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

Summary

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.

Conditions

• Cirrhosis, Liver
• Gastroesophageal Varices
• Fontan Procedure

Interventions

OTHER

Ensure Plus®

In-between two MRI exams, patients will ingest a standardized meal of two cans (16oz) of Ensure Plus® (Abbott Laboratories), providing a 700cal meal (13g protein, 11g fat, 50g carbohydrates), proven to elicit a strong hyperemic splanchnic response.

OTHER

Pre-clinical validation contrast enhanced MRI

Participants will be asked to complete a single research visit that will include a contrast enhanced MRI scan lasting up to 1 hour. Participants will be asked to fast for at least 5 hours prior to the exam. Participants will be screened a final time for contraindications to contrast enhanced MR imaging; an IV will be placed; and participants will be positioned in the MR scanner, asked to lie as still as possible and to follow some breath hold instructions.

OTHER

Clinical validation MRI

Participants will be screened for any previous reactions to Ferumoxytol or GBCAs and dosing will be consistent with standard of care. Participants will then undergo a research MRI lasting approximately 1.5 hours. * All participants will be positioned in the MRI scanner for the initial scanning session (30 min) during which a 1/2 or 3/4 of the full dose of gadolinium based contrast agent (GBCA) or the total dose of Ferumoxytol will be administered. * The first 50 participants will be removed from the scanner bore, repositioned, and scanned for an additional 15 minutes (repeatability testing). * All participants will then be removed from the scanner and asked to consume 16 ounces of Ensure Plus®. After 20 minutes, they will be repositioned in the scanner for an additional scanning session (15 minutes) during which, the remaining 1/4 or 1/2 dose of GBCA will be administered, if required.

OTHER

Pre-clinical validation contrast enhanced MRI + fasting

Participants will be asked to complete a single research visit that will include a contrast enhanced MRI scan lasting up to 1.5 hours. Participants will be asked to fast for at least 5 hours prior to the exam. Participants will be screened a final time for contraindications to contrast enhanced MR imaging; an IV will be placed; and participants will be positioned in the MR scanner, asked to lie as still as possible and to follow some breath hold instructions.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  collaborator NIH

• University of Wisconsin, Madison

  lead OTHER

Principal Investigators

• Scott Reeder, MD, PhD · University of Wisconsin, Madison

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2021-10-28

Primary Completion

2026-06-30

Completion

2026-06-30

FDA Device

Yes

Countries

• United States

Study Locations