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，对单一或多个部分的高剂量辐射的反应 治疗(HD-RT)效果显著，表明HD-RT控制肿瘤的效果至少与 常规分割放射治疗(CF-RT)的生物等量剂量，即使在辐射抵抗中也是如此 肿瘤。尽管其有效机制尚不清楚，但HD-RT正在被人们接受 为各种肿瘤行医，包括脑瘤。 我们最近的临床前研究使用MRI测量HD-RT后肿瘤生理的短期变化。 脑肿瘤的小动物模型显示了包括血管效应在内的生理反应，但 多因素且随时间变化。假设这些短期变化可能都解释了 HD-RT的有效性增加，并作为长期应答的预测因子，我们建议研究 血液透析-放射治疗后短期生理变化与远期预后的关系 那是心理治疗。作为对照，我们还将研究CF-RT中和之后的生理变化。详细 建议使用孔弹性建模来生成局部固体和流体参数(应力、流动)的地图，该地图将 有助于解释生理上的短期变化。目的1研究肿瘤指标的短期变化 作为反应预测因子的生理学。目标2描述了这些相同措施在整个课程中的行为 Cf-RT.我们的长期目标是开发预测肿瘤控制的非侵入性生物反应标记物 HD-RT和CF-RT后，并描述生理变化和相关生物标志物可能用于 优化放疗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.