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Glioblastoma (GBM) has less than one-year survival rate due to local recurrence post treatment or growth of “left-over” residual disease post surgical resection. To personalize treatment strategies and reduce the rate of recurrence, it is important to develop imaging based therapeutic strategies and prediction markers to identify GBM recurrence. Given the role of the vasculature in tumor growth and survival, here we utilize multi-parametric ultrasound and photoacoustic imaging to validate if changes in vascular structure and function could be predictive of treatment response in patient- derived orthotopic Glioblastoma xenograft models.
Patient-derived GBM cell lines were implanted in the brain of Swiss nu/nu mice. After the tumors reached 2-4 mm in diameter, the mice were divided into 4 groups namely – no treatment, surgical resection, therapy and surgical resection with therapy. Photodynamic therapy (PDT), a light based cytotoxic therapy, with photosensitizer Benzoporphyrin derivative (BPD) or FDA approved chemotherapy temozolomide were administered in the mice. Fujifilm VisualSonics LAZR system with a 20 MHz transducer was used to obtain power Doppler (%vascularity in tumors) and photoacoustic oxygen saturation (StO2) maps of the brain tumors at different time points pre and post treatment. The mice were either euthanized for immunofluorescence to validate the imaging markers or longitudinally monitored for tumor volume until moribund.The no-treatment group or the surgery only group did not have significant changes in vascular density or StO2. We observed a statistically significant decrease in StO2 immediately post BPD-PDT (primarily a vascular therapy) but not with temozolomide (a cellular therapy). Furthermore, we also observed that the sustenance of hypoxia or low StO2 in tumors for 24-72 hours can be a predictive biomarker for tumor recurrence. Overall, these results suggest the utility of ultrasound and photoacoustic imaging in monitoring treatment response and developing treatment prediction strategies for glioblastoma.
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