SUPPLEMENTARYMATERIAL:

Pathology scores / Grade 1 / Grade 2 / Grade 3
Inflammation / 14 (31.8%) / 14 (31.8%) / 16 (36.4%)
Fibrosis / 3 (6.8%) / 25 (56.8%) / 16 (36.4%)
Trichromic / 13 (29.6%) / 13 (29.6%) / 18 (40.8%)
Edema / 13 (29.6%) / 22 (50%) / 9 (20.4%)
Vessel score / 11 (25%) / 13 (29.6%) / 20 (45.4%)

Supplementary table 1. Pathological grading of inflammation, fibrosis, trichromic, edema and vessel score of CD lesions. Grading of inflammation was obtained from the most severe pathological areas, using H&E stain. Fibrosis score measured the severity of fibrosis and was performed using a semi-quantitative evaluation using H&E stain combined with the Masson’s trichrome stain. The “trichromic score”, specifically used to quantify the degree of collagen deposition was performed using trichromic stain. Vessels were quantitatively scored (number of vessels in a x100 optic microscopic field; Olympus BX41).

Fibrosis grade 1 and 2* (n=20) / Fibrosis grade 3*
(n=15) / p
High signal intensity on T2 / 14 (70%) / 11 (73.3%) / 1
Mucosal hyperenhancement / 15 (75%) / 13 (86.6%) / 0.67
Enhancement 70 seconds:
Homogeneous
Layered
Mucosal only / 5 (25%)
10 (50%)
5(25%) / 1 (6.6%)
5 (33.3%)
9 (60%) / 0.11
Enhancement 7 minutes:
Homogeneous
Layered
Mucosal only / 9 (45%)
7 (35%)
4 (20%) / 14 (93.3%)
1 (6.6%)
0 (0%) / <0.01
Progression of enhancement:
Stable over time
Progression over time / 15 (75%)
5 (25%) / 2 (13.3%)
13 (86.6%) / <0.01
Upstream dilatation / 16 (80%) / 11 (73.3%) / 0.95
Ulcerations / 11 (55%) / 10 (66.7%) / 0.73
Blurredmargins / 10 (50%) / 7 (46.6%) / 1
Wall thickness (mm) / 8 (7; 9) / 9 (8.53; 10.1) / 0.16
SI submucosa 70 seconds / 398.5 (339.2; 542) / 359.5 (285; 423.8) / 0.05
SI submucosa 7 minutes / 475.5 (404; 623.8) / 491 (375.5; 573) / 0.46
Enhancement gain 70 seconds-7 minutes (%) / 14 (12.5; 18.2) / 35 (31; 46.5) / <0.01

Supplementary table 2. Association between MRI findings and pathological fibrosis score on segments with luminal stenosis. *Grade 1:mild or non-active CD ; grade 2: moderately active CD; grade 3: severely active CD. Grade 1 and 2 were grouped because there was only 1 segment with stenosis and fibrosis Grade 1. SI: signal intensity

Variables / Univariate model / Multivariate model
OR (95% CI) / Wald test p / OR (95% CI) / Wald test p
High signal intensity T2 / 1 (0.25-4.5) / 1.00 / --- / ---
Mucosal hyperenhancement / 1.5 (0.2-11.6) / 0.64 / --- / ---
Progression of enhancement / <0.01 / --- / ---
Stable over time / reference
Progression over time / 32.2 (6.5-254)
Enhancement 70’’ / 0.15 / --- / ---
Layered/ Mucosal only / reference
Homogeneous / 0.2 (0.01-1.3)
Enhancement 7’ / <0.01 / 0.02
Layered/ Mucosal only / reference / reference
Homogeneous / 23.2 (3.9-450) / 475.8 (9.2-6.8·105)
Luminal stenosis / 6 (1-117.6) / 0.11 / --- / ---
Upstream dilatation / 1.2 (0.3-4.8) / 0.76 / --- / ---
Ulcerations / 1.4 (0.4-5.6) / 0.60 / --- / ---
Blurred margins / 0.5 (0.1-1.7) / 0.28 / --- / ---
Wall thickness (mm) / 1.4 (1.0-2.0) / 0.09 / --- / ---
SI submucosa 70’’ / 1.0 (1.0-1.0) / 0.11 / --- / ---
SI submucosa 7’ / 1.0 (1.0-1.0) / 0.80 / --- / ---
Percentage of enhancement gain 70 seconds-7 minutes / 1.2 (1.1-1.4) / <0.01 / 1.4 (1.2-2) / <0.01

Supplementary table 3. Univariate and multivariate logistic regression of the MRI variables with the binary fibrosis score; where 0 indicates none or mild to moderate fibrosis (fibrosis scores 1, 2) and 1 marked fibrosis (fibrosis score 3).

