Interpretable model based on multisequence magnetic resonance imaging radiomics for predicting the pathological grades of hepatocellular carcinomas

Table 1 Magnetic resonance imaging scan sequences and parameters

Sequence	Layer thickness (mm)	Field (mm2)	TR/TE (ms)	Flip angle (°)	Matrix size (mm2)
RTr Ax fs T2	6	320 × 320 - 380 × 380	2609/97	110	384 × 384
BH Ax LAVA +C	5	320 × 320 - 360 × 360	4/2	12	224 × 192

TR: Repetition time; TE: Echo time.

Table 2 Comparison of the clinical characteristics between the training and validation groups, n (%)

Clinical features	Training group (n = 87)		Validation group (n = 38)		P value
	Nonpoorly differentiated HCC (n = 73)	Poorly differentiated HCC (n = 14)	Nonpoorly differentiated HCC (n = 32)	Poorly differentiated HCC (n = 6)
Age (years)	55.00 (48.00, 65.00)	52.50 (44.50, 64.00)	53.50 (47.75, 63.25)	58.00 (37.00, 64.75)	0.621
NLR	2.56 (2.07, 3.33)	3.09 (2.50, 3.75)	2.86 (1.85, 5.66)	4.67 (2.88, 6.95)	0.185
PLR	94.83 (70.66, 134.21)	129.27 (120.54, 177.77)	128.36 (75.52, 194.57)	155.89 (140.21, 222.43)	0.063
LMR	3.98 (2.97, 4.58)	3.03 (2.43, 3.58)	3.53 (1.98, 4.44)	1.94 (1.41, 2.68)	0.041
Maximum tumor diameter (cm)	4.60 (3.10, 6.10)	8.30 (6.30, 10.57)	5.65 (4.52, 7.73)	9.20 (6.10, 10.43)	0.052
AST (U/L)	40.00 (30.00, 68.00)	42.50 (29.50, 66.50)	44.00 (38.00, 64.25)	81.50 (65.25, 86.50)	0.102
ALT (U/L)	32.00 (21.00, 59.00)	45.00 (24.75, 58.25)	34.50 (23.75, 49.50)	57.00 (26.00, 74.50)	0.906
GGT (U/L)	62.00 (30.00, 112.00)	81.50 (25.75, 254.75)	87.00 (43.80, 150.75)	363.00 (131.00, 600.25)	0.058
NEU (109/L)	3.49 (2.78, 4.33)	5.29 (3.34, 7.73)	4.02 (2.43, 6.06)	4.87 (4.38, 5.61)	0.399
LYMPH (109/L)	1.34 (1.05, 1.72)	1.34 (1.10, 2.08)	1.27 (0.88, 1.49)	1.25 (0.91, 1.50)	0.125
PLT (109/L)	136.00 (100.00, 180.00)	193.50 (137.75, 224.50)	156.50 (109.25, 203.00)	198.00 (190.50, 203.25)	0.251
MONO (109/L)	0.39 (0.30, 0.46)	0.42 (0.38, 0.72)	0.40 (0.31, 0.48)	0.69 (0.59, 0.80)	0.263
A/G ratio	1.29 (1.13, 1.53)	1.18 (0.96, 1.41)	1.31 (1.21, 1.44)	1.08 (1.01, 1.10)	0.646
Sex					0.214
Female	6 (8.22)	3 (21.43)	6 (18.75)	1 (16.67)
Male	67 (91.78)	11 (78.57)	26 (81.25)	5 (83.33)
Portal vein tumor thrombus					0.400
No	63 (86.30)	9 (64.29)	27 (84.38)	2 (33.33)
Yes	10 (13.70)	5 (35.71)	5 (15.62)	4 (66.67)
Lymph node metastasis					0.674
No	63 (86.30)	10 (71.43)	31 (96.88)	2 (33.33)
Yes	10 (13.70)	4 (28.57)	1 (3.12)	4 (66.67)
Liver cirrhosis					0.385
No	14 (19.18)	7 (50.00)	11 (34.38)	1 (16.67)
Yes	59 (80.82)	7 (50.00)	21 (65.62)	5 (83.33)
HBV					0.336
No	8 (10.96)	7 (50.00)	2 (6.25)	2 (33.33)
Yes	65 (89.04)	7 (50.00)	30 (93.75)	4 (66.67)
AFP (ng/mL)					0.276
< 400	48 (65.75)	9 (64.29)	18 (56.25)	3 (50.00)
≥ 400	25 (34.25)	5 (35.71)	14 (43.75)	3 (50.00)
ALBI grade					0.642
1	38 (52.05)	5 (35.71)	14 (43.75)	4 (66.67)
2	15 (20.55)	6 (42.86)	10 (31.25)	2 (33.33)
3	20 (27.40)	3 (21.43)	8 (25.00)	0 (0.00)

HCC: Hepatocellular carcinoma; NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; LMR: Lymphocyte-to-monocyte ratio; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transferase; NEU: Neutrophil count; PLT: Platelet count; MONO: Monocyte count; LYMPH: Lymphocyte count; A/G ratio: Albumin-globulin ratio; HBV: Hepatitis B virus; AFP: Alpha-fetoprotein; ALBI: Albumin-bilirubin index.

