Correlation of dynamic contrast-enhanced ultrasonography and the Ki-67 labelling index in pancreatic ductal adenocarcinoma

Table 1 Explanations for quantitative parameters

Parameters	Explanations
Contrast agent arrival time (second)	Time from 0 to the start of enhancement
Peak enhancement (a.u.)	Maximum enhancement intensity during the arterial phase
Half-decrease time (second)	The time required to decrease from PE to 1/2 PE of the arterial phase
Fall time (second)	The time for the contrast agent intensity to decrease from 95% to 5% of PE during the arterial phase
Rise time (second)	The time it takes for the contrast agent intensity to go from 5% to 95% of PE during the arterial phase
Time to peak (second)	The time required to reach PE of the arterial phase after contrast agent injection
Wash-in area under the curve (a.u.)	Area under the TIC from the time of arrival to the PE of arterial phase
Wash-in perfusion index (a.u./second)	WiAUC/RT
Wash-in rate (a.u./second)	The maximum slope of the rising part of the TIC
Wash-out area under the curve (a.u.)	The area under the TIC from the PE of the arterial phase to the end of the curve
Wash-out rate (a.u./second)	The minimum slope of the descending part of the curve
Wash-in and wash-out area under the curve (a.u.)	WiAUC + WoAUC, representing the area under the entire curve
Mean transit time (second)	Time from the rising of the intensity up to decrease to 50% of maximum

TIC: Time-intensity curve; PE: Peak enhancement; WiAUC: Wash-in area under the curve; RT: Rise time; WoAUC: Wash-out area under the curve.

Table 2 Clinical data and gray-scale ultrasonography characteristics of the patients, n (%)

Characteristics	The high Ki-67 expression group (n = 13)	The low Ki-67 expression group (n = 17)	P value
Age, mean ± SD (years)	62.62 ± 6.86	63.06 ± 7.00	0.864
Gender			0.061
Male	5 (38.5)	13 (76.5)
Female	8 (61.5)	4 (23.5)
BMI			1.000
≥ 23.9	3 (23.1)	5 (29.4)
< 23.9	10 (76.9)	12 (70.6)
Diabetes mellitus			0.440
Yes	3 (23.1)	7 (41.2)
No	10 (76.9)	10 (58.8)
Location			1.000
Head and neck	9 (69.2)	12 (70.6)
Body and tail	4 (30.8)	5 (29.4)
Tumor size, mean ± SD (cm)	4.22 ± 1.51	3.52 ± 1.26	0.186
Echogenicity			0.492
Isoechoic	0 (0)	2 (11.8)
Hypoechoic	13 (100)	15 (88.2)
Margin			0.460
Well-defined	6 (46.2)	11 (64.7)
Ill-defined	7 (53.8)	6 (35.3)
Texture			0.492
Solid	0 (0)	15 (88.2)
Solid-cystic	13 (100)	2 (11.8)
Shape			0.705
Regular	8 (61.5)	12 (70.6)
Irregular	5 (38.5)	5 (29.4)
Blood flow signal			0.033a
Present	3 (23.1)	11 (64.7)
Absent	10 (76.9)	6 (35.3)
Main pancreatic duct dilation (> 3 mm)			1.000
Present	7 (53.8)	9 (52.9)
Absent	6 (46.2)	8 (47.1)

^aP < 0.05.

BMI: Body mass index.

Table 3 Comparison of quantitative parameters between the pancreatic ductal adenocarcinoma lesions and pancreatic parenchyma

Parameters	Tumor	Parenchyma	P value
The high Ki-67 expression group
CAT	4.66 (3.12, 11.33)	5.10 (4.28, 11.19)	0.457
FT	36.46 (25.29, 49.72)	28.24 (21.38, 38.44)	0.209
HDT	51.56 (44.12, 59.09)	47.76 (41.11, 61.04)	0.739
PE	5.31 × 107 (3.31 × 107, 7.54 × 107)	1.09 × 108 (6.43 × 107, 1.77 × 108)	0.006a
RT	12.31 (10.33, 18.11)	12.44 (8.21, 14.34)	0.293
TTP	20.92 (16.24, 25.17)	18.42 (13.15, 26.74)	0.369
WiAUC	3.98 × 108 (2.46 × 108, 8.48 × 108)	7.51 × 108 (5.02 × 108, 1.11 × 109)	0.038a
WiPI	3.32 × 107 (2.15 × 107, 4.80 × 107)	6.86 × 107 (3.97 × 107, 1.08 × 108)	0.006a
WiR	6.40 × 106 (3.94 × 106, 9.05 × 106)	1.72 × 107 (8.70 × 106, 2.68 × 107)	0.004a
WiWoAUC	1.70 × 109 (9.58 × 108, 2.16 × 109)	3.51 × 109 (1.68 × 109, 3.61 × 109)	0.026a
WoAUC	1.03 × 109 (6.94 × 108, 1.52 × 109)	2.55 × 109 (1.20 × 109, 2.80 × 109)	0.015a
WoR	-2.05 × 106 (-3.75 × 106, -8.11 × 105)	-3.46 × 106 (-7.13 × 106, -2.86 × 106)	0.033a
mTT	18.25 (14.61, 27.72)	18.33 (11.83, 22.52)	0.555
The low Ki-67 expression group
CAT	6.99 (4.76, 12.63)	7.52 (5.03, 12.42)	0.986
FT	37.95 (25.28, 43.16)	35.55 (22.82, 54.05)	0.877
HDT	47.68 (40.47, 56.70)	62.98 (45.22, 81.97)	0.117
PE	8.05 × 107 (5.06 × 107, 1.22 × 108)	1.17 × 108 (9.61 × 107, 1.63 × 108)	0.065
RT	13.47 (11.56, 16.13)	12.28 (11.69, 21.52)	0.850
TTP	21.28 (18.02, 24.76)	22.43 (18.36, 26.92)	0.524
WiAUC	6.77 × 108 (4.34 × 108, 1.02 × 109)	1.02 × 109 (6.58 × 108, 1.68 × 109)	0.060
WiPI	5.07 × 107 (3.15 × 107, 7.38 × 107)	7.52 × 107 (5.92 × 107, 1.01 × 108)	0.060
WiR	9.63 × 106 (4.33 × 106, 1.33 × 107)	1.27 × 107 (7.60 × 106, 1.89 × 107)	0.185
WiWoAUC	2.19 × 109 (1.46 × 109, 3.46 × 109)	3.18 × 109 (2.12 × 109, 7.45 × 109)	0.048a
WoAUC	1.63 × 109 (1.05 × 109, 2.46 × 109)	2.35 × 109 (1.55 × 109, 5.39 × 109)	0.071
WoR	-2.63 × 106 (-3.73 × 106, -1.47 × 106)	-3.10 × 106 (-7.64 × 106, -2.08 × 106)	0.249
mTT	22.12 (16.89, 24.99)	18.09 (17.14, 31.93)	0.918

