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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

基本信息

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
项目类别：
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

项目摘要

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.

儿童癌症幸存者化疗所致脑损伤的影像学研究