Evaluation of hepatic liver disease using multinuclear magnetic resonance techniques

Paige Nicole Hopewell, Purdue University

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States. Risk factors for NAFLD include insulin resistance, diabetes, and obesity. NAFLD encompasses a spectrum of disease stages: steatosis, steatosis with hepatitis or nonalcoholic steatohepatitis (NASH), NASH with fibrosis, and cirrhosis. Currently, biopsy, an invasive technique with associated risks, is the gold standard for NAFLD diagnosis. Development of techniques to noninvasively diagnose and stage NAFLD is greatly needed for monitoring disease progression and treatment response clinically and in small animal models. Of all the modalities available, magnetic resonance (MR) has the greatest potential to make use of the different physiological mechanisms underlying the transition from steatosis to NASH to cirrhosis in NAFLD. In these studies, chronic liver disease was examined using 1H MR imaging (MRI)I, localized 1H MR spectroscopy (MRS), single quantum (SQ) and triple quantum-filtered (TQF) 23Na MRI, shift reagent- (SR-) aided 23Na and 31P MRS, and TQF 23Na MRS. The results showed that the progression of liver disease from simple steatosis to advanced fibrosis involves many factors. First, steatosis can be assessed with localized 1H MRS more accurately than 1H MRI frequency-based techniques. Second, SQ and TQF 23Na MRI signal decreases with increasing steatosis, but increases with increasing fibrosis. Lastly, the changes in TQF 23Na MRI is not due to changes in TQF relaxation rates, and a large component of the TQF signal arises from the ECS in response to fibrosis-associated ECM deposition. Diffusion-weighted 1H MRI (DWI) and SQ and TQF 23Na MRI were also used to examine an ischemic model of liver dysfunction. After ischemic onset, DWI showed a large decrease in signal that is due to perfusion and motionrelated artifacts that did not change significantly afterwards. However, TQF 23Na MRI did show a gradual, but significant increase that plateaued at 3 hours after ischemia that was expected and consistent with the findings of other ischemia studies. Therefore, TQF 23Na techniques are promising and may be more advantageous than DWI in some cases of hepatic liver disease where the cellular energetics and the transmembrane sodium gradient is disrupted. In conclusion, 23Na MR techniques hold much promise for evaluation of liver disease, prompting further development for possible clinical translation.

Degree

Ph.D.

Advisors

Talavage, Purdue University.

Subject Area

Biomedical engineering|Medical imaging

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