First-In-Human Study of 3D Protoacoustic Imaging for Proton Therapy Monitoring
Abstract
Purpose
Proton therapy is an increasingly adopted cancer treatment due to its high dose conformity enabled by the Bragg peak (BP), reducing radiation exposure to surrounding healthy tissue. However, this steep dose gradient makes treatment accuracy highly sensitive to uncertainties such as patient setup errors or intra- and inter-fraction anatomical motion. Real-time, in vivo proton range verification remains a major unmet clinical need. This study demonstrates the first application of three-dimensional protoacoustic (PA) imaging for volumetric proton range verification in human anatomy, representing a critical step toward clinical translation.
Methods
Experiments were performed using a clinical proton beamline (Mevion) to irradiate the liver and head of a female human cadaver. Treatment plans targeting liver and brain pseudo-tumors were generated in RayStation based on prior CT imaging. Liver irradiation used a single energy layer of 154.09 MeV with the gantry at 180°, while brain irradiation used 107.66 MeV with the gantry at 90°. A 256-channel, 1 MHz central-frequency matrix ultrasound array was coupled via a water bag and positioned perpendicular to the proton beam. Protoacoustic signals synchronized to proton beam pulses (750 Hz) were recorded using a custom data acquisition system. Data were processed using a physics-informed neural network based on time-reversal reconstruction, with 50 signal averages to enhance signal-to-noise ratio.
Results
Three-dimensional protoacoustic reconstructions accurately resolved proton range and Bragg peak location in both liver and head anatomies. Despite acoustic heterogeneities from the rib cage and skull, measured proton ranges closely matched planned dose distributions, demonstrating robust volumetric localization.
Conclusion
This study demonstrates the feasibility of three-dimensional protoacoustic imaging for volumetric proton range verification in human anatomy. The results establish protoacoustic imaging as a promising, non-ionizing modality for real-time proton therapy monitoring and support its integration into clinical and adaptive proton therapy workflows.