MRI study of chemobrain in pediatric oncology patients

确实有 美国约45万名儿科癌症幸存者 。 不幸的是，许多人 这些幸存者(高达75%)经历了严重的神经认知和心理社会功能障碍，与 化疗(即化疗)。儿科的化疗性肺炎尤其令人担忧，因为它发生在 发展中最具形成性的几年。临床管理和研究面临的主要挑战 儿科肿瘤学是早期、准确和准确地识别化疗引起的神经认知影响的能力。 客观地说。表现为临床神经认知的神经关联和化疗效应的轨迹 这个队列中的损害在很大程度上是未知的。这种知识鸿沟造成了以最佳方式执行的障碍 治疗选择和浓缩干预计划，以最大限度地减少化疗导致的认知障碍。 因此，我们必须清楚地界定化疗对发育中的大脑造成的损害，这种损害会导致 儿童肿瘤患者的临床神经认知功能障碍。 这项建议将使用多参数磁共振纵向评估化疗的效果。 发育中的大脑。我们将研究：a)认知功能通过事件相关任务fMRI，b)功能连接通过 静息状态功能磁共振成像，c)弥散张量磁共振灰质和白质微结构完整性，d)脑 解剖磁共振的体积和皮质厚度，e)高碳酸血症的功能磁共振成像的神经血管健康，和f)氧气 定量血氧水平依赖(BOLD)功能磁共振成像的代谢应激。将与以下内容进行比较 临床神经认知评估。研究将在4个时间点纵向进行：i)诊断，ii)6 化疗开始后几个月，三)治疗结束(不超过3.5年)，四)治疗结束一年后，连同年龄- 与健康对照组相匹配。此外，我们将对化疗后10-25年的患者进行研究，以评估慢性 化疗的效果，以及年龄匹配的对照组。我们的中心假设是化疗 导致神经血管健康、氧代谢活动、认知功能、功能 连通性和发育中大脑的微观结构，这些变化是依赖于时间的，并且 它们导致了儿科肿瘤患者临床上显著的神经认知能力下降。

There are approximately 450,000 pediatric cancer survivors in the United States . Unfortunately, many of these survivors (up to 75%) experience significant neurocognitive and psychosocial dysfunction associated with chemotherapy (i.e., chemobrain). Chemobrain in pediatrics is particularly concerning because it occurs during the most formative years of development. A major challenge that faces clinical management and research in pediatric oncology is the ability to identify chemotherapy-induced neurocognitive effects early, accurately and objectively. The neural correlates and the trajectory of chemobrain effects that manifest as clinical neurocognitive impairment in this cohort are largely unknown. This knowledge gap creates a barrier to optimally execute treatment options and enrichment intervention programs to minimize chemotherapy-induced cognitive deficits. Thus, it is critical that we clearly define the chemotherapy-induced damage to the developing brain that leads to clinical neurocognitive impairment in pediatric oncology patients. This proposal will use multiparametric MRI to longitudinally evaluate the effects of chemotherapy on the developing brain. We will study: a) cognitive function by event-related task fMRI, b) functional connectivity by resting-state fMRI, c) gray-matter and white-matter microstructural integrity by diffusion-tensor MRI, d) brain volume and cortical thickness by anatomical MRI, e) neurovascular health by fMRI of hypercapnia, and f) oxygen metabolic stress by quantitative blood-oxygen level-dependent (BOLD) fMRI. Comparisons will be made with clinical neurocognitive assessment. Studies will be carried out longitudinally at 4 time points: i) diagnosis, ii) 6 months after chemo initiation, iii) end of therapy (up to 3.5yrs), iv) 1 year after end-of-therapy, along with age- matched healthy controls. In addition, we will study patients 10-25 years post chemo to evaluate the chronic effects of chemotherapy, along with age-matched controls. Our central hypothesis is that chemotherapy induces changes in neurovascular health, oxygen metabolic activity, cognitive function, functional connectivity, and microstructure of the developing brain, that these changes are time dependent, and that they contribute to clinically significant neurocognitive decline in pediatric oncology patients.