Collagenolysis of the transverse carpal ligament

腕横韧带胶原溶解

基本信息

批准号：
10200675
负责人：
Zong-Ming Li
金额：
$ 19.65万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-23 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10200675
关键词：
3-Dimensional Acoustics Activities of Daily Living Anatomy Animals Area Biological Cadaver Carpal Tunnel Syndrome Clinic Clinical Trials Collagen Collagen Fiber Contracture Custom Deposition Disease Dose Dupuytren&apos s Contracture FDA approved Flexor Future General Population Goals Hand Hand Strength Health Care Costs Hour Human Hypertrophy Image In Situ In Vitro Injections Knowledge Length Ligaments Measures Mechanics Medical Care Costs Microbial Collagenase Morphology Motion Muscle Nerve Operative Surgical Procedures Pain Pathologic Patients Pharmaceutical Preparations Productivity Property Public Health Radiation Reproducibility Robot Robotics Scanning Site Structure Surgical complication System Technology Tendon structure Testing Thick Time Tissues Treatment Efficacy Ultrasonography United States carpus bone collagenase grasp in vivo innovation mechanical properties median nerve nerve decompression novel pressure reconstruction response robot assistance virtual

项目摘要

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.

抽象的腕管综合症（CTS）是最常见的手部疾病，近半百万腕管每年在美国进行释放手术。手术期间，横向腕韧带（TCL）转移以解压缩中位神经。然而，横断TCL降低了握力强度，引起支柱疼痛，导致更大的腕骨运动，并可能损坏周围神经，容器或肌腱。为了避免这些手术并发症，具有非手术方法的创新治疗解决方案非常需要。 TCL作为腕管综合征的手术治疗的横向与 Dupuytren的手术筋膜切除术。随着胶原酶注入成功治疗Dupuytren的缔约合，探索对TCL的胶原式效应是令人信服的。我们的长期目标是开发通过酶促降解TCL的腕管综合征的新型非手术治疗。目的该项目是将胶原酶注入TCL，并评估其酶促作用对TCL形态和使用最先进的机器人和超声技术的力学。我们的中心假设是胶原酶有效地降解了TCL，导致TCL厚度和体外刚度降低 TCL长度和原位拱形区域增加。该假设将以两个具体的目的进行检验：（1）至研究剂量和时间依赖性的胶原式化对形态和机械性能体外TCL，并确定可以实现有效且安全胶原蛋白分解的最佳胶原酶剂量 24小时后的TCL；（2）检查响应于TCL的结构特性的变化注射胶原酶并确定注射构型以达到2 mm的TCL伸长率。在AIM 1中，各种剂量的胶原酶将被从尸体手中注入TCL组织。 B模式和声音辐射力冲动（ARFI）将进行超声成像，以测量厚度和刚度随时间变化长达24小时。 TCL的刚度将来自剪切波速度由Arfi测量。我们还将确定可以达到80％的最低有效胶原酶剂量在24小时时降低厚度和剪切波速度。在AIM 2中，胶原酶将使用沿TCL原位的纵向中线确定在AIM 1中确定的最佳剂量。腕管压力将应用于在注射部位获得局部应变，并将其总体伸长延伸，将用于确定注射以实现所需的TCL伸长。机器人辅助胶原酶注射和将进行超声扫描以实现TCL的精确注入和可重复的扫描重建。拟议项目的实施是探索可能性的关键第一步 TCL作为CTS的新型非手术治疗方法的胶原蛋白分解。从中获得的知识项目将指导未来的原位腕管研究，体内动物研究和临床试验，并将其利用胶原酶注射作为CTS的新型非手术治疗的潜力。