Segmental analysis of liver cirrhosis with different etiologies: a study based on iodine mixed imaging in port-venous phase

Abstract

Background

Computed tomography (CT) in port-venous phase can display the intra-hepatic vessels, and may provide the possibility for segment function evaluation for cirrhosis.

Purpose

To assess the value of iodine mixed imaging of dual-source dual-energy CT in port-venous phase in segmental evaluation of liver cirrhosis with different etiologies.

Material and Methods

Patients diagnosed with liver cirrhosis were enrolled. Patients without cirrhosis were included as a control group. Each patient underwent iodine-contrast enhanced multi-phase dual-energy CT scanning. Parameters were analyzed by SPSS, version 22.0, and Medcalc.

Results

In total, 256 patients were investigated, including 114 Child-Pugh A, 51 Child-Pugh B, 41 Child-Pugh C and 50 control patients. Total iodine content (ICt)/body surface area (BSA) in the cirrhosis group was significantly lower than the control group (P < 0.05) and the standardized-iodine parameter (SI) of each segment decreased with cirrhosis progression. In Child-Pugh A and B, SI increased more significantly in the caudal and lateral segment in A (alcholism) than in the V (virus-related) and N (non-alcoholic steatohepatitis) groups (P < 0.001). ICt/BSA showed the best diagnosis power of cirrhosis with an area under the curve of 0.765, sensitivity of 76.0% and specificity of 71.8%.

Conclusion

Blood flow compensated in the left lateral and caudal lobe in the early stage of liver cirrhosis. The compensation in alcoholism in the middle and early stages is significantly higher than that of V and N cirrhosis. Iodine mixed imaging in portal phase may provide the possibility of an incremental value in segmented blood flow perfusion and functional evaluation of liver cirrhosis on a morphological basis.

Keywords

Liver cirrhosis computed tomography dual-energy couinaud segment functional imaging

Introduction

Liver cirrhosis is a progressive diffuse hepatic damage disease caused by various pathogenic factors (1). The Child-Pugh classification system is commonly used to grade liver cirrhosis (2). However, this classification only evaluates the liver function changes at an overall level. Recent data revealed that the characteristics of blood flow changes in each segment might be different in patients with liver cirrhosis (3 –7), although there is still no perfect tool for evaluating those changes. At present, because of the superiority of detailed display of anatomy, enhanced computed tomography (CT) is a common method for imaging evaluation of liver cirrhosis (8 –10). Some studies have shown that CT might be useful for investigating both morphology and blood perfusion in patients with liver cirrhosis (11 –13). The changes in blood perfusion in each segment of liver cirrhosis may also change with the progression of cirrhosis (14,15). However, as a result of its narrow scanning scope and the high dose of radiation that Ct perfusion generates (12,16), its clinical application is limited.

Iodine mixed imaging of dual-energy CT (DECT) indirectly reflects the blood supply of tissues (17,18) and can accurately reflect the functional changes (19,20). In the present study, we analyzed the differences in iodine parameters of DECT in different segments of subgroups with different etiologies for cirrhosis patients.

Material and Methods

Patients

The study was approved by the institutional ethics committee of the hospital, and informed consent was obtained from all patients.

Patients who were diagnosed with liver cirrhosis caused by different etiologies from January 2019 to June 2022 were continuously and prospectively enrolled in the study. Inclusion criteria were: (1) liver cirrhosis related to virus-induced, alcoholism and non-alcoholic steatohepatitis (NASH) diagnosed through clinical data. Clinical history and imaging results comprise essential data. Fifty patients with other diseases (e.g. stomach, pancreas and other diseases) who were scheduled for abdominal CT scans were randomly included in the control group.

The exclusion criteria were as follows: (1) no serious dysfunction such as cardiac attenuation and renal decline; (2) allergic to iodine; (3) liver metastasis and hepatocellu-lar carcinoma; (4) portal, hepatic or splenic vein thrombosis; and (5) after review of images, patients with internal hepatic veins not clearly displayed or in whom intrahepatic arterial and venous perfusion was abnormal.

CT scanning parameters

The dual-source CT (SOMATOM Flash; Siemens Healthcare, Munich, Germany) was used for CT scanning. Contrast medium was injected in an antecubital or cubital vein at the rate of 3.5 mL/s with a saline flush of 50 mL at the same rate. The portal phase scan was started with a 15-s delay after the end of the arterial. The automatic trigger of arterial phase was set to a default threshold of 100 HU (Siemens Healthcare). The scanning ranged from the top of diaphragm to the line of horizon of anterosuperior iliac). The dual-energy scanning protocol was set as follows: tube A, tube voltage of 80 kV, tube current of 160 mAs; tube B, tube voltage of 140 kV, tube current of 230 mAs; acquisition thickness 1 mm. Images were reconstructed with a slice thickness of 1.0 mm with an increment of 0.6 mm (SAFIRE; Siemens Healthcare). Before the contrast-enhanced scanning, a non-contrast scanning was taken for each patient using a single-energy protocol with a voltage of 120 kV and a reference tube current in care-dose model. The other scanning parameters and reconstruction setting are the same as for the dual-energy model.

