We aim to investigate the hemodynamics in focal steatosis and focal spared lesion of the liver using contrast-enhanced ultrasonography (CEUS) with Sonazoid. The subjects were 47 patients with focal steatosis and focal spared lesion. We evaluated enhancement patterns (hyperenhancement, isoenhancement, and hypoenhancement) in the vascular phase and the presence or absence of a hypoechoic area in the postvascular phase for these lesions using CEUS. Of the 24 patients with focal steatosis, the enhancement pattern was isoenhancement in 19 and hypoenhancement in 5. Hypoechoic areas were noted in the postvascular phase in 3 patients. Of the 23 patients with focal spared lesions, the enhancement pattern was isoenhancement in 18 and hyperenhancement in 5. No hypoechoic areas were noted in the postvascular phase in any patient. The hemodynamics in focal steatosis and focal spared lesions in nondiffuse fatty liver can be observed using low-invasive procedures in real-time by CEUS. It was suggested that differences in the dynamics of enhancement in the vascular phase of CEUS were influenced by the fat deposits in the target lesion, the surrounding liver parenchyma, and the third inflow.
Nondiffuse fatty liver is considered to develop when the fat accumulation ability of hepatocytes or fat deposition becomes heterogeneous throughout the liver and is classified into the following 4 types: focal steatosis, multifocal steatosis, lobar or segmental steatosis, and focal spared lesion in fatty liver [
Some cases of focal steatosis and focal spared lesion exhibit an oval or mass-like appearance on imaging, and differentiation from liver tumors may be problematic. In this study, we performed contrast-enhanced ultrasonography (CEUS) for focal steatosis and focal spared lesions using Sonazoid (Daiichi Sankyo Pharmaceutical, Tokyo, Japan), in order to diagnose liver mass lesions, and obtained information on the hemodynamics of focal steatosis and focal spared lesions. Herein, we report these data with a review of the literature.
The subjects were 47 patients in whom liver mass lesions were detected on abdominal ultrasonography during health check-up and underwent CEUS with Sonazoid. The findings of these patients were investigated retrospectively. These were diagnosed with focal steatosis (24 cases) or a focal spared lesion (23 cases) on dynamic computed tomography (CT) and magnetic resonance imaging [
All CEUS images were reviewed by two hepatologists, one was with 15 years of experience and other was with 27 years of experience.
The presence or absence of an existing blood vessel in the lesion and the enhancement pattern (hyperenhancement, isoenhancement, and hypoenhancement) in the vascular phase were compared using Fisher’s exact test. Statistical analyses were performed using SPSS version 11.0 (Statistical Package for the Social Sciences) for Windows (Microsoft) and
This study was approved by the Ethical Review Board of Toho University Medical Center, Omori Hospital.
Of the 24 patients with focal steatosis (Table
Of the 24 lesions with focal steatosis, patients character, location, size, enhancement pattern in the vascular phase of CEUS, presence of existing blood vessel in the CDUS and/or the vascular phase, presence of hypoechoic area in the postvascular phase, and ADF mode of CEUS.
No. | Age | Sex | Location | Size (mm) | Vessels seen on CDUS or/and CEUS | CEUS | |
---|---|---|---|---|---|---|---|
Vascular | Postvascular/ADF | ||||||
1 | 60 | F | S4/Transverse portion | 28 | + | Iso | −* |
2 | 73 | F | S4/Sappey’s vein area | 25 | + | Hypo | − |
3 | 72 | M | S5/GB bed | 25 | + | Iso | − |
4 | 80 | M | S4/Transverse portion | 36 | + | Iso | − |
5 | 45 | M | S4/GB bed | 8 | + | Iso | + |
6 | 49 | M | S4/Sappey’s vein area | 21 | + | Iso | − |
7 | 62 | M | S4/Sappey’s vein area | 15 | + | Hypo | − |
8 | 76 | F | S4/Transverse portion | 20 | Iso | − | |
9 | 85 | F | S3/Umbilical portion | 7 | Iso | − | |
10 | 59 | M | S4/Transverse portion | 18 | Hypo | − | |
11 | 48 | F | S4/Sappey’s vein area | 12 | Iso | − | |
12 | 68 | F | S4/Transverse portion | 14 | Iso | − | |
13 | 67 | F | S4/Adjacent to IVC | 40 | Iso | − | |
14 | 50 | M | S5/Right lobe surface | 15 | Iso | − | |
15 | 31 | M | S8/Right lobe surface | 8 | Iso | − | |
16 | 66 | F | S5/GB bed | 30 | Iso | − | |
17 | 74 | M | S4/Transverse portion | 8 | Iso | − | |
18 | 80 | F | S4/Transverse portion | 27 | Iso | − | |
19 | 64 | M | S4/Sappey’s vein area | 31 | Iso | − | |
20 | 45 | F | S4/Sappey’s vein area | 20 | Iso | − | |
21 | 65 | M | S5/GB bed | 19 | Hypo | − | |
22 | 40 | M | S5/Other area of the right lobe | 15 | Iso | − | |
23 | 49 | F | S5/Other area of the right lobe | 8 | Iso | + | |
24 | 75 | M | S4/Transverse portion | 30 | Hypo | + |
GB: gall bladder, Iso: isoenhancement, hypo: hypoenhancement, ADF: advanced dynamic flow.
