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At clinically-relevant depths, the frequency content of photoacoustic signals encodes information about the size, concentration and spatial distribution of non-resolvable blood vessels. This study evaluates whether photoacoustics can detect cancer therapy-induced vascular perturbations. Photoacoustic/ultrasound (PA/US) spectral analysis was combined with functional, PA-based oxygenation and power Doppler (PD) perfusion estimates to assess treatment response.
Co-registered, in-vivo US/PA/PD imaging of mice bearing breast cancer tumors was performed pre-treatment and 30m/2h/5h/24h/7d post-treatment (VevoLAZR, Fujifilm VisualSonics). Hyperthermia treatment (1h, 43C) was performed after systemic injections of doxorubicin-loaded thermosensitive liposomes (TSL, n=13) or free doxorubicin (DOX, n=11). Response was classified according to 2h, PA-based oxygenation drop and endpoint (>9d), caliper-based volume reduction. At all time-points/wavelengths (750/850nm), the spectral-slope (SS) was computed from the normalized US/PA power spectra using depth-matched reference phantoms. The percent-vascularity (PV) was estimated for the animal with the largest oxygenation-drop at 2h.
TLS-treated responders decreased their PA-SS by 1.9x @750nm and 5.8x @850nm 30m post-treatment and remained constant for 24h; tumor oxygenation followed the same trend. Non-responding SS remained unchanged for 24h. The 750nm SS was 18.7x lower than 850nm suggesting the TSL is sensitive vessel oxygenation. Responder PV decreased 100% when the 30m oxygenation dropped 15% and increased 7x when the 7d oxygenation increased 20%. DOX-responders exhibited similar trends to TSL-responders although the 750nm PA-SS was 1.6x smaller and post-treatment PV was 50% higher. The US-SS remained unchanged until 7d post-treatment suggesting its sensitivity to tumor cell-death. These findings suggest that PA spectral analysis has potential in monitoring cancer treatment response.
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