Multiparametric magnetic resonance imaging of deep learning-based super-resolution reconstruction for predicting histopathologic grade in hepatocellular carcinoma

Table 1 Baseline characteristics of included patients

	Training cohort (n = 459)			Validation cohort (n = 196)			Test cohort (n = 171)
	PD HCC (n = 89)	nPD HCC (n = 370)	P value	PD HCC (n = 30)	nPD HCC (n = 166)	P value	PD HCC (n = 36)	nPD HCC (n = 135)	P value
Age (years)	55.67 ± 10.56	57.24 ± 9.69	0.18	58.07 ± 9.12	58.95 ± 9.96	0.65	57.58 ± 8.75	59.67 ± 10.41	0.16
Sex (male), n (%)	73 (82.02)	312 (84.32)	0.71	25 (83.33)	141 (84.94)	1.00	27 (75.00)	112 (82.96)	0.15
BMI (kg/m2)	25.39 ± 3.39	25.14 ± 3.58	0.60	24.69 ± 3.68	24.95 ± 3.28	0.61	24.55 ± 3.23	25.07 ± 3.08	0.40
HBV, n (%)	61 (68.54)	253 (68.38)	1.00	23 (76.67)	125 (75.30)	1.00	26 (72.22)	92 (68.15)	0.79
HCV, n (%)	6 (6.74)	23 (6.22)	1.00	0 (0)	5 (3.01)	0.74	1 (2.78)	7 (5.19)	0.87
Cirrhosis, n (%)	64 (71.91)	236 (63.78)	0.19	25 (83.33)	100 (60.24)	0.03	24 (66.67)	76 (56.30)	0.35
AFP (ng/mL), n (%)
< 20	21 (23.60)	215 (58.11)	< 0.001	6 (20.00)	89 (53.61)	0.001	11 (30.56)	88 (65.19)	< 0.001
20-400	29 (32.58)	83 (22.43)	0.06	11 (36.67)	49 (29.52)	0.57	12 (33.33)	27 (20.00)	0.14
> 400	39 (43.82)	72 (19.46)	< 0.001	13 (43.33)	28 (16.87)	0.002	13 (36.11)	20 (14.81)	0.01
ALT (U/L)	39.43 ± 31.08	33.74 ± 27.29	0.06	30.81 ± 12.57	33.48 ± 26.51	0.47	37.92 ± 34.03	31.51 ± 25.20	0.17
AST (U/L)	32.54 ± 23.91	30.03 ± 22.88	0.13	29.26 ± 9.25	28.70 ± 18.83	0.09	32.58 ± 22.14	27.73 ± 14.45	0.11
TB (umol/L)	18.91 ± 27.90	13.55 ± 5.85	0.31	14.38 ± 5.32	13.78 ± 6.48	0.45	13.76 ± 9.14	12.16 ± 5.22	0.35
Albumin (g/L)	41.65 ± 4.19	41.53 ± 3.95	0.79	41.64 ± 4.63	41.14 ± 3.90	0.53	40.58 ± 4.12	41.78 ± 3.86	0.08
PT (S)	13.45 ± 0.97	13.51 ± 1.07	0.56	13.63 ± 0.85	13.39 ± 1.01	0.34	13.56 ± 1.14	13.60 ± 0.84	0.77
Tumors size (mm)	47.57 ± 22.08	47.91 ± 21.1	0.73	48.10 ± 25.78	49.83 ± 23.06	0.52	45.64 ± 19.51	50.90 ± 21.53	0.19
Number of tumors, n (%)
Solitary	80 (89.89)	330 (89.19)	1.00	26 (86.67)	153 (92.17)	0.53	36 (100.00)	126 (93.33)	0.24
Multiple	9 (10.11)	40 (10.81)		4 (13.33)	13 (7.83)		0 (0)	9 (6.67)

PD: Poorly differentiated; HCC: Hepatocellular carcinoma; nPD: Non-poorly differentiated; BMI: Body mass index; HBV/HCV: Hepatitis B/C virus; AFP: Alpha-fetoprotein; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TB: Total bilirubin; PT: Thromboplastin time.

Table 2 Predictive performance of different radiomics models based on XGBoost

Models	Cohorts	Original NR MRI				Deep learning-based SR MRI
		AUC (95%CI)	Accuracy	Sensitivity	Specificity	AUC (95%CI)	Accuracy	Sensitivity	Specificity
T2WI	Training	0.782 (0.732-0.832)	0.741	0.708	0.749	0.813 (0.765-0.861)	0.717	0.854	0.684
	Validation	0.721 (0.613-0.828)	0.745	0.600	0.771	0.738 (0.636-0.840)	0.755	0.633	0.777
	Test	0.685 (0.585-0.785)	0.637	0.722	0.615	0.721 (0.620-0.820)	0.637	0.833	0.585
DWI	Training	0.785 (0.732-0.834)	0.678	0.742	0.662	0.770 (0.716-0.825)	0.715	0.708	0.716
	Validation	0.697 (0.595-0.800)	0.653	0.733	0.639	0.721 (0.614-0.827)	0.801	0.500	0.855
	Test	0.695 (0.595-0.795)	0.550	0.861	0.467	0.694 (0.586-0.802)	0.696	0.639	0.711
PVP	Training	0.816 (0.765-0.866)	0.778	0.685	0.800	0.834 (0.791-0.877)	0.741	0.764	0.735
	Validation	0.727 (0.610-0.844)	0.801	0.567	0.843	0.762 (0.664-0.859)	0.816	0.567	0.861
	Test	0.713 (0.620-0.805)	0.678	0.611	0.696	0.752 (0.659-0.845)	0.743	0.667	0.763
All-sequences1	Training	0.890 (0.854-0.925)	0.793	0.876	0.773	0.884 (0.847-0.920)	0.815	0.809	0.816
	Validation	0.792 (0.700-0.883)	0.842	0.533	0.898	0.832 (0.748-0.915)	0.735	0.800	0.723
	Test	0.779 (0.695-0.862)	0.667	0.778	0.637	0.798 (0.720-0.875)	0.766	0.695	0.785

