Noninvasive Differentiation between Hepatic Steatosis and Steatohepatitis with MR Imaging Enhanced with USPIOs in Patients with Nonalcoholic Fatty Liver Disease: A Proof-of-Concept Study.
OBJECTIVE
To (a) study the optimal timing and dosing for ultrasmall superparamagnetic iron oxide particle (USPIO)-enhanced magnetic resonance (MR) imaging of the liver in nonalcoholic fatty liver disease, (b) evaluate whether hepatic USPIO uptake is decreased in nonalcoholic steatohepatitis (NASH), and (c) study the diagnostic accuracy of USPIO-enhanced MR imaging to distinguish between NASH and simple steatosis.


METHODS
This prospective study was approved by the local institutional review board, and informed consent was obtained from all patients. Quantitative R2* MR imaging of the liver was performed at baseline and 72 hours after USPIO administration in patients with biopsy-proven NASH (n = 13), hepatic steatosis without NASH (n = 11), and healthy control subjects (n = 9). The hepatic USPIO uptake in the liver was quantified by the difference in R2* (ΔR2*) between the contrast material-enhanced images and baseline images. Between-group differences in mean ΔR2* were tested with the Student t test, and diagnostic accuracy was tested by calculating the area under the receiver operating characteristic curve.


RESULTS
Patients with NASH had a significantly lower ΔR2* 72 hours after USPIO administration when compared with patients who had simple steatosis and healthy control subjects (mean ± standard deviation for patients with NASH, 37.0 sec(-1) ± 16.1; patients with simple steatosis, 61.0 sec(-1) ± 17.3; and healthy control subjects, 72.2 sec(-1) ± 22.0; P = .006 for NASH vs simple steatosis; P < .001 for NASH vs healthy control subjects). The area under the receiver operating characteristic curve to distinguish NASH from simple steatosis was 0.87 (95% confidence interval: 0.72, 1.00).


CONCLUSIONS
This proof-of-concept study provides clues that hepatic USPIO uptake in patients with NASH is decreased and that USPIO MR imaging can be used to differentiate NASH from simple steatosis.
From the Departments of Vascular Medicine (L.P.S., M.D.P., W.H.N., M.N., E.S.S.), Radiology (B.F.C., J.H.R., J.S., A.J.N.), Pathology (J.V.), and Gastroenterology & Hepatology (U.H.B.), Academic Medical Center, Meijbergdreef 9, Room F4-140, 1105 AZ Amsterdam, the Netherlands.
Loek P
LP
Smits
From the Departments of Vascular Medicine (L.P.S., M.D.P., W.H.N., M.N., E.S.S.), Radiology (B.F.C., J.H.R., J.S., A.J.N.), Pathology (J.V.), and Gastroenterology & Hepatology (U.H.B.), Academic Medical Center, Meijbergdreef 9, Room F4-140, 1105 AZ Amsterdam, the Netherlands.
Bram F
BF
Coolen
From the Departments of Vascular Medicine (L.P.S., M.D.P., W.H.N., M.N., E.S.S.), Radiology (B.F.C., J.H.R., J.S., A.J.N.), Pathology (J.V.), and Gastroenterology & Hepatology (U.H.B.), Academic Medical Center, Meijbergdreef 9, Room F4-140, 1105 AZ Amsterdam, the Netherlands.
Maria D
MD
Panno
From the Departments of Vascular Medicine (L.P.S., M.D.P., W.H.N., M.N., E.S.S.), Radiology (B.F.C., J.H.R., J.S., A.J.N.), Pathology (J.V.), and Gastroenterology & Hepatology (U.H.B.), Academic Medical Center, Meijbergdreef 9, Room F4-140, 1105 AZ Amsterdam, the Netherlands.
Jurgen H
JH
Runge
From the Departments of Vascular Medicine (L.P.S., M.D.P., W.H.N., M.N., E.S.S.), Radiology (B.F.C., J.H.R., J.S., A.J.N.), Pathology (J.V.), and Gastroenterology & Hepatology (U.H.B.), Academic Medical Center, Meijbergdreef 9, Room F4-140, 1105 AZ Amsterdam, the Netherlands.
Wouter H
WH
Nijhof
From the Departments of Vascular Medicine (L.P.S., M.D.P., W.H.N., M.N., E.S.S.), Radiology (B.F.C., J.H.R., J.S., A.J.N.), Pathology (J.V.), and Gastroenterology & Hepatology (U.H.B.), Academic Medical Center, Meijbergdreef 9, Room F4-140, 1105 AZ Amsterdam, the Netherlands.
Joanne
J
Verheij
From the Departments of Vascular Medicine (L.P.S., M.D.P., W.H.N., M.N., E.S.S.), Radiology (B.F.C., J.H.R., J.S., A.J.N.), Pathology (J.V.), and Gastroenterology & Hepatology (U.H.B.), Academic Medical Center, Meijbergdreef 9, Room F4-140, 1105 AZ Amsterdam, the Netherlands.
Max
M
Nieuwdorp
From the Departments of Vascular Medicine (L.P.S., M.D.P., W.H.N., M.N., E.S.S.), Radiology (B.F.C., J.H.R., J.S., A.J.N.), Pathology (J.V.), and Gastroenterology & Hepatology (U.H.B.), Academic Medical Center, Meijbergdreef 9, Room F4-140, 1105 AZ Amsterdam, the Netherlands.
Jaap
J
Stoker
From the Departments of Vascular Medicine (L.P.S., M.D.P., W.H.N., M.N., E.S.S.), Radiology (B.F.C., J.H.R., J.S., A.J.N.), Pathology (J.V.), and Gastroenterology & Hepatology (U.H.B.), Academic Medical Center, Meijbergdreef 9, Room F4-140, 1105 AZ Amsterdam, the Netherlands.
Ulrich H
UH
Beuers
From the Departments of Vascular Medicine (L.P.S., M.D.P., W.H.N., M.N., E.S.S.), Radiology (B.F.C., J.H.R., J.S., A.J.N.), Pathology (J.V.), and Gastroenterology & Hepatology (U.H.B.), Academic Medical Center, Meijbergdreef 9, Room F4-140, 1105 AZ Amsterdam, the Netherlands.
Aart J
AJ
Nederveen
From the Departments of Vascular Medicine (L.P.S., M.D.P., W.H.N., M.N., E.S.S.), Radiology (B.F.C., J.H.R., J.S., A.J.N.), Pathology (J.V.), and Gastroenterology & Hepatology (U.H.B.), Academic Medical Center, Meijbergdreef 9, Room F4-140, 1105 AZ Amsterdam, the Netherlands.
Erik S
ES
Stroes
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003287:Contrast Media / Q000008:administration & dosage*; D003911:Dextrans / Q000008:administration & dosage*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000008:administration & dosage*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000473:pathology*; D011446:Prospective Studies
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; C097921:ferumoxtran-10