Post-process and measurement

Two radiologists (with more than 5 years experience) who were blinded took a preliminary review of the images to exclude cases not meeting the inclusion criteria.

Post-processing workstation “Syngo.via dual-energy mode” was used to measure the iodine concentration for each segment according to the Couinaud segmentation system. Caudal lobe C1 = I; left lateral lobe C2 = II + III; medial segment C3 = IV; right anterior segment C4 = VIII + V; right posterior segment C5 = VII + VI (19,20). The measurement procedure was completed by two experienced radiologists (diagnosis experience of more than 5 years) using a blind method. At the same time, the corresponding region of interest (ROI) in the portal vein was drawn to standardize the calculation of iodine concentration (IC) values and obtain a final standardized iodine (SI) parameter as the final result for statistical analysis.

The ROI with an area of 1–2 cm² was selected. Blood vessels should be avoided during the ROI drawing. The segmental volume was measured by the semi-automatic volume measuring tool “Volume. Syngo Via, Siemens”. The iodine content of each section is calculated using the formula: IC (iodine concentration) × V (volume) = ICS(segmental iodine content), and the Vt (total volume) and ICt (total iodine content) are the sum value of volume and iodine content of each segment. For the patients of the Child-Pugh C group, C4 and C5 were combined as the right lobe (20). A diagrammatic sketch of the segmented liver method is shown in Fig. 1.

Fig. 1.

Diagram of liver segmental method used in the present study. (a, b) Frontage view of liver marked by Couinaud segmentation and the measuring method used, respectively; (c, d) Bottom view of the segmental method used in the study, respectively. C1, caudate lobe; C2, left lateral lobe; C3, medial segment; C4, right anterior segment; C5, right posterior segment.

Radiation dose

The radiation dose was recorded by the CT dose length product (DLP) according to the scanning radiation dose report. Abdominal radiation coefficient (K) was used to calculate the effective dose (ED) (21): ED = DLP × coefficient K (K = 0.015 msv/mgycm).

Statistical analysis

Quantitative variables were expressed as the mean ± [SD] if normally distributed, whereas the median and interquartile range were used for non-normally distributed data. Categoric variables (such as sex), were expressed as frequencies. For normally distributed data (such as age, SI and V), analysis of variance test was used; otherwise, a Mann–Whitney U-test was applied. The inter-reader agreement of the qualitative iodine parameters was evaluated by the Kendall's tau_b . The area under the curve (AUC) was calculated and the comparison was conducted by a DeLong test. Statistical analyses were performed using SPSS, version 22.0.0 (IBM Corp., Armonk, NY, USA) and Medcalc, version 18.2 (MedCalc Software, Flanders, Belgium). P < 0.5 (two-sided) was considered statistically significant.

Results

Clinical characteristics of patients

In total, 257 cases were finally selected, including 207 cirrhosis patients and 50 controls (Fig. 2).

Fig. 2.

Workflow of the cases included and excluded.

One hundred and fifteen patients had Child-Pugh A; the number of cases in the V (virus-related), A (alcholism) and N (non-alcoholic steatohepatitis [NASH]) groups was 61, 38 and 16, respectively; there were 76 males and 39 females; mean ± SD age 55.5 ± 12.8/52.8 ± 10.9/51.8 ± 9.7 years (F = 0.812, P = 0.489); the body surface area (BSA) ratio was 1.57 ± 0.03/1.58 ± 0.03/1.58 ± 0.04 (F = 1.422, P = 0.239). Calculation formula: BSA = 0.0061 × height (cm) + 0.0124 × body weight (kg) − 0.0099)

Fifty-one patients had Child-Pugh B; the number of cases in the V, A and N groups was 31, 11 and 9, respectively; there were 31 males and 20 females; mean ± SD age 52.6 ± 11.6/53.0 ± 10.9/54.6 ± 10.3 years (F = 0.117, P = 0.890); the BSA was 1.58 ± 0.05/1.58 ± 0.06/1.56 ± 0.05 (F = 0.559, P = 0.575).

Forty-one patients had Child-Pugh C; the number of cases in the V, A and N groups was 24, 10 and 7, respectively; there were 27 males and 14 females, mean ± SD age 65.7 ± 12.0/60 ± 15.8/56.3 ± 17.9 years (F = 2.439, P = 0.100); the BSA was 1.57 ± 0.04/1.56 ± 0.03/1.57 ± 0.03 (F = 0.007, P = 0.993).

Fifty patients were grouped in the control, including 30 cases of gastropathy disease, four cases of pancreatic lesions, six cases of adrenal lesions and 10 cases of nephropathy; there were 35 males and 16 females; mean ± SD age 48.7 ± 13.5 years; the BSA was 1.55 ± 0.04.

General comparison for cirrhosis groups

The test results of the two reviewers showed a high consistency for measured parameters (all K values, R > 0.9, P < 0.01).