¹Including tree sequences (T2-weighted imaging, diffusion-weighted imaging, portal venous phase).

NR: Normal-resolution; SR: Super-resolution; MRI: Magnetic resonance imaging; AUC: Area under the curve; T2WI: T2-weighted imaging; DWI: Diffusion-weighted imaging; PVP: Portal venous phase.

Table 3 Difference of selected radiomics features for all-sequence model between normal-resolution and super-resolution magnetic resonance imaging

	Original NR MRI	Deep learning-based SR MRI
1	DWI_original_glrlm_RunVariance	DWI_original_glrlm_LongRunEmphasis
2	DWI_original_glszm_ZonePercentage	DWI_original_glszm_SmallAreaEmphasis
3	DWI_original_shape_Elongation	DWI_wavelet_HLL_glcm_ClusterShade
4	DWI_wavelet_LHH_firstorder_Skewness	DWI_wavelet_LLL_ngtdm_Complexity
5	DWI_wavelet_LHL_firstorder_RobustMeanAbsoluteDeviation	DWI_log_sigma_5_0_mm_3D_glcm_DifferenceVariance
6	DWI_wavelet_LLL_glszm_GrayLevelVariance	PVP_original_firstorder_Kurtosis
7	PVP_log_sigma_5_0_mm_3D_glrlm_ShortRunEmphasis	PVP_wavelet_HLL_firstorder_Kurtosis
8	PVP_wavelet_LHH_glcm_ClusterShade	PVP_wavelet_LHL_firstorder_Median
9	PVP_wavelet_LHH_glcm_Correlation	PVP_wavelet_LLL_glszm_ZonePercentage
10	PVP_wavelet_LHL_firstorder_Median	T2WI_wavelet_HHL_glszm_SmallAreaEmphasis
11	T2WI_wavelet_HHL_firstorder_Kurtosis	T2WI_wavelet_HLH_firstorder_Median
12	T2WI_wavelet_HHL_firstorder_Median	T2WI_wavelet_HLH_glszm_SmallAreaEmphasis
13	T2WI_wavelet_LLL_firstorder_RootMeanSquared

NR: Normal-resolution; SR: Super-resolution; MRI: Magnetic resonance imaging; DWI: Diffusion-weighted imaging; T2WI: T2-weighted imaging; PVP: Portal venous phase.

Table 4 Univariable and multivariable cox proportional hazards analyses for overall survival and recurrence-free survival

Variable	Overall survival				Recurrence-free survival
	Univariable analysis		Multivariable analysis		Univariable analysis		Multivariable analysis
Signature from SR MRI	1.67 (1.21, 2.30)	0.002	1.81 (1.29, 2.55)	0.001	1.39 (1.04, 1.88)	0.028	1.36 (1.02, 1.85)	0.042
Age (> 65 years)	1.20 (0.80, 1.79)	0.381			1.12 (0.79, 1.59)	0.533
Gender (male)	1.08 (0.70, 1.67)	0.723			1.13 (0.75, 1.71)	0.559
HBV	0.97 (0.67, 1.39)	0.855			0.93 (0.67, 1.29)	0.677
Cirrhosis	1.30 (0.94, 1.80)	0.118			1.15 (0.86, 1.54)	0.341
MVI	1.78 (1.28, 2.47)	< 0.001	1.48 (1.04, 2.09)	0.029	1.80 (1.34, 2.42)	0.001	1.67 (1.23, 2.28)	0.001
INR (> 1.5 ratio)	2.31 (0.32, 16.64)	0.405			2.61 (0.64, 10.54)	0.179
AFP	1.48 (1.02, 2.14)	0.04	1.53 (1.06, 2.19)	0.219	1.44 (1.03, 2.02)	0.031
Multiple	1.07 (0.67, 1.72)	0.766			1.59 (1.07, 2.37)	0.021	1.53 (1.03, 2.28)	0.036
Pseudocapsule	0.74 (0.52, 1.04)	0.083			0.88 (0.65, 1.20)	0.426
Tumor size	1.38 (1.01, 1.90)	0.049	1.53 (1.06, 2.19)	0.022	1.38 (1.01, 1.91)	0.048	1.38 (0.96, 1.98)	0.08

Hazard ratio, 95%CI and P value were reported to measure the effects; SR: Super-resolution; MRI: Magnetic resonance imaging; HBV: Hepatitis B virus; MVI: Microvascular invasion; INR: International normalized ratio; AFP: Α-fetoprotein.