METABOLIC EFFECTS OF BRAIN RADIATION IN CHILDREN

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。积极的放射治疗（RT）有助于儿童癌症的长期无病生存。尽管RT具有治疗益处，但其与中枢神经系统的急性、早期延迟和晚期延迟毒性谱相关。因此，接受脑放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伤，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），以确定a）如通过MR技术测量的脑功能如何与递送到脑的总辐射剂量相关，以及B）测量参数的变化是否（代谢物浓度、肺叶组织体积和水扩散特性）可用作预测RT的神经心理学结果的替代标志物。 我们计划进行一项纵向MR研究，随访30个月，以评估脑代谢的变化（使用质子MR波谱）、脑组织的损失（使用体积MRI）和组织微结构的损伤（使用扩散张量成像）。同时进行神经心理学评估，以评价神经心理状态。线性混合效应（LME）回归分析将被应用于检查辐射剂量对局部脑代谢物水平的影响，在脑叶脑容量和水在脑组织中的扩散特性的变化，并评估神经心理测试分数和参数之间的关系所提出的MR方法测量。

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.