The general SI value comparison for the Child-Pugh groups and etiological groups are shown in Fig. 3(a). In the Child-A group, SI1 and SI2 are larger than in the control group, indicating significant blood flow compensation. However, there a is significant decrease in SI4. In the Child-B group, the values of SI1 and SI2 are decreased compared to the Child-A group, indicating that, as liver cirrhosis progressed, the compensation of the caudal and left lobe of the liver gradually weakened, but there was no statistically significant difference compared to the control group, whereas the S4 value further decreased. In the Child-C group, the SI value of each segment were significantly reduced, with the values of SI1, SI2 and SI4 all being lower than those of the other Child-Pugh and control groups. No statistically significant difference was found for the S3 and S2 segments.

Fig. 3.

Box and whisker graph of the SI value of the control group and the Child-Pugh A–C groups in the C1–C5 segments (b–c) and in the C1–C4-5 segments (d). Differences in SI value of the C1–C5 segments of Child-Pugh A and the control group, as well as among the S1–S5 segments of Child-Pugh B and Child-Pugh C subgroups, respectively. As a result of the significant atrophy of right lobe in most patients in the Child C group, SI4–5 is the SI value of the right lobe of the liver totally.①, ② and ③in (a) show the differences between this variable with the Child-Pugh A, B and C groups, respectively. The ＊shows a difference in the SI value in this parameter compared to the control group. The details of the SI value of etiologic subgroups in (b) to (d) are shown in Tables 1 –3. From (a), we can generally observe that, in the Child-Pugh A group, the S1 and S2 segments are larger than the control group, indicating a significant compensatory. However, there are differences in SI4 between the control group and the Child-Pugh B and C groups. In the Child-Pugh B group, the values of SI1 and SI2 decreased in the Child-Pugh A group, indicating that, as liver cirrhosis progressed, the compensatory of the caudal and left lobe of the liver gradually weakened, but there was no statistically significance compared to the control group, whereas SI4 further decreased. In the Child-Pugh C group, the SI value of each segment was significantly reduced, with SI1, SI2 and SI4 all being decreased compared to those of the other Child-Pugh and control groups. No statistically significant differences were found in SI3 and SI2.

Table 1.

Segmental volume and iodine parameters for control group and etiology subgroups in Child-Pugh A.

Segments	Parameters		Control	Virus	Alcholism	NASH	χ²	P
C1	SI		0.44 ± 0.09	0.48 ± 0.09	0.52 ± 0.09	0.47 ± 0.06	4.91	0.860
	V	mL	62.0 ± 11.6	115.5 ± 19.5	161.7 ± 23.3	125.4 ± 26.1	190.0	0.000
	V	Ratio (%)	5.4 ± 1.1	10.5 ± 1.8	11.5 ± 1.6	10.7 ± 1.8	135.58	0.000
	ICS	mg	98.1 ± 18.2	180.2 ± 39.3	256.5 ± 47.2	197.4 ± 54.9	125.68	0.000
	ICS	Ratio (%)	5.0 ± 1.0	10.6 ± 2.5	12.7 ± 2.1	10.8 ± 2.6	106.04	0.000
C2	SI		0.42 ± 0.07	0.46 ± 0.09	0.50 ± 0.07	0.44 ± 0.06	6.77	0.444
	V	mL	199.3 ± 56.3	301.5 ± 49.3	370.7 ± 43.9	269.9 ± 26.9	82.11	0.000
	V	Ratio (%)	17.4 ± 1.9	27.3 ± 4.0	26.7 ± 2.8	23.3 ± 2.1	55.44	0.000
	ICS	mg	342.8 ± 93.4	495.6 ± 89.0	607.1 ± 96.3	450.8 ± 48.0	69.23	0.000
	ICS	Ratio (%)	16.7 ± 5.2	29.1 ± 4.7	29.4 ± 4.0^△	25.1 ± 3.0	73.11	0.000
C3	SI		0.46 ± 0.08	0.42 ± 0.08	0.44 ± 0.07	0.47 ± 0.05	2.94	0.035
	V	mL	171.7 ± 27.9	129.8 ± 20.7	170.0 ± 32.9	148.4 ± 27.3	25.06	0.000
	V	Ratio (%)	14.7 ± 1.8	11.7 ± 1.9	12.3 ± 2.6	12.8 ± 2.7	19.90	0.000
	ICS	Mg	274.6 ± 56.3	186.3 ± 36.6	248.3 ± 62.7	222.9 ± 43.6	26.58	0.000
	ICS	Ratio (%)	14.3 ± 2.5	11.1 ± 2.6	12.0 ± 3.0	12.4 ± 2.6	12.17	0.000
C4	SI		0.48 ± 0.08	0.43 ± 0.09	0.45 ± 0.07	0.47 ± 0.07	4.009	0.009
	V	mL	405.4 ± 60.8	280.9 ± 47.5	350.9 ± 56.8	331.0 ± 46.7	44.17	0.000
	V	Ratio (%)	35.3 ± 3.3	25.3 ± 3.3	25.2 ± 2.9	28.4 ± 2.7	100.99	0.000
	ICS	mg	731.7 ± 3.5	429.7 ± 100.1	498.5 ± 106.9	505.0 ± 92.1	51.28	0.000
	ICS	Ratio (%)	36.1 ± 3.9	24.9 ± 3.6	23.8 ± 3.2^△	27.7 ± 2.6	107.32	0.000
C5	SI		0.50 ± 0.10	0.40 ± 0.08	0.43 ± 0.07	0.43 ± 0.07	14.08	0.000
	V	mL	309.4 ± 63.9	278.5 ± 60.4	333.0 ± 51.5	285.5 ± 39.1	6.13	0.001
	V	Ratio (%)	27.6 ± 3.3	25.1 ± 4.3	23.9 ± 3.1	24.5 ± 2.4	4.25	0.007
	ICS	mg	534.3 ± 140.0	419.7 ± 129.0	466.1 ± 114.7	432.7 ± 78.7	7.54	0.000
	ICS	Ratio (%)	26.7 ± 4.3	24.2 ± 5.0	22.3 ± 3.5^△	23.8 ± 2.9	10.65	0.000
Right lobe	SI		0.48 ± 0.11	0.44 ± 0.08	0.44 ± 0.08	0.44 ± 0.20	5.59	0.000
	V	mL	714.8 ± 118.3	559.4 ± 84.3	684.0 ± 91.4	616.5 ± 68.9	23.1	0.000
	V	Ratio (%)	62.0 ± 5.3	50.4 ± 4.6	49.2 ± 4.0	53.0 ± 18.9	68.9	0.000
	ICS	mg	1273.7 ± 239.4	850.3 ± 243.2	962.8 ± 230.3	948.5 ± 129.4	29.5	0.000
	ICS	Ratio (%)	66.1 ± 7.0	49.4 ± 10.2	46.0 ± 6.7^△	52.8 ± 8.5	48.9	0.000

