Collagenolysis of the transverse carpal ligament

摘要 腕管综合征(CTS)是最常见的手部疾患，近50万腕管 在美国，每年都会进行释放手术。手术中，腕横韧带 切断(TCL)以减压正中神经。然而，横切TCL会降低握力， 导致柱状疼痛，导致腕骨更大的运动，并可能损害周围的神经、血管或 肌腱。为了避免这些手术并发症，采用非手术方法的创新治疗方案 都是非常需要的。横断TCL作为治疗腕管综合征的外科治疗类似于 外科筋膜切除术治疗Dupuytren肌挛缩症胶原酶注射治疗Dupuytren‘s成功 对于肌挛缩症，有必要探讨其对TCL的溶胶原作用。我们的长期目标是开发一种 非手术治疗腕管综合征的新方法--酶降解TCL。的目标是 本研究向TCL内注入胶原酶，并评价其对TCL形态和功能的影响。 使用最先进的机器人和超声波技术的机械师。我们的中心假设是 胶原酶有效地降解TCL，导致TCL的厚度和硬度在体外以及 增加TCL长度和原位牙弓面积。这一假设将以两个具体的目标进行检验：(1) 研究剂量和时间依赖的胶原酶对骨形态和力学性能的影响 TCL的体外实验，并确定能实现有效和安全的胶原酶分解的最佳胶原酶剂量 24小时后TCL的变化；(2)原位观察TCL结构特性的变化 胶原酶注射并确定注射配置，以实现TCL延长2 mm。在目标1中， 将不同剂量的胶原酶注射到身体手解剖的TCL组织中。B模式和 将进行声辐射力脉冲(ARFI)超声成像以测量厚度和 刚性随时间变化，最长可达24小时。TCL的刚度将由剪切波速度推导出来 由ARFI测量。我们还将确定可以达到80%的最小有效胶原酶剂量 24小时后厚度和横波速度降低。在目标2中，胶原酶将使用 目标1中确定的最佳剂量沿原位TCL的纵向中线。腕管加压会 用于获得注射部位的局部应变和大体组织伸长率，将用于 确定要达到所需TCL延伸率的注射剂。机器人辅助胶原酶注射和 将进行超声扫描，以实现TCL的精确注射和可重复扫描 重建。拟议项目的实施是探索以下可能性的关键第一步 胶原酶溶解术作为治疗CTS的一种新的非手术方法。从这个过程中获得的知识 该项目将指导未来的原位腕管研究、活体动物研究和临床试验，利用 胶原酶注射作为治疗CTS的一种新的非手术治疗的可能性。

ABSTRACT Carpal tunnel syndrome (CTS) is the most common hand disorder, and nearly half a million carpal tunnel release surgeries are performed annually in the United States. During surgery, the transverse carpal ligament (TCL) is transected to decompress the median nerve. However, transecting the TCL reduces grip strength, causes pillar pain, results in greater carpal bone motion, and may damage the surrounding nerves, vessels or tendons. To avoid these surgical complications, innovative treatment solutions with non-operative approaches are sorely needed. Transection of the TCL as a surgical treatment for carpal tunnel syndrome is analogous to surgical fasciectomy for Dupuytren's contracture. As collagenase injection successfully treats Dupuytren's contracture, it is compelling to explore this collagenolytic effect on the TCL. Our long-term goal is to develop a novel non-operative treatment for carpal tunnel syndrome by enzymatically degrading the TCL. The objective of this project is to inject collagenase into the TCL and evaluate its enzymatic effect on TCL morphology and mechanics using state-of-the-art robotic and ultrasound technologies. Our central hypothesis is that collagenase effectively degrades the TCL, leading to decreased TCL thickness and stiffness in vitro as well as increased TCL length and arch area in situ. This hypothesis will be tested with two specific aims: (1) to investigate dose- and time-dependent collagenolytic effects on the morphological and mechanical properties of the TCL in vitro, and to identify an optimal collagenase dose that can achieve effective and safe collagenolysis of the TCL after 24 hours; (2) to examine the changes in structural properties of the TCL in situ in response to collagenase injections and determine an injection configuration to achieve TCL elongation of 2 mm. In Aim 1, collagenase at various doses will be injected into TCL tissues dissected from cadaveric hands. B-mode and acoustic radiation force impulse (ARFI) ultrasound imaging will be performed to measure thickness and stiffness changes over time up to 24 hours. The stiffness of the TCL will be derived from shear wave velocity measured by ARFI. We will also identify the minimum effective collagenase dose that can achieve 80% reduction of thickness and shear wave velocity at 24 hours. In Aim 2, collagenase will be injected using the optimal dose determined in Aim 1 along the longitudinal midline of the TCL in situ. Carpal tunnel pressure will be applied to obtain local strain at the injection sites and gross tissue elongation, which will be used to determine an injection to achieve the desired TCL elongation. Robot-assisted collagenase injection and ultrasound scanning will be performed to achieve precise injection and reproducible scanning for TCL reconstruction. The implementation of the proposed project is the critical first step to exploring the possibility of collagenolysis of the TCL as a novel non-operative treatment for CTS. The knowledge obtained from this project will guide future in situ carpal tunnel studies, in vivo animal studies, and clinical trials, tapping into the potential of collagenase injection as a novel non-operative treatment for CTS.