In vivo magnetic resonance studies of experimental liver disease: Carbon tetrachloride hepatotoxicity and alcohol-induced fatty liver in rat

John Darwin Hazle, The University of Texas Graduate School of Biomedical Sciences at Houston


Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) were used to non-invasively determine if cirrhosis induced by carbon tetrachloride (CCl$\sb4$) and phospholipase-D (PLD) could be distinguished from fatty infiltration in rat. MRS localization and water suppression methods were developed, implemented and evaluated in terms of their application to in vivo proton NMR studies of experimental liver disease. MRS studies were also performed to quantitate fatty infiltration resulting from carbon tetrachloride (CCl$\sb4$) or alcohol (ethanol) administration and the MRS results were confirmed using biochemical total lipid analysis and histology. $\rm T\sb1$ weighted MR images acquired weekly, 48 hours post administration, demonstrated only a slight increase in overall liver intensity with CCl$\sb4$ or alcohol administration, which is consistent with previously reported results. The MR images were able to detect nodules resulting from CCl$\sb4$+PLD induced cirrhosis as hypointense regions, also consistent with previous reports. Localized in vivo water and lipid proton $\rm T\sb1$ relaxation time measurements were performed and demonstrated no statistically significant trends for either agent. In vivo proton spectra were also acquired using stimulated echo techniques to quantitatively follow the changes in liver lipid content. The changes in liver lipid content observed using MRS were verified by total lipid analysis using the Folch technique and histology. The in vivo $\rm T\sb1$ and lipid quantification data str inconsistent with the previous hypothesis that the changes in $\rm T\sb1$ weighted images were the result of increased "free" water content and, therefore, increased water $\rm T\sb1$ relaxation times. These data indicate that the long term changes are more likely the result of changes in lipid content. The data are also shown to agree with the accepted hypothesis that the time course and mechanism of fatty infiltration are different for CCl$\sb4$ and alcohol. The hypothesis that the lipids resulting from either protocol are from the same lipid fraction(s), presumably triglycerides, is also supported. And lastly, on the basis of MR images and quantitative MRS lipid information, it was shown that cirrhosis could be distinguished from fatty infiltration.

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Recommended Citation

Hazle, John Darwin, "In vivo magnetic resonance studies of experimental liver disease: Carbon tetrachloride hepatotoxicity and alcohol-induced fatty liver in rat" (1989). Texas Medical Center Dissertations (via ProQuest). AAI9016340.