Multimodal imaging biomarkers for investigating fascia, muscle and vasculature in myofascial pain.

用于研究肌筋膜疼痛中的筋膜、肌肉和脉管系统的多模态成像生物标志物。

基本信息

批准号：
10569868
负责人：
Siddhartha Sikdar
金额：
$ 148.37万
依托单位：
GEORGE MASON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-21 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10569868
关键词：
Address Anisotropy Biological Markers Biological Process Blood Vessels Blood flow Classification Clinical Clinical Trials Collaborations Communities Complex Connective Tissue Data Data Scientist Development Diagnosis Doppler Ultrasound Double-Blind Method Electromyography Extracellular Fluid Fascia Functional disorder Hyaluronidase Impairment Inflammatory Injections Intercellular Fluid Intervention Lead Liquid substance Longitudinal observational study Lymphatic Measures Methods Modality Monitor Motor Multimodal Imaging Muscle Myofascial Pain Syndromes Needles Nerve Neurogenic Inflammation Observational Study Pain Pain management Pain-Free Pathogenesis Pathologic Processes Pathway interactions Patient Self-Report Patients Perfusion Phase Phenotype Physical Examination Physicians&apos Offices Physiological Physiological Processes Placebo Control Play Prediction of Response to Therapy Radiology Specialty Randomized Randomized Clinical Trials Recording of previous events Reproducibility Role Scanning Sensitivity and Specificity Spectrum Analysis Surface Time Tissues Ultrasonography Vascular remodeling base clinical heterogeneity clinical imaging clinical phenotype clinical practice clinical predictors data acquisition density design diagnostic tool elastography evidence base fluid flow imaging biomarker imaging scientist improved innovation insight interstitial lymphatic drainage multimodality neurobiological mechanism novel response soft tissue success ultrasound

项目摘要

Summary/Abstract Myofascial pain syndrome (MPS) is highly prevalent in the community. It is primarily diagnosed using patient self reports and physical examination, which lack reliability, sensitivity and specificity and does not provide insights into the abnormal biological and physiological processes in soft tissues. While a number of treatment methods are available to patients, there are currently no criteria to determine which treatments might be best for each patient’s unique myofascial pain phenotype. To improve evidence-based management of myofascial pain, there is a critical need to develop quantitative measures that advance our understanding of the physiological processes in the underlying the soft tissues across the clinical continuum of MPS. The objective of this project is to develop a quantitative biomarker informed by the current understanding of underlying tissue-level mechanisms at the level of the “myofascial unit” (muscle, nerve, fascia, vasculature, lymphatics) that are likely to be involved in MPS. This project has two phases: a R61 phase for developing and validating the biomarker and an R33 phase for utilizing the biomarker for treatment monitoring in a randomized clinical trial of two different mechanism-based interventions. The R61 phase has two specific aims: Specific Aim 1: Develop and refine quantitative measures of muscle, fascia, interstitium and blood flow and determine reproducibility. The measures will be based on quantifying three physiological mechanisms: (1) Aim 1a: impaired myofascial gliding quantified through measures of shear anisotropy using ultrasound shear wave elastography; (2) Aim 1b: abnormal accumulation of interstitial fluid and impaired perfusion quantified through ultrasound elastography, Doppler ultrasound and bioimpedance spectroscopy; (3) Aim 1c: increased motor unit excitability associated with segmental sensitization quantified through high-density surface electromyography. Specific Aim 2: Develop and clinically validate a composite classifier of myofascial state. We will measure the tissue-level biomarkers in a longitudinal observational study of patients with myofascial pain and pain-free controls. The classifier will be designed to predict clinical phenotypes that include within subject variability over time, as well as variability between subjects with myofascial pain and controls. The transition criteria from the R61 to R33 phase will be achieving >90% classification accuracy using a classifier based on tissue-level biomarkers to differentiate between normal, latent, and active phases. Our objective in the R33 phase is to determine the sensitivity and specificity of the composite classifier to predict treatment response. To evaluate whether the composite measure is sensitive to mechanism-based changes, we will evaluate two interventions that target two different mechanistic pathways: dry needling targeting segmental sensitization, and hyaluronidase injections targeting impaired fascial gliding. We will conduct a randomized, placebo-controlled double-blind clinical trial of the two interventions using a factorial design.

摘要/摘要肌筋膜疼痛综合征（MPS）在社区中非常普遍。它主要使用患者自我诊断报告和体格检查缺乏可靠性，敏感性和特异性，并且没有提供见解进入软组织中的异常生物过程和物理过程。而多种治疗方法患者可以使用，目前尚无标准可以确定哪种治疗方法最适合每种治疗患者独特的肌筋膜疼痛表型。为了改善基于证据的肌筋膜疼痛管理是制定定量措施的迫切需要，以提高我们对物理过程的理解在MPS的临床连续体中的基础软组织中。该项目的目的是开发通过对目前对基础组织水平机制的理解所告知的定量生物标志物可能参与国会议员。该项目有两个阶段：用于开发和验证生物标志物的R61阶段和R33阶段在两种不同机制的随机临床试验中，使用生物标志物进行治疗监测干预措施。 R61阶段有两个具体的目标：特定目标1：开发和完善肌肉，筋膜，间质和血流的定量测量，以及确定可重复性。这些措施将基于量化三种物理机制：（1）目标 1a：通过使用超声剪切波的剪切各向异性测量的肌筋膜滑行受损弹性；（2）AIM 1B：通过量化的间隙液和灌注受损的异常积累超声弹性图，多普勒超声和生物阻抗光谱；（3）AIM 1C：增加电机单元通过高密度表面肌电图量化了与节段性灵敏度相关的兴奋性。特定目标2：开发和临床验证肌筋膜状态的复合分类器。我们将衡量在一项肌膜疼痛和无疼痛患者的纵向观察性研究中，组织水平的生物标志物控件。分类器将旨在预测包括主题可变性内的临床表型时间，以及具有肌筋膜疼痛和控制的受试者之间的变异性。从R61到R33阶段的过渡标准将使用分类器实现> 90％的分类精度基于组织水平的生物标志物，以区分正常，潜在和活性相。我们在R33阶段的目标是确定复合分类器的灵敏度和特异性以预测治疗反应。为了评估复合度量是否对基于机制的变化敏感，我们将评估针对两种不同机械途径的两种干预措施：干针靶标段敏感性和透明质酸酶注射剂，靶向筋膜滑行受损。我们将进行一个随机的，使用阶乘设计对两种干预措施进行安慰剂对照的双盲临床试验。