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The role of CEUS in indeterminate liver lesions: A case example
Authors: Rachel Stephens, Olivia Goldberg, Adrian Lim
This video captures the enhancement pattern of the focal liver lesion in our case, where it illustrates the crucial entrifugal enhancement and “spoke-wheel” vascular pattern with no “wash-out” pathognomic for FNH. Note that there are two timers as the video is taken after the second injection of ultrasound contrast (SonoVue). This real time assessment and ability to perform multiple injections is significantly advantageous when compared with contrast enhanced MRI and if often a problem solver.
1Clinical History
A 41-year-old asymptomatic woman was referred for further imaging after a private ultrasound incidentally identified incidental indeterminate liver lesions in the right lobe.
2Image Findings
A MRI demonstrated a 45 mm well-circumscribed lesion in hepatic segment VIII and another 32 mm lesion in segment VI. The MRI characteristics were somewhat indeterminate, with mild T1 and T2 hyperintensity, no diffusion restriction, patchy arterial enhancement with gadolinium and contrast retention on the delayed phase. Their size and morphology were unchanged on an MRI with Primovist 7 months later, which additionally showed a possible central hypoenhancing scar on the delayed phase. However, owing to its indeterminate nature and that possibility of an adenoma could not be excluded entirely on MRI, a subsequent contrast-enhanced ultrasound (CEUS) with SonoVue to confirm the diagnosis and to obviate the need for further follow up was performed.
CEUS revealed an avid arterially enhancing lesion in an organised centrifugal pattern with no washout in the portal venous or late phases. There was also a spoke-wheel vascular pattern delineated on microflow imaging and all these characteristics were pathognomonic for focal nodular hyperplasia.
CEUS revealed an avid arterially enhancing lesion in an organised centrifugal pattern with no washout in the portal venous or late phases. There was also a spoke-wheel vascular pattern delineated on microflow imaging and all these characteristics were pathognomonic for focal nodular hyperplasia.
3Diagnosis
Focal nodular hyperplasia (FNH).
4Discussion
BACKGROUND:
FNH is the second most common benign liver lesion following haemangiomas, thought to originate from disorganised hyperplastic growth of hepatocytes due to vascular malformations and associated blood supply variations [1,2]. They typically present as a solitary (although can be multiple in 20-30% of cases), well-circumscribed mass composed of multiple fibrous septa that converge into a central ‘scar’ with an associated feeder artery and branches [3]. It has no malignant potential. A common differential for FNH are hepatocellular adenomas (HCA), which similarly typically present as a singular, well-defined lesion, however these often have a fibrous pseudo-capsule and lack intralobular bile ducts, allowing for differentiation [4]. HCAs are rarer, with a prevalence of 0.05% within the general population, and are divided into 5 main subtypes based on the genetic (beta-catenin mutated, HNF 1 alpha mutated, sonic hedgehog activated) or inflammatory origins [4].
Both FNH and HCA are primarily discovered incidentally in routine imaging in women (8:1 female predilection) of reproductive age and are thought to be hormone-driven, with HCAs especially demonstrating strong links with oral contraception use [2]. Whilst usually asymptomatic, HCAs have additional associated risks including haemorrhage (25%) and malignant transformation (5%), meaning patients may present with abdominal pain, and in severe cases of rapid bleeding into the peritoneal cavity, HCAs can become life-threatening [4]. As FNH mainly remains stable over many years, this difference in risk highlights the necessity of swift and accurate diagnosis as this has significant impact on management strategies.
CLINICAL PERSPECTIVE:
Contrast-enhanced MRI (CEMRI) has been widely recognised as the gold standard for characterisation of liver lesions, however developments in ultrasound technology are proving highly effective in providing an accurate, quick, cost-effective, and widely available alternative [2]. Conventional B-mode ultrasound and colour Doppler lack sensitivity to provide a high level of diagnostic certainty, especially given that some lesions are isoechoic to the liver parenchyma, making them challenging to detect [3].
Contrast-Enhanced ultrasound (CEUS) relies on microbubble agents such as SonoVue, which consist of sulphur hexafluoride gas bubbles contained within a lipid shell. These microbubbles are a similar size to red blood cells and therefore purely contained within vessels [5], allowing multi-phase imaging of the early (10-30 seconds post-contrast injection), portal venous (30-120 seconds), and late (<120 seconds) phases [2]. In comparison to CEMRI, CEUS has the advantages of speed, real time evaluation of tumour perfusion patterns and lack of nephrotoxic contrast agents [5]. The risk of anaphylaxis is small.
