Addressing respiratory gating latency for accurate pulse delivery in preclinical electron FLASH irradiation on a
Rakesh Manjappa1, Jinghui Wang1, Stavros Melemenidis1
1Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Background:
Clinical linear accelerators are an accessible platform for preclinical research on the biological effects of ultra-rapid electron irradiation (FLASH). However, they are not inherently designed for the accurate pulse control required for experiments using a small number of relatively high-dose pulses, and available methods for beam control such as respiratory gating can be error-prone owing to system latency.
Purpose:
Here we experimentally characterize the temporal latency of the respiratory gating system for controlling beam-on and beam-off at the individual linac pulse level. We use this information to develop accurate pulse delivery methods for preclinical FLASH research.
Methods And Materials:
We used programmable controller boards and a relay circuit to monitor and control delivery of specific numbers of pulses through the built-in monitor chamber and respiratory gating system of a Varian Trilogy linac. We modeled system response latency as a normally distributed random variable and experimentally recorded the probability of successful pulse delivery and inhibition relative to the time of beam-on and beam-off request signals to derive the mean and standard deviation of latency times at different pulse repetition frequencies. We implemented two methods - an adaptive method using only the delivered-pulse signal, and a synchronization method additionally using the linac's internal pulse-timing signal - and characterized their performance for standard and customized pulse sequences.
Results:
The mean and standard deviation values of the respiratory gating latency at 60, 90 and 180 Hz pulse repetition frequency were respectively 2.0±0.8 ms, 2.1±2.8 ms, and 2.4±1.9 ms for beam-on and 1.3±0.9 ms, 1.9±2.9 ms, and 1.8±2.1 ms for beam-off. Beam-on and beam-off latencies were similar to each other, and similar across pulse repetition frequencies. Characterizing the latency parameters permitted choosing optimal timing parameters that maximized the rate of successfully delivering the desired number of pulses using both adaptive and synchronization methods, exceeding 99% at 90 Hz for both methods, and reaching 95% (adaptive) and 80% (synchronization) at 180 Hz. This also enabled successful implementation of custom pulse sequences not natively available on the system.
Conclusions:
We demonstrated that accounting for latency and/or using the ability to read the prior information on expected pulse timing can provide high accuracy in delivering specified numbers of pulses. This reliability is critical for accurate dose delivery in preclinical FLASH research of single fraction and especially fractionated dosing regimens. The ability to generate custom pulse sequences enables more detailed exploration of the temporal dependence of biological FLASH effects.
