Technical Validation of MR Biomarkers of Obesity-Associated NAFLD

Study Overview
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Brief Summary
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The overall goal of this collaborative research program is to develop, validate and translate advanced quantitative magnetic resonance (MR) biomarkers of obesity-associated non-alcoholic fatty liver disease (NAFLD). This protocol represents the research plan for two distinct phases. The first phase is an optimization phase. The second phase is designed to complete a rigorous test of conventional and advanced MRE techniques. Complementary anthropometric, laboratory, and MR measures will also be collected to characterize the cohort and identify factors that affect MRE performance

Detailed Description
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The long-term objective of this research is to improve the health of the millions of Americans with or at risk for NAFLD, the most common chronic liver disease and most rapidly growing indication for liver transplantation in the United States. To achieve this objective, an advanced MR-based imaging method will be used to measure liver stiffness which is an early sign of disease. This technique has been previously developed and validated and ready to be used for further research. This current protocol will extend previous work by optimizing and validating advanced 2 dimensional and 3 dimensional-magnetic resonance elastography (MRE) methods as non-invasive biomarkers of hepatic inflammation and fibrosis in obese patients at risk for non-alcoholic steatohepatitis (NASH), the histologically more aggressive subset of NAFLD. Per Amendment approved 4/8/22: MRE exams will be conducted using a PDFF Pocket Phantom purchased by the UCSD from Calimetrix. This phantom consists of vials with known fat fraction which are captured when taking images of the liver. The known fat fractions provide an independent reference and are used for quality assurance purposes.

Official Title
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Technical Validation of Magnetic Resonance Biomarkers of Obesity-Associated Non-Alcoholic Fatty Liver Disease

Conditions
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Non-Alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis

Intervention / Treatment
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* Other: Magnetic Resonance Elastography (MRE)
* Diagnostic Test: Liver biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Phase 1 and 2 participants) Age of at least 18 years Severely obese (BMI ≥ 35 kg/m2) patient Inclusion Criteria (Phase 2 participants only) Cleared for weight-loss surgery Willing and able to complete all safety and follow-up procedures Willing to allow for the banking of biological samples Exclusion Criteria (Phase 1 and 2 participants) Contraindications to MRI Girth or weight that exceeds scanner capacity Women of childbearing potential that are pregnant or will be attempting to become pregnant during the study duration. Exclusion Criteria (Phase 2 participants only) Known liver malignancies Regular & excessive alcohol consumption within 2 years prior to recruitment Use of steatogenic or hepatotoxic drugs Clinical or laboratory evidence of liver disease other than Nonalcoholic fatty liver disease (NAFLD)/ Nonalcoholic steatohepatitis (NASH) (e.g. HCV Ab, HBV Ab, ceruloplasmin) The subject has increased bleeding risk (i.e., decreased platelets, von Willebrand disease)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Control Group<br>Subjects with a BMI of 35 or more will be asked to undergo a single MRE imaging session. | Other: Magnetic Resonance Elastography (MRE)<br>* The MRE scan will several breath holds and will take approximately 30 minutes to complete.<br>* Other names: MRI;|
| Patient Group<br>Adults that are candidates for weight loss surgery will be asked to participate in four study visits that include MRE imaging and 1 - 2 liver biopsy procedures. | Other: Magnetic Resonance Elastography (MRE)<br>* The MRE scan will several breath holds and will take approximately 30 minutes to complete.<br>* Other names: MRI;Diagnostic Test: Liver biopsy<br>* Subjects undergoing WLS will be asked to allow for liver biopsy samples to be collected during their surgical procedure. The collection of these samples will take approximately 5 minutes to complete.<br>* Other names: Intraoperative Biopsy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optimization of MRE for 2 dimensional and 3 dimensional methods | Optimize MRE wave-field generation in this subject population to maximize the area of invertible shear waves in the liver into interpretable shear stiffness maps. | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, MRE, Liver Disease, Liver Fibrosis