EX VIVO VALIDATION OF IMAGE-BASED BIOMARKER OF PEDAL BONE QUALITY

描述(申请人提供)：足部截肢费用昂贵且普遍存在，尤其是在患有糖尿病、神经病变和血管疾病的老年人中。截肢的途径包括骨折、结构畸形、缺血性血管病变和溃疡。对骨骼并发症的迟发认识推迟了可以防止截肢的干预措施。这项建议意义重大，因为它将确定基于图像的踏骨质量和数量指数，这些指数是高危人群足部截肢的早期预测指标。这项赠款申请的目的是测试基于图像的脚踏骨质量和数量测量作为人类第二跖骨和第二楔骨骨折强度的预测因子。在目标1中，PI将使用机械测试来测试基于图像的踏板骨强度指数。在目标2中，他们将把基于体积定量计算机断层扫描(VQCT)图像的测量方法与MicroCT的参考标准进行比较。PI提出了一项新的基于图像的脚踏骨质量和数量测量的研究，这些测量来自高龄糖尿病患者的截肢和身体足部。他们将使用microCT得出的骨质量和数量指数进行多元回归分析，以预测全骨单调最终骨折力。人们的期望是，预测骨折的最佳模型将包括一个或多个骨质量指标。为了测试这些测量的临床相关性，PI将MicroCT测量方法与骨切除前获得的类似的vQCT测量方法进行了比较。这一应用将继续由临床、影像、工程科学家和外科医生组成的多专业团队的成功合作，他们专注于开发和评估基于图像的生物标记物，以提高对导致截肢的神经病变和血管病变引起的足部骨骼并发症的认识。 公共卫生相关性：这项应用旨在评估从高分辨率MicroCT和临床vQCT扫描中获得的基于图像的新的候选踏骨质量生物标记物。PI旨在确定每个生物标记物在多大程度上预测截肢和身体足部切除的人类踝骨和跖骨的最终单调负荷导致骨折/失效(骨强度的参考标准)。基于图像的踏板骨质量生物标记物将被用于预测患有神经疾病和血管疾病的个体的下肢截肢风险。

DESCRIPTION (provided by applicant): Foot amputation is costly and prevalent, especially in older adults with diabetes, neuropathy, and vascular disease. The pathway to amputation includes fracture, structural deformities, ischemic vasculopathy and ulceration. Late recognition of bony complications delays interventions that could prevent amputation. This proposal is significant as it will identify image-based indices of pedal bone quality and quantity that are eary prognosticators of foot amputation in high-risk populations. The objective of this grant application is to test image-based measures of pedal bone quality and quantity as predictors of fracture strength in human 2nd metatarsals and 2nd cuneiforms. In Aim 1 the PIs will test image-based indices of pedal bone strength using mechanical testing. In Aim 2 they will compare volumetric quantitative computed tomography (vQCT) image-based measures to the reference standard of microCT. The PIs propose a novel study of image-based pedal bone quality and quantity measures from amputated and cadaver feet of advanced age with diabetes. They will perform multiple regression analysis using microCT-derived bone quality and quantity indices to predict whole-bone monotonic ultimate fracture force. The expectation is that the best model to predict bone fracture will include one or more bone quality indices. To test the clinical relevance of these measures the PIs compare microCT measures to similar vQCT-derived measures obtained prior to bone excision. This application will continue successful collaborations of a multi-professional team of clinical, image, engineering scientists and surgeons who have focused their expertise on developing and assessing image-based biomarkers to improve the recognition of neuropathy- and vasculopathy-induced bony complications of the foot that lead to amputation. PUBLIC HEALTH RELEVANCE: This application aims to assess novel candidate image-based biomarkers of pedal bone quality obtained from high resolution microCT and clinical vQCT scans. The PIs aim to determine the extent each biomarker predicts ultimate monotonic loading to fracture/failure (the reference standard for bone strength) in excised human tarsal and metatarsal bones from amputated and cadaver feet. Image-based biomarkers of pedal bone quality will be used to predict risk for lower extremity amputation in individuals with neuropathy and vascular diseases.