BREEZE: New Ventricular Direct Cooling Stylet to Mitigate Secondary Brain Injury

摘要 全世界每年有数百万人遭受严重的创伤性脑损伤、中风、癫痫持续状态和癫痫发作。 心脏骤停后缺氧除非迅速且有效地进行，否则这些脑部损伤会导致高死亡率、发病率和残疾。 妥善处理。快速冷却可以通过显著减少肿胀，炎症， 代谢和氧气消耗，最终保护神经功能并促进恢复。 不幸的是，目前的低温干预需要长时间的全身性身体冷却， 复温这种限制导致健康的器官功能障碍，并减少了大脑减少的益处。 温度通过外部头部制冷进行选择性大脑冷却显示了一些前景，但冷却是 仅限于大脑表面。其他提出的选择性大脑冷却方法依赖于不方便，昂贵， 和潜在危险的流体循环系统。因此，一个有效的，安全的，方便的，负担得起的 一种快速冷却受伤大脑而不对其他器官产生负面影响的装置仍然是一个尚未满足的关键临床需求， 需要的 为了满足这一迫切需求，我们设想了一种用于颅内的新型快速冷却装置， 广泛使用的脑室体外引流（EVD）导管。EVD导管在全球范围内用于监测和减少 颅内压（ICP）的损伤患者通过脑脊液（CSF）清除。由于脑脊液循环 在整个中枢神经系统中，EVD导管是脑和脊髓的理想导管 降温BREEZE（零液体交换脑快速焓提取器）将方便地取代电流 导引EVD导管进入脑室的探针。在不干扰CSF引流的情况下，BREEZE可诱导快速 大脑冷却是一种基于热管和离子风的新型设计。通过利用毛细作用和蒸汽膨胀， 热管将脑热快速传递到离子风风扇，离子风风扇将脑热消散到较冷的外部环境。 我们的长期目标是通过将我们的低成本 开创性的冷却技术应用于临床实践。我们的方法的基本原理是， 热管，热电冷却，离子风，自适应控制，我们可以提供有效的选择性脑 冷却以减轻急性脑损伤并改善患者恢复。我们的基本假设是 尖端的冷却技术可以微型化到EVD兼容的探针（H1）中，自适应控制， 仿生体模（H2）和非人类灵长类动物（H3）中的用户定义热曲线。因此，我们建议 这些具体目标：（SA 1）将BREEZE技术优化为直径1.5 mm的颅内/脑室脑冷却 探针;（SA 2）使用生物精确模型/体模为BREEZE构建自适应脑冷却算法;（SA 3） 在五种非人类灵长类动物中研究BREEZE选择性/自适应脑冷却的初步可行性。 该项目的预期成果是开发和初步临床前验证我们的新型冷却 设备.快速、有效、方便、选择性脑降温，控制精细 最大化低温在减少脑损伤患者的继发性损伤中的神经保护益处。

ABSTRACT Millions of people worldwide suffer annually from severe traumatic brain injury, stroke, status epilepticus and anoxia after cardiac arrest. These brain insults lead to high mortality, morbidity and disability unless rapidly and properly treated. Rapid cooling can significantly mitigate brain injuries by notably reducing swelling, inflammation, metabolism, and oxygen consumption ultimately preserving neurological function and enhancing recovery. Unfortunately, current hypothermic intervention requires prolonged systemic body cooling and suboptimal rewarming. This limitation results in healthy organ dysfunction and diminishes the benefits of reduced brain temperature. Selective brain cooling through external head refrigeration shows some promises, but cooling is limited to the brain surface. Other proposed selective brain cooling methods rely on inconvenient, expensive, and potentially dangerous fluid circulation systems. Therefore, an effective, safe, convenient, and affordable device to rapidly cool the injured brain without affecting negatively other organs remains an unmet crucial clinical need. To address this urgent need, we conceived a novel rapid cooling device for intracranial use or as a stylet for widely used external ventricular drain (EVD) catheters. EVD catheters are used globally to monitor and reduce intracranial pressure (ICP) in injured patients through cerebrospinal fluid (CSF) removal. Since CSF circulates throughout the entire central nervous system, EVD catheters are an ideal conduit for brain and spinal cord cooling. BREEZE (Brain Rapid Enthalpy Extractor with Zero-liquid Exchange) would conveniently replace current stylets guiding EVD catheters into ventricles. Without interfering with CSF drainage, BREEZE could induce rapid brain cooling a novel heat pipe- and ionic wind-based design. By exploiting capillary action and vapor expansion, the heat-pipe transfers rapidly brain heat to an ionic wind fan, which dissipates it to colder external environments. Our long-term objective is to improve neurological outcome of brain-injured patients by translating our low-cost groundbreaking cooling technology into clinical practice. The rationale for our approach is that by integrating heat-pipe, thermoelectric cooling, ionic wind, and adaptive control, we can provide effective selective cerebral cooling to mitigate acute brain injury and improve patient recovery. Our underlying hypotheses are that our cutting-edge cooling technology can be miniaturized into an EVD-compatible stylet (H1), adaptively controlled to a user-defined thermal profile in biomimetic phantom (H2) and in non-human primates (H3). Thus, we propose these specific aims: (SA1) Optimize BREEZE technology into a 1.5mm dia brain cooling intracranial/ventricular stylet; (SA2) Build an adaptive brain-cooling algorithm for BREEZE using a bio-accurate model/phantom; (SA3) Study initial feasibility of BREEZE selective/adaptive brain cooling in five non-human primates. The expected outcome of this project is the development and initial preclinical validation of our novel cooling device. Rapid, effective, convenient, and selective cerebral temperature reduction with exquisite control maximizes the neuroprotective benefits of hypothermia in reducing secondary damage for brain injury patients.