Senior Research Career Scientist

高级研究职业科学家

• 批准号: 10754191
• 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 2030-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10754191
• 关键词: 3-Dimensional; Activities of Daily Living; Address; Adult; Affect; Age; Agreement; American; Amputation; Anatomy; Ankle; Applications Grants; Area; Arthritis; Arthrodesis; Biomechanics; Cadaver; Classification; Clawtoe; Clinical; Clinical Treatment; Collaborations; Complex; Computer Models; Computer software; Data; Degenerative polyarthritis; Development; Devices; Diabetes Mellitus; Diabetic Foot; Diabetic Foot Ulcer; Diagnosis; Disease; Dissection; Elements; Environment; Etiology; Exhibits; Flatfoot; Fluoroscopy; Foot Deformities; Foot Ulcer; Foot joint structure; Fracture Fixation; Functional disorder; Funding; Gait; General Population; Geometry; Goals; Hallux Rigidus; High Prevalence; Hip Osteoarthritis; Human; Image; Impairment; Implant; Incidence; Intervention; Joints; Knee Osteoarthritis; Laboratories; Limb structure; Link; Location; Lower Extremity; Magnetic Resonance Imaging; Measurement; Mechanics; Metatarsal bone structure; Metatarsophalangeal joint structure; Methods; Modeling; Motion; Musculoskeletal; Neuropathy; Operative Surgical Procedures; Orthopedics; Pain; Paper; Pathology; Patient-Focused Outcomes; Patients; Physiological; Pilot Projects; Population; Population Study; Positioning Attribute; Prevalence; Prevention; Prevention strategy; Preventive care; Procedures; Process; Property; Quality of life; Reaction; Replacement Arthroplasty; Research; Resolution; Risk; Robotics; Scanning; Scientist; Shapes; Site; Skin Temperature; Structure; Study models; Sum; Surface; System; Talipes cavus; Techniques; Technology; Tendon structure; Testing; Tissues; Toes; Ulcer; Ultrasonography; United States National Institutes of Health; Vascularization; Veterans; Woman; Work; achilles tendon; arthropathies; bone; career; design; diabetic; digital; elastography; evidence base; experimental study; foot; foot bone; improved; insight; interest; joint biomechanics; joint function; kinematics; limb amputation; limb loss; mechanical load; men; military veteran; neural network; non-diabetic; novel; pain reduction; pathomechanics; pelvis fracture; pressure; prevent; programs; prospective; residual limb; response; sample fixation; sensor; shear stress; simulation; soft tissue; success; tool; treatment strategy; trend; ultrasound

PROJECT SUMMARY/ABSTRACT Dr. Ledoux’s current research program 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, where loss of the foot 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 great toe arthritis, and severe foot deformities; (2) quantitative comparison of different treatment options for foot pathologies that can lead to improved limb function or prevention of amputation; and (3) the development of novel research tools. Dr. Ledoux is working on several projects related to hallux rigidus, or arthritis of the first metatarsophalangeal joint (MTPJ1). Various designs for MTPJ1 arthroplasties have been proposed, but none have been particularly successful. Development of new implants aimed at addressing these problems has been limited by insufficient quantitative data on the MTPJ1 mechanical environment. Similarly, due to previous technological limitations, no precise 3D data are available on either the kinematics of this disease. CLiMB is engaged in novel research to identify the kinematic envelope of normal MTPJ1 function required during activities of daily living (RX0032590). We will build on our initial successes generating novel, evidence-based implant concepts that emphasize strong initial component fixation to improve MTPJ1 implant technology through computational modeling and robotic gait simulation of human cadavers (R01AR076475). These better-performing implants will ultimately lead to improved patient outcomes. It is our working hypothesis that a successful MTPJ1 implant will exhibit both strong initial component fixation and physiologically normative joint biomechanics. Additionally, Dr. Ledoux is collaborating with Dr. Sangeorzan on a multisite hallux rigidus study comparing motion sparing procedures (joint replacement or bone shaping) to arthrodesis (fusion). This study will determine factors associated with treatment success. Developing improved treatment options requires a better fundamental understanding of diabetic disease pathomechanics. Despite growing agreement that aberrant pressures and shear stresses are linked to ulceration, the specific causative mechanism of ulceration remains poorly understood. From a structural perspective—in which tissues of different material properties and different geometries interact to create a bulk response—most studies have been 2D and limited in the number of locations considered. Given the complex structure and functional motion of the foot, it should be investigated in 3D across the entire plantar surface. However, many techniques that afford volumetric inquiry have other concerns: dissection is disruptive, finite element models rely on assumptions and simplifications, CT has poor soft tissue resolution, and MRI is computationally and fiscally expensive. Ultrasound has good soft tissue resolution, but most commercial systems create planar images or are limited to small, angularly swept volumes. Ultrasound can also be difficult to read for the naïve user. In order to overcome these barriers, we propose these specific aims: 1) Develop a mechanical system and the necessary software to generate a 3D scan of the entire plantar soft tissue, using B-mode ultrasound for structural information and shear wave elastography for tissue properties. 2) Collect plantar soft tissue scans for 7 diabetic non-neuropathic subjects and 7 non-diabetic subjects. 3) Analyze these scans using segmentation and strain information calculated with digital volume correlation as well as an interpretable classification neural network. The successful completion of this NIH funded pilot study (5U24DK115255-04, subaward 32307-94) will demonstrate the utility of the proposed methods and support a larger grant application.

