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.

项目总结/摘要 博士Ledoux目前的研究活动旨在通过以下方式减少功能性和解剖性肢体损失：探索 导致异常肢体功能的疾病过程;量化保守和手术的影响 治疗方案;以及开发用于研究足部的新颖的最先进技术。他的研究重点 两个退伍军人群体：那些在足部和脚踝肌肉骨骼损伤，疼痛和 移动性的限制是关键问题（即，功能性肢体丧失）;和那些有下肢截肢风险， 糖尿病和足部溃疡，其中足部或腿部的丧失是主要关注的问题（即，解剖学肢体丧失）。的 他的研究的总体目标包括：（1）深入了解病理机制：糖尿病足溃疡，踝关节 和中足关节炎，和严重的足部畸形;（2）定量比较不同的治疗方案， 可导致改善肢体功能或预防截肢的足部畸形/病理;以及（3） 开发新的研究工具，可用于广泛的临床研究。第三个目标是 前两者都隐含着这一点，但它已经并将继续指导勒杜博士的大部分研究工作。比如说， 他的实验室开发了一种最先进的尸体步态模拟器， 生物力学/临床医师组。此外，他还在开发方面投入了大量资源， 他的双平面荧光镜的验证，这是少数几个主要设计用于研究脚和脚踝之一。 展望未来，两个研究领域将主导Ledoux博士的努力。首先，他有一个资助的退伍军人管理局功绩审查 （RX 002008）研究鞋内足部矫形器如何改善患有以下疾病的人的足部和踝关节功能： 踝关节骨关节炎（OA）和/或成人获得性扁平足。这些都是常见的，痛苦的，往往是高度衰弱 条件，它已被证明，脚矫形器可以是一个有效的保守干预，可以帮助 推迟或取消手术的必要性使用传统的测量方法来测量足部的各个骨骼是如何移动的， 由于脚骨的大小和位置，并且由于软 组织伪影，这将显著误差引入测量中。这是进一步复杂化的需要， 穿鞋使用矫形器。双平面透视系统可以准确测量足部骨骼运动学 在整个站立阶段，并且具有能够测量足部矫形器的效果的优势 鞋这个项目将提高我们对足部矫形器如何工作的理解，并将帮助我们开处方， 设计更有效的设备，以满足个别患者的需求。这将使大量的 患有踝关节骨关节炎和成人获得性扁平足的退伍军人。 其次，Ledoux博士最近提出了一项题为“减少畸形糖尿病足的内应力”的NIH提案 得分很高（20%）;如果没有资金，将重新提交。脚的结构，结合 组织的固有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、神经性溃疡相关，但由于方法学困难， 量化活体中的压力然而，计算机建模是一种可以用来 探索这个问题;最近的有限元足部建模研究表明， 糖尿病足本研究的目的是使用一种新颖的、解剖学上详细的、患者特异性的计算方法， 模型来探索足部畸形和僵硬的糖尿病组织如何导致内应力增加， 量化保守和手术治疗方案如何调节这些压力。我们会用核磁共振- 兼容的加载装置来开发受试者的患者特异性计算足部模型，所述受试者是：i）健康的， ii）糖尿病性神经病，和iii）具有爪状趾的糖尿病性神经病。两者都是保守的（即，鞋垫）和外科手术 (i.e.,矫正爪状脚趾）治疗将被建模。这将提高临床理解如何微妙 组织特性和足部形状的差异改变了内部应力并改变了溃疡发展的风险。