Quantitative characterization of the liver-pancreas axis in diabetes via multiparametric magnetic resonance elastography

通过多参数磁共振弹性成像定量表征糖尿病肝胰轴

• 批准号: 10718333
• 负责人: Meng Yin
• 金额: $ 39.8万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-09 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10718333
• 关键词: 3-Dimensional; Abdomen; Adipose tissue; Adult; Advanced Development; Affect; Agreement; Algorithms; American; Assessment tool; Benchmarking; Biological Markers; Body Weight decreased; Breathing; Caloric Restriction; Centers for Disease Control and Prevention (U.S.); Clinical; Clinical Data; Coupled; Cross-Sectional Studies; Development; Diabetes Mellitus; Diabetes prevention; Diagnosis; Diffuse; Diffusion Magnetic Resonance Imaging; Disease; Early Diagnosis; Enzymes; Epigenetic Process; Fatty Liver; Fatty acid glycerol esters; Fibrosis; Frequencies; General Population; Gland; Glucagon; Glucose; Goals; Guidelines; Health; Hepatic; Hepatic Tissue; High Prevalence; Hormones; Hybrids; Hyperglycemia; Image; Imaging Device; Imaging Techniques; Impairment; Inflammation; Inflammatory; Insulin; Intervention; Islets of Langerhans; Knowledge; Laboratories; Life Style; Link; Liver; Liver Fibrosis; Liver diseases; Magnetic Resonance Elastography; Magnetic Resonance Imaging; Measurement; Measures; Mechanics; Metabolic; Metabolic Diseases; Metabolic Pathway; Methods; Modeling; Modification; Modulus; Monitor; Motion; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oral; Organ; Outcome; Pancreas; Pancreatic Diseases; Pancreatitis; Patients; Pharmaceutical Preparations; Prediabetes syndrome; Process; Protocols documentation; Radial; Relaxation; Research; Resolution; Risk; Risk Assessment; Risk Factors; Scanning; Steatohepatitis; Structure; Techniques; Technology; Testing; Therapeutic Intervention; Time; Tissues; Training; Translations; Validation; Water; Weight; Withdrawal; Work; clinical practice; comorbidity; data acquisition; diabetic; elastography; end stage liver disease; follow-up; healthy volunteer; image reconstruction; imaging biomarker; improved; insight; insulin secretion; insulin sensitivity; liver biopsy; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; novel; obese person; precision medicine; programs; progression risk; quantitative imaging; reconstruction; recruit; risk prediction; statistics; success; technology development; temporal measurement; treatment effect; vector

PROJECT SUMMARY / ABSTRACT Nonalcoholic fatty liver disease (NAFLD) is closely associated with the impairment of many metabolic pathways, including decreased hepatic insulin sensitivity and secretion, increased glucagon, and the risk of developing type 2 diabetes mellitus (T2DM). Conversely, patients with diabetes have a higher prevalence of steatohepatitis and end- stage liver disease. As an intermediate state of hyperglycemia easily detectable in clinical settings, prediabetes is the condition that precedes T2DM but the progression is variable, which could increase over time with associated risk factors. To date, the mechanisms underlying prediabetic progression are still not understood. We think simultaneous imaging of the abdominal organs’ abnormalities along the liver-pancreas axis and measures of insulin action, secretion, and hepatic extraction can provide insights into T2DM development, a better understanding of the relationship between NAFLD and diabetes, and an opportunity to intervene in prediabetic progression. The overall goal of this work is to develop an advanced multiparametric abdominal MRE method for characterizing pathophysiologic state of the liver-pancreas axis and prediabetic progression in NAFLD. • In Aim 1, A multifrequency, self-navigating, and hybrid radial-Cartesian 3D vector magnetic resonance elastography (MRE) technology will be developed and expanded on the liver, pancreas and fat data acquisition and image reconstruction. Ten healthy volunteers will be recruited during MRE driver, imaging sequence and reconstruction development and optimization. Benchmark for technical success will be evaluated with a test-retest repeatability and measurement agreement study on ten patients with diagnosed NAFLD. • In Aim 2, We will perform quantitative imaging assessments of the liver-pancreas axis in a cross-sectional study in 150 patients with diagnosed NAFLD with varying risk or progression to diabetes (i.e., 50 patients without diabetes, 50 patients with prediabetes, 50 patients with diabetes). Laboratory and clinical data, as well as insulin secretion and action measurements, will be collected within 30 days of MRI/MRE. Precursory tissue abnormalities and integrative metabolic-mechanical models will be trained and evaluated to assess the risk of developing T2DM. • In Aim 3, assuming 20% withdrawal rate, we plan to have one-year follow-up examinations in 120 patients out of those who have baseline examinations in Aim 2. The models trained in Aim 2 will be further tuned with longitudinal MRI/MRE changes for assessing bi-directional treatment effects on tissue composition, structural and metabolic features, bridging the cellular, gland, enzymes, and hormones to the liver-pancreas axis, thereby predicting progression or regression direction of diabetes development in NAFLD. We anticipate that this program will provide initial validation of multiparametric MRI/MRE and the derived surrogate to assess the liver-pancreas axis of diabetes progression in NAFLD. This project’s success will also provide a valuable noninvasive assessment tool for emerging therapeutic interventions.

