RR&D Research Career Scientist Award Application

RR

• 批准号: 10261368
• 负责人: William R. Ledoux
• 金额: --
• 依托单位: VA PUGET SOUND HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-10-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10261368
• 关键词: Address; Adult; Affect; Age; American; Amputation; Anatomy; Ankle; Area; Arthritis; Arthrodesis; Award; Biomechanics; Cadaver; Clawtoe; Clinical; Clinical Research; Clinical Treatment; Computer Models; Deformity; Degenerative polyarthritis; Development; Devices; Diabetes Mellitus; Diabetic Foot; Diabetic Foot Ulcer; Diagnosis; Disease; Elements; Etiology; Flatfoot; Fluoroscope; Fluoroscopy; Foot Deformities; Foot Ulcer; Foot joint structure; Foundations; Functional disorder; Funding; Future; Gait; General Population; Goals; Head; High Prevalence; Hip Osteoarthritis; Impairment; Incidence; Individual; Intervention; Joints; Knee Osteoarthritis; Laboratories; Lead; Leg; Limb structure; Literature; Location; Lower Extremity; Magnetic Resonance Imaging; Measurement; Measures; Mechanics; Medical; Metatarsal bone structure; Methodology; Modeling; Morphologic artifacts; Motion; Musculoskeletal; Neuropathy; Operative Surgical Procedures; Orthopedics; Orthotic Devices; Pain; Pathology; Patients; Phase; Population; Population Study; Positioning Attribute; Prevalence; Prevention; Prevention strategy; Preventive care; Process; Property; Quality of life; Reaction; Replacement Arthroplasty; Research; Research Activity; Resources; Risk; Scientist; Shapes; Shoes; Site; Stress; Structure; Study models; Suggestion; Sum; System; Talipes cavus; Techniques; Technology; Tendon structure; Testing; Time; Tissues; Toes; Ulcer; United States National Institutes of Health; Validation; Veterans; Work; achilles tendon; arthropathies; career; design; diabetic; diabetic ulcer; experimental study; follow-up; foot; foot bone; improved; individual patient; insight; interest; joint function; kinematics; limb amputation; limb loss; mechanical load; military veteran; novel; pain reduction; pathomechanics; pressure; prevent; prospective; soft tissue; tool; treatment strategy; trend

PROJECT SUMMARY/ABSTRACT Dr. Ledoux’s current research activity aims to reduce both functional and anatomical limb loss by: exploring the disease processes that lead to aberrant limb function; quantifying the effects of conservative and surgical treatment options; and developing novel, state-of-the-art technologies for studying the foot. His research focuses on two veteran populations: those with musculoskeletal impairment at the foot and ankle, where pain and limitations in mobility are the key issues (i.e., functional limb loss); and those at risk of lower limb amputation due to diabetes and foot ulceration, where loss of the foot or leg is a major concern (i.e., anatomical limb loss). The overarching goals of his research include: (1) insight into the pathomechanics of: diabetic foot ulceration, ankle and midfoot arthritis, and severe foot deformities; (2) quantitative comparison of different treatment options for foot deformities/pathologies that can lead to improved limb function or prevention of amputation; and (3) the development of novel research tools that can be employed in a wide range of clinical studies. This third goal is implicit in the first two, but has and will continue to guide much of Dr. Ledoux’s research efforts. For instance, his lab has developed a state-of-the-art cadaveric gait simulator that has been licensed by another foot biomechanist/clinician group. Additionally, he has invested significant resources in the development and validation of his biplane fluoroscope, which is one of only a few primarily designed to study the foot and ankle. Moving forward, two areas of research will dominate Dr. Ledoux’s efforts. First, he has a funded VA Merit Review (RX002008) to study how in-shoe foot orthoses achieve improvements in foot and ankle function for people with ankle osteoarthritis (OA) and/or adult acquired flatfoot. These are common, painful, and often highly debilitating conditions, and it has been shown that foot orthoses can be an effective conservative intervention that can help to postpone or negate the need for surgery. Measuring how the individual bones of the foot move using traditional motion analysis techniques is very difficult due to the size and position of the foot bones, and because of soft tissue artifact, which introduces significant errors into the measurements. This is further complicated by the need to wear shoes to use orthoses. The biplane fluoroscopy system can accurately measure foot bone kinematics throughout the stance phase, and has the advantage of being able to measure the effects of foot orthotics in shoes. This project will improve our understanding of how foot orthotics work and will help us to prescribe and design more effective devices to meet the needs of individual patients. This will benefit the large number of veterans who suffer from ankle osteoarthritis and adult acquired flat foot. Second, Dr. Ledoux has a recent NIH proposal entitled “Reducing Internal Stresses in Deformed Diabetic Feet” that was well scored (20 percentile); if not funded, it will be resubmitted. The structure of the foot, combined with the intrinsic tissue properties, dictates the loading within the tissue. Aberrant internal stresses are thought to be associated with diabetic, neuropathic ulceration, but due to methodological difficulties, it is not possible to quantify these stresses in living subjects. Computer modeling, however, is a technique that can be used to explore this issue; recent finite element foot modeling studies are suggestive of aberrant internal stresses in diabetic feet. The purpose of this study is to use a novel, anatomically detailed, patient-specific computational model to explore how foot deformity and stiffer diabetic tissues can lead to increased internal stresses, and to quantify how conservative and surgical treatment options can modulate these stresses. We will use an MRI- compatible loading device to develop patient-specific computational foot models of subjects that are: i) healthy, ii) diabetic neuropathic, and iii) diabetic neuropathic with claw toes. Both conservative (i.e., insoles) and surgical (i.e., correction of clawed toes) treatments will be modeled. This will improve clinical understanding of how subtle differences in tissue properties and foot shape alter internal stress and change the risk for ulcer development.

