Histogram Analysis of Diffusion-Weighted Magnetic Resonance Imaging as a Biomarker to Predict Lymph Node Metastasis in T3 Stage Rectal Carcinoma

Figures & data

Figure 1 Flow chart of inclusion and exclusion criteria of the study sample.

Figure 2 An example of manual segmentation of primary tumor on rectal cancer magnetic resonance imaging. (A) Maximum cross-section of primary tumor on T2-weighted (T2W) image in a T3 stage rectal cancer patient. (B) Maximum cross-section of primary tumor on diffusion-weighted (DW) image in the same patient. (C) Regions of interest were outlined directly along the margin of the whole tumor on maximum cross-section of the DW images, excluding the intraluminal gas, obvious necrosis and cystic areas using T2W imaging sequence as a reference standard (red region). (D) Copy of delineated area on the corresponding apparent diffusion coefficient map (magenta region).

Table 1 Comparison of Clinical Data Between the LN− and LN+ Groups

		LN+	LN−	p value
Sex	Male	37 (59.7%)	76 (67.3%)	0.316
	Female	25 (40.3%)	37 (32.7%)
Age (yr)		58.86±10.52	62.09±10.72	0.056
Height (cm)		165.50 (160.0–174.25)	168.0 (162.0–172.0)	0.880
Weight (kg)		66.50 (59.75–72.0)	65.0 (59.0–73.0)	0.851
Smoking	No	38 (61.3%)	63 (55.8%)	0.478
	Yes	24 (38.7%)	50 (44.2%)
Alcohol	No	40 (64.5%)	74 (65.5%)	0.897
	Yes	22 (35.5%)	39 (34.5%)
CEA	Normal	31 (51.7%)	73 (65.2%)	0.084
	Abnormal	29 (48.3%)	39 (34.8%)
CA199	Normal	50 (84.7%)	106 (96.4%)	0.007
	Abnormal	9 (15.3%)	4 (3.6%)
CA724	Normal	42 (80.8%)	73 (85.9%)	0.429
	Abnormal	10 (19.2%)	12 (14.1%)
AFP	Normal	30 (100.0%)	61 (96.8%)	0.324
	Abnormal	0	2 (3.2%)

Notes: Continuous variables are presented as mean ± standard deviation. Categorical variables are presented as n (%). Significant p values are in bold.

Abbreviations: LN+, lymph node positive; LN−, lymph node negative; CEA, carcinoembryonic antigen; CA199, carbohydrate antigen 199; CA724, carbohydrate antigen 724; AFP, α-fetoprotein.

Table 2 Comparison of Radiological Characteristics Between the LN− and LN+ Groups

		LN+	LN−	p value
Thickness (mm)		13.00 (11.–16.0)	13.0 (10.0–16.0)	0.255
Length (mm)		49.00 (41.0–59.0)	45.0 (40.0–54.0)	0.306
Invasion scope	1/4–1/2	7 (11.3%)	13 (11.5%)	0.997
	1/2–3/4	30 (48.4%)	54 (47.8%)
	>3/4	25 (40.3%)	46 (40.7%)
mrT stage	3a	1 (1.6%)	3 (2.7%)	0.212
	3b	36 (58.1%)	71 (62.8%)
	3c	17 (27.4%)	17 (15.0%)
	3d	8 (12.9%)	22 (19.5%)
mrN stage	N0	26 (41.9%)	98 (86.7%)	<0.001
	N1	26 (41.9%)	15 (13.3%)
	N2	10 (16.2%)	0
EMVI	Negative	55 (88.7%)	107 (95.5%)	0.089
	Positive	7 (11.3%)	5 (4.5%)
MRF	Negative	45 (72.6%)	100 (88.5%)	0.008
	Positive	17 (27.4%)	13 (11.5%)
Tumor Location	Lower	25 (40.3%)	46 (40.7%)	0.325
	Middle	27 (43.5%)	39 (34.5%)
	Upper	10 (16.1%)	28 (24.8%)

Notes: Data expressed as n (%). Significant p values are in bold.

Abbreviations: LN+, lymph node positive; LN−, lymph node negative; mrN Stage, N stage with magnetic resonance; mrT stage, T stage with magnetic resonance; EMVI, extramural venous invasion; MRF, mesorectal fascia.

