Development of 4D Flow MRI for Risk Stratification of Variceal Bleeding in Cirrhosis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 2
- 主要终点
- Receiver operation characteristic (ROC) curve analysis to determine diagnostic accuracy
研究概览
简要总结
The goal of this research is to validate novel non-invasive Magnetic resonance imaging (MRI) biomarkers to detect Gastroesophageal varices (GEV) in patients with cirrhosis, including fractional flow change in the portal vein and elevated azygos flow.
End-stage liver disease (cirrhosis) is characterized by advanced fibrosis, liver failure, and portal hypertension. There are many causes of cirrhosis, including viral hepatitis, alcohol abuse, and perhaps most importantly, non-alcoholic fatty liver disease (NAFLD) and its aggressive subset, non-alcoholic steatohepatitis (NASH). 3 million new cases of end-stage liver disease (cirrhosis) are expected over the next decade. In cirrhosis, portosystemic collaterals that shunt blood away from the liver develop due to increased portal pressure. Gastroesophageal varices (GEV) are the most clinically relevant because they can cause fatal internal bleeding. GEV bleeding carries ~20% mortality at 6 weeks, and ~34% overall mortality. Identification of at-risk varices, prior to bleeding, is of paramount importance to initiate primary prophylaxis. To identify and treat at-risk patients, current guidelines recommend regular esophagogastroduodenoscopy (EGD) and variceal band ligation. Detection of high-risk GEV is key to initiating primary prophylaxis, which can reduce mortality by 50-70%.
However, endoscopy is invasive and often unnecessary when no treatment is required. Therefore, the American Association for the Study of Liver Diseases has identified the development of "non-invasive markers that predict the presence of high-risk varices" as a major unmet need.
详细描述
The overall goal of this research is to implement advanced non-invasive 4D flow MRI biomarkers to predict the presence of treatable but potentially lethal GEV in patients with cirrhosis. This would facilitate the triage of patients with high-risk GEV to therapeutic EGD, while reducing unnecessary EGD procedures in patients without them.
The primary biological mechanism for development of GEV is elevated portal pressure and reversal of flow in the left gastric vein (LGV). Applying 4D flow MRI, investigators aim to detect and quantify reversed flow in the LGV to detect GEV at risk for bleeding.
Aim 1: Perform pre-clinical validations of an optimized, accelerated radial 4D flow MRI strategy, and of fat mitigation strategies for radial 4D flow MRI.
Aim 2: Determine the diagnostic performance of radial 4D flow MRI, in cirrhotic adults including
- diagnostic accuracy to identify high-risk GEV using EGD as reference standard, and
- test-retest repeatability Aim 3: Evaluate the effects and added value of a meal challenge to assess for high-risk GEV.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy volunteers: Adults (>18 years) with no known liver pathology
- •Obese volunteers: Adults (>18 years), no known liver pathology, body mass index (BMI) ≥ 35
- •Patients: Adults (>18 years) with known cirrhosis and known Gastroesophageal varices
排除标准
- •contraindications to MRI
- •hypersensitivity reactions to both contrast agents
- •patients with recent treatment for varices with embolization, TIPS, or other endovascular treatment
- •patients with active GEV bleeding; known occlusive thrombus in portal vein, splenic vein, or superior mesenteric vein.
- •patients with large HCC with known PC involvement.
- •Inclusion criteria for Aim 2-4:
- •Adults (>18 years) with known cirrhosis
- •Exclusion Criteria for Aim 2-4:
- •Contraindications to MRI
- •Recent treatment (< 1 year) for varices
- •Known occlusive thrombus in portal vein; splenic vein, or superior mesenteric vein
- •Large hepatocellular carcinoma (HCC) with known PV involvement
- •Hypersensitivity reactions to both contrast agents
- •Participants requiring conscious sedation for imaging are not eligible; participants requiring mild, oral anxiolytics for the clinical MRI scan will be allowed to participate as long as the following criteria are met:
- •The participant has their own prescription for the medication
- •The informed consent process is conducted prior to the self-administration of the medication.
- •The participant comes to the research visit with a driver.
- •Inclusion Criteria for Aim 5:
- •Adults (>18 years) with Fontan repair and diagnosed FALD
- •Exclusion Criteria for Aim 5:
- •Contraindications to MRI
- •Recent treatment (< 1 year) for varices
- •Known occlusive thrombus in portal vein; splenic vein, or superior mesenteric vein
- •Large hepatocellular carcinoma (HCC) with known PV involvement
- •Hypersensitivity reactions to both contrast agents
- •Participants requiring conscious sedation for imaging are not eligible; participants requiring mild, oral anxiolytics for the clinical MRI scan will be allowed to participate as long as the following criteria are met:
- •The participant has their own prescription for the medication
- •The informed consent process is conducted prior to the self-administration of the medication.
- •The participant comes to the research visit with a driver.
研究组 & 干预措施
Obese patients
20 obese patients will be recruited
干预措施: Pre-clinical validation contrast enhanced MRI + fasting (Other)
Healthy volunteers
7 healthy participants will be recruited.
干预措施: Pre-clinical validation contrast enhanced MRI (Other)
Patients with small, low-risk GEV
Patients with small, low-risk Gastroesophageal varices (GEV) will be recruited.
干预措施: Pre-clinical validation contrast enhanced MRI (Other)
Patients with large, high-risk GEV
Patients with large, high-risk Gastroesophageal varices (GEV) will be recruited.
