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 名儿科癌症幸存者 。 不幸的是，许多 这些幸存者（高达 75%）经历了与以下疾病相关的严重神经认知和心理社会功能障碍： 化疗（即化疗脑）。儿科中的化学脑尤其令人担忧，因为它发生在 发展最具形成性的几年。临床管理和研究面临的重大挑战 儿科肿瘤学能够及早、准确和准确地识别化疗引起的神经认知效应 客观地。神经相关性和化学脑效应的轨迹表现为临床神经认知 这一群体的损伤很大程度上是未知的。这种知识差距为最佳执行造成了障碍 治疗选择和强化干预计划可最大限度地减少化疗引起的认知缺陷。 因此，我们必须清楚地定义化疗对发育中的大脑造成的损害，从而导致 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 来纵向评估化疗对患者的影响。 正在发育的大脑。我们将研究：a）通过事件相关任务功能磁共振成像来研究认知功能，b）通过 静息态功能磁共振成像，c) 通过扩散张量 MRI 观察灰质和白质微结构完整性，d) 大脑 通过解剖 MRI 测量体积和皮质厚度，e) 通过高碳酸血症 fMRI 测量神经血管健康状况，以及 f) 氧气 通过定量血氧水平依赖 (BOLD) 功能磁共振成像 (fMRI) 检测代谢应激。将与进行比较 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，iii) 治疗结束（最多 3.5 年），iv) 治疗结束后 1 年，以及年龄- 匹配的健康对照。此外，我们将研究化疗后 10-25 年的患者，以评估慢性 化疗的效果以及年龄匹配的对照。我们的中心假设是化疗 引起神经血管健康、氧代谢活动、认知功能、功能性的变化 发育中的大脑的连通性和微观结构，这些变化是时间依赖性的，并且 它们会导致儿科肿瘤患者出现临床上显着的神经认知下降。