RR&D Research Career Scientist Award Application

项目摘要/摘要 勒杜博士目前的研究活动旨在通过以下方式减少功能和解剖上的肢体损失： 导致肢体功能异常的疾病过程；量化保守和手术的影响 治疗选择；以及开发研究脚部的新的、最先进的技术。他的研究重点是 在两个退伍军人群体上：那些有脚部和脚踝肌肉骨骼损伤的人，那里的疼痛和 活动受限是关键问题(即功能性肢体丧失)；以及那些有可能因此而截肢的人 对于糖尿病和足部溃疡，足部或腿部的丧失是一个主要问题(即，解剖性肢体的丧失)。这个 他研究的主要目标包括：(1)深入了解糖尿病足部溃疡、脚踝的病理机制 和足中关节炎，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截肢的足部畸形/病理；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 隐含在前两个方面，但已经并将继续指导勒杜博士的大部分研究工作。例如, 他的实验室开发了一种最先进的身体步态模拟器，并已获得另一只脚的许可 生物机械师/临床医师组。此外，他还投入了大量资源用于开发和 他的双平面透视得到了验证，这是为数不多的主要用于研究脚和脚踝的透视之一。 展望未来，勒杜博士的努力将主要集中在两个研究领域。首先，他有一个由退伍军人事务部资助的功绩评估 (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脚踝功能 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，而且往往使人非常虚弱。 足部矫形器可以是一种有效的保守干预措施，可以帮助 推迟手术推迟或取消手术的需要使用传统方法测量脚部单个骨骼的移动方式 由于脚部骨骼的大小和位置，以及由于柔软的原因，运动分析技术非常困难 组织伪影，这给测量带来了显著的误差。这一点因需要 穿鞋使用矫形器。双平面透视系统可精确测量足部骨骼运动学 在整个站姿阶段，具有能够测量足部矫形术的效果的优势 鞋子。这个项目将提高我们对足部矫形术工作原理的理解，并将帮助我们规定和 设计更有效的设备，以满足个别患者的需求。这将使大量的 患有脚踝骨关节炎和成人的退伍军人获得了扁平足。 其次，勒杜博士最近在美国国立卫生研究院提出了一项题为“减少糖尿病足畸形的内部压力”的建议 这是很好的分数(20%)；如果没有资金，它将被重新提交。脚的结构，结合 固有的组织属性决定了组织内的负荷。异常的内部应力被认为是 与糖尿病、神经性溃疡有关，但由于方法上的困难，不可能 对活体受试者的这些压力进行量化。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。这项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 模型来探索足部畸形和糖尿病组织僵硬如何导致内部压力增加，并 量化保守和手术治疗方案如何调节这些压力。我们将使用核磁共振- 兼容的加载装置以开发患者特定的受试者的计算足部模型：i)健康， Ii)糖尿病神经病变，以及iii)有爪趾的糖尿病神经病变。保守的(即鞋垫)和外科的 (例如，矫正爪趾)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改变了内部压力，改变了溃疡发展的风险。

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.