Abstract
Focal liver lesions (FFLs) evaluated using contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT) may have the same or similar findings or substantial discrepant findings. Such phenomenon can be found in two performances of CEUS that the second performance of CEUS conducted shortly following the initial performance of CEUS. Discrepancy of two performances of CEUS for FFLs occurring in the same patient at a short internal has not been well addressed, which raises challenge for CEUS for the evaluation of FFLs. In this case study, such phenomenon is illustrated and implication is obtained.
Introduction
Contrast-enhanced ultrasound (CEUS) has been used widely for the evaluation of focal liver lesions (FFLs) in the world, for dynamic perfusion ultrasound imaging can obtain more information than that by conventional ultrasound [1–5]. Hepatocellular carcinoma is a fatal disease, and a number of FFLs need to differentiate from it, such as hemagioma, focal nodular hyperplasia, regenerative nodules, focal fat sparing, focal steatosis areas, metastatic tumor, intrahepatic cholangiocarcinoma, hepatic abscess, and so on. It’s hard to make a definitive diagnosis using gray-scale ultrasound and color Doppler flow imaging(or power Doppler angiogram, or super-resolution ultrasound microvessel imaging), especially for some atypical cases, while on contrast-enhanced ultrasound, it’s easy to identify the lesions with typical features, and can render additional information for the assessment of some lesions with atypical features [6–8]. In clinical practice, we found that some FFLs presented consistent characteristics and patterns, some others presented discrepant characteristics and patterns, comparing the second performance of CEUS conducted shortly following the initial performance of CEUS. Why there was discrepancy of image characteristics of FFLs occurring in the same patient at a short internal had not been well addressed. These raised challenge for CEUS for the evaluation of FFLs. Such phenomena may be illustrated by the following example.
Case description
A 54 year-old-woman referred to a physician because of right epigastric region uncomfortable 5 days. She declared she had no history of unusual diseases. Physical examination revealed her liver was enlarged, with unambiguous stiff mass, and no tenderness and abdominal guard were elicited. Clinical laboratory tests showed the serum tumor markers were in normal limits. A Siemens Acuson S2000 ultrasound system (Siemens Healthcare, Ultrasound Business Unit, Mountain View, CA, USA) with a multifrequency curved array transducer was used for the evaluation of the liver. Gray-scale ultrasound and color Doppler flow imaging examination of the liver showed there was an ovoid mass in the segment VIII of the liver, the maximal sectional size was 96 mm×83 mm, with discernible border and blurring margin and internal heterogeneous isoechogenicity, without posterior acoustic enhancement effect, and vasculature was invisible (Figs. 1a and a’). On the first performance of CEUS, after 2.4 mL suspension medium of sulphur hexafluoride microbubbles (SonoVue) was injected in bolus via left radial vein, a little hyper-enhancement presented at the periphery of the FFL at the arterial (Figs. 1b c) and portal phases (Figs. 1d e), it presented hyper-echogenicity at delayed phase (Fig. 1f), and majority of the mass did not show enhancement. The transducer was placed at right subcostal and subxiphoid region, with the acoustic beam directing to the FFL. For further evaluation, the burst model was performed to break the residual contrast agent 5 times, and 2.4 mL suspension medium of sulphur hexafluoride microbubbles was injected in bolus again over 20 minutes. The peripheral region of FFL presented rapid irregular centripetal hyper-enhancement at early arterial phase (Figs. 1b’ c’) and portal phase (Figs. 1d’ e’), it presented hyper-echogenicity at delayed phase (Fig. 1f), and majority of the FFL did not show enhancement. At this time, the transducer was placed at the right anterior intercostal space, with the acoustic beam directing to the FFL. To make proper management, contrast-enhanced CT and MRI were performed for further evaluation, and the imaging characteristics of the FFL at arterial phase (Figs. 1g and g’ of CT) and portal phase ( Figs. 1h and h’ of CT; and Figs. 1i of MRI) were consistent with those at the second CEUS, indicating the pathology of the FFL is a hemangioma, with internal degeneration and necrosis.
A 54 year-old-woman with a FFL in the liver. On gray-scale sonography, the mass presented ovoid in the segment VIII of the liver, the size was 96 mm×83 mm, with discernible border and blurring margin and internal heterogeneous isoechogenicity, without post acoustic enhancement effect (a); Color Doppler flow imaging did not show vasculature (a’).
At arterial phase, the FFL presented a little hyper-enhancement presented at the periphery at first performance of CEUS (b), and it presented rapid irregular centripetal hyper-enhancement at the second performance of CEUS (b’).
At arterial phase, the FFL presented a little hyper-enhancement presented at the periphery at first performance of CEUS (c), and it presented rapid concentric irregular hyper-enhancement at the second performance of CEUS (c’).
At portal phase, the FFL presented a little increased hyper-enhancement presented at the periphery at first performance of CEUS (d), and it presented sustained irregular centripetal hyper-enhancement at the second performance of CEUS (d’).
At portal phase, the FFL presented a little increased hyper-enhancement presented at the periphery at first performance of CEUS (e), and it presented sustained irregular centripetal hyper-enhancement at the second performance of CEUS (e’).
