Improved non-invasive MR brain thermometry for therapeutic hypothermia

项目摘要 脑温对创伤后神经保护和恢复的重要性不容低估。 心脏骤停和中风后的患者结局与体温密切相关， 体温和脑温的升高与脑损伤的严重程度和死亡率呈正相关。 相反，诱导的低温或冷却被认为是一种治疗措施，以减轻进一步的损伤， 心脏骤停、中风和脑外伤后，最大限度地保留组织以供恢复。治疗 使用核心体温监测和生物反馈来实现低温，但它很好- 确定这些测量是不准确和不一致的大脑温度的代理。植入 温度探针已经证明大脑温度高于体温， 在受伤后，差异进一步扩大。由于冷却在剂量方面没有得到优化， 患者选择和治疗后的患者结果是可变的，脑温度测量可能是 这是改进和优化这种有希望的干预措施的一个关键但尚未探索的方面。临床脑 温度测量仅限于手术植入在单个位置的侵入式温度探针， 在大多数患者队列中不切实际。虽然几种基于磁共振（MR）的温度测量方法已经 在研究环境中提出和证明，大多数仍然局限于相对估计 温度，并且非常容易受到组织异质性相关错误的影响。此次R21的总体目标 开拓者的建议是开发一种新的MR化学位移测温方法，同时， 表征低温治疗期间患者的脑-体温差异。我们将开发一个 用于MR测温的组织特异性方法，校正温度无关的化学位移， 在绝对测量中引入误差（目标1）。由于脑-体温解耦可能是一种 损伤和治疗监测的重要标志物，脑温度测量将在心脏骤停时实施 接受治疗性低温以非侵入性测量脑-体温差的患者 (Aim 2）。我们预计，这些研究将扩大我们对大脑温度调节的理解， 在治疗性低温过程中的神经保护，并提供了关键的第一步， 温度管理方法。

Project Summary The importance of brain temperature for neuroprotection and recovery after trauma cannot be understated. Patient outcomes after cardiac arrest and stroke are strongly associated with temperature, where modest increases in body and brain temperatures correlate positively with severity of brain injury and mortality. Conversely, induced hypothermia or cooling is recognized as a therapeutic measure to mitigate further injury of the brain and maximally preserve tissue for recovery after cardiac arrest, stroke, and brain trauma. Therapeutic hypothermia is implemented using core body temperature monitoring and biofeedback, but it is well- established that these measurements are inaccurate and inconsistent proxies of brain temperature. Implanted temperature probes have demonstrated that brain temperature is higher than body temperature and these differences are further exaggerated after injury. As cooling has not been optimized in terms of dosage or patient selection, and patient outcomes after treatment are variable, brain temperature measurements may be a critical yet unexplored aspect of improving and optimizing this promising intervention. Clinical brain thermometry is limited to invasive temperature probes surgically implanted at a single location and is impractical in most patient cohorts. While several magnetic resonance (MR)-based thermometry methods have been proposed and demonstrated in research environments, most are still limited to relative estimations of temperature and are highly vulnerable to tissue heterogeneity-related errors. The overall goal of this R21 Trailblazer proposal is to develop a new approach for MR chemical shift thermometry and, in parallel, characterize brain-body temperature differences in patients during hypothermia treatment. We will develop a tissue-specific approach for MR thermometry, correcting for temperature-independent chemical shifts that introduce errors in absolute measurements (Aim 1). As brain-body temperature decoupling may be an important marker for injury and treatment monitoring, brain thermometry will be implemented in cardiac arrest patients undergoing therapeutic hypothermia to non-invasively measure brain-body temperature differences (Aim 2). We anticipate that these studies will expand our understanding of brain thermoregulation and neuroprotection during therapeutic hypothermia and provide a crucial first step towards a personalized approach to temperature management.