Bridging Photoacoustic and Protoacoustic Imaging: Material Heterogeneity Effects on Proton Range Verification Using Time-of-Flight Analysis.

Photoacoustic and protoacoustic imaging share the common principle of acoustic wave generation through different excitation sources: optical absorption vs. proton Bragg-peak. These acoustic signals exhibit heterogeneity within the tissue, which strongly influence wave propagation and detection accuracy. In this study, we investigate how material variation affects time-of-flight (TOF)-based acoustic signal analysis in the context of protoacoustic proton range verification, providing insights relevant to broader photoacoustic imaging methodologies. A ±15 °C temperature difference in water caused only a 0.04 μs delay and thus had a minimal effect. In heterogeneous phantoms, lung-containing cases produced range errors up to 3.72 mm. In clinical scenarios, detectors aligned with air or low-density tissues showed large overestimations, up to 192.4 mm. Only 2 of 25 detector positions met the <2 mm error criterion. These results highlight that tissue composition and acoustic heterogeneity significantly influence protoacoustic wave propagation and range accuracy. Accurate range verification using protoacoustics must account for material variations along the wave path, particularly in lung regions, to ensure clinical applicability.