Variables / Univariate model / Multivariate model
OR (95% CI) / Wald test p / OR (95% CI) / Wald test p
High signal intensity T2 / 6.5 (1.5-31.6) / 0.01 / 6.0 (0.8-62.8) / 0.1
Mucosal hyperenhancement / 7.8 (1.4-61.4) / 0.03 / --- / ---
Progression of enhancement / 0.98 / --- / ---
Stable over time / reference
Progression over time / 1.0 (0.3-3.8)
Enhancement 70’’ / 0.65 / --- / ---
Layered/ Mucosal only / reference
Homogeneous / 1.5 (0.3-11.3)
Enhancement 7’ / 0.40 / 0.1
Layered/ Mucosal only / reference / reference
Homogeneous / 1.7 (0.5-6.4) / 4.6 (0.9-37.4)
Luminal stenosis / 0.2 (0.01-1.3) / 0.16 / --- / ---
Upstream dilatation / 0.7 (0.16-2.6) / 0.60 / --- / ---
Ulcerations / 10 (2.5-48.4) / <0.01 / 12.3 (2.4-96.9) / <0.01
Blurred margins / 5 (1.3-22.2) / 0.02 / --- / ---
Wall thickness (mm) / 1.5 (1.1-2.3) / 0.02 / --- / ---
SI submucosa 70’’ / 1.0 (1.0-1.0) / 0.51 / --- / ---
SI submucosa 7’ / 1.0 (1.0-1.0) / 0.48 / --- / ---
Percentage of enhancement gain 70 seconds-7 minutes / 3.0 (0.05-340) / 0.62 / --- / ---

Supplementary table 4. Univariate and multivariate logistic regression of the MRI variables with the binary inflammation score; where 0 indicates absent/mild inflammation (inflammation score 1) and 1 indicates to moderate/severe inflammation (inflammation scores 2, 3). SI: signal intensity.

PROPOSED FIBRO-INFLAMMATION CLASSIFICATION / Low
(n=10) / Only severeInflammation
(n=18) / Only markedfibrosis (n=4) / High
(n=12) / p
High signal on T2 / 6 (60%) / 15 (83.3%) / 1 (33.3%) / 11 (91.6%) / 0.02
Mucosal hyperenhancement / 7 (70%) / 16 (88.9%) / 2 (50%) / 12 (100%) / 0.04
Enhancement 70 seconds:
Homogeneous
Layered
Mucosal only / 2 (20%)
4 (40%)
4 (40%) / 5 (27.7%)
6 (33.3%)
7 (39%) / 0 (0%)
1 (25%)
3 (75%) / 1 (8%)
5 (42%)
6 (50%) / 0.76
Enhancement 7 minutes:
Homogeneous
Layered
Mucosal only / 3 (30%)
3 (30%)
4 (40%) / 8 (44.4%)
4 (22.2%)
6 (33.3%) / 4 (100%)
0 (0%)
0 (0%) / 11 (92%)
1 (8%)
0 (0%) / 0.03
Progression of enhancement:
Progression over time
Stable over time / 2 (20%)
8 (80%) / 3 (16.7%)
15 (83.3%) / 4 (100%)
0 (0%) / 10 (83.3%)
2 (16.7%) / <0.01
Stenosis at MR / 9 (90%) / 11 (61.1%) / 4 (100%) / 11 (91.7%) / 0.08
Upstream dilatation / 7 (70%) / 11 (61.1%) / 3 (75%) / 8 (66.6%) / 0.97
Ulcers / 3 (30%) / 14 (77.8%) / 1 (25%) / 10 (83.3%) / 0.01
Blurred margins / 4 (40%) / 13 (72.2%) / 0 (0%) / 7 (58.3%) / 0.05
Wall thickness (mm) / 6.75 (5.4; 8.1) / 8.7 (7.55; 9.75) / 8.8 (7.7; 9) / 9.55 (8.83; 10.55) / 0.06
SI submucosa 70 seconds / 342 (323.5; 400.2) / 424.5 (352; 522) / 386.5 (318.5; 394.2) / 340.5 (289; 435) / 0.35
SI submucosa 7 minutes / 421 (372; 463.2) / 500.5 (386.2; 590.8) / 522.5 (427; 540) / 482.5 (392.2; 569.8) / 0.80
Enhancement gain submucosa 70 seconds – 7 minutes (%) / 14 (14; 17.8) / 13 (11; 14) / 31.5 (27.5; 39) / 36 (31.8; 45.8) / <0.01

Supplementary table 5. Proposed new classification based on a combination of coexisting histological inflammation and fibrosis, and its association with MRI.

SI: signal intensity; Low: low degree of both inflammation (inflammation score grade 1) and fibrosis (fibrosis score grade 1-2); high: high degree of both inflammation (inflammation score grade 2-3) and fibrosis (fibrosis score grade 3); only high fibrosis: high degree of fibrosis (fibrosis score grade 2) but low degree of inflammation (inflammation score grade 1); only high inflammation: high degree of inflammation (inflammation score grade 2-3) but low degree of fibrosis (fibrosis score grade 1-2).SI: signal intensity.

Supplementary figure1. Flow chart of the included patients.