Lack of online range verification limits efficacy of particle therapy for many tumor sites. Real-time thermoacoustic range verification could enable more aggressive treatment planning and hypofractionation for tumor sites that can be imaged with ultrasound during treatment. Our objective was to experimentally demonstrate accuracy and robustness of thermoacoustic range estimates relative to ultrasound images despite acoustic heterogeneity and discrepancies between assumed and true soundspeed. Prior results were for weak acoustic scatterers with known soundspeeds. 250 ns pulses of 0.26 Gy of 16 MeV protons and 2.3 Gy of 60 MeV helium ions were delivered to water and oil targets, respectively. Thermoacoustic signals with DC-4 MHz bandwidth were detected by a 96-channel ultrasound array placed 6-10 cm distal to the Bragg peak. One-way beamforming with an assumed soundspeed was performed to estimate range. The same soundspeed and transducer array were used to generate ultrasound images via two-way ultrasound beamforming. An air gap phantom displaced the Bragg peak by 6.5 mm to demonstrate accuracy. The scanner’s soundspeed setting was altered by ±5% to demonstrate robustness to soundspeed errors. Tissue mimicking gelatin and a 5 mm thick bone sample were introduced to demonstrate robustness to acoustic heterogeneity. Single ion pulse measurements sufficed during the helium run, but signal averaging was required for protons. Estimates of the entry point agreed with the air-target interface in ultrasound images and range estimates agreed with Monte Carlo simulations to within 300 μm microns, even when TA emissions traveled through a strong acoustic scatterer. Estimated Bragg peak locations were translated 6.5 mm by the air gap phantom and correctly identified scenarios when the beam stopped inside bone, but did not accurately estimate range in bone. Soundspeed errors dilate and acoustic heterogeneities deform ultrasound images. Thermoacoustic range estimates are transformed similarly and are robust relative to ultrasound images of underlying anatomy. When the target can be visualized with ultrasound during treatment, thermoacoustic range verification may enable real-time motion management and range verification. Therapeutic systems deliver higher (200+ MeV) energy protons using pulse durations exceeding 5 μs and generate thermoacoustic emissions with sonar bandwidths (DC-100 kHz). Therefore, custom acoustic hardware will be required to detect low frequency thermoacoustic emissions and also generate high-resolution ultrasound images.Abstract 3713; Table 1Experimentwaterwater & bonewater & air gapsafflower oilIonprotonprotonproton4HeBeam Energy (MeV)16.0±0.1516.0±0.1516.0±0.1560.7±0.4Bragg curve FWHM (μm)390240390230distal HWTM (μm)1609016080Monte Carlo Range (mm)2.471.948.952.51Thermoacoustic Range (mm)2.65±0.091.36±0.616.59±0.042.76±0.04N8887 Open table in a new tab