Which is more favorable surrogate marker to predict liver fibrosis on Gd-EOB-DTPA enhanced MRI at 1.5T, ADC value on diffusion weighted imaging or quantitative enhancement ratio?

Subject

Eighty-three patients (age: mean 67.0; men: female= 59: 24) with surgically resected 99 hepatic lesions were enrolled in this study.

MRI acquisition

MR images were obtained by using a 1.5 T MRI system (Avanto; Siemens, Erlangen, German) before surgery. The respiratory-triggered diffusion weighted imaging (DWI) parameters were as follows: TR/TE, 3000/71 msec; matrix, 128 × 128; slice thickness, 6 mm; intersection gap, 1 mm; 6 signals acquired; FOV, 40 cm; 30 sections in 5-8 min; chemical shift selective method; PAT factor 2 with the GRAPPA algorithm; b factor, 100 and 800 s/mm2. The DWI motion-probing gradient pulses were placed in 3 orthogonal axes, and DWI was reconstructed by combining these 3 images. Chemical shift selective fat suppression was preferred over inversion-recovery fat suppression. The hepatobiliary phase on Gd-EOB-DTPA-enhanced MRI was performed with a T1-weighted 3D gradient echo sequence with fat saturation and volumetric interpolated breath-hold examination (VIBE; Siemens). The sequence parameters were as follows: repetition time/echo time (TR/TE), 3.96/1.79 msec; slice thickness, 2 mm; field of view, 400 mm; effective matrix size, 320 × 70%; signal average, 1; acquisition time, 19 s; k-space trajectory, linear filling.

Analysis

A radiologist set five regions of interests (ROIs) as follows (Fig. 1); 1st ROI was set on ADC map at a distance of 5-10 mm from the tumor where the pathologist evaluated the fibrosis grade, 2nd ROI was set at same location as 1st on hepatobiliary phase, 3rd and 4th ROIs were set at erector spine, and spleen on hepatobiliary phase, respectively and 5th ROI was set at same location as 1st on pre enhanced MRI. Liver-to-muscle ratio (LMR), liver-to-spleen ratio (LSR) and contrast enhancement ratio (CEI) were calculated as follows:

LMR = signal intensity (SI) of 2nd ROI / SI of 3rd ROI

LSR = SI of 2nd ROI / SI of 4th ROI

CEI = SI of 2nd ROI / SI of 5th ROI

Fibrosis grade was classified using New Inuyama Classification. Fat deposition was also pathologically evaluated. The correlation between fibrosis grade, and fat deposition with ADC, LMR, LSR and CEI were evaluated. We used One-way analysis of variance (ANOVA), and Tukey post hoc comparison to analyze correlation between each parameters and histological grade. And we used unpaired t-test to analyze correlation between low stage fibrosis (F0, F1, and F2) and high stage fibrosis (F3 and F4) in each parameter. A p value less than .05 was considered to indicate statistical significance

The patients classified into F0, 1, 2, 3 and 4 were 14, 53, 15, 6 and 11, respectively. ADC value showed no significant difference among fibrosis grades (p=0.320). LMR. LSR and CEI showed significant differences (p<0.001, p=0.008 and 0.013, respectively) (Table 1). LMR and CEI showed significant differences between high stage fibrosis group and low stage fibrosis group (p<0.01 and p=0.04), while LSR did not show significant difference (p=0.053) (Table 2). To diagnose low grade fibrosis, LMR yielded with 82.4% sensitivity and 75.6% specificity (cut-off value >2.80 ), and CEI yielded with 76.5% sensitivity and 75.6% specificity (cut-off value >2.05 ) (Fig. 2).LMR did show best correlation with fibrosis grade, while ADC showed no correlation with fibrosis grade. However, several papers reported that the significant correlation was observed between ADC value and the liver fibrosis grade ¹⁾ On the other hand, a few paper reported no correlation ²⁾ The reason why there was no correlation between liver fibrosis and ADC value may be direct comparison in this study (the region where ADC value was measured and area of pathological evaluation was almost same). This method was different from the previous many reports. Comparison at the different area may be included bias (portal perfusion, etc.). Furthermore, this study had advantage of enough resected specimen could be used for pathological evaluation ^{3, 4)}. Underlying condition such as fatty infiltration ⁵⁾, iron deposition, etc. might contribute the ADC in this study.LMR was best surrogate parameters to distinguish high stage fibrosis from low stage fibrosis, and they were available in routine clinical examination.