Noninvasive detection of NASH by magnetic resonance elastography (MRE)

项目摘要 非酒精性脂肪性肝炎（NASH）是终末期肝病和肝细胞性肝炎的一种确定的前兆。 carcinoma.迄今为止，肝活检仍然是唯一可用于检测NASH的两个诊断特征的测试： 肝细胞气球样变和小叶炎症，但它受到侵袭性和潜在并发症的限制。 该应用的中心假设是磁共振弹性图（MRE）可以区分 单纯性脂肪变性引起的NASH。这一假设得到了强有力的初步数据的支持，这些数据表明， 新的技术改进，MRE可以分离与炎症相关的成像参数， 气球。通过MRE结合炎症和气球样膨胀评估的单一多参数测试， 和脂肪变性测量MRI质子密度脂肪分数有可能提供一个全面的 在一种情况下估计组织学NAFLD活动评分（NAS）的3个组成部分。的目的 本研究旨在确定和验证该单一多参数测试的诊断性能（此后 命名为Hepatogram）用于检测人类受试者中的NASH。我们将在第3节中检验中心假设 瞄准器在AIM 1中，我们将使用计划进行减肥手术的肥胖受试者队列来评估NASH 通过在减肥手术期间获得的肝活检和手术前的非侵入性组织学检查， 肝脏造影炎症、气球样变和脂肪变性的成像参数将用于开发一个 统计模型预测组织学NAS评分。在AIM 2中，我们将在 独立的非肥胖NAFLD队列，其中NASH将通过肝活检诊断，并通过 肝脏造影在AIM 3中，我们将检查肝图在检测中的纵向诊断性能。 减肥干预后NASH的消退。我们将重新评估目标1中描述的减肥队列， 在减肥手术后一年，通过肝图和肝活检评估NASH消退。的 在目标1中开发并在目标2中验证的统计模型的预测性能将通过以下方法进行检验： 将预测的NAS评分的基于MRE的变化与组织学NAS的变化进行比较。这项建议会 将技术创新方法应用于大量严格表征的NAFLD人群，以测试 假设肝图是NASH诊断、监测和反应的准确成像生物标志物 干预措施。避免在纤维化发作前进行肝活检以诊断NASH的不切实际的需要 会对NAFLD患者的护理产生积极影响。这项工作将在一个学术上培养 马约诊所的环境。候选人将由一个强大的专家指导委员会指导， 候选人确定需要进行必要培训的领域。这位候选人在以下方面打下了坚实的基础： 在她任职期间，在疾病风险评估、统计和结果评估方面的统计技能 博士培训。她现在建议巩固她的基础，并获得一套新的和互补的 非酒精性脂肪肝临床研究独立职业所需的技能。

PROJECT SUMMARY Nonalcoholic steatohepatitis (NASH) is an established precursor of end-stage liver disease and hepatocellular carcinoma. To date, liver biopsy remains the only test available to detect the two diagnostic features of NASH: hepatocyte ballooning and lobular inflammation, but it is limited by invasiveness and potential complications. The central hypothesis of this application is that magnetic resonance elastogram (MRE) can discriminate NASH from simple steatosis. The hypothesis is supported by strong preliminary data which show that with novel technological modifications, MRE can isolate imaging parameters that correlate with inflammation and ballooning. A single multiparametric test that combines inflammation and ballooning assessment by MRE, and steatosis measurement by MRI-proton density fat fraction has the potential to provide a comprehensive estimation of the 3 components of histologic NAFLD activity score (NAS) in one setting. The objective of this study is to determine and validate the diagnostic performance of this single multiparametric test (henceforth named Hepatogram) for the detection of NASH in human subjects. We will test the central hypothesis in 3 AIMs. In AIM 1 we will use a cohort of obese subjects scheduled for bariatric surgery to assess NASH histologically by liver biopsy obtained during bariatric surgery and noninvasively before surgery by Hepatogram. The imaging parameters of inflammation, ballooning and steatosis will be used to develop a statistical model to predict histologic NAS score. In AIM 2 we will validate this statistical model in an independent, non-bariatric NAFLD cohort, in whom NASH will be diagnosed by liver biopsy and assessed by Hepatogram. In AIM 3 we will examine the longitudinal diagnostic performance of Hepatogram in the detection of NASH regression after weight-loss interventions. We will reevaluate the bariatric cohort described in Aim 1, one year after bariatric surgery by assessing for NASH regression by Hepatogram and liver biopsy. The predictive performance of the statistical model developed in Aim 1 and validated in Aim 2 will be examined by comparing the predicted MRE-based change in NAS score to the change in histologic NAS. This proposal will apply technically innovative approaches to a large, rigorously characterized population with NAFLD to test the hypothesis that Hepatogram is an accurate imaging biomarker for NASH diagnosis, monitoring and response to interventions. Obviating the impractical need for liver biopsy to diagnose NASH before onset of fibrosis would positively impact the care of NAFLD patients. This work will be performed in an academically nurturing environment within Mayo Clinic. The candidate will be guided by a strong mentorship committee of experts in the areas that the candidate identified for necessary training. The candidate acquired a strong foundation in statistical skills in assessment of disease risk, prognostication and outcomes evaluation during her post- doctoral training. She now proposes to solidify her foundation and acquire a set of new and complementary skills necessary for an independent career in clinical research in nonalcoholic fatty liver disease.