The recent development of dissolution dynamic nuclear polarization (DNP) technology for hyperpolarized (HP) 13C imaging offers a promising new avenue for non-invasively accessing fundamental metabolic changes associated with the progression of fatty liver disease in vivo. The purpose of this pilot study is to optimize sequence parameters for hyperpolarized 13C acquisition in the human liver and determine which metabolic changes can be seen in humans with simple, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) when compared to healthy volunteers.
PRIMARY OBJECTIVES: 1. Optimize scan parameters in order to maximize the signal-to-noise ratio of the HP 13C-pyruvate magnetic resonance imaging (MRI) in the liver. 2. 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: 1. Develop data analysis methods to quantify HP C-13 pyruvate MRI data. 2. Further characterize the safety profile of HP C-13 pyruvate injections. EXPLORATORY OBJECTIVES: 1. Examine the impact of the dual liver blood supply on the vascular kinetics of observed hyperpolarized 13C metabolism. 2. 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.
Study Type
OBSERVATIONAL
Enrollment
44
A dosage of 0.43 mL/kg body weight at the maximum dosage will be injected intravenously at a rate of 5 mL/second.
Given intravenously (IV)
Imaging procedure
A 20 milliliter (mL) saline flush at 5 mL/second will be given after each dose of HP 13C
University of California, San Francisco
San Francisco, California, United States
Optimal coil placement (Part 1)
Establishing suitable radiofrequency (RF) coils for individual applications and proper use of MRI techniques such as parallel imaging to achieve optimal image quality will be conducted during the participant's scan. There is no formal analytic plan for Part 1 of the study, which is focused on optimizing the image acquisition protocol.
Time frame: 1 day
Optimal pulse sequences (Part 1)
Establishing the pulse sequences for individual applications and proper use of MRI techniques such as parallel imaging to achieve optimal image quality will be conducted during the participant's scan. There is no formal analytic plan for Part 1 of the study, which is focused on optimizing the image acquisition protocol.
Time frame: 1 day
Optimal respiratory parameter (Part 1)
Establishing the magnitude of respiratory motion for individual applications and proper use of MRI techniques such as parallel imaging to achieve optimal image quality will be conducted during the participant's scan. There is no formal analytic plan for Part 1 of the study, which is focused on optimizing the image acquisition protocol.
Time frame: 1 day
Mean lactate/pyruvate conversion rate (kPL) (Part 1, Cohort B)
Mean lactate-to-pyruvate conversion will be calculated with 95% confidence intervals.
Time frame: 1 day
Signal-to-noise ratio (SNR) (Part 1, Cohort B)
SNR will be calculated..
Time frame: 1 day
Mean lactate-to-pyruvate ratio (Part 2)
The mean lactate-to-pyruvate ratio will be calculated for each of the diagnostic groups: (1) NAFL without steatohepatitis, (2) NASH, and (3) healthy volunteers.
Time frame: 1 day
Mean kPL(Part 2)
The mean kPL will be calculated for each of the diagnostic groups: (1) NAFL without steatohepatitis, (2) NASH, and (3) healthy volunteers.
Time frame: 1 day
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