School of Chemical Engineering, College of Engineering and Physical Science, University of Birmingham, B15 2TT, UK.
School of Chemical Engineering, College of Engineering and Physical Science, University of Birmingham, B15 2TT, UK; Department of Physics, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, UK.
Exp Neurol. 2024 Dec;382:114960. doi: 10.1016/j.expneurol.2024.114960. Epub 2024 Sep 18.
The development of an optical interface to directly distinguish the brain tissue's biochemistry is the next step in understanding traumatic brain injury (TBI) pathophysiology and the best and most appropriate treatment in cases where in-hospital intracranial access is required. Despite TBI being a globally leading cause of morbidity and mortality in patients under 40, there is still a lack of objective diagnostical tools. Further, given its pathophysiological complexity the majority of treatments provided are purely symptomatic without standardized therapeutic targets. Our tailor-engineered prototype of the intracranial Raman spectroscopy probe (Intra-RSP) is designed to bridge the gap and provide real-time spectroscopic insights to monitor TBI and its evolution as well as identify patient-specific molecular targets for timely intervention. Raman spectroscopy being rapid, label-free and non-destructive, renders it an ideal portable diagnostics tool. In combination with our in-house developed software, using machine learning algorithms for multivariate analysis, the Intra-RSP is shown to accurately differentiate simulated TBI conditions in rat brains from the healthy controls, directly from the brain surface as well as through the rat's skull. Using clinically pre-established methods of cranial entry, the Intra-RSP can be inserted into a 2-piece optimised cranial bolt with integrated focussing and correctly identify a sample in real-life conditions with an accuracy >80 %. To further validate the Intra-RSP's efficiency as a TBI monitoring device, rat brains mildly damaged from inflicted spinal cord injury were found to be correctly classified with 94.5 % accuracy. Through optimization and rigorous in-vivo validation, the Intra-RSP prototype is envisioned to seamlessly integrate into existing standards of neurological care, serving as a minimally invasive, in-situ neuromonitoring tool. This transformative approach has the potential to revolutionize the landscape of neurological care by providing clinicians with unprecedented insights into the nature of brain injuries and fostering targeted, timely and effective therapeutic interventions.
开发一种光学接口,直接区分脑组织的生物化学物质,是理解创伤性脑损伤(TBI)病理生理学的下一步,也是在需要院内颅内进入的情况下,提供最佳和最合适治疗的关键。尽管 TBI 是全球导致 40 岁以下患者发病率和死亡率的主要原因之一,但目前仍缺乏客观的诊断工具。此外,由于其病理生理学的复杂性,大多数提供的治疗方法纯粹是对症治疗,没有标准化的治疗目标。我们定制设计的颅内拉曼光谱探头(Intra-RSP)原型旨在弥合这一差距,并提供实时光谱学见解,以监测 TBI 及其演变,并确定针对特定患者的分子靶点,以便及时进行干预。拉曼光谱具有快速、无标记和非破坏性的特点,使其成为理想的便携式诊断工具。结合我们内部开发的软件,使用机器学习算法进行多变量分析,Intra-RSP 被证明能够准确地区分大鼠大脑中的模拟 TBI 条件与健康对照,直接从大脑表面以及通过大鼠颅骨进行区分。使用临床预先建立的颅骨进入方法,Intra-RSP 可以插入带有集成聚焦功能的 2 件式优化颅骨螺栓中,并在真实条件下以>80%的准确率正确识别样本。为了进一步验证 Intra-RSP 作为 TBI 监测设备的效率,我们发现轻度脊髓损伤引起的大鼠大脑损伤被正确分类,准确率为 94.5%。通过优化和严格的体内验证,Intra-RSP 原型有望无缝集成到现有的神经护理标准中,成为一种微创、原位神经监测工具。这种变革性方法有可能通过为临床医生提供对脑损伤本质的前所未有的洞察力,并促进有针对性、及时和有效的治疗干预,彻底改变神经护理领域。