SUPPLEMENTARY MATERIAL

Impact of hepatobiliary phase liver MRI versus Contrast Enhanced Ultrasound after an

inconclusive extracellular based gadolinium-contrast enhanced MRI for the diagnosis of

benign hepatocellular tumors

1 TABLE OF CONTENTS

Page 3: Supplementary Table 1: Typical FNH diagnostic criteria on CE-MRI

Page 4: Supplementary Table 2: Atypical features for FNH identified on CE-MRI

Page 5: Supplementary Table 3: MRI sequence parameters

Page 6: Supplementary Table 4: FNH diagnostic criteria on HBP-MRI and CEUS

Page 7: Supplementary Table 5: Inter observer concordance of SET-1 and SET-2.

2 Supplementary Table 1: Typical FNH diagnostic criteria on CE-MRI

General aspect Lobulated No capsule

Signal Homogeneous (except the central scar)

Iso or faint hypo T1 and hyper T2

Central scar Hyper T2

Hypo T1

Enhancing on venous phase

Enhancement Early (arterial phase), Intense

No wash-out

3 Supplementary Table 2. Atypical features for FNH identified on CE-MRI

All lesions FNH HCA N = 83 N = 46 N = 37

Atypical or absence of central scar including low T2 SI or absent 74 (89.1%) 41 (89.1%) 33 (89.2%) enhancement on delayed phase

Other atypical features including at least heterogeneous SI or High 27 (32.5%) 8 (17.4%) 19 (51.4%) T2 SI or High T1 SI (fat or hemorrhage) or capsule

Absent or faint arterial 31 (37.3%) 8 (17.4%) 23 (62.2%) enhancement

Results are expressed as number of lesions and percentages (%) SI is for signal intensity

4 Supplementary Table 3. MRI sequence parameters

Identical T1 IP, T1 OP, VIBE and FS T1-WI were performed before Gd-BOPTA and

repeated on delayed HBP imaging.

Slice Echo TR TE Flip Sequences thickness train (ms) (ms) angle (α) (mm) length GRE IP and OP T1-WI 121 2.38-4.76 70° 5 NA

Breath-hold FS TSE T2-WI 2400 86 150° 5 23

Additional TSE T2-WI 2400 138 150° 5 23

Breath-hold HASTE T2-WI 600 74 150° 3 156

Dynamic breath-hold 3D VIBE T1-WI 3.31 1.25 15° 3 NA

FS T1-WI 117 2.78 70° 5 NA

TR = repetition time, TE = echo time, α = flip angle, T1 or T2-WI = T1 or T2-weighted imaging, GRE = gradient recalled echo, IP = in phase, OP = out-of-phase, FS = fat- suppressed, TSE = turbo spin echo, HASTE = half-Fourier acquisition single-shot turbo spin- echo, VIBE = volumetric interpolated breath-hold examination, 3D = three-dimensional, NA = Not Applicable

5 Supplementary Table 4: FNH diagnostic criteria on HBP-MRI and CEUS

HBP-MRI CEUS (Using hepatospecific contrast agents)

Contrast uptake of the tumor on delayed phase Early intense, centrifugal enhancement

(in comparison with pre-injection images) Central artery

- Homogeneous uptake Spoked-wheel pattern

- Heterogeneous uptake No wash-out

- Peripheral rim (“Hypointense with ring type Homogenous on delayed phase (except the

enhancement”) [1] central scar)

1 van Kessel CS, de Boer E, ten Kate FJ, Brosens LA, Veldhuis WB, van Leeuwen MS (2013) Focal nodular hyperplasia: hepatobiliary enhancement patterns on gadoxetic-acid contrast-enhanced MRI. Abdom Imaging 38:490-501

6 Supplementary Table 5: Inter observer concordance of SET-1 and SET-2.

SET-1 SET-2 CE-MRI + HBP-MRI CE-MRI + CEUS

All lesions n = 83 (46 FNH + 37 HCA)

wκ (95%CI) 0.83 (0.77-0.90) 0.72 (0.65-0.80)

Lesions ≤ 35 mm n = 58 (36 FNH + 22 HCA)

wκ (95%CI) 0.80 (0.71-0.89) 0.73 (0.64-0.82)

Lesions > 35 mm n = 25 (10 FNH + 15 HCA)

wκ (95%CI) 0.9 (0.82-0.98) 0.64 (0.47-0.81)

wκ for Cohen’s quadratic weighted kappa coefficient and 95% confidence intervals are in parenthesis

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