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

总结/摘要 肌筋膜疼痛综合征（MPS）在社区中非常普遍。它主要是利用病人自我诊断 报告和体检缺乏可靠性、敏感性和特异性，不能提供深入的见解 软组织中异常的生物和生理过程。虽然一些治疗方法 目前还没有标准来确定哪种治疗方法可能对每种患者最好。 患者独特的肌筋膜疼痛表型。为了改善肌筋膜疼痛的循证管理， 是一个迫切需要发展的定量措施，促进我们的理解的生理过程， 在MPS的临床连续性中的底层软组织中。该项目的目标是开发 一种定量生物标志物，由目前对组织水平机制的理解提供信息， 可能涉及的“肌筋膜单位”（肌肉、神经、筋膜、脉管系统、神经纤维）的水平 MPS。该项目分为两个阶段：R61阶段用于开发和验证生物标志物，R33阶段用于开发和验证生物标志物。 用于在两种不同的基于机制的随机临床试验中利用生物标志物进行治疗监测， 干预措施。 R61阶段有两个具体目标： 具体目标1：开发和完善肌肉、筋膜、筋膜和血流的定量测量， 确定再现性。这些措施将基于量化三种生理机制：（1）目标 1a：通过使用超声剪切波测量剪切各向异性量化受损的肌筋膜滑动 弹性成像;（2）目标1b：间质液异常积聚和灌注受损，通过 超声弹性成像、多普勒超声和生物阻抗谱;（3）目的1c：运动单位增加 通过高密度表面肌电图定量与节段性敏化相关的兴奋性。 具体目标2：开发并临床验证肌筋膜状态的复合分类器。我们将测量 在肌筋膜疼痛和无痛患者的纵向观察性研究中的组织水平生物标志物 对照分类器将被设计为预测临床表型，包括受试者内的变异性， 时间以及肌筋膜疼痛受试者和对照组之间的变异性。 从R61到R33阶段的过渡标准是使用分类器实现>90%的分类准确度 基于组织水平的生物标志物来区分正常、潜伏和活动期。 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。为了评估复合测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制途径的两种干预措施： 致敏和针对受损筋膜滑行的透明质酸酶注射。我们将进行一个随机的， 采用析因设计的两种干预措施的安慰剂对照双盲临床试验。

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.