MRI Signatures of Response to High-Dose Radiotherapy in Rat Models of Cerebral Tumor

在某些情况下，例如小的脑肿瘤转移，对单次或多次高剂量放射的反应 HD-RT治疗（HD-RT）的效果是显著的，这表明HD-RT肿瘤控制至少与 生物等效剂量的常规分割放射治疗（CF-RT），即使在放射抗性 肿瘤的虽然其有效性的机制还不清楚，但HD-RT正在被接受 包括脑肿瘤在内的各种肿瘤的实践。 我们最近的临床前研究使用MRI测量HD-RT后肿瘤生理学的短期变化， 脑肿瘤的小动物模型表明包括血管效应的生理反应，但 多因素和时间变量。假设这些短期变化可以解释 增加HD-RT的有效性，并作为长期反应的预测因子，我们建议研究 HD-RT后短期生理变化与长期结果之间的关系 这种治疗。相反，我们还将研究CF-RT期间和之后的生理变化。详细 多孔弹性建模被提出来生成局部固体和流体参数（应力、流动）的图， 有助于解释生理学上的短期变化目的1研究肿瘤测量的短期变化 生理学作为反应的预测器。目标2描述了这些相同的措施在整个过程中的行为 我们的长期目标是开发预测肿瘤控制的非侵入性反应生物标志物 HD-RT和CF-RT后，并描述生理变化和相关生物标志物，可用于 优化RT和辅助化疗的顺序和时机。

In some cases, e.g. small brain tumor metastases, responses to single or multiple fraction high-dose radiation therapy (HD-RT) have been remarkable, suggesting that HD-RT tumor control is at least as effective as biologically equivalent doses of conventional fractionated radiation therapy (CF-RT), even in radioresistant tumors. Although the mechanism for its effectiveness is not well understood, HD-RT is becoming accepted practice for a variety of tumors, including brain tumors. Our recent preclinical study using MRI measures of short-term changes in tumor physiology after HD-RT in a small-animal model of cerebral tumor suggests a physiological response that includes vascular effects, but is multifactorial and temporally variable. Hypothesizing that these short-term changes may both explain the increased effectiveness of HD-RT, and serve as a predictor of long-term response, we propose to investigate the relationship between short-term physiological changes after HD-RT and long-term outcome as a result of that therapy. In counterpoint, we will also study physiological changes during and after CF-RT. Detailed poroelastic modeling is proposed to generate a map of local solid and fluid parameters (stress, flow) that will help explain short-term changes in physiology. Aim 1 studies short-term changes in measures of tumor physiology as predictors of response. Aim 2 describes the behavior of these same measures over the course of CF-RT. Our long-range goals are to develop noninvasive biomarkers of response that predict tumor control after HD-RT and CF-RT, and to describe physiological changes and related biomarkers that might be used to optimize the order and timing of RT and adjuvant chemotherapies.