Comprehensive noninvasive assessment of liver histopathology in nonalcoholic fatty liver disease (NAFLD) via magnetic resonance imaging, cytometry and elastography (MR-ICE)

通过磁共振成像、细胞计数和弹性成像 (MR-ICE) 对非酒精性脂肪性肝病 (NAFLD) 的肝脏组织病理学进行综合无创评估

• 批准号: 10689311
• 负责人: Meng Yin
• 金额: $ 35.78万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10689311
• 关键词: 3-Dimensional; Address; Adult; Affect; Assessment tool; Biological Markers; Biopsy; Cell Size; Chemical Shift Imaging; Cirrhosis; Clinical; Clinical Research; Clinical Trials; Cytometry; Development; Diagnosis; Diagnostic; Diet; Diffusion; Disease; Elasticity; Ensure; Evaluation; Evolution; Fatty acid glycerol esters; Fibrosis; Frequencies; Goals; Guidelines; Hepatic; Hepatocyte; Histologic; Histopathology; Hybrids; Image; Imaging technology; Inflammation; Intercellular Fluid; Intervention; Iron; Knowledge; Liver; Liver Fibrosis; Liver diseases; Magnetic Resonance Elastography; Magnetic Resonance Imaging; Measurement; Mechanics; Methods; Modeling; Modification; Modulus; Monitor; Motion; Patients; Performance; Phase; Prevalence; Protocols documentation; Radial; Rattus; Research; Research Personnel; Risk; Scheme; Severities; Signal Transduction; Staging; Statistical Models; Steatohepatitis; Structure; Techniques; Technology; Testing; Therapeutic Intervention; Tissues; Training; Treatment Efficacy; United States; Water; Work; advanced disease; biomarker validation; cell injury; clinical practice; design; elastography; hepatocellular injury; high risk; imaging biomarker; imaging modality; in vivo; in vivo imaging; liver biopsy; liver inflammation; liver stiffness; mechanical properties; multiparametric imaging; non-alcoholic fatty liver disease; non-invasive imaging; nonalcoholic steatohepatitis; novel; preclinical study; primary endpoint; reconstruction; research clinical testing; secondary endpoint; simple steatosis; success; treatment effect; vector; virtual; viscoelasticity

PROJECT SUMMARY / ABSTRACT The growing prevalence of nonalcoholic fatty liver disease (NAFLD) creates an imperative to reliably distinguish between patients with simple steatosis and those with nonalcoholic steatohepatitis (NASH). However, hepatic inflammation and cellular injury diagnoses often require invasive liver biopsies for histopathologic staging. There is an urgent need for safe and reliable noninvasive imaging methods for diagnosing NASH and longitudinal assessing hepatic inflammation and hepatocellular injury to monitor treatment efficacy. The presence of and severity of steatosis and fiborosis are now well addressed with chemical shift imaging and magnetic resonance elastography (MRE). Our current cycle of research has confirmed that MRE-assessed loss modulus is a very promising biomarker for inflammation. In this renewal application, we propose to continue validation of this biomarker for inflammation and to add noninvasive assessment of cell injury (ballooning) by introducing a novel MR cytometry modification into the MRE protocol. The overall goal of this work is to develop and validate multiparametric MR-ICE imaging technologies for fully assessing disease states during NAFLD evolution, especially inflammation and hepatocellular injury. • In Aim 1, we will develop the MR-ICE imaging protocol. Fat fraction will be evaluated with a 6-point Dixon method. A dual-frequency, self-navigating, and hybrid radial-Cartesian 3D vector hepatic MRE technique will be optimized for characterizing multiple mechanical properties of viscoelasticity and nonlinearity. MRC sequence and reconstruction will be developed with gradient waveforms and diffusion signal fitting that are specifically designed for hepatocyte cytometry, with or without simultaneous MRE acquisition. • In Aim 2, we will perform longitudinal application of the MR-ICE in an in vivo rat model (N=96, diet-induced NASH). Technical integrity and diagnostic performance will be assessed by comparing multiple in vivo imaging biomarkers (fat fraction, hepatocyte size, viscoelasticity, nonlinearity) with ex vivo tissue composition (water and fat contents), dynamic mechanical analysis (DMA) testing and histologic features (steatosis, inflammation, ballooning, fibrosis), respectively. Statistical models will be trained to diagnose NASH. • Prior to pilot clinical evaluation, we will aseess the repeatability of MR-ICE biomarkers in 5 controls and 5 clinical patients using a test-retest strategy. Finally, a pilot clinical evaluation in 10 controls and 40 patients with biopsy-proven NAFLD/NASH will be performed to provide preliminary evidence of the diagnostic performance of the MR-ICE protocol for staging NAFLD/NASH. Emerging therapeutic interventions may require life-long treatment, creating the need for more precise non- invasive methods for identifying those patients who need such interventions. The development of MR-ICE will make it possible for us and other investigators to advance the precise noninvasive assessment of NASH.

