Imaging Chemotherapy-Induced Brain Damage in Pediatric Cancer Survivors

儿童癌症存活者影像化疗所致脑损伤 许多儿科癌症幸存者由于化疗而面临慢性和改变生活的副作用。 接受大剂量甲氨蝶呤(MTX)化疗的儿童可能会经历神经认知功能减退 这包括记忆力、注意力和注意力的损害。本病总累积发病率 神经认知疾病的发病率从25%到45%不等。在接受治疗之间有一段时间 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，往往就为时已晚。 用于养生干预。为了预防治疗后药物引起的临床问题，重要的是要 开发诊断工具来检测组织损伤的早期阶段，这些损伤仍然是可逆的。然而， 令人惊讶的是，相关生物标记物的开发在该领域几乎没有受到关注。为了缩小这一差距，我们的目标是 开发新的诊断生物标记物，在临床问题出现之前检测早期组织损伤 很明显。然后，所获得的信息可以用来在长期的 疾病会发生，并最终保护我们患者的健康。我们项目的总体目标是 检测化疗所致脑损伤的早期影像征象可预测慢性 几个月或几年后出现神经认知问题。我们处于独特的地位来追求这一目标，因为我们 可以利用图像配准，其中包含连续正电子发射断层扫描(PET)和 儿科癌症患者化疗前、中、后的磁共振成像扫描我们的 初步数据显示，新的PET/MRI技术能够同时评估大脑 形态和新陈代谢，可以检测和量化大脑的高生理障碍 敏感度。使用这项新的成像技术，我们将测量大脑体积、皮质厚度(T1 SPGR)、 脑白质病变(T2)、脑血流灌注(动脉自旋标记)和脑局部代谢率 糖代谢(RCMRglc)。我们假设前额背外侧的成像生物标记物 用PET/MRI测量的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。甲氨蝶呤神经毒性的预测和早期检测 将使我们能够确定哪些患者将从早期干预中受益，开出个性化的治疗方案， 并最终防止长期的疾病。

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.