*−: no hypoechoic area, +: hypoechoic area.
The enhancement pattern in the vascular phase of CEUS was isoenhancement in 19 patients and hypoenhancement in 5 (Figure
A 75-year-old male (case no. 24) with focal steatosis in the S4 (transverse portion). (a) In-phase T1-weighted magnetic resonance image (MRI) scan shows the isointense lesion (arrow) in the S4 (transverse portion). (b) The lesion is hypointense on an out of-phase T1-weighted MRI scan (arrow) and is diagnosed as focal steatosis. (c) Gray-scale ultrasonography (US) (right intercostal axis) shows a hyperechoic lesion (arrow). (d) Left: in the vascular phase (17 seconds) of contrast-enhanced ultrasonography (CEUS) (right subcostal axis), the lesion (arrow) is hypoenhancement compared with the surrounding liver. Right: gray-scale US (monitor mode) (arrow). (e) In the advanced dynamic flow (ADF) mode of the postvascular phase of CEUS (right intercostal axis), the lesion shows a hypoechoic area (arrow).
A hypoechoic area was noted in the postvascular phase in 3 patients, which was also evident using the ADF mode in these same 3 patients.
Of the 23 patients with focal spared lesions (Table
Of the 23 lesions with focal spared lesions, patients character, location, size, enhancement pattern in the vascular phase of CEUS, presence of existing blood vessel in the CDUS and/or the vascular phase, presence of hypoechoic area in the postvascular phase, and ADF mode of CEUS.
No. | Age | Sex | Location | Size (mm) | Vessels seen on CDUS or/and CEUS | CEUS | |
---|---|---|---|---|---|---|---|
Vascular | Postvascular/ADF | ||||||
1 | 44 | M | S4/GB bed | 60.9 | + | hyper | −* |
2 | 75 | F | S5/GB bed | 12 | + | Iso | − |
3 | 69 | F | S6/Right hepatic hilum | 14 | + | hyper | − |
4 | 48 | M | S5/GB bed | 12 | + | Iso | − |
5 | 35 | F | S4/Sappey’s vein area | 21 | + | hyper | − |
6 | 52 | M | S5/GB bed | 17 | Iso | − | |
7 | 45 | M | S6/Right lobe surface | 19 | Iso | − | |
8 | 70 | M | S7/Right lobe surface | 41 | Iso | − | |
9 | 37 | F | S6/Right lobe surface | 20 | Iso | − | |
10 | 62 | F | S8/Other area of the right lobe | 18 | Iso | − | |
11 | 52 | M | S5/Right lobe surface | 12 | hyper | − | |
12 | 59 | M | S8/Right lobe surface | 23 | hyper | − | |
13 | 64 | M | S4/Transverse portion | 22 | Iso | − | |
14 | 45 | M | S5/GB bed | 18 | Iso | − | |
15 | 24 | M | S5/GB bed | 20 | Iso | − | |
16 | 71 | F | S8/Other area of the right lobe | 15 | Iso | − | |
17 | 47 | F | S3/Umbilical portion | 13 | Iso | − | |
18 | 59 | M | S4/Transverse portion | 40 | Iso | − | |
19 | 34 | M | S4/Transverse portion | 20 | Iso | − | |
20 | 36 | M | S6/Right lobe surface | 30 | Iso | − | |
21 | 60 | M | S7/Right lobe surface | 35 | Iso | − | |
22 | 56 | M | S6/Right lobe surface | 27 | Iso | − | |
23 | 72 | F | S5/GB bed | 14 | Iso | − |
GB: gall bladder, hyper: hyperenhancement, Iso: isoenhancement, ADF: advanced dynamic flow.
*−: no hypoechoic area.
