Metabolic effects of brain radiation in children

描述(由申请人提供)：脑放射治疗(RT)对儿童癌症的长期无病生存做出了积极贡献。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童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白质受损，还是皮质区域也受到了影响。是否有可以非侵入性测量的标记物来反映脑损伤的程度？这些标记物能否在治疗过程的早期预测是否会发生脑损伤？这些标记物能用来评估不同大脑区域对辐射的敏感性吗？辐射引起的局部变化的时间进程能否在大脑中进行非侵入性绘制？我们打算使用基于磁共振(MR)的非侵入性方法来回答这些问题：磁共振波谱、扩散张量成像和体积磁共振成像。使用磁共振的方法已被证明是检测辐射损伤的有前途的工具。然而，他们解释儿童神经心理缺陷的能力仍有待评估。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、组织微结构的损伤和脑组织的丢失。同时进行的神经心理评估将进一步加强我们对神经心理状态与所建议的MR方法测量的参数之间的关系的理解。 我们研究的主要目标是确定a)通过磁共振技术测量的大脑功能和完整性如何与传递到大脑的总辐射剂量相关联，以及b)测量参数(代谢物浓度、水扩散特性以及脑叶灰白体积)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。

DESCRIPTION (provided by applicant): Brain 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, children 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 white matter or if cortical areas are also involved. Are there markers that could be measured non-invasively that reflect the degree of brain injury? Could these markers predict early in the course of treatment if brain damage will occur? Could these markers be used to evaluate sensitivity of different brain regions to radiation? Can the temporal course of regional changes due to radiation be mapped in the brain, non-invasively? We intend to answer these questions using non-invasive methods based on magnetic resonance (MR): magnetic resonance spectroscopy, diffusion tensor imaging, and volumetric MRI. Methods using MR have been demonstrated to be promising tools for detection of radiation damage. However, their ability to explain neuropsychological deficits in children remains to be evaluated. We plan to perform a longitudinal MR study with a 30 months follow-up to assess changes in brain metabolism, damage to tissue microstructure, and loss of brain tissue. Concurrent neuropsychological assessments will further enhance our understanding of the relationship between neuropsychological status and parameters measured by the proposed MR methods. The broad objectives of our research are to determine a) how brain function and integrity, as measured by MR techniques, can be correlated with total radiation dose delivered to the brain and b) whether changes in measured parameters (metabolite concentrations, water diffusion characteristics, and lobar gray and white volumes) can be used as surrogate markers to predict the neuropsychological outcome from RT.