MRI study of chemobrain in pediatric oncology patients

有 在美国大约有45万儿童癌症幸存者 . 不幸的是，许多 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， 化疗（即，chemobrain）。儿科中的化疗尤其令人担忧，因为它发生在 最具成长性的几年临床管理和研究面临的一个主要挑战是， 儿科肿瘤学是能够早期、准确地识别化疗引起的神经认知效应， 客观地说神经相关因素和表现为临床神经认知的化学效应的轨迹 这一组中损伤在很大程度上是未知的。这种知识差距会阻碍最佳执行 治疗方案和丰富的干预计划，以尽量减少化疗引起的认知缺陷。 因此，至关重要的是，我们明确定义化疗对发育中的大脑造成的损害， 儿科肿瘤患者的临床神经认知障碍。 该提案将使用多参数MRI纵向评估化疗对肿瘤的影响。 大脑发育我们将研究：a）事件相关任务功能磁共振成像的认知功能，B）功能连接， 静息状态fMRI，c）通过扩散张量MRI的灰质和白质微结构完整性，d）脑 通过解剖MRI测量的体积和皮质厚度，e）通过高碳酸血症的fMRI测量的神经血管健康，和f）氧气 代谢应激通过定量血氧水平依赖（BOLD）fMRI。比较将与 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3个月，iii）治疗结束（长达3.5年），iv）治疗结束后1年，沿着年龄- 匹配的健康对照。此外，我们还将研究化疗后10-25年的患者，以评估慢性 化疗的影响，沿着年龄匹配的对照。我们的中心假设是化疗 诱导神经血管健康、氧代谢活动、认知功能、功能性 连接和发育中的大脑的微观结构，这些变化是时间依赖性的， 它们导致儿科肿瘤患者临床上显著的神经认知下降。

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.