Liver Surface Nodularity Score as a New Noninvasive Biomarker for Chronic Viral Hepatitis

 描述(申请人提供)：慢性病毒性肝炎在临床上无症状，直到发展为肝硬变和肝脏失代偿。失代偿性肝硬变是肝功能衰竭的先兆，并与严重食道出血、严重心血管事件和死亡的风险增加有关。诊断肝硬变的黄金标准是肝活检，尽管这一过程存在的问题包括有创方法、采样错误、无法评估肝硬化的严重程度以及疼痛、出血、感染等并发症，而且很少有死亡。此外，在最初诊断为代偿性(早期)肝硬变的患者中，目前还没有经过验证的非侵入性方法来预测未来的肝脏失代偿。因此，需要广泛适用的非侵入性方法来诊断肝硬变和晚期肝纤维化，并预测未来肝脏失代偿和死亡的风险。我们开发了一种计算机算法，用于测量常规计算机断层扫描(CT)和磁共振(MR)图像上的肝脏表面结节数量。我们有初步的数据提供证据，证明肝表面结节是一种有用的定量成像生物标志物，可用于诊断和分期肝硬变，并预测未来的肝脏失代偿和死亡。该技术的主要优势包括评估以前获得的肝脏CT和MR图像的能力(这使得进行大规模的回溯性人口研究成为可能)，在肝硬变患者中广泛使用和频繁使用CT和MR成像，处理时间快(&lt；4分钟)，不需要静脉造影剂，不需要新的硬件或特殊的图像采集程序，并且&gt；1200名独特的患者没有测量失败。虽然我们的初步结果令人信服，但在这项技术成功商业化和临床实施供肝脏专家使用之前，进一步的完善和验证是必要的。这项提议旨在填补这些空白。项目目标1：将肝脏表面结节软件转换为供FDA批准的图像查看器使用的插件。将算法转换为OsiriX(一个开源的可下载查看器)的插件将使算法更易于使用，因为它能够直接从临床PACS接收图像，使软件更易于分发，并允许我们为该插件寻求FDA 510(K)批准途径。项目目标2：评估肝表面结节(LSN)评分诊断肝硬变和晚期肝纤维化的准确性 接受CT引导下肝活检的患者(N=100)。这一目的是为了扩大该技术的适用性，以避免侵入性肝活检。项目目标3：建立必要的团队和基础设施，以支持一项旨在验证LSN评分作为慢性肝病新的非侵入性生物标志物的大型多机构研究。LSN评分作为诊断肝硬变和晚期肝纤维化以及预测未来肝脏失代偿和死亡的新的非侵入性生物标志物的有效性将推动这项技术的商业化，最终改善对慢性肝病患者的护理。

 DESCRIPTION (provided by applicant): Chronic viral hepatitis is clinically silent until development of cirrhosis and hepatic decompensation. Decompensated cirrhosis is a precursor to liver failure and is associated with increased risk of severe esophageal bleeding, significant cardiovascular events, and death. The gold standard for diagnosing cirrhosis is liver biopsy, though problems with the procedure include the invasive approach, sampling errors, inability to assess the severity of cirrhosis, and complications such as pain, bleeding, infection and rarely death. Furthermore, in patients with an initial diagnosis of compensated (early stage) cirrhosis, there are currently no validated noninvasive methods for predicting future hepatic decompensation. Therefore, there is a need for widely applicable noninvasive methods to diagnose cirrhosis and advanced liver fibrosis and to predict future risk of hepatic decompensation and death. We have developed a computer algorithm for measuring the amount of liver surface nodularity on routine computed tomography (CT) and magnetic resonance (MR) images. We have preliminary data providing evidence that liver surface nodularity is a useful quantitative imaging biomarker that can be used to diagnose and stage cirrhosis and to predict future hepatic decompensation and death. Major strengths of the technology include the ability to assess previously acquired liver CT and MR images (making it possible to conduct large-scale retrospective population studies), wide availability and frequent use of CT and MR imaging in cirrhosis, rapid processing time (<4 min), no requirement for intravenous contrast, no need for new hardware or special image acquisition procedures, and no measurement failures in >1200 unique patients. While our initial results are compelling, further refinement and validation are necessary prior to successful commercialization and clinical implementation of this technology for use by liver specialists. This proposal is designed to fill those gaps. Project Aim 1: Convert the Liver Surface Nodularity Software into a plugin for a FDA-approved image viewer. Converting the algorithm into a plugin for OsiriX, an open source downloadable viewer, will make the algorithm easier to use because of the ability to receive images directly from the clinical PACS, make the software easier to distribute, and will allow us to pursue the FDA 510(k) approval pathway for the plugin. Project Aim 2: Assess the accuracy of the liver surface nodularity (LSN) score for diagnosing cirrhosis and advanced liver fibrosis in patients who underwent CT-guided liver biopsy (N=100). This aim is intended to extend the applicability of the technology to avoid an invasive liver biopsy. Project Aim 3: Establish the necessary team and infrastructure to support a large-scale multi-institutional study designed to validate LSN score as a new noninvasive biomarker for chronic liver disease. Validation of the LSN score as a new noninvasive biomarker to diagnose cirrhosis and advanced liver fibrosis and predict future hepatic decompensation and death will advance the commercialization of this technology, ultimately leading to improved care for patients with chronic liver disease.