assess the efficacy of VDAs in cancer therapy. PA signals acquired from single and a collection of red blood cells (RBCs) were examined before and after acid sphingomyelinase exposure (SMase is a signaling molecule excreted due to endothelial cells damage) to investigate changes at the cellular level. Bleeding of tumour vasculature was simulated using a fractal-based model of bifurcating cylinders and the diffusion of blood to the tumour interstitium. Wavelength selection and fluence matching approaches were proposed to improve chromophore quantification in real time for PA imaging. In-vivo experiments were conducted to examine how PA imaging can be used to monitor the effect of the VDA 5,6-dimethylxanthenone-4-acetic acid (DMXAA). PA ultrasound frequency analysis and multi-spectral PA imaging were used to detect structural…
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