NASH, non-alcoholic steatohepatitis; SI, standardized iodine parameter; V, volume; ICS, segmental iodine content.

C1, caudate lobe; C2, lateral segment; C3, medial segment; C4, right anterior segment; C5, right posterior segment.

Table 2.

Segmental volume and iodine parameters for and etiology sub-groups in Child-Pugh B.

Segments	Parameters		Virus	Alcholism	NASH	χ²	P
C1	SI		0.39 ± 0.08	0.45 ± 0.09	0.39 ± 0.05	2.61	0.083
	V	mL	110.9 ± 10.2	154.1 ± 10.2	110.7 ± 14.5	66.0	0.000
	V	Ratio (%)	11.1 ± 1.2	12.1 ± 1.3	11.1 ± 1.6	17.44	0.000
	ICS	mg	148.5 ± 30.0	271.3 ± 80.6	153.1 ± 29.1	24.50	0.000
	ICS	Ratio (%)	11.5 ± 2.0	11.8 ± 2.4	11.5 ± 2.1	7.77	0.001
C2	SI		0.40 ± 0.08	0.47 ± 0.09	0.40 ± 0.19	2.42	0.099
	V	mL	290.1 ± 27.5	364.0 ± 27.1	286.8 ± 19.8	34.9	0.000
	V	Ratio (%)	29.1 ± 3.1	31.2 ± 1.7	26.7 ± 2.4	6.11	0.004
	ICS	mg	378.9 ± 52.8	500.4 ± 89.4	365.7 ± 39.4	18.4	0.000
	ICS	Ratio (%)	29.5 ± 3.8	31.5 ± 3.1	26.9 ± 3.1	3.93	0.026
C3	SI		0.39 ± 0.06	0.37 ± 0.08	0.43 ± 0.08	1.66	0.200
	V	mL	105.2 ± 13.8	112.8 ± 12.4	136.7 ± 28.7	12.1	0.000
	V	Ratio (%)	10.5 ± 1.2	9.6 ± 1.1	12.7 ± 1.8	10.9	0.000
	ICS	mg	141.9 ± 24.3	163.3 ± 34.5	191.1 ± 38.1	4.38	0.018
	ICS	Ratio (%)	11.2 ± 1.7	10.1 ± 1.4	12.9 ± 3.5	4.84	0.012
C4	SI		0.40 ± 0.08	0.39 ± 0.08	0.39 ± 0.05	0.145	0.865
	V	mL	244.2 ± 39.2	259.3 ± 26.1	293.8 ± 34.6	6.62	0.003
	V	Ratio (%)	24.2 ± 2.7	22.1 ± 1.9	27.3 ± 2.2	10.95	0.000
	ICS	mg	320.3 ± 72.2	341.7 ± 42.5	373.6 ± 49.6	2.5	0.089
	ICS	Ratio (%)	24.6 ± 3.7	21.6 ± 2.3	27.5 ± 2.9	7.5	0.001
C5	SI		0.37 ± 0.07	0.38 ± 0.08	0.36 ± 0.05	0.195	0.824
	V	mL	251.6 ± 32.5	281.2 ± 38.0	245.9 ± 42.5	3.34	0.053
	V	Ratio (%)	25.0 ± 2.2	24.0 ± 2.4	22.7 ± 3.1	3.02	0.059
	ICS	mg	298.9 ± 52.4	360.4 ± 57.4	292.1 ± 51.9	6.05	0.005
	ICS	Ratio (%)	23.2 ± 2.7^△	23.9 ± 2.6	22.8 ± 3.2	1.31	0.278
Right lobe	SI		0.38 ± 0.08	0.38 ± 0.09	0.37 ± 0.06	0.157	0.955
	V	ml	495.8 ± 61.9	540.5 ± 40.8	539.7 ± 64.0	3.48	0.039
	V	Ratio (%)	49.3 ± 3.4	46.0 ± 2.0	50.1 ± 3.4	5.20	0.009
	ICS	mg	621.5 ± 105.8	697.8 ± 81.0	654.6 ± 84.9	2.62	0.009
	ICS	Ratio (%)	48.1 ± 4.8	44.1 ± 3.6	48.1 ± 4.9	3.05	0.044

