MR Spectroscopy of the Liver in Correlation with Histology in NASH Patients

描述（由申请人提供）：非酒精性脂肪肝（NAFL）包括广泛的过程，包括肝脂肪变性和非酒精性脂肪性肝炎（NASH），在20%-40%的NASH患者中可进展为终末期肝病。我们建议比较NASH患者的磁共振波谱（MRS）谱模式与肝脏组织学1至4期纤维化程度（Kleiner等），以及单纯脂肪变性对照组。我们的目标是证明PME/PDE比率随着纤维化的增加而增加。这种差异的证明将导致非侵入性方法的发展，以评估NASH在其自然史中的纵向进展或回归，以及提供对治疗干预反应的跟踪手段。成功鉴定独特的MRS光谱可能被证明是未来NASH病理生理学研究的潜在模式，以及MRS作为肝活检的无创替代方法在理解线粒体异常（包括呼吸链缺陷）中的作用。NASH患者不同纤维化阶段的MRS谱将通过标准MRS信号量化算法（高级磁共振算法）确定PME、Pi、PDE和NTP的峰面积来分析，并分别与单纯性脂肪变性对照组以及每组NASH患者进行比较。将计算峰面积比（PME/NTP、PDE/NTP、PME/PDE和Pi/NTP），并进行统计分析。研究设计允许对86例患者进行充分的统计评估。该奖项将为我提供必要的工具，以进一步扩大我在脂肪肝疾病领域的专业知识，重点是NASH/NAFL的研究，以及评估疾病严重程度和对不同治疗方式的反应性的无创技术。我也期待未来NIH和其他资助机构的资助，在NAFL患者中进行磁共振光谱，并将磁共振光谱与纤维化的生化标志物联系起来。我们还可以将该工具与接受NAFLD治疗管理的患者的肝活检结合使用，即胰岛素增敏剂、抗氧化剂和其他非酒精性脂肪性肝病患者的研究疗法。公共卫生相关性：在美国和世界范围内，非酒精摄入导致的脂肪肝疾病正在增加，但尚未得到满足。目前，唯一可用于研究疾病进展和干预措施有效性的方法是通过侵入性肝活检，这给患者带来不便，并且容易出现并发症和采样误差。我们建议探索是否可以使用非侵入性成像技术（磁共振波谱）来提供更准确和信息丰富的方法来研究这些患者。

DESCRIPTION (provided by applicant): Nonalcoholic fatty liver (NAFL) includes a wide spectrum of processes, including hepatic steatosis and nonalcoholic steatohepatitis (NASH), which can progress to end-stage liver disease in 20%-40% of patients with NASH. We are proposing to compare the Magnetic Resonance Spectroscopy (MRS) spectra patterns of patients with NASH to the degree of fibrosis on liver histology stages 1 through 4 (Kleiner, et al), and a control group with simple steatosis. Our goal is to demonstrate increased PME/PDE ratios with increasing fibrosis. Demonstration of such a difference will lead to the development of noninvasive methods of evaluating longitudinal progression, or regression, of NASH in its natural history, as well as providing a means to follow up on the response to therapeutic interventions. Successful identification of unique MRS spectra may prove to be a potential modality for future investigation into the pathophysiology of NASH and the role of MRS as a noninvasive surrogate to liver biopsy in understanding mitochondrial abnormalities, including respiratory chain defects. MRS spectra from different stages of fibrosis in subjects with NASH will be analyzed by determining peak areas from PME, Pi, PDE, and NTP via a standard MRS signal quantitation algorithm (Advanced Magnetic Resonance algorithm) and compare them to the control group of simple steatosis, as well as to each group of NASH patients separately. Peak area ratios (PME/NTP, PDE/NTP, PME/PDE, and Pi/NTP) will be calculated, and statistically analyzed. The study design permits adequate statistical assessment upon examination of eighty-six patients. This award will provide me with the necessary tools to further expand my expertise in the field of fatty liver disease, with an emphasis on research in NASH/NAFL and the noninvasive techniques of assessment of disease severity and responsiveness to different therapeutic modalities. I also anticipate the facilitation of future grant funds from NIH and other funding agencies, to conduct MR Spectroscopy in NAFL patients and correlate the MR spectra to biochemical markers of fibrosis. We would also be able to use this tool in conjunction with liver biopsy in patients undergoing therapeutic management of NAFLD, i.e., Insulin sensitizers, anti-oxidant, and other studied therapies in patients with nonalcoholic fatty liver disease. PUBLIC HEALTH RELEVANCE: Fatty liver disease that is not the result of alcohol intake is an increasing and unmet need in the US and worldwide. Currently, the only method available to study disease progression and the effectiveness of interventions is through invasive liver biopsies, which inconvenience the patient, and are subject to complications and sampling error. We are proposing to explore whether a non-invasive imaging technique (magnetic resonance spectroscopy) can be used to provide a more accurate and informative method to study these patients.