Home The Possibility of Differentiation between Nonalcoholic Steatohepatitis and Fatty Liver in Rabbits on Gd-EOB-DTPA-enhanced Open-type MRI Scans
Post
Cancel

The Possibility of Differentiation between Nonalcoholic Steatohepatitis and Fatty Liver in Rabbits on Gd-EOB-DTPA-enhanced Open-type MRI Scans

Posted Mar 31, 2011 Updated Apr 10, 2023
By Akinaga Sonoda MD , Norihisa Nitta MD , Shinich Ohta MD , Ayumi Nitta-Seko MD , Keiko Tsuchiya MD , Yukihiro Nagatani MD , Kenichi Mukaisho MD , Masashi Takahashi MD , Kiyoshi Murata MD
5 min read

Rationale and Objectives

We used rabbits to investigate the possibility of differentiating between nonalcoholic steatohepatitis (NASH) and fatty liver (FL) on scans acquired by open-type‒ and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)‒enhanced magnetic resonance imaging (MRI).

Materials and Methods

We divided 15 adult rabbits into three equal groups; they received standard (control group), high-fat (FL) content (FL group), or choline-deficient chow (NASH group). With the animals under general anesthesia we acquired scans on an open 0.3-Tesla MRI system. Signal intensity (SI) was measured before and after contrast administration and defined as SI-pre and SI-post, respectively. Relative SI enhancement (Sr) was calculated using the equation: Sr = (average of three SI-post- minus average of three SI values in no-signal fields)/(average of three SI-pre- minus average of three SI values in no-signal fields) × 100. Maximum Sr (Srmax), the time (in seconds) required to reach Srmax (Tmax), and the difference between Srmax and Sr at 30 minutes (Sr 30m R) were analyzed.

Results

Srmax was significantly higher in the NASH rabbits than the other two groups ( P < .05).

Conclusions

In rabbits, the Srmax value made it possible to differentiate NASH from normal and fatty liver.

Nonalcoholic steatohepatitis (NASH) was first named by Ludwig et al to describe biopsy findings in patients with no history of significant alcohol consumption . In autopsy studies performed in the United States, approximately 20% of liver specimens revealed hepatic steatosis and about 3% manifested NASH. NASH has also been reported in children . Approximately 1% of hepatic steatosis advances to NASH and 40% of NASH is considered fibrotic; 3%–10% of cases advance to liver cirrhosis . Therefore, early detection and treatment are important . At present, there are no biochemical diagnostic tests for NASH and biochemical studies may return normal results even in patients with serious liver disease. An unequivocal clinical diagnosis requires liver biopsy .

Criteria for the evaluation of hepatic magnetic resonance imaging (MRI) scans have not been established . In their rat experiments, Tsuda et al used a 1.5 Tesla MRI scanner and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), a hepatobiliary contrast agent in rats, to differentiate between NASH and fatty liver (FL). Because different species and MRI scans acquired at different field strengths may affect the results, we subjected rabbits with NASH induced by a choline-deficient diet, rabbits with FL induced by a high-fat diet, and rabbits fed a standard diet to open-type MRI scanning.

Material and methods

Get Radiology Tree app to read full this article<

Rabbit NASH Model

Get Radiology Tree app to read full this article<

MRI

Get Radiology Tree app to read full this article<

Data Analysis

Get Radiology Tree app to read full this article<

Statistical Analysis

Get Radiology Tree app to read full this article<

Histological Analysis

Get Radiology Tree app to read full this article<

Results

MRI

Get Radiology Tree app to read full this article<

Figure 1, Magnetic resonance imaging scans obtained in nonalcoholic steatohepatitis (NASH) (a-d) , fatty liver (FL) (e-h) , and control rabbits (i-l) before (a, e, i) , and 90 seconds (b, f, j) and 4- (c, g, h) and 30 minutes (d, h, j) after gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) administration. (a) NASH precontrast, (b) NASH 90 seconds postcontrast, (c) NASH 4 minutes postcontrast, (d) NASH 30 minutes postcontrast, (e) FL precontrast, (f) FL 90 seconds postcontrast, (g) FL 4 minutes postcontrast, (h) FL 30 minutes postcontrast, (i) control precontrast, (j) control 90 seconds postcontrast, (k) control 4 minutes postcontrast, (l) control 30 minutes postcontrast. Note the high signal in the vessel at 4 minutes after contrast administration. Contrast inflow into the gallbladder is seen at 30 minutes after the start of contrast administration. There was no obvious signal change in the liver parenchyma.