NASH, non-alcoholic steatohepatitis; SI, standardized iodine parameter; V, volume; ICS, segmental iodine content.

Table 3.

Segmental volume and iodine parameters for etiology sub-groups in Child-Pugh C.

Segments	Parameters		Virus	Alcholism	NASH	χ²	P
C1	SI	mg/mL	0.36 ± 0.07	0.37 ± 0.08	0.34 ± 0.08	0.263	0.770
	V	mL	91.1 ± 9.2	116.7 ± 17.1	95.0 ± 20.3	13.06	0.000
	V	(%)	12.2 ± 1.5	12.9 ± 1.0	11.6 ± 1.8	1.968	0.153
	ICS	mg	109.2 ± 27.6	132.4 ± 28.3	112.5 ± 28.7	2.50	0.095
	ICS	Ratio (%)	12.4 ± 1.7	14.0 ± 2.6	11.6 ± 2.3	3.02	0.060
C2	SI	mg/mL	0.36 ± 0.07	0.37 ± 0.08	0.35 ± 0.06	0.214	0.808
	V	mm³	207.5 ± 21.7	259.5 ± 50.5	235.9 ± 39.7	9.0	0.001
	V	Ratio (%)	27.7 ± 2.7	28.7 ± 3.3	28.9 ± 3.5	0.675	0.515
	ICS	mg	240.4 ± 45.3	269.4 ± 47.2	270.5 ± 43.1	2.12	0.133
	ICS	Ratio (%)	27.8 ± 3.2	28.5 ± 3.7	28.1 ± 4.2	0.16	0.85
C3	SI	mg/mL	0.36 ± 0.07	0.37 ± 0.08	0.35 ± 0.07	0.415	0.800
	V	mL	90.6 ± 8.8	109.6 ± 8.4	93.4 ± 9.0	17.0	0.000
	V	Ratio (%)	12.1 ± 0.9	12.3 ± 1.8	11.6 ± 1.7	0.669	0.518
	ICS	mg	106.4 ± 25.8	115.3 ± 30.0	107.7 ± 20.1	0.423	0.658
	ICS	Ratio (%)	12.1 ± 1.1	12.1 ± 2.6	11.2 ± 1.8	0.85	0.435
Right lobe	SI	mg/mL	0.31 ± 0.06	0.33 ± 0.05	0.30 ± 0.05	1.224	0.303
	V	mL	361.3 ± 47.1	414.5 ± 66.8	390.3 ± 53.9	3.74	0.033
	V	Ratio (%)	48.0 ± 3.6	45.9 ± 4.1	47.8 ± 4.6	1.03	0.366
	ICS	mg	421.8 ± 85.1	441.7 ± 98.1	476.1 ± 70.6	1.112	0.339
	ICS	Ratio (%)	48.5 ± 5.8	46.1 ± 4.9	49.3 ± 4.6	0.914	0.409

NASH, non-alcoholic steatohepatitis; SI, standardized iodine parameter; V, volume; ICS, segmental iodine content.

Segmental comparisons

The segmental parameters comparison between the Child-Pugh A and control group are shown in Fig. 3(b) and Table 1. The SI values of the left and caudal lobes of the liver are not significantly reduced compared to the control group as a result of compensation (P > 0.05), whereas the left inner segment and right lobes atrophy and the SI values decrease (P < 0.05). In addition, the volume and iodine content compensation of the left lateral segment and caudate lobe in the cirrhosis group increased in the right anterior segment and decreased in the posterior segment compared to the others (P < 0.001). Also, the proportion of compensation of the ICS proportion in group A is more obvious than that of the volume proportion.

