Development of 4D Flow MRI for Risk Stratification of Variceal Bleeding in Cirrhosis

开发 4D Flow MRI 用于肝硬化静脉曲张出血风险分层

• 批准号: 10211545
• 负责人: Scott B. Reeder
• 金额: $ 52.12万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10211545
• 关键词: 3-Dimensional; 3D Print; 4D MRI; Acceleration; Address; Adult; American; Anatomy; Anesthesia procedures; Biological; Biological Markers; Blood; Blood Circulation; Blood Platelets; Blood Vessels; Blood flow; Caring; Catheters; Cirrhosis; Clinical; Clinical Management; Clinical Practice Guideline; Complex; Complication; Data; Detection; Development; Diagnostic; Diagnostic tests; Early identification; Esophagogastroduodenoscopy; Esophagus; Future; Gastroenterologist; Goals; Guidelines; Health; Hemorrhage; Hepatic; Hepatology; Intervention; Left; Length; Life; Ligation; Liver; Liver diseases; Magnetic Resonance Imaging; Measurement; Measures; Methods; Mission; Monitor; National Institute of Diabetes and Digestive and Kidney Diseases; Non-Invasive Cancer Detection; Patient Triage; Patients; Performance; Portal Hypertension; Portal Pressure; Preventive treatment; Procedures; Prophylactic treatment; Radial; Reference Standards; Reproducibility; Research; Resistance; Risk; Rupture; Sedation procedure; Sensitivity and Specificity; Serum; Shunt Device; Societies; Specificity; Spleen; Surface; Testing; Therapeutic; Time; Translating; Translations; Ultrasonography; Validation; Varicosity; Venous; Venous Pressure level; Work; base; blood flow measurement; clinical center; clinically relevant; design; diagnostic accuracy; follow-up; gastric vein; hemodynamics; high risk; improved; innovation; mortality; novel; pre-clinical; predictive marker; prevent; prophylactic; response; risk stratification; specific biomarkers; validation studies; vector

PROJECT SUMMARY: The overarching goal of our research is to improve the management and health of an estimated 1 million Americans suffering from end-stage liver disease (cirrhosis) through non-invasive MRI-based blood flow measurements. In cirrhosis, increased resistance to blood flow leads to formation of collateral vessels that shunt blood away from the liver. Many forms of collaterals can develop, but gastroesophageal varices (GEV) are the most important to monitor - GEV are fragile submucosal vessels that can rupture without warning and cause fatal internal bleeding. Once bleeding starts, mortality is extraordinarily high: 1/3 of patients who bleed will die. Current clinical guidelines recommend esophagogastroduodenoscopy (EGD) surveillance every 1-3 years, to facilitate prophylactic treatment and avoid life-threatening bleeding. Unfortunately. EDG is invasive, expensive, and requires sedation. Importantly, most patients undergoing EGD do not have treatable varices, and compliance with surveillance is very poor. For these reasons, the AASLD has identified the development of non-invasive markers that predict the presence of high-risk varices as a major unmet need in the management of cirrhosis. We aim to address this need through development of non-invasive MRI-based markers of portal blood flow that leverage the primary biological mechanism for development and rupture of GEV: reversed flow from the portal circulation into GEV via the left gastric vein. Currently available markers include catheter-based hepatic venous pressure gradient measurements, and emerging non-invasive markers such as platelet-to-spleen ratio, and liver and spleen stiffness (using ultrasound or MRI). Unfortunately, these markers only provide a global assessment of liver disease, and do not have the specificity necessary to identify high-risk GEV. The investigative team at UW are pioneers in radial 4D flow MRI for comprehensive hemodynamic characterization of blood flow in the liver. Our pilot data demonstrates that radial 4D flow MRI can accurately identify high-risk GEV, by quantifying reversed flow in the LGV, with high sensitivity and specificity. We propose to translate advanced 4D flow MRI to address this unmet clinical need by overcoming remaining technical challenges, performing preclinical validation and optimization, and determining its diagnostic performance. Aim 1: Technical development of velocity-optimized, accelerated 4D flow MRI, to quantify flow in the portal circulation, in < 3 minutes. Aim 2: Rigorous validation of the proposed method in anatomically correct 3D-printed flow phantoms. Aim 3: Determine the diagnostic performance of the proposed method in cirrhotic adults undergoing EGD, to assess diagnostic accuracy and test-retest repeatability. Aim 4: evaluate the effects and added value of a meal challenge to assess for high-risk GEV. If successful, the proposed strategy would transform the management of cirrhosis, through: 1) prompt triage of patients to therapeutic EGD 2) reduction of unnecessary EGD procedures, and 3) increased compliance of GEV surveillance through access to a non-invasive method, ultimately improving the care and long-term survival of patients with cirrhosis.

项目摘要： 我们研究的总体目标是改善估计100万的管理和健康 通过非侵入性MRI的血流患有末期肝病（肝硬化）的美国人 测量。在肝硬化中，对血液流动的抗性增加导致形成分流的侧支血管 血从肝脏流血。许多形式的抵押品可以发展，但是胃食管静脉曲张（GEV）是 最重要的是监视 - GEV是脆弱的粘膜下船，可以破裂而不会警告并引起 致命的内部出血。一旦出血开始，死亡率就非常高：1/3流血的患者将死亡。 目前 促进预防性治疗并避免威胁生命的出血。很遗憾。 EDG是侵入性的，昂贵的， 需要镇静。重要的是，大多数接受EGD的患者没有可治疗的静脉曲张和合规性 监视非常差。由于这些原因，AASLD已经确定了非侵入性的发展 预测高风险静脉曲张的标记是管理的主要需求 肝硬化。我们旨在通过开发非侵入性MRI基于门户血液的标记来满足这一需求 利用GEV发育和破裂的主要生物学机制的流动：从 门户通过左胃静脉进入GEV。目前可用的标记包括基于导管的肝 静脉压力梯度测量和出现的非侵入性标记，例如血小板与刺比的比例， 以及肝脏和脾脏刚度（使用超声或MRI）。不幸的是，这些标记只提供了全球 评估肝病，并且没有鉴定高风险GEV所需的特异性。这 UW的调查团队是径向4D流MRI的先驱，用于全面血流动力学特征 肝脏中的血液流动。我们的飞行员数据表明​​，径向4D流MRI可以准确识别高风险 GEV，通过量化LGV中的反向流，具有高灵敏度和特异性。我们建议翻译 高级4D流MRI通过克服剩余的技术挑战来满足这种未满足的临床需求， 执行临床前验证和优化，并确定其诊断性能。目标1： 速度优化，加速4D流MRI的技术开发，以量化门户循环中的流量， 在<3分钟内。目标2：在解剖上正确的3D打印流中对所提出的方法的严格验证 幻影。 AIM 3：确定cirrhotic成年人提出方法的诊断性能 进行EGD，以评估诊断准确性和重复测试重复性。目标4：评估效果和 进餐挑战的附加值，以评估高风险GEV。如果成功，拟议的策略将 转化肝硬化的管理，通过：1）迅速分类患者到治疗EGD 2）还原 不必要的EGD程序，以及3）通过访问GEV监视的依从性提高 非侵入性方法，最终改善了肝硬化患者的护理和长期生存。