项目摘要/摘要 非酒精性脂肪性肝病(NAFLD)与多种代谢途径的损伤密切相关， 包括肝脏胰岛素敏感性和分泌量降低，高血糖素升高，以及患2型糖尿病的风险 糖尿病(T2 DM)。相反，糖尿病患者脂肪性肝炎和终末期糖尿病的患病率更高。 肝病分期。作为临床上容易检测到的高血糖的中间状态，糖尿病前期是 T2 DM之前的情况，但进展是可变的，可能会随着时间的推移而增加 风险因素。到目前为止，糖尿病前期进展的机制仍不清楚。我们认为 腹部脏器沿肝胰轴异常的同步成像及胰岛素测定 作用、分泌和肝脏提取可以为T2 DM的发展提供洞察力，更好地理解 非酒精性脂肪肝与糖尿病的关系，以及干预糖尿病前期进展的机会。 这项工作的总体目标是开发一种先进的多参数腹部磁共振成像方法 NAFLD的肝-胰轴病理生理状态和糖尿病前期进展的特征。 ·在目标1中，一种多频率、自导航和混合的径向-笛卡尔三维矢量磁共振 弹性成像(MRE)技术将在肝脏、胰腺和脂肪数据采集方面得到开发和推广 和图像重建。10名健康志愿者将在MRE驱动、成像序列和 重建、发展和优化。技术成功的基准将通过重测进行评估 10例诊断为NAFLD患者的重复性和测量一致性研究。 ·在目标2中，我们将在#年的一项横断面研究中对肝-胰轴进行定量成像评估 150名确诊为NAFLD的患者，具有不同的风险或进展为糖尿病(即，50名没有糖尿病的患者， 糖尿病前期患者50例，糖尿病患者50例)。实验室和临床数据以及胰岛素分泌 和行动测量，将在MRI/MRE后30天内收集。前兆组织异常和 将对综合代谢-机械模型进行培训和评估，以评估发生T2 DM的风险。 ·在目标3中，假设撤销率为20%，我们计划对120名患者进行为期一年的随访检查 那些在目标2中有基线考试的人。在目标2中训练的模型将进一步通过纵向调整 MRI/MRE改变评价双向治疗对组织成分、结构和代谢的影响 特征，将细胞、腺体、酶和激素与肝-胰轴连接起来，从而预测 非酒精性脂肪肝患者糖尿病进展或消退方向。 我们预计，该计划将提供多参数MRI/MRE和派生的 非酒精性脂肪肝患者评估糖尿病进展的肝-胰轴的替代物。这个项目的成功将 也为新出现的治疗干预提供了一个有价值的非侵入性评估工具。