At delayed phase, the FFL presented limited hyper-enhancement at the periphery at first performance of CEUS (f), and it presented sustained irregular hyper-enhancement at the second performance of CEUS (f’).
On the images of contrast-enhanced CT, at arterial phase, the FFL presented nodular irregular centripetal hyper-enhancement (g and g’).
On the images of contrast-enhanced CT, at portal phase, the FFL presented sustained irregular hyper-enhancement at peripheral region (h and h’). It presented sustained irregular hyper-enhancement at peripheral region at delayed phase, and majority of the FFL did not show enhancement (not shown).
On the images of contrast-enhanced MRI, the FFL presented nodular irregular centripetal hyper-enhancement at arterial and portal phase at peripheral region, it presented irregular centripetal hyper- enhancement at delayed phase, and majority of the FFL did not show enhancement (i: Coronal section image of contrast-enhanced T1 FSPGR).
In this case, on the first performance of CEUS, the FFL appeared no enhancement at early arterial phase, and only a small section hyper-enhancement at late arterial phase, portal phase and delayed phase. These findings were different from those found at contrast-enhanced CT and MRI, and many of the rim enhancement characteristics missed. On the second performance of CEUS, the transducer placed in a different position, which was proximal to the well perfusion region and shunned the overlay of unenhanced section on well perfusion (hyper-enhancement) region, the FFL presented earlier and more rapid hyper-enhancement than those at the first imaging, the central unenhanced section showed more marked than that at the first imaging. These findings were consistent with those found at contrast-enhanced CT and MRI in general, and a few of the rim enhancement characteristics missed. The reasons that discrepancy of image render and characterization of FFLs among different imaging modalities have been explained as different imaging protocols and / or different contrast agents [5, 9–15]. In regard to this report, we believe that discrepancy of image characterization between two rounds of CEUS may lay that the differences of image rendering capability and low mechanical index of the ultrasound system (for purpose of CEUS) in the application. When a FFL is scanned by using standard output power (conventional ultrasonography), the image rendered with higher quality; however, when it is scanned by lower output power (9% of standard output power) and low mechanical index (MI 0.06) model (CEUS), the imaging quality is compromised, the image of unenhanced section shows obscurely and is vaguely visible or invisible. The proximal field of FFL can be rendered and characterized better than that in the distal field on CEUS, acoustic attenuation causes the distal region more vaguely visible. The factors affect the visualization of FFL on conventional ultrasound may affect the visualization of FFL on CEUS too, such as the subphrenic location of the tumor [9, 10]. Different from conventional ultrasound imaging, when a patient undergoes CEUS, the transducer is not allowed to be moved arbitrarily at arterial phase and early portal venous phase, the acoustic beam is usually pointing constantly at the same direction, the patient is required to suspend respiration at arterial phase, and these affect the image acquisition of different zones. Taking together, acoustic beam direction, size of FFL and position of the transducer can influence the display, render and characterization of FFL on CEUS. To acquire better characterization of a larger FFL, a second injection of contrast agent and alternative scanning may obtain sufficient information.
Some studies have showed that CEUS has the same or superior capability as that of contrast-enhanced CT or contrast-enhanced MRI for assessment of the therapeutic effect of ablation or transhepatic arterial chemoembolization (TACE) or other procedures for the treatment of larger liver tumors, however, the discrepancies of characterization and diagnostic efficiency among different imaging modalities have been existed [4, 16–19]. The findings of this case suggest that CEUS cannot characterize competently the therapeutic effect of large liver tumors in a single injection of contrast medium, a second CEUS with alternative performance is necessary, which can characterize sufficiently the treated tumors and obtain more reliable assessment information, and thus spare contrast-enhanced CT/MRI.
In this case, the vast majority of the lesion did not present contrast agent perfusion, the reason was believed there was partial necrosis and/or bleeding in the lesion. When a tumor occurs necrosis, the blood vessels in it are disrupted, the contrast-agent perfusion becomes impossible; as a result, no enhancement is observed. Atypical hemangioma with partially necrosis needs to differentiate from intrahepatic cholangiocarcinoma, partially necrotic hepatocellular carcinoma, and hepatic abscess in the non-cirrhotic liver on contrast-enhanced ultrasound [20]. Table 1 shows the typical features of the above lesions.
A concise summary of the typical features of intrahepatic cholangiocarcinoma, partially necrotic hepatocellular carcinoma, hepatic abscess and atypical hemangioma with partially necrosis in the non-cirrhotic liver on contrast-enhanced ultrasound
Collectively, contrast-enhanced ultrasound exhibits great advantage over the characterization of FFLs, as well as the post treatment evaluation of transcatheter arterial chemoembolization for the hepatocellular carcinoma or tumor ablation, however, it cannot completely show the whole tissues of larger tumor. A consecutive second infusion of contrast medium for a second contrast-enhanced ultrasound with the transducer placing at different locations and focusing on different regions of the larger tumor may make up the limitation and realize sufficient characterization and assessment.
Ethical statement
The study was approved by the Ethics Committee of the First Affiliated Hospital of Hainan Medical University[2021 (Scientific Research) No.70], and written informed consent was obtained.
Conflict of interest statement
The authors declare that they have no conflict of interests.