Hyperpolarized Pyruvate (13C) Magnetic Resonance Imaging In Patients With Fatty Liver Disease

PRIMARY OBJECTIVES:

• Optimize scan parameters in order to maximize the signal-to-noise ratio of the HP 13C-pyruvate magnetic resonance imaging (MRI) in the liver.
• Determine whether the level of lactate production (as measured by the lactate/pyruvate ratio) in NASH participants, participants with simple NAFL, and healthy volunteers.

SECONDARY OBJECTIVES:

• Develop data analysis methods to quantify HP C-13 pyruvate MRI data.
• Further characterize the safety profile of HP C-13 pyruvate injections.

EXPLORATORY OBJECTIVES:

• Examine the impact of the dual liver blood supply on the vascular kinetics of observed hyperpolarized 13C metabolism.
• Improve methods of quantification and motion correction for hyperpolarized 13C acquisition, incorporating perfusion information derived from 13C Urea

OUTLINE:

Part 1: (Imaging Optimization, N=50): Participants enrolled in Part 1 will predominantly be healthy volunteers. As the protocol optimization is completed, there is a possibility that testing in using data from participants with fatty liver disease may be performed. Participants in this part will be divided into two cohorts:

• Cohort A: Participants will undergo MRI but no injection of hyperpolarized 13C.
• Cohort B: Participants will receive one HP 13C injection. Participants in this cohort will have the option of undergoing repeated dose imaging studies of HP 13C-pyruvate or HP 13C-pyruvate+HP 13C-urea "copol", for up to a total of two injections per imaging visit.

Part 2: (Pilot Study, N=30): Participants enrolled in Part 2 will receive the HP 13C-pyruvate or HP13C-pyruvate+HP13C-urea "copol" protocol that was optimized in Part 1 as well as standard liver MRI pulse sequences. Participants will be stratified into the following groups based on diagnosis:

• Group 1 (n=10): Participants with a diagnosis of non-alcoholic fatty liver without steatohepatitis (NAFL)
• Group 2 (n=10): Participants with a diagnosis of non-alcoholic steatohepatitis (NASH)
• Group 3 (n=10): Participants with no known liver disease (healthy volunteers)

Participants will be followed for 2-4 days following imaging procedure.

Inclusion criteria

Part 1 (Imaging Optimization):

• Able and willing to sign informed consent.
• Age >= 18 years old at the time of study entry.

Part 2 (Pilot Study):

• Group 1 (Fatty Liver Patients without NASH):

• NAFL as determined by either clinical suspicion of fatty liver disease based on:

• steatosis by imaging or histology,
• no significant alcohol consumption,
• absence of coexisting liver disease OR NAFL determined by liver biopsy 3 months prior to the scan, with the presence of fat on histology but absent ballooning or fibrosis. (nonalcoholic steatohepatitis activity score (NAS) <= 3).
• Able and willing to sign informed consent.
• Age ≥ 18 years old at the time of study entry.
• Alcohol consumption < 2 drinks/day for men and <1 drink/day for women
• Hepatitis B surface antigen (HBsAg), Hepatitis C Virus (HCV) antibody, human immunodeficiency virus (HIV) antibody negative.
• Serum alanine aminotransferase (ALT) < 400 microliter (uL)
• Group 2 (NASH Patients):

• NASH as determined by liver biopsy 3 months prior to the scan.

a) NASH defined as NAS score greater than or equal to 4 with confirmation of NASH by an anatomic pathologist.

• Able and willing to sign informed consent.
• Age >= 18 years old at the time of study entry.
• Alcohol consumption < 2 drinks/day for men and <1 drink/day for women
• HBsAg, HCV antibody, HIV antibody negative.
• Group 3 (Healthy volunteer):

• No known history of diabetes or liver disease.
• Able and willing to sign informed consent.
• Age >= 18 years old at the time of study entry.
• Body mass index < 25.
• Liver panel normal (aspartate aminotransferase (AST), ALT, alkaline phosphatase, bilirubin).
• HBsAg, HCV antibody, HIV antibody negative.
• Hemoglobin A1c < 5.7%.
• Estimated glomerular filtration rate (eGFR) >= 60 mL/min/1.73m^2

Exclusion criteria

Part 1 (Imaging Optimization): For Cohorts 1/B only:

• Poorly controlled hypertension, with blood pressure at study entry > 160 mmHg systolic or > 100 mmHg diastolic.
• Congestive heart failure with New York Heart Association (NYHA) status ≥ 2.
• Pregnant or nursing.
• Participants unwilling or unable to undergo magnetic resonance (MR) imaging, including participants with contra-indications to MRI, such as cardiac pacemakers or non-compatible intracranial vascular clips.
• Participant size too large to fit in MR scanner.

Part 2 (Pilot Study): All groups

• Poorly controlled hypertension, with blood pressure at study entry > 160 mmHg systolic or > 100 mmHg diastolic.
• Current treatment with oral medication for diabetes.
• Pregnant or nursing.
• Participants unwilling or unable to undergo MR imaging, including patients with contra-indications to MRI, such as cardiac pacemakers or non-compatible intracranial vascular clips.
• Participant size too large to fit in MR scanner.
• Congestive heart failure with New York Heart Association (NYHA) status >= 2.