Wang Jinghui, Melemenidis Stavros, Manjappa Rakesh, Viswanathan Vignesh, Ashraf Ramish M, Levy Karen, Skinner Lawrie B, Soto Luis A, Chow Stephanie, Lau Brianna, Ko Ryan B, Graves Edward E, Yu Amy S, Bush Karl K, Surucu Murat, Rankin Erinn B, Loo Billy W, Schüler Emil, Maxim Peter G
Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California, USA.
Department of Gynecologic Oncology, Stanford University School of Medicine, Stanford, California, USA.
Med Phys. 2024 Dec;51(12):9166-9178. doi: 10.1002/mp.17432. Epub 2024 Sep 27.
FLASH radiation therapy (RT) offers a promising avenue for the broadening of the therapeutic index. However, to leverage the full potential of FLASH in the clinical setting, an improved understanding of the biological principles involved is critical. This requires the availability of specialized equipment optimized for the delivery of conventional (CONV) and ultra-high dose rate (UHDR) irradiation for preclinical studies. One method to conduct such preclinical radiobiological research involves adapting a clinical linear accelerator configured to deliver both CONV and UHDR irradiation.
We characterized the dosimetric properties of a clinical linear accelerator configured to deliver ultra-high dose rate irradiation to two anatomic sites in mice and for cell-culture FLASH radiobiology experiments.
Delivered doses of UHDR electron beams were controlled by a microcontroller and relay interfaced with the respiratory gating system. We also produced beam collimators with indexed stereotactic mouse positioning devices to provide anatomically specific preclinical treatments. Treatment delivery was monitored directly with an ionization chamber, and charge measurements were correlated with radiochromic film measurements at the entry surface of the mice. The setup for conventional dose rate irradiation utilized the same collimation system but at increased source-to-surface distance. Monte Carlo simulations and film dosimetry were used to characterize beam properties and dose distributions.
The mean electron beam energies before the flattening filter were 18.8 MeV (UHDR) and 17.7 MeV (CONV), with corresponding values at the mouse surface of 17.2 and 16.2 MeV. The charges measured with an external ion chamber were linearly correlated with the mouse entrance dose. The use of relay gating for pulse control initially led to a delivery failure rate of 20% (± 1 pulse); adjustments to account for the linac latency improved this rate to < 1/20. Beam field sizes for two anatomically specific mouse collimators (4 × 4 cm for whole-abdomen and 1.5 × 1.5 cm for unilateral lung irradiation) were accurate within < 5% and had low radiation leakage (< 4%). Normalizing the dose at the center of the mouse (∼0.75 cm depth) produced UHDR and CONV doses to the irradiated volumes with > 95% agreement.
We successfully configured a clinical linear accelerator for increased output and developed a robust preclinical platform for anatomically specific irradiation, with highly accurate and precise temporal and spatial dose delivery, for both CONV and UHDR irradiation applications.
闪束放射治疗（RT）为拓宽治疗指数提供了一条有前景的途径。然而，要在临床环境中充分发挥闪束的潜力，深入了解其中涉及的生物学原理至关重要。这需要具备专门为临床前研究设计的、用于常规（CONV）和超高剂量率（UHDR）照射的优化设备。进行此类临床前放射生物学研究的一种方法是改造一台临床直线加速器，使其能够进行CONV和UHDR照射。
我们对一台经配置可向小鼠的两个解剖部位进行超高剂量率照射以及用于细胞培养闪束放射生物学实验的临床直线加速器的剂量学特性进行了表征。
UHDR电子束的输送剂量由一个微控制器和与呼吸门控系统相连的继电器控制。我们还制作了带有索引立体定向小鼠定位装置的射束准直器，以提供针对特定解剖部位的临床前治疗。用一个电离室直接监测治疗输送情况，并将电荷测量结果与小鼠体表处的放射变色胶片测量结果进行关联。常规剂量率照射的设置使用相同的准直系统，但源皮距增加。利用蒙特卡罗模拟和胶片剂量测定法来表征射束特性和剂量分布。
在均整滤过器之前，电子束的平均能量分别为18.8 MeV（UHDR）和17.7 MeV（CONV），在小鼠体表处的相应值分别为17.2 MeV和16.2 MeV。用外部电离室测量的电荷与小鼠入口剂量呈线性相关。最初使用继电器门控进行脉冲控制导致输送失败率为20%（±1个脉冲）；针对直线加速器延迟进行的调整将该比率提高到了小于1/20。两种针对特定解剖部位的小鼠准直器（全腹照射为4×4 cm，单侧肺照射为1.5×1.5 cm）的射野尺寸精确到误差小于5%，且辐射泄漏低（小于4%）。将小鼠中心处（约0.75 cm深度）的剂量归一化后得出，照射体积的UHDR和CONV剂量一致性超过95%。
我们成功地对一台临床直线加速器进行了配置以提高输出，并开发了一个强大的临床前平台，用于针对特定解剖部位的照射，在CONV和UHDR照射应用中都具有高度准确和精确的时间和空间剂量输送。
