MRI study of chemobrain in pediatric oncology patients

儿科肿瘤患者化学脑的 MRI 研究

• 批准号: 10643832
• 负责人: Timothy Q. Duong
• 金额: --
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-16 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10643832
• 关键词: Affect; Age; Anatomy; Brain; Cerebrovascular system; Chronic; Clinical; Clinical Management; Clinical Research; Cognitive; Cognitive deficits; Development; Diagnosis; Diffusion; Event; Face; Functional Magnetic Resonance Imaging; Functional disorder; Health; Hypercapnia; Hypoxia; Image; Imaging Device; Knowledge; Magnetic Resonance Imaging; Metabolic; Metabolic dysfunction; Metabolic stress; Myelin; Neurocognitive; Neurocognitive Deficit; Oxygen; Patients; Pediatric Oncology; Pediatrics; Pharmaceutical Preparations; Quality of life; Rest; Schools; Structure; Survivors; Symptoms; Therapeutic Intervention; Thick; Time; United States; Work; analytical tool; blood oxygen level dependent; brain volume; cerebrovascular; chemobrain; chemotherapy; childhood cancer survivor; clinically significant; cognitive function; cognitive task; cohort; design; experience; functional improvement; gray matter; improved; innovation; intervention program; neural correlate; neurovascular; pre-clinical; psychosocial; targeted treatment; treatment strategy; white matter

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.

有 美国大约有450,000个小儿癌症幸存者 。 不幸的是，很多 这些幸存者（高达75％）经历了与 化学疗法（即Chemobrain）。儿科中的Chemobrain尤其令人担忧，因为它发生在 发展最成长的岁月。面临临床管理和研究的主要挑战 小儿肿瘤学是能够早期，准确和 客观地。表现为临床神经认知的化学探针效应的神经相关性和轨迹 该队列中的损害在很大程度上是未知的。此知识差距为最佳执行而造成了障碍 治疗选择和富集干预计划，以最大程度地减少化学疗法引起的认知缺陷。 因此，至关重要的是，我们清楚地定义了化学疗法引起的对发育中的大脑的损害，从而导致 小儿肿瘤患者的临床神经认知障碍。 该建议将使用多参数MRI纵向评估化学疗法对 发展大脑。我们将研究：a）通过事件相关的任务fMRI，b）功能连接的认知功能 静止状态fMRI，c）扩散tensor MRI，d）大脑 通过解剖学MRI的体积和皮质厚度，e）fMRI的神经血管健康，f）氧气 定量血氧水平依赖性（BOLD）fMRI的代谢应激。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 化学启动后的几个月，iii）治疗终结（最多3.5元），iv），术后1年，以及年龄 - 匹配的健康对照。此外，我们将在化学疗法后10 - 25年研究患者以评估慢性 化学疗法的影响以及年龄匹配的对照。我们的中心假设是化学疗法 诱导神经血管健康，氧代谢活性，认知功能，功能性变化 连通性和发展中大脑的微观结构，这些变化是依赖时间的，并且 它们有助于小儿肿瘤患者的临床上显着的神经认知下降。