METABOLIC EFFECTS OF BRAIN RADIATION IN CHILDREN

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。积极的放射治疗(RT)对儿童癌症的长期无病生存做出了积极的贡献。尽管RT对治疗有好处，但它与中枢神经系统的一系列急性、早期和晚期毒性有关。因此，接受脑辐射治疗的儿科患者通常会出现神经和神经认知缺陷，表现为行为或学习障碍。目前尚不清楚神经认知缺陷是否主要是由于皮质下结构的损害，或者是否也涉及皮质区域。我们计划使用基于磁共振的非侵入性方法(MR-磁共振波谱、体积MRI和扩散张量成像)来确定a)通过MR技术测量的脑功能如何与输送到大脑的总辐射剂量相关联，以及b)测量参数(代谢物浓度、叶组织体积和水扩散特性)的变化是否可以作为替代标记物来预测RT的神经心理结果。我们计划进行一项为期30个月的纵向MR研究，以评估脑代谢的变化(使用质子磁共振波谱)、脑组织的丢失(使用容量磁共振成像)和组织微结构的损伤(使用扩散张量成像)。同时进行神经心理评估，以评估神经心理状态。线性混合效应(LME)回归分析将被用来检验辐射剂量对局部脑代谢物水平、脑叶体积的变化和脑组织中水的扩散特性的影响，并评估神经心理测试分数与所建议的MR方法测量的参数之间的关系。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Aggressive radiation therapy (RT) has contributed positively to long term disease-free survival from childhood cancer. Despite its therapeutic benefit, RT has been associated with a spectrum of acute, early-delayed, and late-delayed toxicities to the central nervous system. As a consequence, pediatric patients treated with brain radiation often develop neurological and neurocognitive deficits manifesting as behavioral or learning disabilities. It is unclear whether the neurocognitive deficits are due mainly to damage to the subcortical structures or if cortical areas are also involved. We plan using non-invasive methods based on magnetic resonance (MR - magnetic resonance spectroscopy, volumetric MRI, and diffusion tensor imaging) to determine a) how brain function, as measured by MR techniques, can be correlated with total radiation dose delivered to the brain and b) whether changes in measured parameters (metabolite concentration, lobar tissue volumes, and water diffusion characteristics) can be used as surrogate markers to predict the neuropsychological outcome from RT. We plan to perform a longitudinal MR study with a 30 months follow-up to assess changes in brain metabolism (using proton MR spectroscopy), loss of brain tissue (using volumetric MRI), and damage to tissue microstructure (using diffusion tensor imaging). Concurrent neuropsychological assessments will be performed to evaluate the neuropsychological status. Linear mixed effects (LME) regression analyses will be applied to examine the effect of radiation doses on regional brain metabolite levels, changes in lobar brain volumes and diffusion properties of water in the brain tissue and to evaluate the relationship between neuropsychological test scores and parameters measured by the proposed MR methods.