^aP < 0.05.

CAT: Contrast agent arrival time; FT: Fall time; HDT: Half-decrease time; PE: Peak enhancement; RT: Rise time; TTP: Time to peak; WiAUC: Wash-in area under the curve; WiPI: Wash-in perfusion index; WiR: Wash-in rate; WiWoAUC: Wash-in and wash-out area under the curve; WoAUC: Wash-out area under the curve; WoR: Wash-out rate; mTT: Mean transit time.

Table 4 Comparison of relative quantitative parameters between the high and low Ki-67 expression groups

Parameters	The high Ki-67 expression group (n = 13)	The low Ki-67 expression group (n = 17)	P value
rCAT	1.01 (0.76, 1.06)	0.95 (0.88, 1.10)	0.368
rFT	1.26 (0.78, 1.78)	0.93(0.67, 1.17)	0.098
rHDT	1.13 (0.78, 1.78)	0.86 (0.68, 1.00)	0.018a
rPE	0.46 (0.20, 0.66)	0.76 (0.56, 0.88)	0.025a
rRT	1.22 (0.81, 1.58)	0.98 (0.70, 1.03)	0.090
rTTP	1.04 (0.91, 1.37)	0.97 (0.81, 1.06)	0.069
rWiAUC	0.45 (0.26, 0.77)	0.60 (0.45, 0.94)	0.137
rWiPI	0.45 (0.20, 0.66)	0.73 (0.52, 0.86)	0.028a
rWiR	0.30 (0.16, 0.95)	0.72 (0.58, 0.96)	0.035a
rWiWoAUC	0.50 (0.20, 0.98)	0.57 (0.44, 0.84)	0.346
rWoAUC	0.52 (0.20, 1.03)	0.57 (0.43, 0.85)	0.414
rWoR	0.24 (0.19, 1.27)	0.73 (0.59, 1.10)	0.137
rmTT	1.12 (0.68, 1.66)	0.99 (0.71, 1.17)	0.233

^aP < 0.05.

rCAT: Relative contrast agent arrival time; rPE: Relative peak enhancement; rHDT: Relative half-decrease time; rFT: Relative fall time; rRT: Relative rise time; rTTP: Relative time to peak; rWiAUC: Relative wash-in area under the curve; rWiPI: Relative wash-in perfusion index; rWiR: Relative wash-in rate; rWoAUC: Relative wash-out area under the curve; rWoR: Relative wash-out rate; rWiWoAUC: Relative wash-in and wash-out area under the curve; rmTT: Relative mean transit time.

Table 5 Correlation study of quantitative dynamic contrast-enhanced ultrasonography parameters with Ki-67 expression in patients with pancreatic ductal adenocarcinoma

Parameters	Ki-67 expression
	r value	P value
rCAT	-0.167	0.377
rFT	0.307	0.099
rHDT	0.439	0.015a
rPE	-0.416	0.022a
rRT	0.315	0.090
rTTP	0.338	0.068
rWiAUC	-0.276	0.140
rWiPI	-0.408	0.025a
rWiR	-0.392	0.032a
rWiWoAUC	-0.175	0.355
rWoAUC	-0.152	0.424
rWoR	-0.276	0.140
rmTT	0.144	0.448

^aP < 0.05.

rCAT: Relative contrast agent arrival time; rPE: Relative peak enhancement; rHDT: Relative half-decrease time; rFT: Relative fall time; rRT: Relative rise time; rTTP: Relative time to peak; rWiAUC: Relative wash-in area under the curve; rWiPI: Relative wash-in perfusion index; rWiR: Relative wash-in rate; rWoAUC: Relative wash-out area under the curve; rWoR: Relative wash-out rate; rWiWoAUC: Relative wash-in and wash-out area under the curve; rmTT: Relative mean transit time.

Table 6 Parameter of receiver operating characteristic curves

Parameter	AUC	P value	95%CI	Cut-off point	Sensitivity	Specificity
rHDT	0.756	0.018a	0.575-0.936	1.07	0.538	0.941

^aP < 0.05.

AUC: Area under the curve; rHDT: Relative half-decrease time; CI: Confidence interval.