[论文解读] Multi-Institutional Audit of FLASH and Conventional Dosimetry with a 3D-Printed Anatomically Realistic Mouse Phantom

M. Ramish Ashraf, Stavros Melemenidis+23 more|arXiv (Cornell University)|Sep 28, 2023

Nuclear Physics and ApplicationsPhysics and Astronomy被引用 3

一句话总结

这项多机构研究利用3D打印的解剖学上逼真的小鼠模型，评估了FLASH与常规电子束照射的剂量学变异性。该模型采用双喷嘴3D打印技术，使用匹配软组织、骨骼和肺组织密度的材料制造，表现出高度可重复性，各模型间剂量差异极小（<0.5%），且模型间重复测量的剂量变异性从4.3%降至1.2%，支持其在临床前FLASH研究认证中的应用。

ABSTRACT

We conducted a multi-institutional audit of dosimetric variability between FLASH and conventional dose rate (CONV) electron irradiations by using an anatomically realistic 3D-printed mouse phantom. A CT scan of a live mouse was used to create a 3D model of bony anatomy, lungs, and soft tissue. A dual-nozzle 3D printer was used to print the mouse phantom using acrylonitrile butadiene styrene ($~1.02 g/cm^3$) and polylactic acid ($~1.24 g/cm^3$) simultaneously to simulate soft tissue and bone densities, respectively. The lungs were printed separately using lightweight polylactic acid ($~0.64 g/cm^3$). Hounsfield units (HU) and densities were compared with the reference CT scan of the live mouse. Print-to-print reproducibility of the phantom was assessed. Three institutions were each provided a phantom, and each institution performed two replicates of irradiations at selected mouse anatomic regions. The average dose difference between FLASH and CONV dose distributions and deviation from the prescribed dose were measured with radiochromic film. Compared to the reference CT scan, CT scans of the phantom demonstrated mass density differences of $0.10 g/cm^3$ for bone, $0.12 g/cm^3$ for lung, and $0.03 g/cm^3$ for soft tissue regions. Between phantoms, the difference in HU for soft tissue and bone was &lt;10 HU from print to print. Lung exhibited the most variation (54 HU) but minimally affected dose distribution (&lt;0.5% dose differences between phantoms). The mean difference between FLASH and CONV from the first replicate to the second decreased from 4.3% to 1.2%, and the mean difference from the prescribed dose decreased from 3.6% to 2.5% for CONV and 6.4% to 2.7% for FLASH. The framework presented here is promising for credentialing of multi-institutional studies of FLASH preclinical research to maximize the reproducibility of biological findings.

研究动机与目标

• 评估使用标准化模型在多机构间FLASH与常规电子束照射的剂量学变异性。
• 开发一种具有组织等效密度的3D打印、解剖学上逼真的小鼠模型，用于临床前剂量学研究。
• 评估多机构间打印到打印的可重复性及剂量分布的一致性。
• 建立多机构FLASH临床前研究认证的框架。

提出的方法

• 利用活体小鼠的CT扫描创建骨骼结构、肺部和软组织的3D模型。
• 采用双喷嘴3D打印机，使用丙烯腈-丁二烯-苯乙烯（1.02 g/cm³）制造软组织，使用聚乳酸（1.24 g/cm³）制造骨骼。
• 使用轻质聚乳酸（0.64 g/cm³）单独打印肺部，以匹配低密度肺组织。
• 通过与活体小鼠参考CT扫描对比，验证亨氏单位（HU）和质量密度。
• 使用放射敏感胶片测量在选定解剖区域中FLASH与常规剂量率之间的剂量差异。
• 三家机构各自执行两次照射重复实验，比较各机构之间及不同条件下的剂量分布。

实验结果

研究问题

• RQ1 3D打印的小鼠模型在多大程度上准确复现了真实小鼠解剖结构的亨氏单位和质量密度？
• RQ2 在使用相同模型的情况下，FLASH与常规电子束照射在多机构间的剂量输送变异性如何？
• RQ3 在多机构间，模型打印的可重复性在亨氏单位和剂量分布方面表现如何？
• RQ4 模型变异性在多大程度上影响了FLASH与常规照射的剂量差异？
• RQ5 该模型能否作为多机构FLASH临床前研究的标准化认证工具？

主要发现

• 与参考CT扫描相比，该模型的密度差异为：骨骼0.10 g/cm³，肺组织0.12 g/cm³，软组织0.03 g/cm³。
• 打印到打印的可重复性显示，软组织和骨骼的亨氏单位差异小于10 HU，肺组织差异为54 HU，但对剂量影响极小（<0.5%差异）。
• FLASH与常规剂量分布之间的平均剂量差异从4.3%降至1.2%。
• 在重复实验中，常规照射的处方剂量偏差从3.6%降至2.5%，FLASH照射的偏差从6.4%降至2.7%。
• 该框架表现出高度可重复性及低多机构间变异性，支持其在多机构FLASH临床前研究认证中的应用。
• 本研究确立了标准化、解剖学上逼真的模型作为提升临床前FLASH剂量学一致性的可行工具。