The enhancement pattern in the vascular phase of CEUS was isoenhancement of the lesion in 18 patients and hyperenhancement of the lesion in 5 (Figure
A 35-year-old female (case No. 5) with focal spared lesion in the S4 (near the falciform ligament of liver so called Sappey’s vein area). (a) Unenhanced computed tomography (CT) scan shows a hyperattenuating lesion (arrow) in the S4. (b) Enhanced CT scan shows the lesion (arrow) of hyperattenuation in the portal phase. (c) Gray-scale US (right intercostal axis) shows a hypoechoic lesion (arrow). (d) Color Doppler ultrasonography (CDUS) (right intercostal axis) shows hepato petal flow (arrow head) toward the lesion (arrow). (e) Left: In the vascular phase (13 seconds) of CEUS (right intercostal axis), the lesion (arrow) is hyperenhancement compared with the surrounding liver. Right: Gray-scale US (monitor mode) (arrow).
An existing blood vessel was noted in the lesion in the vascular phase in 5 patients. On comparison of the enhancement patterns, the patterns were hyperenhancement and isoenhancement of the lesions in 3 and 2 of the 5 patients with existing blood vessels, respectively, and in 2 and 16 of the lesions of the 18 patients with no existing blood vessels, respectively, showing a significant difference (
No hypoechoic areas were noted in the postvascular phase in any patient. Nine patients were observed using the ADF mode, but no hypoechoic areas were noted.
Fatty liver is caused by the accumulation of triglycerides and other nutrients within hepatocytes and is roughly divided into diffuse and nondiffuse fatty liver. Nondiffuse fatty liver is further classified into 4 types: focal steatosis, multifocal steatosis, lobar or segmental steatosis, and focal spared lesion in the fatty liver [
For focal steatosis and focal spared lesions, hemodynamics has been reported on CEUS using SonoVue (Bracco, Milan, Italy) [
Liu et al. [
Liu et al. also investigated the time required for contrast agent to reach and enter the lesion with focal steatosis [
Among the 23 patients with focal spared lesions, isoenhancement and hyperenhancement of the lesions were noted in the vascular phase of CEUS in 18 and 5 patients, respectively, and no hypoenhancement was noted in any patient. In the focal steatosis cases described above, enhancement tended to decrease in the focal steatosis lesion, compared with that in the surrounding liver parenchyma, due to the influence of fatty cells. In these focal spared lesions, isoenhancement was noted in most cases, but hyperenhancement was noted in some cases. This may have been due to fatty cell-induced exclusion and narrowing of blood vessels in the surrounding liver parenchyma by fatty cells [
Regarding the existing blood vessels and the enhancement pattern in focal steatosis and focal spared lesions, no significant correlation was noted between the presence of an existing blood vessel and the enhancement pattern in focal steatosis. In contrast, in focal spared lesions, existing blood vessels were noted in 3 of the 5 cases with hyperenhancement, showing a significant difference. The presence or absence of an existing blood vessel may influence the enhancement dynamics in focal spared lesions.
In the postvascular phase, hypoechoic areas were noted in 3 of the 24 focal steatosis cases, and these hypoechoic areas were also observed using the ADF mode in each of these cases. In contrast, no hypoechoic areas were noted in any of the 23 cases of focal spared lesion or of the 9 cases observed using the ADF mode. These findings suggest that the phagocytic ability of Kupffer cells is reduced in fat-containing cells compared with normal liver cells.
It was clarified that hemodynamics in lesions can be observed using low-invasive procedures in real-time by CEUS using Sonazoid in comparison with the previous CT angiography. And it was suggested that Kupffer function (phagocytosis) in the lesions could be evaluated by observing the postvascular phase. In addition, hypoechoic areas were noted in some of the focal steatosis cases in the postvascular phase. We require attention for differentiation of these lesions and malignant tumors.
Among the limitations, this study was retrospective in nature, that is, the number of cases was small, the lesions were not diagnosed histologically, and it was unclear whether the existing blood vessel within the lesions represented an artery, vein, or portal vein. It may be necessary to increase the number of cases and perform further evaluations including histopathological investigation.
We investigated the hemodynamics in focal steatosis and focal spared lesions in nondiffuse fatty liver by CEUS using Sonazoid. It was suggested that differences in the dynamics of enhancement in the vascular phase of CEUS were influenced by fat deposits in the target lesion and the surrounding liver parenchyma and the third inflow and that the fat deposition-associated phagocytic ability of Kupffer cells is involved with the presence or absence of the hypoechoic area in the postvascular phase.
As for the knowledge provided in this study, it will seem that it is necessary in future in distinguishing a malignant tumor from these lesion.
Contrast-enhanced ultrasonography
Computed tomography
Color Doppler ultrasonography
Mechanical index
Advanced Dynamic Flow
CT during arterial portography.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 [
There are no financial or other relations that could lead to a conflict of interests.