The comparison of the Child-Pugh B groups is shown in Fig. 3(c) and Table 2. The SI in the caudate and left lateral segment is higher compared to the other two, with no statistical significance (P > 0.05), whereas the ICS reaches statistical significance (P < 0.05). There were no significant differences in the other segments (C3–C5) (P > 0.05). Moreover, the volume and iodine content in the caudate lobe and left lateral segment in the alcholism group was significantly higher compared to the virus-related and NASH groups (all P < 0.05). Also, the decrease in volume and content of iodine in the medial segment is more obvious in group V than in groups A and N (P < 0.05). The iodine content of the right anterior segment in the alcholism group did not significantly differ from those in the other two groups (P > 0.05), but its proportion atrophied significantly (P < 0.05). The iodine content of the right posterior segment in the virus group atrophied more significantly than volume.

The comparison for the Child-Pugh C groups is shown in Fig. 3(d) and Table 3. In each segment, the volume of alcoholism cirrhosis was still higher than that of the other two etiologies of cirrhosis (P < 0.05), but there was no statistically significant difference in SI value and ICS compared to the other pathological types (P > 0.05). The volume compensation of each segment alcholism group was higher than in the other two groups (P < 0.05), but the relative proportion showed no significant difference (P > 0.05), whereas the SI value and the ICS and its proportion also showed no significant difference (P > 0.05).

ROC curve

The ROC curve of ICt_BSA, Vt-BSA and the segmental SI for the diagnosis of liver cirrhosis is shown in Fig. 4. The best two parameters of AUC (i.e. area under the receiver operating characteristic curve) for cirrhosis diagnosis were the SI4 and ICt_BSA, which were 0.730 and 0.765, respectively. There was no statistically significant difference between the two (P > 0.05), but the AUC of both was higher than the SI1, SI2, SI3 and Vt values. The sensitivity and specificity of ICt_BSA were 76.0% and 71.8%, respectively.

Fig. 4.

ROC analysis for the parameters for liver cirrhosis. (a) ICt_ BSA, Vt_BSA (total hepatic iodine content and liver volume to BSA) and standardized iodine value in C1, C2, C3 and C4 segments for liver cirrhosis. The AUC differences in parameters were compared using DeLong's test. P < 0.05 indicates statistical significance. In the table below, ○, ●, ▽ and * indicate that this variable has statistical differences compared to SI1, SI2, SI3 and SI4, respectively. (b) * Indicates a statistically signifcant difference between this parameter compared to ICt_BSA.

Radiation dosage

The effective radiation dose length of DLP was 345.8 ± 53.4 gy/cm for single energy scanning and 290.5 ± 36.2 gy for dual-energy scanning. The effective radiation dose (21) of the dual-energy scanning was lower than that of the single energy scanning (5.18 ± 0.80 vs. 4.35 ± 0.54 mSv, P < 0.001).

Discussion

In the present study, regarding the compensatory stage of liver cirrhosis, our results showed that the SI value in the caudate lobe and the left lateral lobe did not change much, but decreased in the left inner lobe and the right lobe. However, in terms of volume, the right lobe of atrophied and left lobe and caudate lobe compensated for hypertrophy, and the compensatory hypertrophy was predominant for alcoholism cirrhosis. With the development of liver cirrhosis, as well as that for the Child-Pugh C group, our results indicated that the segmental SI value with different etiologies in the three groups did not show a statistical difference. In terms of volume, the hypertrophy of each segment still demonstrated significance compared to the other two groups, but no difference in iodine content. In the early stage of liver cirrhosis, it is valuable to show the difference in blood flow changes and volume changes of the alcoholic liver with other two causes, and, with the progression of liver cirrhosis, this difference gradually disappears, although the volume of alcoholic cirrhosis is still larger compared to that of the other types.

The SI value decreased with liver cirrhosis progression. The standardized iodine (SI) parameters in the left lateral segment and the caudate lobe did not significantly change compared to the control group, but significantly decreased in the medial segment and the right lobe, which was consistent with previous studies (19,20). The iodine value in the portal phase is the average iodine content perfusion in the veins and microvessels, which indirectly reflects local blood perfusion of the liver (18,19). In the early stage of liver cirrhosis, the perfusion of the lateral segment and caudate lobe acts in a compensatory manner instead of restrictively, whereas the right lobe atrophies, which is considered to be related to the characteristics of blood supply for each segment in the process of liver cirrhosis (19,20). When the portal vein entries the liver, it ramifies into two main branches supplying the left and the right lobes, whereas the short hepatic vein supplies the caudal lobe from the portal vein (22 –24). As a result of the stimulation of chronic diseases and hepatic fibrosis, sclerotic nodules are gradually formed in the sclerotic liver, decreasing the elasticity of liver parenchyma, which in turn increases the compression of the blood vessels and decreases blood perfusion (24 –26). However, the left portal vein goes through the hepatic fissure first after being separated from the portal trunk, which is significantly widened in the liver cirrhosis, thus ensuring that this segment of the blood vessel is not compressed by surrounding tissue. The short hepatic vein supplying the caudate lobe, which is directly separated from the portal trunk with no obvious pressure around it, also has a compensatory ability in liver cirrhosis (19,20).

