In-Vivo Confocal Imaging of Meissner's Corpuscles as a Measure of HIV Neuropathy

迈斯纳氏小体的体内共聚焦成像作为 HIV 神经病变的测量

• 批准号: 7361392
• 负责人: DAVID N HERRMANN
• 金额: $ 23.1万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-21 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7361392
• 关键词: Affect; Autopsy; Axon; Biopsy; Caliber; Clinical; Clinical Trials Cooperative Group; Complex; Complication; Confocal Microscopy; Contrast Media; Count; Cross-Sectional Studies; Data; Dermatology; Detection; Development; Devices; Digit structure; Disease; Distal; Early identification; Effectiveness; Esthesia; Evaluation; Fiber; Frequencies; Goals; HIV; HIV Infections; HIV neuropathy; Hand; Heating; Highly Active Antiretroviral Therapy; Human; Image; Immunofluorescence Immunologic; Incidence; Individual; Invasive; Lasers; Leg; Length; Lesion; Life; Localized; Longevity; Malignant Neoplasms; Measures; Medial; Mediating; Modality; Monitor; Myelinated nerve fiber; Nerve Endings; Nerve Fibers; Nervous System Trauma; Neural Conduction; Neurologic; Neurologic Examination; Neuropathy; Outcome; Outcome Measure; Pain; Pain Threshold; Painless; Pathology; Pathway interactions; Patients; Peripheral; Peripheral Nervous System; Peripheral nerve injury; Pilot Projects; Polyneuropathy; Prevalence; Process; Psychophysiology; Relative (related person); Research Personnel; Risk; Sensitivity and Specificity; Sensory; Sensory Receptors; Severities; Site; Skin; Specific qualifier value; Standards of Weights and Measures; Structure; Testing; Therapy Clinical Trials; Time; Touch sensation; United States Food and Drug Administration; afferent nerve; base; cohort; compliance behavior; concept; density; fluorophore; foot; foot sole; in vivo; interest; novel; oncology; pressure; receptor; sensory neuropathy; vibration

DESCRIPTION (provided by applicant): Distal sensory polyneuropathy (DSP) is the most common neurological complication of HIV infection; however measures to detect and monitor DSP are suboptimal. The main goal of this revised R21 proposal is to assess the potential of in-vivo reflectance confocal microscopy (RCM) of Meissner's Corpuscles (MCs) to serve as a novel, painless, rapid and non-invasive measure of HIV-associated DSP. MCs are sensory receptors composed of both myelinated and unmyelinated fibers found in non-hairy skin of the hands and feet that mediate touch-pressure sensation. The investigators, in early preliminary data, have identified MCs using a portable in-vivo RCM device and found reduced MC densities in the skin of subjects with HIV DSP compared to HIV negative controls. This proof of concept proposal will test the hypothesis that in-vivo RCM of MCs can serve as a non-invasive measure of peripheral nerve injury associated with HIV infection, and detect reductions in MC density (relative to normal controls) in HIV subjects with clinically-defined DSP, as well as subclinical sensory neuropathy in HIV-infected subjects without clinical evidence of DSP. In order to test this hypothesis the PI will 1) Compare in a cross-sectional study MC density by in-vivo RCM at the sole of the foot and hand between HIV infected subjects with clinically-defined DSP and healthy control subjects; 2) Compare in a cross-sectional study MC density by in-vivo RCM at the sole of the foot and hand between HIV infected subjects without clinical evidence of DSP and healthy control subjects; 3) Determine in the HIV infected cohort, relationships among MC density at the hand and foot and standard measures of peripheral sensory function and structure (quantitative sensory testing, nerve conduction studies and epidermal nerve fiber density). Development of in-vivo RCM assessment of MC density may prove to have wide application for early identification and monitoring of HIV DSP during the course of disease and therapy, and as a novel outcome measure for therapeutic trials in HIV DSP and other sensory neuropathies. The main goal of this revised R21 proposal is to assess the potential of in-vivo reflectance confocal microscopy (RCM) of Meissner's Corpuscle (MC) nerve endings in the skin, to serve as a new, painless, rapid and non-invasive approach to detect and monitor HIV-associated distal sensory neuropathy, the commonest neurological complication of HIV infection. In-vivo RCM of MCs may prove to have wide application for early identification of sensory peripheral neuropathies, and to assess effectiveness of therapy.

描述（由申请人提供）：远端感觉性多发性神经病（DSP）是 HIV 感染最常见的神经系统并发症；然而，检测和监控 DSP 的措施并不理想。修订后的 R21 提案的主要目标是评估迈斯纳氏小体 (MC) 体内反射共焦显微镜 (RCM) 作为一种新颖、无痛、快速和非侵入性的 HIV 相关 DSP 测量方法的潜力。 MC 是由有髓鞘和无髓鞘纤维组成的感觉受体，存在于手和脚的无毛皮肤中，介导触觉压力感觉。研究人员在早期初步数据中使用便携式体内 RCM 设备识别了 MC，并发现与 HIV 阴性对照相比，HIV DSP 受试者皮肤中的 MC 密度降低。该概念验证提案将测试以下假设：MC 的体内 RCM 可以作为与 HIV 感染相关的周围神经损伤的非侵入性测量方法，并检测具有临床定义的 DSP 的 HIV 受试者中 MC 密度的降低（相对于正常对照），以及没有 DSP 临床证据的 HIV 感染受试者中的亚临床感觉神经病变。为了检验这一假设，PI 将 1) 在横断面研究中通过体内 RCM 比较具有临床定义的 DSP 的 HIV 感染受试者和健康对照受试者之间脚底和手底的 MC 密度； 2) 在横断面研究中通过体内 RCM 比较没有 DSP 临床证据的 HIV 感染受试者和健康对照受试者之间足底和手底的 MC 密度； 3) 确定 HIV 感染人群中手足 MC 密度与外周感觉功能和结构标准测量之间的关系（定量感觉测试、神经传导研究和表皮神经纤维密度）。 MC 密度的体内 RCM 评估的发展可能被证明在疾病和治疗过程中早期识别和监测 HIV DSP 方面具有广泛的应用，并作为 HIV DSP 和其他感觉神经病治疗试验的新结果测量。修订后的 R21 提案的主要目标是评估皮肤中迈斯纳氏小体 (MC) 神经末梢的体内反射共焦显微镜 (RCM) 的潜力，作为一种新的、无痛、快速和非侵入性的方法来检测和监测 HIV 相关的远端感觉神经病变，这是 HIV 感染最常见的神经系统并发症。 MC 的体内 RCM 可能被证明在感觉周围神经病变的早期识别和评估治疗效果方面具有广泛的应用。

项目成果

HIV neuropathy: an in vivo confocal microscopic study.

• DOI: 10.1007/s13365-012-0130-1
• 发表时间: 2012-12
• 期刊: JOURNAL OF NEUROVIROLOGY
• 影响因子: 3.2
• 作者: Almodovar, Jorge L.;Schifitto, Giovanni;McDermott, Michael P.;Ferguson, Michele;Herrmann, David N.
• 通讯作者: Herrmann, David N.

Noninvasive and minimally invasive detection and monitoring of peripheral neuropathies.

• DOI: 10.1586/14737175.8.12.1807
• 发表时间: 2008-12-01
• 期刊: Expert review of neurotherapeutics
• 影响因子: 4.3
• 作者: Herrmann, David N