Noninvasive detection of NASH by magnetic resonance elastography (MRE)

项目总结 非酒精性脂肪性肝炎(NASH)是终末期肝病和肝细胞疾病的先兆 癌症。到目前为止，肝活检仍然是检测NASH两个诊断特征的唯一方法： 肝细胞肿胀和小叶炎症，但受侵袭性和潜在并发症的限制。 这一应用的中心假设是磁共振弹性图(MRE)可以区分 纳什死于单纯性脂肪变性。这一假说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可以分离与炎症和 气球在膨胀。一个单一的多参数测试，结合了炎症和MRE的气球评估， 而用核磁共振测量脂肪变性的质子密度脂肪分数有可能提供全面的 一次评估组织学NAFLD活动评分(NAS)的3个组成部分。这样做的目的是 研究是为了确定和验证这种单一的多参数检验的诊断性能(此后 称为肝图)，用于检测人体NASH。我们将在3个月测试中心假设 目标。在目标1中，我们将使用一组计划接受减肥手术的肥胖受试者来评估NASH 在减肥手术期间和手术前非侵入性地获得肝脏活检的组织学检查 肝图检查。炎症、气球膨胀和脂肪变性的成像参数将用于开发一种 预测组织学NAS评分的统计模型。在AIM 2中，我们将在一个 独立的、非肥胖的NAFLD队列，其中NASH将通过肝脏活检诊断，并通过 肝图检查。在AIM 3中，我们将检查肝脏造影在检测中的纵向诊断性能 减肥干预后的Nash回归。我们将重新评估目标1中描述的减肥队列， 通过肝脏造影和肝活检评估减肥手术后一年的NASH回归。这个 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由 将预测的基于MRE的NAS评分变化与组织学NAS的变化进行比较。这项提议将 将技术创新方法应用于具有NAFLD特征的大量人群，以测试 假设肝脏造影是NASH诊断、监测和反应的准确影像生物标志物 干杯干杯。在肝纤维化发作之前，不需要肝活检来诊断NASH 将对NAFLD患者的护理产生积极影响。这项工作将在学术培养中进行 梅奥诊所内的环境。候选人将由一个强大的专家指导委员会指导 应聘者确定进行必要培训的领域。这位候选人在…方面获得了坚实的基础 在疾病风险评估、预测和结果评估方面的统计技能 博士生培训。她现在建议巩固自己的基础，并获得一套新的和互补的 独立从事非酒精性脂肪性肝病临床研究所需的技能。

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.