Experimental demonstration of accurate Bragg peak localization with ionoacoustic tandem phase detection (iTPD).

Accurate knowledge of the exact stopping location of ions inside the patient would allow full exploitation of their ballistic properties for patient treatment. The localized energy deposition of a pulsed particle beam induces a rapid temperature increase of the irradiated volume and leads to the emission of ionoacoustic (IA) waves. Detecting the time-of-flight (ToF) of the IA wave allows inferring information on the Bragg peak location and can henceforth be used for in-vivo range verification. A challenge for IA is the poor signal-to-noise ratio (SNR) at clinically relevant doses and viable machines. We present a frequency-based measurement technique, labeled as ionoacoustic tandem phase detection (iTPD) utilizing lock-in amplifiers. The phase shift of the IA signal to a reference signal is measured to derive the ToF. Experimental IA measurements with a 3.5MHz lead zirconate titanate (PZT) transducer and lock-in amplifiers were performed in water using 22MeV proton bursts. A digital iTPD was performed in-silico at clinical dose levels on experimental data obtained from a clinical facility and secondly, on simulations emulating a heterogeneous geometry. For the experimental setup using 22MeV protons, a localization accuracy and precision obtained through iTPD deviates from a time-based reference analysis by less than 15μm. Several methodological aspects were investigated experimentally in systematic manner. Lastly, iTPD was evaluated in-silico for clinical beam energies indicating that iTPD is in reach of sub-mm accuracy for fractionated doses <5Gy. iTPD can be used to accurately measure the ToF of IA signals online via its phase shift in frequency domain. An application of iTPD to the clinical scenario using a single pulsed beam is feasible but requires further development to reach <1Gy detection capabilities.