Clinical Validation of BCT - Phase II

BCT 的临床验证 - II 期

• 批准号: 8040218
• 负责人: David Kopperdahl
• 金额: $ 19.42万
• 依托单位: O. N. DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-03 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8040218
• 关键词: Accounting; Address; American; Automation; Back; Biomechanics; Body Weight; Bone Density; Cadaver; Calibration; Caring; Clinic; Clinical; Collaborations; Computer Vision Systems; Computer software; Data; Data Analyses; Databases; Diagnosis; Diagnostic; Disincentive; Dual-Energy X-Ray Absorptiometry; Engineering; Ensure; Etiology; Evaluation; Event; Finite Element Analysis; Fracture; Goals; Healthcare; Height; Hip Fractures; Hip region structure; Iceland; International; Lifting; Location; Measurement; Measures; Mechanics; Medical; Medicare; Methods; Modality; Modeling; Modification; Muscle; Nature; Osteoporosis; Outcome; Patients; Performance; Phase; Process; Research; Risk; Risk Assessment; Scanning; Small Business Innovation Research Grant; Spinal Curvatures; Structure; Techniques; Testing; Thick; Translating; Translations; Validation; Vertebral column; Woman; X-Ray Computed Tomography; age related; arm; base; bone; bone geometry; bone strength; clinical application; clinical practice; cohort; cost; density; design; diagnosis standard; fall risk; falls; high risk; image processing; improved; insight; men; muscle form; osteoporosis with pathological fracture; phase 1 study; prospective; public health relevance; sex; soft tissue; spine bone structure; trend; validation studies

DESCRIPTION (provided by applicant): Fracture risk assessment is integral to the diagnosis and management of osteoporosis, a devastating clinical condition of which over 40 million Americans are at risk. Due to limitations in areal BMD measures obtained from 2D DXA scans - the current clinical standard for diagnosis of osteoporosis - it has recently become clear that those at risk of osteoporotic fracture need to be better identified. A 3D biomechanics-based technique, which we term Biomechanical Computed Tomography (BCT), addresses this need through a combination of engineering finite element analysis, 3D quantitative computed tomography (QCT), and bone fracture biomechanics. The main outcome parameter of BCT is an estimate of the biomechanical risk of a bone fracture that accounts for such factors as the patient's 3D bone geometry and distribution of bone density, body-weight, height, trochanteric soft tissue thickness (for hip fractures), muscle moment arm (for spine), and the age-related risk of sustaining an overload event (such as a fall or lifting of a heavy object with back bent). In the larger context of translating BCT to clinical practice, we seek in this Phase II SBIR project to test the overall hypothesis that BCT is a better predictor of osteoporotic fracture than is areal BMD, for both hip and spine fracture and for both women and men. In Phase I of this project, we successfully applied this technique to explain observed age-related trends in hip fracture rates. For Phase II, we plan in our first Aim to refine our BCT technique to produce a fully automated, highly reliable and highly accurate software suite with the capability to analyze CT scans acquired for any medical test with coverage of the hip and/or spine without an external calibration phantom. For Aim 2, in order to ensure optimal prediction of clinical fractures, we will further refine our overall BCT process by calibrating results from the two cohorts (the Mayo Clinic cohort of 750 men and women in Rochester MN, and the MrOS cohort of 3,500 men in six U.S. locations). Issues to be resolved in this calibration process include determining optimal methods for measuring soft tissue thickness, muscle moment arms, and spine loading. This analysis will also enable us to calibrate our function for age- related risk of sustaining an overload event, which may depend on both fracture type (hip vs. spine) and sex. In Aim 3, we will compile normative data for BCT outcomes, critical information for interpretation of clinical results. Having refined and calibrated the overall BCT technique and identified the most successful BCT predictors of clinical fracture in the Mayo and MrOS cohorts, we will proceed in Aim 4 to test the validity of these predictors in a fully prospective manner, without any further modification of the BCT technique. For this, we will analyze the AGES cohort of 5,500 women and men in Reykjavik, Iceland, for incident hip and spine fracture. Taken together, this multi-cohort international validation study will provide new insight into osteoporotic fracture etiology, important advancements for the BCT method, and a thorough evaluation of BCT clinical performance. This project should therefore have a significant impact on osteoporosis research and clinical practice. PUBLIC HEALTH RELEVANCE: Statement of Relevance This project will provide clinical validation to Biomechanical Computed Tomography, a promising clinical alternative to DXA for the diagnosis of osteoporosis. Successful translation of BCT to clinical practice has the potential to greatly improve non-invasive assessment of fracture risk, which would represent an important advance in the preventative care and treatment of osteoporosis.