Our results showed that the ICS of virus-related cirrhosis decreased most significantly in all stages compared to the other two etiologies (Fig. 5), appearing as a lighter orange color on the portal phase iodine mixed map. The volume and blood perfusion atrophy were lower in alcoholism-related cirrhosis, appearing as a deeper orange color (Fig. 5). These data suggest that not all causes will lead to a decrease in blood perfusion (19,27,28) in the early cirrhosis stage. The segmental evaluation further suggests that the hypertrophy and compensatory perfusion in the lateral lobe and caudate lobe increases more obviously in alcoholic cirrhosis than in patients with virus-related and NASH-related cirrhosis (20).

Fig. 5.

Comparison of portal phase of axial iodine mixed images in (a) a 55-year-old man with virus-related cirrhosis, (b and b*) in a 58-year-old man with alcoholic cirrhosis and (c) in a 62-year-old man with non-alcoholic steatohepatitis (NASH)-related cirrhosis in Child-Pugh A. Comparison of iodine mixed images in (d) a 59-year-old man with virus-related cirrhosis, (e) in a 65-year-old man with alcoholic cirrhosis and (f) in a 55-year-old man with non-alcoholic NASH-related cirrhosis in Child-Pugh B. Comparison of iodine mixed images in (g) a 65-year-old man with virus-related cirrhosis, (h) in a 61-year-old man with alcoholic cirrhosis and (i) in a 49-year-old man with NASH-related cirrhosis in Child-Pugh C. The images showed atrophy of the medial segmengt (③) and right lobe (④ and ⑤) and compensatory hypertrophy of the left lateral (②) segment and caudate lobe (①). The orange pseudo-color gradually becomes lighter in iodine mixed mapping, representing the iodine content decreasing with the progression of liver cirrhosis. In Child-Pugh A and B, the iodine content of alcoholism was higher than that of virus-related group and NASH-related group, showing a deeper orange (marked by white ∗). “V” in the white circle (b, e, i) represents the reference iodine value of the portal vein used to standardize the iodine concentration in each segment.

In the present study, the blood perfusion of the liver was quantified, and the segmental SI parameters in patients with different etiologies were measured and compared. Compared with volume evaluation or general functional indicators of the Chid-Pugh grading system, the quantitative evaluation of iodine parameters in a segmental view may provide a segmental evaluation in a non-invasive way, such that it is beneficial to clinical practice. Furthermore, its radiation dose is relatively lower than that of a single energy scan, making it more beneficial for patients. However, the present study also has a few limitations. First, despite the limited sample size, there were more virus-related cases in the etiological distribution (29), in addition to race subspecies. In addition, our etiological grouping of cirrhosis is mainly based on clinical histories and relevant previous imaging data, which may have some pathological selectivity errors. Thus, further multi-center studies with a larger sample are needed to verify the reliability of the results obtained in the present study. Second, the ROI was analyzed using semi-manual software. Because the top of the liver is close to the diaphragm, there may be manual errors caused by the volume effect. Third, the iodine concentration is the average value of ROIs, which may also have a certain selectivity error.

In conclusion, the present study explored the characteristics of changes in each segment of liver cirrhosis in the process of liver cirrhosis with different causes by quantitative iodine mixed mapping, providing useful reference information for the clinical understanding of segmented blood flow perfusion in different etiological types of liver cirrhosis on the basis of changes in volume morphology. Furthermore, DECT scanning does not increase the radiation dose and also benefits patients.

Footnotes

Author contributions

Changqin Jiang and Qiang Feng were responsible for study conceptualization. Wanwei Zhang and Ruisheng Jiang were responsible for data curation. Changqin Jiang was responsible for formal analysis. Qiang Feng was responsible for funding acquisition. Zhijun Ma and Haixia Dong were responsible for investigations. Changqin Jiang and Qiang Fang were responsible for the methodology. Qiang Feng was responsible for study project administration. Qiang Feng was responsible for resources. Changqin Jiang was responsible for software. Zhaoqian Wang was responsible for supervision. Qiang Feng was responsible for study validation. Changqin Jiang, Ruisheng Jiang, Wanwei Zhang, Haixia Dong, Zhijun Ma, Zhaoqian Wang and Qiang Feng were responsible for visualization. Changqin Jiang, Ruisheng Jiang, Wanwei Zhang, Haixia Dong, Zhijun Ma, Zhaoqian Wang and Qiang Feng were responsible for writing the original draft. Changqin Jiang, Ruisheng Jiang, Wanwei Zhang, Haixia Dong, Zhijun Ma, Zhaoqian Wang and Qiang Feng were responsible for reviewing and editing.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Ethics approval

The study was based on the Declaration of Helsinki. The study was approved by the ethics Committee of Yidu Central Hospital of Weifang Medical University, and informed consent was obtained from all patients.

Consent to participate

Informed consent was obtained from all patients.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Weifang Municipal Health and Health Commission, (grant number WFWSJK-2020-059)

ORCID iD

Qiang Feng

References

Schuppan

Afdhal

. Liver cirrhosis. Lancet 2008;371:838–851.

Pagliaro

. MELD: the end of child-pugh classification? J Hepatol 2002;36:141–142.

