Robust BCT for Clinical Use - Phase II

描述(申请人提供)：骨质疏松症是超过50%的50岁以上人口的主要公共健康威胁，估计有超过1000万美国人患有骨质疏松症，另有3400万人由于骨量不足而风险增加。此外，据报道，在65岁以上的患者中，每年有超过34万人患有骨质疏松性髋部骨折和70万人脊柱骨折。尽管骨质疏松症在临床上很重要，但只有12%-14%的需要检测的人接受了骨质疏松症的诊断和治疗。为了纠正这一点，ON诊断公司开发了临床使用的“辅助BCT”。BCT结合了CT扫描的图像处理、骨生物力学和有限元分析，以提供患者CT扫描的BMD和全骨强度的估计。这个SBIR项目的目标是开发利用各种典型的临床CT检查来提供这些BMD和骨强度测量的能力，其中BCT分析作为针对非骨质疏松适应症而订购的CT检查的“附加”分析来执行，从而能够识别髋部和脊柱骨折的高危患者，同时消除患者接受专门的骨质疏松扫描的不便，并最大限度地提高现有成像检查的成本效益。我们估计，在美国，每年多达800万至1000万次CT扫描包含髋部或脊柱，在技术上适合进行辅助BCT分析。我们的计划是提供辅助BCT以 符合当前临床标准的CT患者进行DXA检查，但尚未进行DXA检查。在这个项目的第一阶段，我们成功地开发了软件(VirtuOst(R))，使用以前获得的临床CT扫描来评估骨强度和骨密度。这个第二阶段的项目将集中于全面临床实施辅助BCT所面临的剩余技术挑战。在目标1中，我们将通过自动化图像处理步骤并将自动质量保证测试集成到分析工作流程中来提高吞吐量和可靠性，消除与分析相关的程序开销，并将成本降低到不超过DXA检查的成本。利用现有的图像处理步骤，我们将增加椎体骨折评估，以增加BCT的价值。在目标2中，我们将优化我们的无模体校准技术，使用患者特定的X射线束能量估计，无论CT扫描仪或采集协议如何，都可以实现可重复的BCT结果。我们将把BCT分析扩展到通过静脉造影剂获得的50%的腹部CT检查，并提出辅助BCT的监测指南。最后，在目标4中，我们将把所有这些进展整合到一项临床研究中，该研究以多台CT扫描仪和从大量不同人口统计学特征的患者中获得的检查类型为特色。以临床翻译为重点，我们还将进行成本效益分析，从卫生经济学的角度确定要分析的最有效的检查类型，以及哪些患者将从辅助BCT中受益最大。在这项SBIR研究结束时，我们将把辅助BCT分析的范围和临床用途扩大到没有DXA检查但有现有CT检查的高危患者，并确定这些患者中哪些患者的BCT将受益最大。

DESCRIPTION (provided by applicant): Osteoporosis is a major public health threat for over 50% of the population over age 50, with over 10 million Americans estimated to have osteoporosis and another 34 million at increased risk due to low bone mass. Additionally, over 340,000 osteoporotic hip and 700,000 spine fractures are reported annually in patients over age 65. Despite the clinical importance of osteoporosis, it is under-diagnosed and under-treated with only 12- 14% of those who need testing receiving it. To rectify this, O.N. Diagnostics has developed "ancillary BCT" for clinical use. BCT combines image processing of CT scans, bone biomechanics, and finite element analysis to provide estimates of BMD and whole-bone strength from patient CT scans. The goal of this SBIR project is to develop the ability to provide these BMD and bone strength measures using a wide range of typical clinical CT exams, in which the BCT analysis is performed as an "add-on" analysis to a CT exam that was ordered for a non-osteoporosis indication, thereby enabling the identification of those patients at high risk o hip and spine fracture while removing the patient inconvenience of undergoing a dedicated osteoporosis scan and maximizing the cost-effectiveness of pre-existing imaging exams. We estimate that up to 8-10 million CT scans taken each year in the U.S. contain the hip or spine and would be technically suitable for ancillary BCT analysis. Our plan is to offer ancillary BCT to those CT patients who meet the current clinical criteria to have a DXA exam but who have not yet had a DXA. In Phase-I of this project, we successfully developed software (VirtuOst(R)) to assess both bone strength and BMD using previously acquired clinical CT scans. This Phase-II project will focus on the remaining technical challenges to the full clinical implementation of ancillary BCT. In Aim 1, we will improve throughput and reliability by automating image processing steps and integrating automatic quality assurance testing into the analysis workflow, eliminating the procedural overhead associated with an analysis and reducing the cost to no more than that of a DXA exam. Utilizing existing image processing steps we will add vertebral facture assessment to add value to BCT. In Aim 2 we will optimize our phantomless calibration technique using patient-specific estimates of x-ray beam energy that will allow repeatable BCT result regardless of CT scanner or acquisition protocol. We will extend BCT analysis to the 50% of abdominal CT exams acquired with intravenous contrast, and address monitoring guidelines for ancillary BCT. Finally, in Aim 4, we will integrate all these advances into a clinical study featuring multiple CT scanners and exam types acquired from a large and demographically diverse patient population. Focusing on clinical translation, we will also perform a cost-effectiveness analysis to determine the most efficient exam types to analyze and which patients would benefit most from ancillary BCT from a health economics perspective. At the end of this SBIR study, we will have expanded the scope and clinical utility of ancillary BCT analysis to at risk patients without DXA exams but with existing CT exams and determined which of these patients BCT will benefit most.