Get Radiology Tree app to read full this article<

Sr of the Liver Parenchyma

Get Radiology Tree app to read full this article<

Figure 2, Changes over time in the relative signal intensity enhancement (Sr) value in the liver parenchyma. In nonalcoholic steatohepatitis (NASH), fatty liver (FL), and control rabbits, the signal in the liver parenchyma peaked within 5 minutes of contrast administration.

Figure 3, Time (in seconds) required to reach maximum relative signal intensity enhancement (Srmax) (Tmax), difference between Srmax and Sr at 30 minutes (Sr 30m R), and Srmax values in control, nonalcoholic steatohepatitis (NASH), and fatty liver (FL) rabbits. (a) There was a strong trend for Tmax to be longer in the NASH group than the controls (225–1270 vs. 90–180 seconds, P = 0.076); in FL rabbits it was 135–270 seconds ( P = 0.120). (b) Srmax was significantly longer in NASH rabbits than the other groups ( P < 0.01). (c) The Sr 30m R value was not significantly different among the three groups of rabbits (control 95.43%, FL group 97.23%, NASH group 97.66%).

Get Radiology Tree app to read full this article<

Histological Analysis

Get Radiology Tree app to read full this article<

Figure 4, Nonalcoholic fatty liver disease (NAFLD) activity score and nonalcoholic steatohepatitis (NASH) stage. The NAFLD activity score was not anomalous in the control rabbits. It was 2–4 in FL rabbits. None of these groups had a score of 5, used as the standard for NASH. NASH rabbits satisfied the criteria set for the NAFLD activity score and the NASH stage.

Get Radiology Tree app to read full this article<

Discussion

Get Radiology Tree app to read full this article<

Get Radiology Tree app to read full this article<

Get Radiology Tree app to read full this article<

Get Radiology Tree app to read full this article<

Get Radiology Tree app to read full this article<

Get Radiology Tree app to read full this article<

References

  • 1. Ludwig J., Viggiano T.R., McGill D.B., et. al.: Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 1980; 55: pp. 434-438.

  • 2. Portincasa P., Grattagliano I., Palmieri V.O., et. al.: The emerging problem of nonalcoholic steatohepatitis (NASH). Rom J Gastroenterol 2005; 14: pp. 43-51.

  • 3. Wanless I.R., Lentz J.S.: Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Hepatology 1990; 12: pp. 1106-1110.

  • 4. Lall C.G., Aisen A.M., Bansal N., et. al.: Nonalcoholic fatty liver disease. AJR Am J Roentgenol 2008; 190: pp. 993-1002.

  • 5. Powell E.E., Cooksley W.G., Hanson R., et. al.: The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology 1990; 11: pp. 74-80.

  • 6. Evans C.D., Oien K.A., MacSween R.N., et. al.: Non-alcoholic steatohepatitis: a common cause of progressive chronic liver injury?. J Clin Pathol 2002; 55: pp. 689-692.

  • 7. Reid A.E.: Nonalcoholic steatohepatitis. Gastroenterology 2001; 121: pp. 710-723.

  • 8. Tsuda N., Okada M., Murakami T.: Potential of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for differential diagnosis of nonalcoholic steatohepatitis and fatty liver in rats using magnetic resonance imaging. Invest Radiol 2007; 42: pp. 242-247.

  • 9. Kleiner D.E., Brunt E.M., Van Natta M., et. al.: Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41: pp. 1313-1321.

  • 10. Brunt E.M.: Nonalcoholic steatohepatitis. Semin Liver Dis 2004; 24: pp. 3-20.

  • 11. Schwenzer N.F., Springer F., Schraml C., et. al.: Non-invasive assessment and quantification of liver steatosis by ultrasound, computed tomography and magnetic resonance. J Hepatol 2009; 51: pp. 433-445.

  • 12. d’Assignies G., Ruel M., Khiat A., et. al.: Noninvasive quantitation of human liver steatosis using magnetic resonance and bioassay methods. Eur Radiol 2009; 19: pp. 2033-2040.

  • 13. DeLeo M.J., Gounis M.J., Hong B., et. al.: Carotid artery brain aneurysm model: in vivo molecular enzyme-specific MR imaging of active inflammation in a pilot study. Radiology 2009; 252: pp. 696-703.

  • 14. Keilholz S.D., Bozlar U., Fujiwara N., et. al.: MR diagnosis of a pulmonary embolism: comparison of P792 and Gd-DOTA for first-pass perfusion MRI and contrast-enhanced 3D MRA in a rabbit model. Korean J Radiol 2009; 10: pp. 447-454.

Academic Radiology, Volume 18, Issue 4
Journals General Radiology
This post is licensed under CC BY 4.0 by the author.
Recently Updated
Contents