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 非酒精性脂肪肝病（NAFLD）与许多代谢途径的损害密切相关， 包括肝胰岛素敏感性和分泌降低，牙齿衣的增加以及发展2型的风险 糖尿病（T2DM）。相反，糖尿病患者的脂肪性肝炎患病率更高 肝病阶段。作为在临床环境中易于检测到的高血糖的中间状态，糖尿病前是 在T2DM之前但进展是可变的条件，随着时间的流逝，随着相关的 风险因素。迄今为止，尚不清楚糖尿病前进展的机制。我们认为 简单地想象沿肝胰腺轴的腹部器官异常和胰岛素的测量 动作，分泌和肝提取可以为T2DM开发提供见解，对 NAFLD与糖尿病之间的关系，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高级多参数腹部MRE方法 表征肝胰腺轴的病理生理状态和NAFLD中糖尿病前的进展。 •在AIM 1中，多频，自动化和混合radial-cartesian 3D矢量磁共振 弹性图（MRE）技术将在肝脏，胰腺和脂肪数据获取上进行开发和扩展 和图像重建。在MRE驱动器，成像顺序和 重建开发和优化。将通过重新测试评估技术成功的基准 对十名诊断NAFLD患者的可重复性和测量协议研究。 •在AIM 2中，我们将在一项横断面研究中对肝胰腺轴进行定量成像评估 150例诊断NAFLD患者的风险或进展为糖尿病的患者（即50例没有糖尿病的患者， 50例糖尿病前期患者，50例糖尿病患者）。实验室和临床数据以及胰岛素分泌 将在MRI/MRE的30天内收集行动测量。先生组织异常和 将训练和评估综合代谢机械模型，以评估开发T2DM的风险。 •在AIM 3中，假设提款率为20％，我们计划在120名患者中进行一年的随访检查 那些在AIM 2中进行了基线检查的人。在AIM 2中训练的模型将通过纵向进一步调整 MRI/MRE变化用于评估双向治疗对组织组成，结构和代谢的影响 将细胞，腺体，酶和恐怖架桥接到肝胰腺轴的特征，从而预测 NAFLD中糖尿病发育的进展或回归方向。 我们预计该程序将提供多参数MRI/MRE的初始验证和派生的 替代NAFLD中糖尿病进展的肝胰腺轴。这个项目的成功将 还为新兴的治疗干预提供了有价值的无创评估工具。