Optical imaging of metabolic effects of transcranial laser stimulation in humans

经颅激光刺激对人体代谢影响的光学成像

• 批准号: 9277460
• 负责人: Fenghua Tian
• 金额: $ 7.88万
• 依托单位: UNIVERSITY OF TEXAS ARLINGTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9277460
• 关键词: Adult; Age; Attention; Bioenergetics; Brain; Cerebrum; Clinical Trials; Control Groups; Diffuse; Energy Metabolism; Enzymes; Human; Hybrids; Imaging technology; Impaired cognition; Individual; Ischemic Stroke; Lasers; Light; Linear Regressions; Major Depressive Disorder; Measurable; Measures; Mental disorders; Metabolic; Metabolism; Mitochondria; Modeling; Near-Infrared Spectroscopy; Neurons; Outcome; Oxidative Phosphorylation; Oxygen; Oxygen Consumption; Participant; Photons; Placebo Control; Placebos; Play; Post-Traumatic Stress Disorders; Recruitment Activity; Research; Respiratory Chain; Spectrum Analysis; System; Therapeutic; Traumatic Brain Injury; Uncertainty; absorption; base; behavior measurement; cognitive enhancement; cognitive function; cognitive performance; cognitive testing; cost effective; cytochrome c oxidase; effective therapy; human study; imaging approach; imaging system; in vivo; innovation; insight; metabolic imaging; metabolic rate; multidisciplinary; nervous system disorder; neuroprotection; novel therapeutic intervention; optical imaging; photoactivation; photonics; preclinical study; sex; success

Abstract: Transcranial laser stimulation (TLS) involves using low-power, high-fluence light (6201100 nm) to regulate neuronal functions. The mechanism of TLS relies on photon absorption by cytochrome c oxidase (CCO). Photoactivation of this terminal enzyme in the mitochondrial respiratory chain plays a key role in cerebral oxygen utilization for energy metabolism. This photonics-bioenergetics mechanism results increased cerebral metabolism that appears to benefit for cognitive enhancement and neuroprotection. In recent years, TLS has shown therapeutic potential for treating a number of neurological and psychological disorders. However, uncertainty remains about the mechanism of action of TLS in the human brain in vivo. There is a lack of evidence of whether or not changes in neuronal functions are associated with changes in cerebral metabolism induced by TLS. Furthermore, there is not a feasible means to measure the cerebral metabolic changes during TLS. Being able to simultaneously deliver TLS and record the cerebral metabolic changes in vivo would be a significant essential step toward making TLS a viable treatment option. The propose research aims to develop a non-invasive and cost-effective optical imaging approach to quantify and better understand the in vivo cerebral metabolic effects of TLS and, importantly, to assess whether these effects correlate with participants’ improvements in cognitive functions. We will build a hybrid system of broadband near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) to quantify relative changes of CCO and cerebral metabolic rate of oxygen (rCMRO2) in the human brain in vivo. Then, we will conduct the first placebo-controlled human study to identify the primary cerebral metabolic effects of TLS (i.e., changes in CCO and rCMRO2), by comparing the results against those from a placebo-treated control group. We will further conduct two sessions of cognitive tests, one before the TLS or placebo stimulation and another immediately following the stimulation, to identify the participants’ potential changes in cognitive performance due to TLS. This will allow us to assess whether there is a significant relationship between the cerebral metabolic changes and changes in cognitive performance in the TLS-treated participants. To complete the research aims outlined above, we have formed a strong and multidisciplinary team with exceptional research acumen in their fields. The success of this study will provide much needed insight into the underlying mechanism of TLS-generated metabolic activity in the human brain in vivo. Furthermore, it will demonstrate the feasibility of a non-invasive and cost-effective treatment-with-imaging approach. This novel therapeutic approach could optimize treatment for individuals who have suffered cognitive impairments resulting from a number of neurological and psychological disorders.

翻译后摘要：经颅激光刺激（TLS）涉及使用低功率，高通量的光（620 nm）， 调节神经元功能。TLS的机制依赖于细胞色素c氧化酶的光子吸收 （CCO）。线粒体呼吸链中这一末端酶的光活化在以下方面起关键作用： 能量代谢的脑氧利用。这种光子学-生物能学机制的结果增加了 大脑代谢，似乎有利于认知增强和神经保护。近年来， TLS已显示出治疗许多神经和心理疾病的治疗潜力。 然而，TLS在人脑中的体内作用机制仍不确定。都缺乏 神经元功能的变化是否与大脑的变化有关的证据 TLS诱导的代谢。此外，还没有一种可行的方法来测量脑代谢 TLS期间的更改。能够同时输送TLS并记录脑代谢变化， 体内将是使TLS成为可行的治疗选择的重要一步。 该研究旨在开发一种非侵入性和成本效益高的光学成像方法， 量化并更好地了解TLS的体内脑代谢效应，重要的是， 这些影响是否与参与者认知功能的改善有关。我们会制造一种混合动力车 系统的宽带近红外光谱（NIRS）和扩散相关光谱（DCS），以量化 在体人脑中CCO和脑氧代谢率（rCMRO 2）的相对变化。然后我们 将进行第一个安慰剂对照的人体研究，以确定TLS的主要脑代谢影响 (i.e., CCO和rCMRO2的变化），通过将结果与安慰剂治疗对照组的结果进行比较 组我们将进一步进行两次认知测试，一次在TLS或安慰剂刺激之前， 另一个紧随刺激之后，以确定参与者在认知方面的潜在变化， 由于TLS的性能。这将使我们能够评估是否有一个显着的关系， 脑代谢变化和TLS治疗参与者认知能力的变化。 为了完成上述研究目标，我们组建了一个强大的多学科团队， 在各自领域的研究能力这项研究的成功将提供急需的洞察力， TLS产生的代谢活性在人脑中的体内的潜在机制。此外，它将 证明了非侵入性和具有成本效益的成像治疗方法的可行性。这本小说 治疗方法可以优化对认知障碍患者的治疗 由一系列神经和心理疾病引起。