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.

项目概要/摘要 Ledoux 博士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丧失： 导致肢体功能异常的疾病过程；量化保守治疗和手术治疗的影响； 他的研究重点是治疗方案、开发新颖、最先进的足部技术。 两个退伍军人群体：脚部和脚踝有肌肉骨骼损伤的人，这些人会感到疼痛和 行动能力受限是关键问题（即肢体功能丧失），以及那些面临下肢截肢风险的人； 糖尿病和足部溃疡，其中足或腿的丧失是主要问题（即解剖学肢体丧失）。 他研究的总体目标包括：(1) 深入了解糖尿病足溃疡、踝关节的病理机制 和中足关节炎，以及严重的足部畸形；（2）不同治疗方案的定量比较 可改善肢体功能或防止放大的足部畸形/病理；以及 (3) 第三个目标是开发可用于广泛临床研究的新型研究工具。 隐含在前两项中，但已经并将继续指导勒杜博士的大部分研究工作。 他的实验室开发了一种最先进的尸体步态模拟器，并已获得另一只脚的许可 此外，他还在开发和临床团队中投入了大量资源。 验证他的双平面荧光镜，这是少数主要设计用于研究脚和脚踝的荧光镜之一。 展望未来，勒杜博士的研究将主要集中在两个领域：首先，他有一项受资助的退伍军人管理局优异评审。 （RX002008）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疾病很常见、令人痛苦，而且常常使人极度虚弱。 事实证明，足部矫形器可以是一种有效的保守干预措施，可以帮助 使用传统方法测量足部各个骨骼的移动情况，从而推迟或消除手术的需要。 由于脚骨的大小和位置以及软性，运动分析技术非常困难 组织伪影，这会给测量带来显着的误差，这因需求而变得更加复杂。 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。 整个站立阶段，并具有能够测量足部矫形器的效果的优点 该项目将提高我们对足部矫形器工作原理的理解，并帮助我们制定和使用鞋子。 设计更有效的设备来满足个体患者的需求这将使大量患者受益。 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 博士最近有一项 NIH 提案，题为“减少畸形糖尿病足的内应力” 得分良好（20%）；如果没有资助，将重新提交足部结构。 组织的内在特性决定了组织内的异常内应力。 与糖尿病、神经性溃疡有关，但由于方法学上的困难，不可能 然而，计算机建模是一种可以用来量化活体中的压力的​​技术。 探讨这个问题；最近的有限元足部建模研究表明存在异常的内应力 本研究的目的是使用一种新颖的、解剖学上详细的、针对患者的计算方法。 模型探索足部畸形和僵硬的糖尿病组织如何导致内应力增加，并 我们将使用 MRI 来量化保守治疗和手术治疗方案如何调节这些压力。 兼容的加载设备，用于开发特定于患者的计算足部模型，这些模型是：i）健康的， ii) 糖尿病神经病变，以及 iii) 爪形趾糖尿病神经病变 保守治疗（即鞋垫）和手术治疗。 （即矫正爪状脚趾）治疗将被建模，这将提高临床对微妙程度的理解。 组织特性和足部形状的差异会改变内部应力并改变溃疡发展的风险。