FNH has a characteristic centrifugal, or ‘spoke-wheel,’ enhancement pattern in the early arterial phase, reflecting the vascular architecture of a central feeding artery with radiating branches, opposed to HCA which typically displays centripetal or mixed perfusion [2,4]. The advantage of CEUS is that there is real time dynamic evaluation of the arterial enhancement as in our case where Cine-clips using CEUS demonstrated centrifugal filling, and persistence of the arterial phase enhancement into the late phase, providing strong evidence for a diagnosis of FNH in this instance, following indeterminate CEMRI with gadolinium and Primovist. The internal microvasculature was partially demonstrated on power Doppler, but CEUS and microflow imaging was superior in delineating the pathognomonic “spoke-wheel” vascular pattern. CEUS also has additional benefits of rapidity, taking less than 5 minutes, and a flash-reperfusion mode allowing assessment of the initial enhancement characteristics. Unlike CEMRI, multiple repeat contrast injections are also possible in cases of uncertainty allowing the rapid arterial enhancement patterns of lesions to be more accurately assessed.
Multiple studies indicate similar success in the utility of CEUS in diagnosis of liver lesions, with one multi-centre study finding a diagnostic accuracy of 98.8% for FNH using CEUS, which was at least equivalent if not better than CEMRI [2]. The reliability of CEUS opens avenues for its increased use, potentially immediately following B-mode ultrasound for incidentally discovered lesions, allowing for immediate diagnostic certainty and avoiding unnecessary anxiety to patients and the need for more time-consuming and expensive imaging in the form of CEMRI [5].
Furthermore, developments in Doppler imaging in B-Mode ultrasound such as superb microvascular imaging (SMI) have proven useful in conjunction with CEUS. SMI involves additional processing technology which removes tiny movement-related artefacts, allowing for accurate demonstration of microvascular and slow flow [3]. In this case, SMI was able to demonstrate the ‘spoke-wheel’ vasculature of FNH and whilst alone this cannot replace time-intensity relationship data from contrast-enhanced imaging, it is an important addition to CEUS in providing a diagnostic certainty of FNH.
THERAPY PLANNING/OUTCOME:
Accurate differentiation between FNH and HCA is essential owing to their varying management strategies. Due to the increased potential for haemorrhage and malignancy seen with some HCA subtypes, routine imaging follow-up and biopsy is recommended in the first instance to establish growth patterns and potential risk. Treatments such as trans-arterial embolization and surgical resection are recommended for lesions with substantial risk factors including size over 5 cm, substantial growth over an interval, and β-catenin-activated subtype [4]. Contrastingly, FNH with typical imaging features requires no routine follow up and intervention is only warranted in exceptional circumstances [1]. As such, the use of CEUS in this instance to establish a diagnosis of FNH was crucial in avoiding unnecessary follow-up, interventions, and associated morbidity for the patient.
FNH is the second most common benign liver lesion following haemangiomas, thought to originate from disorganised hyperplastic growth of hepatocytes due to vascular malformations and associated blood supply variations [1,2]. They typically present as a solitary (although can be multiple in 20-30% of cases), well-circumscribed mass composed of multiple fibrous septa that converge into a central ‘scar’ with an associated feeder artery and branches [3]. It has no malignant potential. A common differential for FNH are hepatocellular adenomas (HCA), which similarly typically present as a singular, well-defined lesion, however these often have a fibrous pseudo-capsule and lack intralobular bile ducts, allowing for differentiation [4]. HCAs are rarer, with a prevalence of 0.05% within the general population, and are divided into 5 main subtypes based on the genetic (beta-catenin mutated, HNF 1 alpha mutated, sonic hedgehog activated) or inflammatory origins [4].
Both FNH and HCA are primarily discovered incidentally in routine imaging in women (8:1 female predilection) of reproductive age and are thought to be hormone-driven, with HCAs especially demonstrating strong links with oral contraception use [2]. Whilst usually asymptomatic, HCAs have additional associated risks including haemorrhage (25%) and malignant transformation (5%), meaning patients may present with abdominal pain, and in severe cases of rapid bleeding into the peritoneal cavity, HCAs can become life-threatening [4]. As FNH mainly remains stable over many years, this difference in risk highlights the necessity of swift and accurate diagnosis as this has significant impact on management strategies.
CLINICAL PERSPECTIVE:
Contrast-enhanced MRI (CEMRI) has been widely recognised as the gold standard for characterisation of liver lesions, however developments in ultrasound technology are proving highly effective in providing an accurate, quick, cost-effective, and widely available alternative [2]. Conventional B-mode ultrasound and colour Doppler lack sensitivity to provide a high level of diagnostic certainty, especially given that some lesions are isoechoic to the liver parenchyma, making them challenging to detect [3].
Contrast-Enhanced ultrasound (CEUS) relies on microbubble agents such as SonoVue, which consist of sulphur hexafluoride gas bubbles contained within a lipid shell. These microbubbles are a similar size to red blood cells and therefore purely contained within vessels [5], allowing multi-phase imaging of the early (10-30 seconds post-contrast injection), portal venous (30-120 seconds), and late (<120 seconds) phases [2]. In comparison to CEMRI, CEUS has the advantages of speed, real time evaluation of tumour perfusion patterns and lack of nephrotoxic contrast agents [5]. The risk of anaphylaxis is small.