项目摘要/摘要 Ledoux博士当前的研究活动旨在通过以下方式减少功能和解剖肢体损失 导致肢体功能异常的疾病过程；量化保守和外科手术的影响 治疗选择；并开发用于研究脚的新型，最先进的技术。他的研究重点 在两个资深人群中：脚和脚踝有肌肉骨骼障碍的人群，疼痛和疼痛 移动性的限制是关键问题（即功能肢体损失）；以及有下肢截肢的风险 糖尿病和脚溃疡，脚或腿损失是主要问题（即解剖肢体损失）。 他的研究的总体目标包括：（1）深入了解：糖尿病足溃疡，踝关节 和中脚关节炎和严重的脚畸形； （2）定量比较不同的治疗选择 脚部畸形/病理可以改善肢体功能或预防截肢； （3） 可以在广泛的临床研究中使用的新型研究工具的开发。第三个目标是 在前两个中隐含，但并将继续指导Ledoux博士的大部分研究工作。例如， 他的实验室已经开发了一个最先进的尸体步态模拟器，该模拟器已获得另一只脚的许可 生物力学主义者/临床医生小组。此外，他还投资了大量资源，并 验证他的双翼荧光镜，这是仅少数用于研究脚和踝关节的主要主要。 展望未来，两个研究领域将主导莱多克斯博士的努力。首先，他有一项资助的VA功绩审查 （RX002008）研究如何为患有患者 脚踝骨关节炎（OA）和/或成人获得的扁平足。这些是常见的，痛苦的，而且通常很衰弱 条件，已经表明，脚矫形器可以是一种有效的保守干预措施，可以帮助 推迟或消除手术的需求。使用传统 运动分析技术由于脚骨的大小和位置非常困难，并且由于柔软 组织伪像，该伪影将重大误差引入了测量中。需求使这更加复杂 穿鞋子使用矫形器。双翼荧光镜系统可以准确测量脚骨运动学 在整个立场阶段，并且具有能够测量脚矫形器在 鞋。该项目将提高我们对脚踏矫正器的工作方式的理解，并将帮助我们准备和 设计更有效的设备以满足个别患者的需求。这将使大量 患有脚踝骨关节炎和成年后脚的退伍军人。 其次，Ledoux博士最近的NIH提案为“减少糖尿病脚变形的内部应力” 得分很好（20％）；如果没有资助，它将被重新提交。脚的结构与 固有的组织特性决定了组织内的负载。异常的内部压力被认为是 与糖尿病，神经性溃疡有关，但由于方法上的困难，不可能 量化生活受试者中的这些压力。但是，计算机建模是一种可用于的技术 探索这个问题；最近的有限元脚建模研究表明，内部应力异常 糖尿病脚。这项研究的目的是使用一种新颖的，解剖学上的，特定于患者的计算 探索脚部畸形和更硬的糖尿病组织如何导致内部应力增加，并 量化保守和手术治疗方案如何调节这些应力。我们将使用MRI- 兼容的加载设备，以开发患者特定的计算脚模型的受试者：i）健康， ii）糖尿病神经性和iii）糖尿病性神经性脚趾的糖尿病性神经性。保守派（即鞋垫）和外科手术 （即，对爪脚趾的校正）将建模。这将提高人们对微妙的临床理解 组织特性和脚形的差异改变了内部压力，并改变了溃疡发育的风险。