项目摘要/摘要 博士勒杜目前的研究计划旨在减少功能和解剖肢体损失：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、最先进的技术。他的研究重点 针对两个退伍军人群体：足部和脚踝肌肉骨骼损伤的人群，其中疼痛和 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， 对于糖尿病，其中足部的丧失是主要关注点（即，解剖学肢体丧失）。他的首要目标是 研究包括：（1）深入了解糖尿病足溃疡，踝关节和大脚趾关节炎， 和严重的足部畸形;（2）定量比较足部病变的不同治疗方案， 可以改善肢体功能或预防截肢;（3）开发新的研究工具。 博士Ledoux正在进行几个与拇趾僵硬或第一跖趾关节炎有关的项目 接头（MTPJ 1）。已经提出了用于MTPJ 1关节成形术的各种设计，但是没有一个是特别合适的。 成功旨在解决这些问题的新植入物的开发受到不充分的限制， MTPJ 1机械环境的定量数据。同样，由于以前的技术限制， 精确的3D数据可用于该疾病的运动学。CLiMB从事新的研究， 确定日常生活活动期间所需的正常MTPJ 1功能的运动学包络线（RX 0032590）。 我们将建立在我们最初的成功产生新的，以证据为基础的植入概念，强调强 通过计算建模和机器人步态改进MTPJ 1植入技术的初始部件固定 人体尸体模拟（R 01 AR 076475）。这些性能更好的植入物最终将改善 患者结局。我们的工作假设是，成功的MTPJ 1植入将表现出强烈的初始 部件固定和生理规范的关节生物力学。此外，勒杜博士正在与 与Sangeorzan博士进行了一项多部位拇趾僵硬研究，比较了运动保留手术（关节置换术） 或骨成形）到关节固定术（融合）。这项研究将确定与治疗成功相关的因素。 开发更好的治疗方案需要对糖尿病有更好的基本了解 病理力学尽管越来越多的人认为异常压力和剪切应力与 虽然溃疡形成的原因是多方面的，但溃疡形成的具体病因机制仍然知之甚少。从结构 透视-其中不同材料特性和不同几何形状的组织相互作用以创建块体 响应-大多数研究都是二维的，并且考虑的位置数量有限。鉴于复杂的 结构和功能运动的脚，它应该在整个足底表面的3D调查。 然而，许多提供体积查询的技术有其他问题：解剖是破坏性的，有限的 元素模型依赖于假设和简化，CT具有较差的软组织分辨率，而MRI 计算上和物理上昂贵。超声具有良好的软组织分辨率，但大多数商业系统 创建平面图像或限于小的、有角度扫描的体积。超声波也可能难以读取 对于天真的用户。为了克服这些障碍，我们提出了这些具体目标：1）开发一种机械 系统和必要的软件，使用B模式生成整个足底软组织的3D扫描 超声用于结构信息，剪切波弹性成像用于组织特性。2)收集足底柔软 对7名糖尿病非神经病受试者和7名非糖尿病受试者进行组织扫描。3)分析这些扫描使用 分割和应变信息计算的数字体积相关性以及可解释的 分类神经网络。成功完成这项NIH资助的试点研究（5 U24 DK 115255 -04， subaward 32307-94）将证明所提出的方法的实用性，并支持更大的赠款申请。

项目成果

Step Activity After Surgical Treatment of Ankle Arthritis.

踝关节炎手术治疗后的步骤活动。

• DOI: 10.2106/jbjs.18.00511
• 发表时间: 2019
• 期刊: The Journal of bone and joint surgery. American volume
• 作者: Shofer,JaneB;Ledoux,WilliamR;Orendurff,MichaelS;Hansen,SigvardT;Davitt,James;Anderson,JohnG;Bohay,Donald;Coetzee,JChris;Houghton,Michael;Norvell,DanielC;Sangeorzan,BruceJ
• 通讯作者: Sangeorzan,BruceJ

The compressive, shear, biochemical, and histological characteristics of diabetic and non-diabetic plantar skin are minimally different.

• DOI: 10.1016/j.jbiomech.2021.110797
• 发表时间: 2021-12-02
• 期刊: Journal of biomechanics
• 影响因子: 2.4
• 作者: Brady L;Pai S;Iaquinto JM;Wang YN;Ledoux WR
• 通讯作者: Ledoux WR

3D Printed lattice microstructures to mimic soft biological materials.

3D 打印晶格微结构来模拟软生物材料。

• DOI: 10.1088/1748-3190/aae10a
• 发表时间: 2018
• 期刊: Bioinspiration & biomimetics
• 影响因子: 3.4
• 作者: Johnson,LukeK;Richburg,Chris;Lew,Madelyn;Ledoux,WilliamR;Aubin,PatrickM;Rombokas,Eric
• 通讯作者: Rombokas,Eric

The effect of diabetes and tissue depth on adipose chamber size and plantar soft tissue features.

• DOI: 10.1016/j.foot.2023.101989
• 发表时间: 2023-09-01
• 期刊: Foot (Edinburgh, Scotland)
• 作者: Brady, Lynda M;Rombokas, Eric;Ledoux, William R
• 通讯作者: Ledoux, William R

Comparison of texture-based classification and deep learning for plantar soft tissue histology segmentation.

• DOI: 10.1016/j.compbiomed.2021.104491
• 发表时间: 2021-07
• 期刊: Computers in biology and medicine
• 影响因子: 7.7
• 作者: Brady L;Wang YN;Rombokas E;Ledoux WR
• 通讯作者: Ledoux WR