FNH has a characteristic centrifugal, or ‘spoke-wheel,’ enhancement pattern in the early arterial phase, reflecting the vascular architecture of a central feeding artery with radiating branches, opposed to HCA which typically displays centripetal or mixed perfusion [2,4]. The advantage of CEUS is that there is real time dynamic evaluation of the arterial enhancement as in our case where Cine-clips using CEUS demonstrated centrifugal filling, and persistence of the arterial phase enhancement into the late phase, providing strong evidence for a diagnosis of FNH in this instance, following indeterminate CEMRI with gadolinium and Primovist. The internal microvasculature was partially demonstrated on power Doppler, but CEUS and microflow imaging was superior in delineating the pathognomonic “spoke-wheel” vascular pattern. CEUS also has additional benefits of rapidity, taking less than 5 minutes, and a flash-reperfusion mode allowing assessment of the initial enhancement characteristics. Unlike CEMRI, multiple repeat contrast injections are also possible in cases of uncertainty allowing the rapid arterial enhancement patterns of lesions to be more accurately assessed.
Multiple studies indicate similar success in the utility of CEUS in diagnosis of liver lesions, with one multi-centre study finding a diagnostic accuracy of 98.8% for FNH using CEUS, which was at least equivalent if not better than CEMRI [2]. The reliability of CEUS opens avenues for its increased use, potentially immediately following B-mode ultrasound for incidentally discovered lesions, allowing for immediate diagnostic certainty and avoiding unnecessary anxiety to patients and the need for more time-consuming and expensive imaging in the form of CEMRI [5].
Furthermore, developments in Doppler imaging in B-Mode ultrasound such as superb microvascular imaging (SMI) have proven useful in conjunction with CEUS. SMI involves additional processing technology which removes tiny movement-related artefacts, allowing for accurate demonstration of microvascular and slow flow [3]. In this case, SMI was able to demonstrate the ‘spoke-wheel’ vasculature of FNH and whilst alone this cannot replace time-intensity relationship data from contrast-enhanced imaging, it is an important addition to CEUS in providing a diagnostic certainty of FNH.
THERAPY PLANNING/OUTCOME:
Accurate differentiation between FNH and HCA is essential owing to their varying management strategies. Due to the increased potential for haemorrhage and malignancy seen with some HCA subtypes, routine imaging follow-up and biopsy is recommended in the first instance to establish growth patterns and potential risk. Treatments such as trans-arterial embolization and surgical resection are recommended for lesions with substantial risk factors including size over 5 cm, substantial growth over an interval, and β-catenin-activated subtype [4]. Contrastingly, FNH with typical imaging features requires no routine follow up and intervention is only warranted in exceptional circumstances [1]. As such, the use of CEUS in this instance to establish a diagnosis of FNH was crucial in avoiding unnecessary follow-up, interventions, and associated morbidity for the patient.
5Teaching Points
CEUS is an excellent alternative or adjunct to MRI in characterizing focal liver lesions. CEUS is quick, can be performed at the same time as conventional ultrasound if expertise allows, permits real-time imaging, and avoids nephrotoxic contrast-agents. In this case, the fine microvasculature was better appreciated on CEUS and SMI compared with MRI, enabling a confident diagnosis of FNH and therefore discharge from further follow-up.
6References
[1] LeGout JD, Bolan CW, Bowman AW, et al. Focal nodular hyperplasia and focal nodular hyperplasia-like lesions. Radiographics. 2022; 42(4):1043-1061.
[2] Şirli R, Sporea I, Popescu A, et al. Contrast-enhanced ultrasound for the assessment of focal nodular hyperplasia – results of a multicentre study. Med Ultrason. 2021;23(2):140-146.
[3] Sawatzki M, Burkart T, Baumeler S, et al. Ultrasound Doppler technique for the diagnosis of focal nodular hyperplasia – case series and systematic review. Medical Ultrasonography 2024, 26(1):72-82
[4] Aziz H, Brown ZJ, Eskander MF, et al. A scoping review of the classification, diagnosis, and management of hepatic adenomas. J Gastrointest Surg. 2022; 26(4): 965-978
[5] Șirli R., Popescu A., Jenssen C, et al. WFUMB Review Paper. Incidental findings in otherwise healthy subjects, how to manage: liver. Cancers (Basel). 2024; 16(16): 2908.
[2] Şirli R, Sporea I, Popescu A, et al. Contrast-enhanced ultrasound for the assessment of focal nodular hyperplasia – results of a multicentre study. Med Ultrason. 2021;23(2):140-146.
[3] Sawatzki M, Burkart T, Baumeler S, et al. Ultrasound Doppler technique for the diagnosis of focal nodular hyperplasia – case series and systematic review. Medical Ultrasonography 2024, 26(1):72-82
[4] Aziz H, Brown ZJ, Eskander MF, et al. A scoping review of the classification, diagnosis, and management of hepatic adenomas. J Gastrointest Surg. 2022; 26(4): 965-978
[5] Șirli R., Popescu A., Jenssen C, et al. WFUMB Review Paper. Incidental findings in otherwise healthy subjects, how to manage: liver. Cancers (Basel). 2024; 16(16): 2908.
