Baseline multimodal clinical-radiomics-pathomics model predicts mucosal healing in Crohn’s disease after infliximab therapy

Table 1 Spectral computed tomography enterography scanning parameters

Manufacturer	General-electric	General-electric
Scanner model	Revolution CT	Discovery CT750
Sequence	Axial	Axial
Gantry rotation time (second)	0.3	0.3
Tube voltage (kV)	80-140	80-140
Tube current (mA)	150-300	150-300
Detector collimation (mm)	256 × 0.625	64 × 0.625
Matrix	512 × 512	512 × 512
Pitch	1.375:1	1.375:1
Slice thickness (mm)	5.0	5.0
Slice spacing (mm)	5.0	5.0

CT: Computed tomography.

Table 2 Clinical factors in the training and testing sets, mean ± SD

Clinical factors	Ileal (n = 102)			Ileocolonic (n = 167)
	Train (n = 71)	Test (n = 31)	P value	Train (n = 116)	Test (n = 51)	P value
Gender			0.387			0.989
Male	56	22		82	36
Female	15	9		34	15
Age at CD diagnosis (year), median IQR	28 (20-38)	30 (21-35)	0.951	24 (19-31)	27 (20-39)	0.126
Disease duration (day), median IQR	5 (2-23)	5 (1-58)	0.835	4 (2-16.75)	3 (1-15)	0.446
CRP at baseline (mg/L), median IQR	5.27 (2.17-17.06)	4.6 (1.30-19.91)	0.991	13.29 (3.19-36.30)	9.49 (4.25-25.20)	0.541
ESR at baseline (mm/hour), median IQR	16.25 (12.00-25.00)	22.00 (7.00-36.00)	0.555	30.40 (17.63-43.75)	16.00 (11.50-31.00)	< 0.001
WBC at baseline (× 109/L)	6.32 ± 2.09	6.31 ± 2.29	0.977	7.34 ± 2.23	6.46 ± 1.78	0.02
Alb at baseline (g/L)	39.66 ± 4.61	38.65 ± 4.73	0.313	37.68 ± 5.88	37.36 ± 4.79	0.74
FC at baseline (μg/g), median IQR	762.58 (394.78-1085.72)	774.94 (429.66-1137.76)	0.952	1086.68 (850.76-1335.94)	1019.20 (798.78-1263.00)	0.078
Perianal involvement			0.641			0.667
-	40	19		45	18
+	31	12		71	33
Smoking status at diagnosis			0.858			0.46
-	64	29		115	49
+	7	2		1	2
Previous steroids or immunomodulators use			0.858			0.478
0	46	21		82	32
1	21	9		26	16
2	4	1		8	3
Montreal behavior			0.355			0.811
Nonstricturing, nonpenetrating (B1)	47	20		98	41
Stricturing (B2)	7	6		11	6
Penetrating (B3)	17	5		7	4
HBI at baseline, median IQR	2 (1-4)	2 (1-5)	0.28	4 (1-6)	3 (1-5)	0.425
MH			0.871			0.971
MH	31	13		39	17
Non-MH	40	18		77	34

CD: Crohn’s disease; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate; IQR: Interquartile range; Alb: Albumin; FC: Fecal calprotectin; WBC: White blood cell; HBI: Harvey-Bradshaw index; MH: Mucosal healing.

Table 3 Positive results of univariate and multivariate logistic regression analysis for predicting mucosal healing in Crohn’s disease

Features	Ileal						Ileocolonic
	Univariate			Multivariate			Univariate			Multivariate
	OR	95%CI	P value	OR	95%CI	P value	OR	95%CI	P value	OR	95%CI	P value
Gender	0.250	0.064-0.983	0.047	0.079	0.006-1.061	0.055	1.908	0.834-4.364	0.126
Age at CD diagnosis	1.029	0.989-1.071	0.155				1.009	0.968-1.053	0.662
Disease duration (day)	1.000	0.997-1.003	0.875				1.001	0.998-1.003	0.669
CRP at baseline	1.002	0.971-1.034	0.896				1.018	1.000-1.036	0.051	1.010	0.987-1.032	0.397
ESR at baseline	0.972	0.931-1.015	0.195				1.000	0.981-1.019	0.997
WBC at baseline	0.826	0.650-1.049	0.117				1.078	0.904-1.285	0.404
Alb at baseline	0.880	0.785-0.986	0.023	0.893	0.754-1.058	0.041	0.997	0.934-1.065	0.931
FC at baseline	0.999	0.998-1.000	0.142				0.999	0.998-1.000	0.015	0.999	0.998-1.001	0.031
Perianal involvement	0.443	0.170-1.159	0.095	0.247	0.051-1.187	0.081	1.352	0.617-2.965	0.451
Smoking status at diagnosis	1.037	0.214-5.016	0.964				828993669.358	0.000	1.000
Previous steroids or immunomodulators use	3.491	1.096-11.124	0.104				1.485	0.559-3.948	0.711
Montreal behavior	1.058	0.343-3.262	0.752				3.187	0.369-27.570	0.566
HBI at baseline	0.799	0.642-0.966	0.059	0.935	0.629-1.389	0.740	1.090	0.942-1.262	0.247
Rad score				1.173	1.010-1.363	0.037				3.820	1.541-9.473	0.004
Pat score				6.135	2.282-16.492	< 0.001				3.992	2.198-7.250	< 0.001

OR: Odds ratio; CI: Confidence interval; CD: Crohn’s disease; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate; Alb: Albumin; FC: Fecal calprotectin; WBC: White blood cell; HBI: Harvey-Bradshaw index.