项目概要/摘要 非酒精性脂肪性肝病 (NAFLD) 的患病率不断上升，因此迫切需要可靠的方法 区分单纯性脂肪变性和非酒精性脂肪性肝炎（NASH）患者。 然而，肝脏炎症和细胞损伤的诊断通常需要侵入性肝活检 迫切需要安全可靠的非侵入性成像方法。 诊断 NASH 并纵向评估肝脏炎症和肝细胞损伤以进行监测 脂肪变性和纤维化的存在及其严重程度现已得到很好的解决。 我们当前的研究周期包括化学位移成像和磁共振弹性成像（MRE）。 证实 MRE 评估的损耗模量是本次更新中非常有前途的炎症生物标志物。 应用中，我们建议继续验证这种炎症生物标志物并添加非侵入性 通过在 MRE 方案中引入新颖的 MR 细胞计数修改来评估细胞损伤（气球）。 这项工作的总体目标是开发和验证多参数 MR-ICE 成像技术，以充分实现 评估 NAFLD 演变过程中的疾病状态，特别是炎症和肝细胞损伤。 • 在目标1 中，我们将开发MR-ICE 成像方案，并使用6 点Dixon 进行评估。 双频、自导航和混合径向笛卡尔 3D 矢量肝脏 MRE 技术将 针对粘弹性和非线性的多种机械特性进行优化。 序列和重建将使用梯度波形和扩散信号拟合来开发 专为肝细胞细胞计数而设计，可同时采集或不采集 MRE。 • 在目标 2 中，我们将在体内大鼠模型（N=96，饮食诱导 NASH）的技术完整性和诊断性能将通过比较多个体内进行评估。 使用离体组织成分对生物标志物（脂肪分数、肝细胞大小、粘弹性、非线性）进行成像 （水和脂肪含量）、动态机械分析（DMA）测试和组织学特征（脂肪变性、 将训练统计模型来诊断 NASH。 • 在试点临床评估之前，我们将评估 MR-ICE 生物标志物在 5 个对照和 5 个对照中的可重复性。 最后，对 10 名对照者和 40 名患者进行了试点临床评估。 将进行活检证实的 NAFLD/NASH，以提供诊断的初步证据 MR-ICE 协议用于 NAFLD/NASH 分期的性能。 新兴的治疗干预措施可能需要终生治疗，这就需要更精确的非治疗方法。 MR-ICE 的开发将用于识别需要此类干预的患者。 使我们和其他研究人员能够推进 NASH 的精确无创评估。

项目成果

Normal Liver Stiffness Values in Children Are the Same as in Adults.

儿童正常肝硬度值与成人相同。

• DOI: 10.1148/radiol.2020203515
• 发表时间: 2020
• 期刊: Radiology
• 影响因子: 19.7
• 作者: Yin,Meng

Ultrasound Shear Wave Elastography as a Measure of Porcine Hepatic Disease in Right Heart Dysfunction: A Pilot Study.

超声剪切波弹性成像作为右心功能不全猪肝病的衡量标准：一项初步研究。

• DOI: 10.1016/j.ultrasmedbio.2018.05.027
• 发表时间: 2018
• 期刊: Ultrasound in medicine & biology
• 影响因子: 2.9
• 作者: Hu,JessieJ;Qureshi,MYasir;Urban,MatthewW;Graham,Rondell;Yin,Meng;Oommen,Saji;Holst,KimberlyA;Edgerton,Sarah;Vasconcelos,Luiz;Nenadic,Ivan;Cetta,Frank;WanekProgramPre-clinicalPipeline
• 通讯作者: WanekProgramPre-clinicalPipeline

Magnetic Resonance Elastography of Liver: Current Update.

• DOI: 10.1097/rmr.0000000000000177
• 发表时间: 2018-10
• 期刊: Topics in magnetic resonance imaging : TMRI
• 作者: Hoodeshenas S;Yin M;Venkatesh SK
• 通讯作者: Venkatesh SK