Befeler

Di Bisceglie

. Hepatocellular carcinoma: diagnosis and treatment. Gastroenterology 2002;122:1609–1619.

Begg

Cramer

Hoskins

, et al. Impact of hospital volume on operative mortality for major cancer surgery. JAMA 1998;280:1747–1751.

Regimbeau

Kianmanesh

Farges

, et al. Extent of liver resection influences the outcome in patients with cirrhosis and small hepatocellular carcinoma. Surgery 2002;131:311–317.

Kawasaki

Makuuchi

Matsunami

, et al. Preoperative measurement of segmental liver volume of donors for living related liver transplantation. Hepatology 1993;18:1115–1120.

Frericks

Kirchhoff

Shin

, et al. Preoperative volume calculation of the hepatic venous draining areas with multi-detector row CT in adult living donor liver transplantation: impact on surgical procedure. Eur Radiol 2006;16:2803–2810.

Ozaki

Matsui

Kobayashi

, et al. Selective atrophy of the middle hepatic venous drainage area in hepatitis C-related cirrhotic liver: morphometric study by using multidetector CT. Radiology 2010;257:705–714.

Zhou

Wei

, et al. Liver volume variation in patients with virus-induced cirrhosis: findings on MDCT. AJR Am J Roentgenol 2007;189:W153–W159.

10.

Jia

Xiaojun

Chen

, et al. The application of multi- slice spiral CT perfusion imaging in evaluation of cirrhosis circulation. J Ningxia Med Univ 2013.

11.

Harbin

Robert

Ferrucci

Jr.

Diagnosis of cirrhosis based on regional changes in hepatic morphology: a radiological and pathological analysis. Radiology 1980;135:273–283.

12.

Sahani

Holalkere

Mueller

, et al. Advanced hepatocellular carcinoma: cT perfusion of liver and tumor tissue–initial experience. Radiology 2007;243:736–743.

13.

Zhou

, et al. A study of CT perfusion imaging in blood distribution of normal liver. J Pract Radiol 2013;29:1266–1268.

14.

Xia

, et al. Assessment of hepatic functional reserve by cirrhosis grading and liver volume measurement using CT. World J Gastroenterol 2007;13:3956–3961.

15.

Talakić

Schaffellner

Kniepeiss

, et al.

CT Perfusion imaging of the liver and the spleen in patients with cirrhosis: is there a correlation between perfusion and portal venous hypertension?

Eur Radiol 2017;27:4173–4180.

16.

Chen

, et al. [Whole-liver perfusion imaging by multi-slice spiral computed tomography based on couinaud segments for evaluation of the blood flow state in patients with hepatitis B cirrhosis]. Zhonghua Gan Zang Bing Za Zhi 2014;22:817–821.

17.

Goo

. Dual-energy CT: new Horizon in medical imaging. Korean J Radiol 2017;18:555–569.

18.

Song

Kim

Park

, et al. Utility of iodine overlay technique and virtual unenhanced images for the characterization of renal masses by dual-energy CT. AJR Am J Roentgenol 2011;197:W1076–W1082.

19.

Jiang

Shen

Xia

, et al. Mixed imaging on port-venous phase of contrast-enhanced dual-source dual-energy computed tomography: a measurement method based on couinaud segments. J Comput Assist Tomogr 2018;42:944–953.

20.

Ozaki

Matsui

Kobayashi

, et al. Morphometric changes in liver cirrhosis: aetiological differences correlated with progression. Br J Radiol 2016;89:20150896.

21.

Golding

. European guidelines on quality criteria for computed tomography. Eur Communities. Report Eur, 1999: 16262.

22.

Heriot

Karanjia

. A review of techniques for liver resection. Ann R Coll Surg Engl 2002;84:371–380.

23.

Hashimoto

Murakami

Dono

, et al. Assessment of the severity of liver disease and fibrotic change: the usefulness of hepatic CT perfusion imaging. Oncol Rep 2006;16:677–683.

24.

Van Beers

Leconte

Materne

, et al. Hepatic perfusion parameters in chronic liver disease: dynamic CT measurements correlated with disease severity. AJR Am J Roentgenol 2001;176:667–673.

25.

Vignaux

Legmann

Coste

, et al. Cirrhotic liver enhancement on dual-phase helical CT: comparison with noncirrhotic livers in 146 patients. AJR Am J Roentgenol 1999;173:1193–1197.

26.

Zhang

Wang

, et al. Quantitative dual energy CT measurements in rabbit VX2 liver tumors: comparison to perfusion CT measurements and histopathological findings. Eur J Radiol 2012;81:1766–1775.

27.

Sherman

Thomas

Chung

. Human immunodeficiency virus and liver disease forum 2012. Hepatology 2014;59:307–317.

28.

McCullough

O’Shea

Dasarathy

. Diagnosis and management of alcoholic liver disease. J Dig Dis 2011;12:257–262.

29.

Wallace

Burt

Wright

. Liver fibrosis. Biochem J 2008;411:1–18.