描述（由申请人提供）：断裂风险评估是骨质疏松症的诊断和管理不可或缺的一部分，骨质疏松症是一种毁灭性的临床状况，超过4000万美国人处于风险状态。由于从2D DXA扫描获得的面积BMD措施的局限性 - 当前的骨质疏松症诊断临床标准 - 最近很明显，那些有骨质疏松性骨折风险的人需要更好地识别出那些患有骨质疏松性骨折的风险。我们将基于3D生物力学的技术称为生物力学计算机断层扫描（BCT），通过工程有限元分析，3D定量计算机断层扫描（QCT）和骨断裂生物力学的结合来解决这一需求。 BCT的主要结果参数是对骨断裂的生物力学风险的估计值，这些因素构成了患者的3D骨几何形状和骨密度的分布和骨密度的分布，身体权威，身高，转子软组织厚度（用于髋部骨折），肌肉臂（用于脊柱）的风险（用于刺激性的体重），以及弯曲的次数过多的事件（例如，弯曲的风险都会增加）或弯曲的物质（例如，弯曲的物质都可以置于弯曲的范围内或体重。在将BCT转换为临床实践的更大背景下，我们在此II阶段SBIR项目中寻求检验总体假设，即BCT比Areal BMD更好地预测了骨质疏松性骨折的预测指标，并且对于髋关节和脊柱骨折以及男性和男性。在该项目的第一阶段，我们成功地应用了该技术来解释髋部断裂率的观察到与年龄相关的趋势。对于第二阶段，我们计划首先要改进BCT技术，以生成完全自动化，高度可靠且高度准确的软件套件，并能够分析用于覆盖髋关节和/或脊柱的任何医疗测试的CT扫描，而无需外部校准phantom。对于AIM 2，为了确保对临床骨折的最佳预测，我们将通过校准这两个队列（Mayo诊所在MN中的750名男性和女性，以及MROS在美国六个位置组成的3500名男性），进一步完善我们的总体BCT过程。在此校准过程中要解决的问题包括确定用于测量软组织厚度，肌肉臂臂和脊柱载荷的最佳方法。该分析还将使我们能够校准与年龄相关的过载事件的风险，这可能取决于断裂类型（髋关节与脊柱）和性别。在AIM 3中，我们将汇编用于BCT结果的规范数据，以解释临床结果的关键信息。在进行了整体BCT技术和校准的整体BCT技术之后，并确定了蛋黄酱和MROS队列中临床断裂的最成功的BCT预测因子，我们将继续以AIM 4的形式以完全前瞻性的方式测试这些预测因子的有效性，而无需对BCT技术进行任何进一步的修改。为此，我们将分析冰岛雷克雅未克的5,500名男性和男性的年龄队列，以造成髋关节和脊柱骨折。综上所述，这项多功能国际验证研究将为骨质疏松性骨折病因，BCT方法的重要进步以及对BCT临床表现的全面评估提供新的见解。因此，该项目应对骨质疏松研究和临床实践产生重大影响。公共卫生相关性：相关性该项目将为生物力学计算机断层扫描提供临床验证，这是DXA诊断骨质疏松症的有希望的临床替代方法。成功地将BCT转换为临床实践有可能大大改善骨折风险的非侵入性评估，这将是预防性护理和骨质疏松症的重要进步。

项目成果

Assessment of incident spine and hip fractures in women and men using finite element analysis of CT scans.

• DOI: 10.1002/jbmr.2069
• 发表时间: 2014-03
• 期刊: JOURNAL OF BONE AND MINERAL RESEARCH
• 影响因子: 6.2
• 作者: Kopperdahl, David L.;Aspelund, Thor;Hoffmann, Paul F.;Sigurdsson, Sigurdur;Siggeirsdottir, Kristin;Harris, Tamara B.;Gudnason, Vilmundur;Keaveny, Tony M.
• 通讯作者: Keaveny, Tony M.