Table 4 Results of all models predictive ability for predicting mucosal healing in Crohn’s disease

Models		AUC (95%CI)	Accuracy	Sensitivity	Specificity	PPV	NPV
Model 1	Train	0.921 (0.860-0.982)	0.859	0.925	0.774	0.841	0.889
	Test	0.799 (0.641-0.957)	0.774	0.778	0.769	0.824	0.714
Model 2	Train	0.724 (0.616-0.833)	0.690	0.650	0.742	0.765	0.622
	Test	0.669 (0.486-0.851)	0.677	0.667	0.692	0.750	0.600
Model 3	Train	0.931 (0.874-0.989)	0.873	0.875	0.871	0.897	0.844
	Test	0.863 (0.703-1.000)	0.742	0.611	0.923	0.917	0.632
Model 4	Train	0.773 (0.656-0.889)	0.747	0.725	0.774	0.806	0.895
	Test	0.731 (0.533-0.928)	0.645	0.611	0.692	0.733	0.615
Model 5	Train	0.910 (0.845-0.975)	0.845	0.925	0.742	0.822	0.885
	Test	0.872 (0.744-1.000)	0.807	0.778	0.846	0.875	0.733
Model 6	Train	0.980 (0.955-1.000)	0.944	0.975	0.903	0.929	0.966
	Test	0.915 (0.808-1.000)	0.774	0.833	0.692	0.790	0.750
Model 7	Train	0.860 (0.778-0.942)	0.803	0.925	0.871	0.882	0.896
	Test	0.812 (0.668-0.956)	0.774	0.944	0.769	0.824	0.833
Model A	Train	0.873 (0.803-0.944)	0.819	0.805	0.846	0.912	0.659
	Test	0.827 (0.716-0.938)	0.706	0.618	0.882	0.913	0.647
Model B	Train	0.756 (0.674-0.839)	0.675	0.714	0.615	0.722	0.522
	Test	0.636 (0.518-0.754)	0.618	0.412	0.882	0.618	0.429
Model C	Train	0.951 (0.915-0.988)	0.922	0.961	0.846	0.925	0.917
	Test	0.866 (0.748-0.984)	0.804	0.882	0.647	0.833	0.733
Model D	Train	0.739 (0.636-0.842)	0.776	0.896	0.744	0.793	0.724
	Test	0.687 (0.501-0.873)	0.765	0.882	0.765	0.790	0.692
Model E	Train	0.919 (0.870-0.968)	0.836	0.792	0.923	0.953	0.784
	Test	0.819 (0.682-0.957)	0.720	0.697	0.765	0.852	0.667
Model F	Train	0.951 (0.916-0.987)	0.897	0.896	0.897	0.945	0.814
	Test	0.922 (0.843-1.000)	0.880	0.909	0.824	0.909	0.824
Model G	Train	0.950 (0.912-0.988)	0.871	0.844	0.923	0.956	0.750
	Test	0.908 (0.822-0.994)	0.820	0.788	0.882	0.929	0.682

Ileal: Model 1-radiomics, model 2-clinical, model 3-pathomics, model 4-radiomics and clinical, model 5-pathomics and clinical, model 6-radiomics and pathomics, model 7 combined. Ileocolonic: Model A-radiomics, model B-clinical, model C-pathomics, model D-radiomics and clinical, model E-pathomics and clinical, model F-radiomics and pathomics, model G-combined. CI: Confidence interval; AUC: Area under the curve; NPV: Negative predictive value; PPV: Positive predictive value.

Table 5 Delong test comparison between models of area under the curves in the testing set

Models		P value
		Clinical	Radiomics	Pathomics	Radiomics and clinical	Pathomics and clinical	Radiomics and pathomics	Combined
Clinical	Ileal		0.259	0.121	0.623	0.029	0.003	0.001
	Ileocolonic		0.004	0.006	0.635	0.012	< 0.001	< 0.001
Radiomics	Ileal	0.259		0.496	0.495	0.227	0.094	0.114
	Ileocolonic	0.004		0.626	0.087	0.905	0.209	0.297
Pathomics	Ileal	0.121	0.496		0.245	0.890	0.503	0.203
	Ileocolonic	0.006	0.626		0.112	0.218	0.446	0.464
Radiomics and clinical	Ileal	0.623	0.495	0.245		0.122	0.044	0.119
	Ileocolonic	0.635	0.087	0.112		0.234	0.007	0.017
Pathomics and clinical	Ileal	0.029	0.227	0.890	0.122		0.321	1.000
	Ileocolonic	0.012	0.905	0.218	0.234		0.142	0.107
Radiomics and pathomics	Ileal	0.003	0.094	0.503	0.044	0.321		1.000
	Ileocolonic	< 0.001	0.209	0.446	0.007	0.142		0.629
Combined	Ileal	0.001	0.114	0.203	0.119	1.000	1.000
	Ileocolonic	< 0.001	0.297	0.464	0.017	0.107	0.629