Table 3 Screened optimal radiomic features

MRI sequence	Feature type	Feature name
FS-T2WI	wavelet-HLL_first order	Kurtosis
	wavelet-HLL_glcm	Idn
	wavelet-HLL_gldm	Large dependence high gray level emphasis
AP	Original_shape	Sphericity
	Original_glcm	Cluster prominence
	Original_glszm	Large area high gray level emphasis
	wavelet-LLL_glcm	Cluster prominence
PVP	Original_shape	Sphericity
	log-sigma-2-5-mm-3D_ gldm	Small dependence high gray level emphasis
	wavelet-HHL_glszm	Large area emphasis
	wavelet-HHL_glszm	Small area emphasis
	wavelet-LLL_glcm	Cluster prominence

MRI: Magnetic resonance imaging; FS-T2WI: Fat-suppressed T2-weighted image; AP: Arterial phase; PVP: Portal venous phase; Idn: Inverse difference normalized.

Table 4 Results of univariate and multivariate logistic regression analyses

Clinical factors	Univariate logistic regression analysis		Multivariate logistic regression analysis
	OR (95%CI)	P value	OR (95%CI)	P value
Age (years)	0.980 (0.934-1.028)	0.406	-	-
Sex	0.328 (0.071-1.510)	0.152	-	-
NLR	1.009 (0.935-1.088)	0.826	-	-
PLR	1.005 (0.997-1.012)	0.209	-	-
LMR	0.675 (0.439-1.039)	0.074	-	-
Maximum tumor diameter (cm)	1.232 (1.051-1.444)	0.0101	1.364 (1.065-1.746)	0.0141
Portal vein tumor thrombus	3.500 (0.972-12.597)	0.055	-	-
Lymph node metastasis	2.520 (0.661-9.603)	0.176	-	-
HBV	0.106 (0.029-0.391)	< 0.0011	0.120 (0.020-0.729)	0.0211
Liver cirrhosis	0.237 (0.072-0.787)	0.0191	0.326 (0.053-2.020)	0.228
AFP (ng/mL)	1.067 (0.323-3.525)	0.916	-	-
PLT (109/L)	1.007 (1.001-1.014)	0.0351	0.994 (0.984-1.005)	0.296
LYMPH (109/L)	1.364 (0.614-3.030)	0.446	-	-
NEU (109/L)	1.140 (0.981-1.325)	0.088	-	-
MONO (109/L)	2.312 (1.324-4.035)	0.0031	2.488 (1.175-5.271)	0.0171
AST (U/L)	1.004 (0.998-1.010)	0.181	-	-
ALT (U/L)	1.004 (0.999-1.008)	0.150	-	-
GGT (U/L)	1.002 (0.999-1.005)	0.211	-	-
A/G ratio	0.198 (0.022-1.779)	0.148	-	-
ALBI grade	-	0.219	-	-
ALBI grade 1	0.877 (0.19-4.052)	0.867	-	-
ALBI grade 2	2.667 (0.572-12.428)	0.212	-	-

¹The significant risk factors or independent predictors of the preoperative pathological classification identified by a univariate or multivariate analysis.

CI: Confidence interval; OR: Odds ratio; NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; LMR: Lymphocyte-to-monocyte ratio; HBV: Hepatitis B virus; AFP: Alpha-fetoprotein; PLT: Platelet; LYMPH: Lymphocyte; NEU: Neutrophil; MONO: Monocyte; AST: Aspartate aminotransferase; ALT: Alanine transaminase; GGT: Gamma-glutamyl transferase; A/G: Albumin/globulin; ALBI: Albumin-bilirubin index.

Table 5 Predictive performance of each model

Group	Model	AUC value (95%CI)	Accuracy	Sensitivity	Specificity	Positive predictive value	Negative predictive value
Training group	FS-T2WI	0.761 (0.562-0.857)	0.862	0.214	0.986	0.750	0.867
	AP	0.870 (0.714-0.918)	0.897	0.500	0.973	0.778	0.910
	PVP	0.868 (0.714-0.959)	0.908	0.500	0.986	0.875	0.911
	Radiomics	0.917 (0.857-0.959)	0.943	0.714	0.986	0.909	0.947
	Clinical	0.869 (0.643-0.973)	0.885	0.429	0.973	0.750	0.899
	Combined	0.941 (0.857-0.945)	0.942	0.714	0.986	0.909	0.947
Validation group	FS-T2WI	0.724 (0.625-0.833)	0.816	0.333	0.906	0.400	0.879
	AP	0.802 (0.686-1.000)	0.763	0.333	0.844	0.286	0.871
	PVP	0.797 (0.688-1.000)	0.763	0.167	0.875	0.200	0.848
	Radiomics	0.901 (0.833-0.906)	0.895	0.667	0.938	0.667	0.938
	Clinical	0.865 (0.594-1.000)	0.895	0.500	0.969	0.750	0.912
	Combined	0.932 (0.812-1.000)	0.895	0.667	0.938	0.667	0.938

CI: Confidence interval; AUC: Area under the receiver operating characteristic curve; FS-T2WI: Fat-suppressed T2-weighted image; AP: Arterial phase; PVP: Portal venous phase.