Table 3 Comparison of ADC Histogram Parameters Between the LN− and LN+ Groups

	Cut-Off Value	LN+	LN−	p value
P5	≤0.71×10^–3 s/mm^2	30 (48.4%)	71 (62.8%)	0.064
	>0.71×10^–3 s/mm^2	32 (51.6%)	42 (37.2%)
P10	≤0.80×10^–3 s/mm^2	40 (64.5%)	90 (79.6%)	0.028
	>0.80×10^–3 s/mm^2	22 (35.5%)	23 (20.4%)
P25	≤0.89×10^–3 s/mm^2	35 (56.5%)	86 (76.1%)	0.007
	>0.89×10^–3 s/mm^2	27 (43.5%)	27 (23.9%)
P50 (Median)	≤0.98×10^–3 s/mm^2	24 (38.7%)	64 (56.6%)	0.023
	>0.98×10^–3 s/mm^2	38 (61.3%)	49 (43.4%)
P75	≤1.13×10^–3 s/mm^2	17 (27.4%)	51 (45.1%)	0.021
	>1.13×10^–3 s/mm^2	45 (72.6%)	62 (54.9%)
P90	≤1.58×10^–3 s/mm^2	48 (77.4%)	100 (89.3%)	0.035
	>1.58×10^–3 s/mm^2	14 (22.6%)	12 (10.7%)
P95	≤1.75×10^–3 s/mm^2	47 (75.8%)	99 (87.6%)	0.045
	>1.75×10^–3 s/mm^2	15 (24.2%)	14 (12.4%)
Mean	≤1.08×10^–3 s/mm^2	33 (53.2%)	86 (76.1%)	0.002
	>1.08×10^–3 s/mm^2	29 (46.8%)	27 (23.9%)
Skewness	>0.534*	49 (79.0%)	82 (72.6%)	0.346
	≤0.534*	13 (21.0%)	31 (27.4%)
Kurtosis	>3.122*	46 (74.2%)	94 (83.2%)	0.155
	≤3.122*	16 (25.8%)	19 (16.8%)
CV	>0.249*	29 (46.8%)	71 (62.8%)	0.040
	≤0.249*	33 (53.2%)	42 (37.2%)

Notes: Data expressed as n (%). Significant p values are in bold.

Abbreviations: LN+, lymph node positive; LN−, lymph node negative; ADC, apparent diffusion coefficient; P5, 5th percentile of ADC value; P10, 10th percentile of ADC value; P75, 75th percentile of ADC value; P90, 90th percentile of ADC value; P95, 95th percentile of ADC value; CV, coefficient of variation.

Figure 3 A51-year-old male patient with confirmed pT3N1 rectal cancer. (A) Maximum axial T2-weighted image showing irregular thickening of the rectal wall with intermediate signal intensity in the lower segment of the rectum. (B) The corresponding maximum axial diffusion-weighted (DW) image with the same lesion for delineation of regions of interest (ROIs). (C) Corresponding apparent diffusion coefficient (ADC) map histogram copying from ROI of DW image showing that the ADC mean of 1.29×10³ s/mm² and coefficient of variation of 0.163. (D) ADC pcolor map showing that the brighter the color, the greater the value.

Figure 4 A 63-year-old male patient with confirmed pT3N0 rectal cancer. (A) Maximum axial T2-weighted image showing irregular thickening of the rectal wall with intermediate signal intensity in the lower segment of the rectum. (B) The corresponding maximum axial diffusion-weighted image (DW) image of the same lesion for delineation of regions of interest (ROIs). (C) The corresponding apparent diffusion coefficient (ADC) map histogram copied from ROI of DW image showing ADC mean of 0.96×10³ s/mm² and coefficient of variation of 0.183. (D) ADC pcolor map showing that the brighter the color, the greater the value.

Table 4 Univariate and Multivariate Analyses

Parameters	Univariate Analysis		Multivariate Analysis
	OR	P	OR	P
mrN stage	7.686	<0.001	8.236	<0.001
MRF	2.906	0.009
CA199	4.770	0.012	8.518	0.004
P10	2.152	0.030
P25	2.457	0.008
P50	2.068	0.024
P75	2.177	0.023
P90	2.431	0.039
P95	2.257	0.048
Mean	2.799	0.002	5.392	<0.001
CV	1.924	0.041	2.192	0.040

Notes: Variables with p<0.05 in univariate logistic regression analysis were applied to multivariate logistic regression analysis. Significant p values are in bold.

Abbreviations: LN+, lymph node positive; LN−, lymph node negative; mrN Stage, N stage with magnetic resonance; MRF, mesorectal fascia; P5, 5th percentile of ADC value; P10, 10th percentile of ADC value; P75, 75th percentile of ADC value; P90, 90th percentile of ADC value; P95, 95th percentile of ADC value; CV, coefficient of variation. OR, odds ratio.

Table 5 Predictive Efficacy of the Four Independent Predictive Factors Model and Combined Model

	AUC	Sensitivity	Specificity	PPV	NPV
mrN stage	0.735	58.1%	86.7%	70.6%	79.0%
CA199	0.558	15.3%	96.4%	69.2%	67.9%
Mean	0.614	46.8%	76.1%	51.8%	72.3%
CV	0.580	53.2%	62.8%	44.0%	71.0%
Combine model	0.838	72.9%	79.1%	65.2%	84.5%

Abbreviations: mrN Stage, N stage with magnetic resonance; CA199, carbohydrate antigen 199; ADC, apparent diffusion coefficient; CV, coefficient of variation; AUC, area under receiver operating characteristic curve; PPV, positive predictive value; NPV, negative predictive value.

Figure 5 Receiver operating characteristic curves and area under the curve values for mrN-stage, carbohydrate antigen 199, apparent diffusion coefficient (ADC) mean, ADC coefficient of variation and combined model with above parameters in predicting pathological lymph node metastasis.