Imaging Chemotherapy-Induced Brain Damage in Pediatric Cancer Survivors

对小儿癌症幸存者化疗引起的脑损伤进行成像

• 批准号: 10054003
• 负责人: Heike Elizabeth Daldrup-Link
• 金额: $ 19.71万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-05 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10054003
• 关键词: Acute; Affect; Age; Anti-Inflammatory Agents; Anxiety; Attention; Attention Concentration; Biological; Biological Markers; Brain; Brain Injuries; Brain imaging; Cancer Patient; Cancer Survivor; Cerebrovascular Circulation; Cerebrum; Child; Childhood; Chronic; Clinical; Clinical Trials; Cross-Sectional Studies; Data; Development; Diagnosis; Diagnostic; Diffusion; Disease; Dose; Drug Exposure; Early Diagnosis; Early Intervention; Emotions; Excision; Exercise; Exposure to; Face; Future; Gender; Goals; Headache; Health; Image; Imaging Techniques; Imaging technology; Impaired cognition; Impairment; Incidence; Individual; Intervention; Leukoencephalopathy; Life; Linear Regressions; MRI Scans; Magnetic Resonance Imaging; Malignant Childhood Neoplasm; Malignant Neoplasms; Measures; Memory; Methotrexate; Microglia; Minor; Minority; Modeling; Monitor; Morbidity - disease rate; Motor; Neurocognitive; Neurocognitive Deficit; Neurologic; Operative Surgical Procedures; Outcome; Patients; Perfusion; Pharmaceutical Preparations; Pharmacotherapy; Physical Exercise; Physiological; Positioning Attribute; Positron-Emission Tomography; Protons; Registries; Reporting; Risk; Safety; Screening for cancer; Seizures; Spin Labels; Stress; Systemic Therapy; Testing; Thick; Time; Tissues; United States; base; brain abnormalities; brain metabolism; brain morphology; brain volume; cancer therapy; chemotherapy; childhood cancer survivor; cingulate gyrus; clinical imaging; early detection biomarkers; executive function; experience; fluorodeoxyglucose; fluorodeoxyglucose positron emission tomography; glucose metabolism; imaging biomarker; imaging study; leukemia/lymphoma; metabolic rate; neuroimaging marker; neurotoxicity; non-invasive monitor; novel; novel diagnostics; novel therapeutics; pediatric patients; personalized medicine; preservation; prevent; sarcoma; side effect; tool; white matter injury

Imaging Chemotherapy-Induced Brain Damage in Pediatric Cancer Survivors Many pediatric cancer survivors face chronic and life-altering side effects as a result of their chemotherapy. Children treated with high dose methotrexate (MTX) chemotherapy can experience neurocognitive decrements that include impairments in memory, attention, and concentration. The overall cumulative incidence of neurocognitive morbidities ranges from 25 to 45%. There is a window of time between the exposure to therapy and future morbidity. Unfortunately, once cancer survivors present with clinical morbidities, it is often too late for health-preserving interventions. To prevent drug-induced clinical problems after therapy, it is important to develop diagnostic tools to detect the early stages of tissue damage that are still reversible. However, the development of related biomarkers has gained surprisingly little attention in the field. To close this gap, we aim to develop novel diagnostic biomarkers for detection of early tissue damage before clinical problems become apparent. The obtained information could then be used to initiate corrective actions before long-term morbidities occur and ultimately preserve the health of our patients. The overall goal of our project is to detect early imaging signs of chemotherapy-induced brain damage that can predict chronic neurocognitive problems months or years later. We are uniquely positioned to pursue this goal because we can leverage an image registry, which contains serial positron emission tomography (PET) and magnetic resonance imaging (MRI) scans of pediatric cancer patients before, during and after chemotherapy. Our preliminary data showed that novel PET/MRI techniques, which enable simultaneous assessment of brain morphology and metabolism, can detect and quantify physiological disturbances of the brain with high sensitivity. Using this new imaging technology, we will measure brain volume, cortical thickness (T1 SPGR), leukoencephalopathy (T2), brain perfusion (arterial spin labeling), and regional cerebral metabolic rate of glucose metabolism (rCMRglc). We hypothesize that imaging biomarkers in the dorsolateral prefrontal brain and cingulate gyrus, as measured with PET/MRI, will correlate with executive function scores, assessed with neurocognitive function tests. Prediction and early detection of MTX-induced neurotoxicity will allow us to identify patients who will benefit from early interventions, prescribe individual treatment regimes, and ultimately prevent long-term morbidities.

对小儿癌症幸存者化疗引起的脑损伤进行成像 许多儿科癌症幸存者因化疗而面临慢性且改变生活的副作用。 接受大剂量甲氨蝶呤 (MTX) 化疗的儿童可能会出现神经认知衰退 包括记忆力、注意力和注意力的障碍。总体累计发生率 神经认知疾病的发病率为 25% 至 45%。接受治疗之间有一个时间窗口 以及未来的发病率。不幸的是，一旦癌症幸存者出现临床症状，往往为时已晚 进行健康保护干预措施。为了预防治疗后药物引起的临床问题，重要的是 开发诊断工具来检测仍可逆的组织损伤的早期阶段。然而， 令人惊讶的是，相关生物标志物的开发在该领域很少受到关注。为了缩小这一差距，我们的目标是 开发新的诊断生物标志物，用于在临床问题出现之前检测早期组织损伤 显而易见。然后，获得的信息可用于在长期实施之前启动纠正措施。 发病并最终保护我们患者的健康。我们项目的总体目标是 检测化疗引起的脑损伤的早期影像学迹象，可以预测慢性 数月或数年后出现神经认知问题。我们处于独特的位置来实现这一目标，因为我们 可以利用图像注册表，其中包含串行正电子发射断层扫描 (PET) 和磁 对儿科癌症患者化疗前、化疗期间和化疗后进行磁共振成像 (MRI) 扫描。我们的 初步数据表明，新型 PET/MRI 技术可以同时评估大脑 形态和新陈代谢，可以检测和量化大脑的生理紊乱 敏感性。使用这种新的成像技术，我们将测量大脑体积、皮质厚度（T1 SPGR）、 白质脑病 (T2)、脑灌注（动脉自旋标记）和局部脑代谢率 葡萄糖代谢（rCMRglc）。我们假设背外侧前额叶的成像生物标志物 通过 PET/MRI 测量，大脑和扣带回将与执行功能评分相关， 通过神经认知功能测试进行评估。 MTX 诱导的神经毒性的预测和早期检测 将使我们能够识别将从早期干预中受益的患者，制定个体化治疗方案， 并最终预防长期发病。