干预措施: Pre-clinical validation contrast enhanced MRI (Other)
Participants with Fontan repair and diagnosed Fontal associated liver disease (FALD)
5 participants with Fontan repair and diagnosed FALD will be recruited.
干预措施: Ensure Plus® (Other)
Patients scheduled for screening or surveillance esophagogastroduodenoscopy (EGD)
100 patients diagnosed with cirrhosis and scheduled for screening or surveillance esophagogastroduodenoscopy (EGD) procedure will be recruited. Participants will complete a single research visit, lasting approximately 2 hours, that will include the following procedures:
- Participants will fast for 12 hours prior to arriving.
- An IV will be placed and a blood sample collected (~11 mL, if necessary).
- All participants will undergo research MRI lasting approximately 1.5 hours
干预措施: Ensure Plus® (Other)
Patients scheduled for screening or surveillance esophagogastroduodenoscopy (EGD)
100 patients diagnosed with cirrhosis and scheduled for screening or surveillance esophagogastroduodenoscopy (EGD) procedure will be recruited. Participants will complete a single research visit, lasting approximately 2 hours, that will include the following procedures:
- Participants will fast for 12 hours prior to arriving.
- An IV will be placed and a blood sample collected (~11 mL, if necessary).
- All participants will undergo research MRI lasting approximately 1.5 hours
干预措施: Clinical validation MRI (Other)
Participants with Fontan repair and diagnosed Fontal associated liver disease (FALD)
5 participants with Fontan repair and diagnosed FALD will be recruited.
干预措施: Clinical validation MRI (Other)
结局指标
主要结局
Receiver operation characteristic (ROC) curve analysis to determine diagnostic accuracy
时间窗: 2 hours
Receiver operation characteristic (ROC) curve analysis will be performed to determine the diagnostic accuracy of 4D flow MRI to differentiate high-risk GEV from absent or low-risk GEV. The area under the curve (AUC) will be estimated for each flow measurement with 95% confidence intervals. The primary analysis is based on fractional flow change in the portal vein.
Variation in postprandial flow after Meal Challenge
时间窗: pre and post meal (approximately 2 hours)
Variations in flow after a meal will be analyzed under(log-)linear mixed effects (LME) models.
Repeatability of 4D flow MRI: measured by summary measures of test-retest agreement with 95% Confidence intervals(CIs).
时间窗: 2 hours
Repeatability of all flow measurements and fractional flow changes will be measured using intra-class correlation coefficient (ICC), and the wishing-subject coefficient of variation (wCV) will be estimated as summary measures of test-retest agreement with 95% CIs.
Diagnostic accuracy of 4D Flow MRI to detect high-risk gastroesophageal varices (GEV) compared to esophagogastroduodenoscopy (EGD) as the reference standard
时间窗: Baseline
Sensitivity and specificity of fractional flow change in the portal vein (FFCPV) and azygos flow thresholds
Receiver operation characteristic (ROC) curve analysis to determine diagnostic accuracy
时间窗: 2 hours
Receiver operation characteristic (ROC) curve analysis will be performed to determine the diagnostic accuracy of 4D flow MRI to differentiate high-risk GEV from absent or low-risk GEV. The area under the curve (AUC) will be estimated for each flow measurement with 95% confidence intervals. The primary analysis is based on fractional flow change in the portal vein.
Variation in postprandial flow after Meal Challenge
时间窗: pre and post meal (approximately 2 hours)
Variations in flow after a meal will be analyzed under(log-)linear mixed effects (LME) models.
Repeatability of 4D flow MRI: measured by summary measures of test-retest agreement with 95% Confidence intervals(CIs).
时间窗: 2 hours
Repeatability of all flow measurements and fractional flow changes will be measured using intra-class correlation coefficient (ICC), and the wishing-subject coefficient of variation (wCV) will be estimated as summary measures of test-retest agreement with 95% CIs.
次要结局
- Aspartate aminotransferase-to-platelet ratio index (APRI)(Within 3 months)
- Fibrosis 4 (FIB-4) index(Within 3 months)
- Liver and spleen stiffness measurement by 2D spin-echo MR elastography(Within 3 months)
- Liver proton density fat fraction (PDFF) as assessed by chemical shift encoded MRI (CSE-MRI)(Within 3 months)
- Hepatic iron level quantitation by in vivo R2* MRI method(Within 3 months)
- Child-Turcotte-Pugh (CTP) score for prognosis of cirrhosis(Within 3 months)
- Aspartate aminotransferase-to-platelet ratio index (APRI)(Within 3 months)
- Fibrosis 4 (FIB-4) index(Within 3 months)
- Repeatability of 4D Flow MRI measurements in cirrhotic patients(Two hours)
- Liver and spleen stiffness measurement by 2D spin-echo MR elastography(Within 3 months)
- Liver proton density fat fraction (PDFF) as assessed by chemical shift encoded MRI (CSE-MRI)(Within 3 months)
- Hepatic iron level quantitation by in vivo R2* MRI method(Within 3 months)
- Child-Turcotte-Pugh (CTP) score for prognosis of cirrhosis(Within 3 months)
- Feasibility of radial 4D Flow MRI and meal challenge protocol in FALD patients(Two hours)
- Postprandial mesenteric and portal flow response in FALD vs cirrhosis and healthy controls(pre and post meal (approximately 2 hours))