Carbogen gas-challenge BOLD MR imaging in a rat model of diethylnitrosamine-induced liver fibrosis.
OBJECTIVE
To investigate the relationship between gas-challenge blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging measurements and hepatic disease progression in a rat model of diethylnitrosamine (DEN)-induced liver fibrosis.


METHODS
The institutional animal care and use committee approved all experiments. Liver fibrosis was induced in 27 male Wistar rats by means of weekly oral gavage with 5 mL of 1.5% DEN solution per kilogram of body weight for 3-11 weeks, which produced varying degrees of liver fibrosis. Eight rats developed nonsubstantial fibrosis; eight rats, substantial fibrosis; and 15 rats, cirrhosis. Four nontreated healthy rats served as controls. Multiple-gradient-echo MR images were acquired in the rats at steady-state normoxia and hyperoxia and then during dynamic gas challenges. The change in R2* (DeltaR2*) during the gas challenge and the ratio of number of activated voxels to total number of voxels in the liver were quantified. Masson trichrome staining of liver tissue was used to identify collagen tissue. Liver fibrosis was assessed by using a semiquantitative METAVIR scoring system and quantitative analysis of the percentage of liver fibrosis. Hepatic hemodynamic responses at BOLD MR imaging were compared across the fibrosis stages at independent-sample t test and linear regression analyses.


RESULTS
DeltaR2* was well correlated with gas-challenge interval. Mean DeltaR2* decreased during liver fibrosis progression, from 19.60 sec(-1) +/- 4.47 (standard deviation) in animals without substantial fibrosis to 14.02 sec(-1) +/- 2.88 and 6.26 sec(-1) +/- 7.40 in animals with substantial fibrosis and cirrhosis, respectively (P = .006 for rats without vs rats with substantial fibrosis, P = .001 for rats with substantial fibrosis vs rats with cirrhosis, P < .001 for rats without substantial fibrosis vs rats with cirrhosis). Mean DeltaR2* (r = -0.773) and liver activation (r = -0.691) were inversely correlated with liver fibrosis (P < .001).


CONCLUSIONS
Carbogen gas-challenge BOLD MR imaging can depict hepatic hemodynamic alterations during the progression of fibrosis and has the potential to serve as a noninvasive, nonenhanced imaging method for liver fibrosis diagnosis and staging.
Jin
Ning
N
Department of Radiology, Northwestern University, 737 N Michigan Ave, Suite 1600, Chicago, IL 60611, USA.
Deng
Jie
J
Chadashvili
Tamuna
T
Zhang
Yue
Y
Guo
Yang
Y
Zhang
Zhuoli
Z
Yang
Guang-Yu
GY
Omary
Reed A
RA
Larson
Andrew C
AC
D000704:Analysis of Variance; D000818:Animals; D002245:Carbon Dioxide / Q000008:administration & dosage*; D004052:Diethylnitrosamine; D018450:Disease Progression; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008103:Liver Cirrhosis / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D010100:Oxygen / Q000008:administration & dosage*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar
D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; D004052:Diethylnitrosamine; C011700:carbogen; D010100:Oxygen