Department of Radiation Oncology, University of California San Francisco, 1600 Divisadero Street, San Francisco, CA, 94143, USA.
Sci Rep. 2024 Nov 4;14(1):26585. doi: 10.1038/s41598-024-77415-5.
The radiobiological mechanisms behind the favorable response of tissues to microbeam radiation therapy (MRT) are not fully described yet. Among other factors, the differential action to tumor and normal tissue vasculature is considered to contribute to MRT efficacy. This computational study evaluates the relevance of tumor growth stage and associated vascular redistribution to this effect. A multiscale approach was employed with two simulation softwares: TOPAS and CompuCell3D. Segmentation images of the angioarchitecture of a non-bearing tumor mouse brain were used. The tumor vasculature at different tumor growth stages was obtained by simulating the tumor proliferation and spatial vascular redistribution. The radiation-induced damage to vascular cells and consequent change in oxygen perfusion were simulated for normal and tumor tissues. The multiscale model showed that oxygen perfusion to tissues and vessels decreased as a function of the tumor proliferation stage, and with the decrease in uniformity of the vasculature spatial distribution in the tumor tissue. This led to an increase in the fraction of hypoxic (up to 60%) and necrotic (10%) tumor cells at advanced tumor stages, whereas normal tissues remained normoxic. These results showed that tumor stage and spatial vascular distribution contribute to the preferential effect of MRT in tumors.
微束放射疗法（MRT）对组织产生有利反应的放射生物学机制尚未完全描述。除其他因素外，肿瘤和正常组织脉管系统的差异作用被认为有助于 MRT 的疗效。这项计算研究评估了肿瘤生长阶段和相关血管重新分布对此效应的相关性。采用多尺度方法，使用两种模拟软件：TOPAS 和 CompuCell3D。使用非承重肿瘤鼠脑的血管结构分割图像。通过模拟肿瘤增殖和空间血管重新分布，获得不同肿瘤生长阶段的肿瘤脉管系统。模拟了正常和肿瘤组织中血管细胞的辐射损伤及其对氧灌注的影响。多尺度模型表明，随着肿瘤增殖阶段的增加，以及肿瘤组织中血管空间分布均匀性的降低，组织和血管中的氧灌注减少。这导致在晚期肿瘤阶段，缺氧（高达 60%）和坏死（10%）肿瘤细胞的比例增加，而正常组织仍保持正常氧合。这些结果表明，肿瘤阶段和空间血管分布有助于 MRT 在肿瘤中的优先作用。
