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: 10538641
• 负责人: Scott B. Reeder
• 金额: $ 61.77万
• 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/10538641
• 关键词: 3-Dimensional; 3D Print; 4D MRI; Acceleration; Address; Adult; American; Anatomy; Anesthesia procedures; Biological; Biological Markers; Blood; Blood Platelets; Blood Vessels; Blood flow; Caring; Catheters; Circulation; 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; Maps; Measurement; Measures; Methods; Mission; Monitor; National Institute of Diabetes and Digestive and Kidney Diseases; Non-Invasive Detection; Patient Triage; Patients; Performance; Portal Hypertension; Portal Pressure; Preventive treatment; Procedures; Prophylactic treatment; Radial; Recommendation; Reference Standards; Reproducibility; Research; Resistance; Risk; Rupture; Sedation procedure; Sensitivity and Specificity; Serum; Severities; Shunt Device; Societies; Specificity; Spleen; Submucosa; Surface; Testing; Therapeutic; Time; Translating; Translations; Validation; Varicosity; Venous; Venous Pressure level; Visualization; Work; biomarker validation; blood flow measurement; clinically relevant; design; diagnostic accuracy; end stage liver disease; follow-up; gastric vein; hemodynamics; high risk; improved; innovation; liver stiffness; mortality; novel; pre-clinical; predictive marker; prevent; prophylactic; response; risk stratification; specific biomarkers; ultrasound; 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.

项目概要： 我们研究的首要目标是改善约100万人的管理和健康。 美国人患有终末期肝病（肝硬化）通过非侵入性MRI为基础的血流 测量.在肝硬化中，血流阻力增加导致形成分流的侧支血管 血液远离肝脏。许多形式的侧支循环可以发展，但胃食管静脉曲张（GEV）是最常见的侧支循环。 GEV是脆弱的粘膜下血管，可能在没有警告的情况下破裂， 致命的内出血一旦开始出血，死亡率非常高：1/3的出血患者会死亡。 目前的临床指南建议每1-3年进行一次食管胃内窥镜检查（EGD）监测， 便于预防性治疗，避免危及生命的出血。不幸的是EDG是侵入性的，昂贵的， 需要镇静剂重要的是，大多数接受EGD的患者没有可治疗的静脉曲张， 监控非常差。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存在的标志物，作为管理中的主要未满足需求 肝硬化我们的目标是通过开发基于MRI的门静脉血标记物来满足这一需求 利用GEV发展和破裂的主要生物学机制的流动： 门静脉循环经胃左静脉进入GEV。目前可用的标记物包括基于导管的肝细胞标志物。 静脉压梯度测量，和新兴的非侵入性标记物，如血小板-脾脏比， 以及肝脏和脾脏僵硬（使用超声或MRI）。不幸的是，这些标记只提供了一个全局 评估肝脏疾病，并且不具有识别高风险GEV所需的特异性。的 华盛顿大学研究小组是径向4D流动MRI用于综合血流动力学表征的先驱 肝脏中的血液流动。我们的试点数据表明，径向4D流动MRI可以准确地识别高风险 GEV，通过定量LGV中的反向流动，具有较高的敏感性和特异性。我们建议翻译 先进的4D流动MRI，通过克服剩余的技术挑战来解决这种未满足的临床需求， 进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血流MRI的技术开发，以量化门静脉循环中的血流， 在< 3分钟。目标2：在解剖学上正确的3D打印流中严格验证所提出的方法 幻影目的3：确定所提出的方法在成人癫痫患者中的诊断性能 进行EGD，以评估诊断准确性和重复性。目标4：评估效果， 膳食挑战的附加价值，以评估高风险GEV。如果成功，拟议的战略将 改变肝硬化的管理，通过：1）及时将患者分诊为治疗性EGD 2）减少 不必要的EGD程序，以及3）通过获得一个 非侵入性方法，最终改善肝硬化患者的护理和长期生存。