Journal of Medical Imaging and Radiation Oncology 58 (2014) 50–55 bs_bs_banner
RADIOLO GY —P I CTO R I A L E SSAY
Part 1: MRI features of focal nodular hyperplasia with an emphasis on hepatobiliary contrast agents Tom Sutherland, Melanie Seale and Kelvin Yap Medical Imaging Department, St. Vincent’s Hospital, Fitzroy, Victoria, Australia
T Sutherland MBBS MMed FRANZCR; M Seale MBBS FRANZCR; K Yap MBBS MMed FRANZCR FRACP. Correspondence Dr Tom Sutherland, Medical Imaging Department, St. Vincent’s Hospital, 41 Victoria Pde, Fitzroy, Vic. 3065, Australia. Email: [email protected]
Summary Focal nodular hyperplasia (FNH) is the second most common benign liver tumour and typically do not require any treatment. An accurate non-invasive diagnosis is therefore vital to avoid unnecessary intervention and to reassure patients. This article discusses the demographics and pathology of FNH and reviews the appearance of FNH at MRI using liver-specific contrast agents. Key words: abdomen; hepatobiliary imaging; MRI.
Conflict of interest: All authors are in agreement with the text. No conflict of interest. Submitted 13 July 2013; accepted 26 September 2013. doi:10.1111/1754-9485.12130
The introduction of hepatobiliary contrast agents (HBCA) at MRI has revolutionised the non-invasive characterisation of focal liver lesions. The characteristics of focal nodular hyperplasia are outlined in Part 1 of this series, whereas the features of other hypervascular liver lesions are described in Part 2.
Introduction Focal nodular hyperplasia (FNH) is, after haemagioma, the second most common benign tumour of liver and is most commonly asymptomatic incidental discoveries. An MRI using liver-specific contrast agents provides both anatomical and functional information, allowing an accurate diagnosis. An understanding of the imaging features of FNH using these agents is important to enable an accurate diagnosis to reassure the patient and avoid unnecessary intervention. The demographic, pathologic and imaging features are outlined below.
Demographics FNH is most frequently solitary, can range in size from subcentimetre to over 10 cm and occur over a wide age 50
range. They are more common in women. With respect to size, the majority of FNH will remain stable over time;1,2 however, up to 10% may increase in size.3 Unlike the known association of oral contraceptive (OCP) use in hepatic adenomas, there is no known relationship between OCP and FNH. The risk of haemorrhage and malignant transformation is extremely rare allowing conservative management.
Pathology Pathologically, FNH is divided into ‘classic’ and ‘nonclassic’ varieties with classic varieties characterised by the following: (i) abnormal nodular architecture; (ii) malformed vessels; and (iii) proliferation of small bile ducts. The non-classical variety conforms to point (iii), but features (i) and (ii) may be absent or atypical or with cellular atypia.4 A stellate central scar comprising fibrous tissue and malformed vessels of thick walled arteries may have fibrous septa radiating from it, and an inflammatory infiltrate around proliferative bile ducts may occur. Kupffer cells are present and can often be imaged along with the sequalae of the small bile duct proliferation allowing accurate characterisation of FNH. © 2013 The Royal Australian and New Zealand College of Radiologists
MRI of FNH
a
b
d
e
c
Fig. 1. T2-weighted MRI (a) demonstrating an isointense focal nodular hyperplasia (FNH) with a hyperintense scar (arrow), and on T1 (b) is isointense with a hypointense scar (arrow). Standard gadolinium shows the lesion is hyperenhancing in the arterial dominant phase (c) apart from the scar, is subtly hyperintense on the portal venous phase (d) with scar still seen, whereas in the 3-minute delay phase, (e) the lesion is now isoenhancing with interval scar enhancement so it is no longer well seen.
It is thought that FNH forms as a localised reaction to hepatic vascular disturbance. This is because of the higher than expected rate of co-existing haemangiomas and the high incidence of FNH in patients with hereditary haemorrhagic telangectasia.5,6
Magnetic resonance imaging with standard extracellular chelates The features of FNH on MRI have been well defined.7–10 They are typically homogenous on T1- and T2-weighted images. When seen on T1, they are hypo to isointense in over 90% of cases, whereas on T2, 60–73% are slightly hyperintense with the remainder being isointense. On T2, they maintain this signal on both long and short TE sequences. Non-contrast visualisation of the central scar varies widely between studies (18–78% on T1 and 25–69% on T2). When seen, it is always hypointense on T1 and is usually hyperintense on T2 with only 4% being hypointense. It may be eccentrically positioned. Using standard extracellular gadolinium chelates produces intense homogenous enhancement in the arterial phase in over 95% of lesions with 46–64% maintaining hyperenhancement into the portal venous phase and 30–40% remaining slightly hyperenhancing in the equilibrium phase. It is rare for an FNH to washout. When seen in the arterial phase, the central scar is typically © 2013 The Royal Australian and New Zealand College of Radiologists
hypoenhancing. In the portal venous phase, the central scar is hyperenhancing in around 95% of cases. Based on the above findings, six features are required to confidently diagnose a typical FNH at MRI using extracellular contrast agents. These are (i) iso or hypointensity on T1 and iso or hyperintensity on T2; (ii) homogenous intensity; (iii) central T2 hyperintense scar; (iv) marked contrast enhancement; (v) delayed phase scar enhancement; and (vi) the absence of a capsule11 (Fig. 1). It is worth remembering that the pre-contrast signal of a lesion will depend on background liver signal. TI images are frequently fat saturated, and so, in fatty liver, FNH may appear hyperintense or as areas of fatty sparing on opposed phase T1. Heterogeneity and high T1 signal can be seen with intralesional fat or haemorrhage, whereas stellate areas are less likely to be seen in small lesions.11 The absence of typical features can reduce diagnostic confidence. Diffusion-weighted imaging (DWI) does not have a significant role as it is unable to accurately differentiate solid malignant lesions from solid benign lesions.12
Magnetic resonance imaging with hepatocyte-specific chelates Hepatocyte-specific contrast agents have been a major addition to the diagnostic algorithm when characterising 51
T Sutherland et al.
hypervascular focal liver lesions. The three main agents are superparamagnetic iron oxide (SPIO), gadobenate dimeglumine (Multihance; Bracco Imaging, Milan, Italy) and gadoxetate disodium (Primovist (Eovist in the United States); Bayer Schering Pharma, Berlin, Germany). SPIO is dependent upon Kupffer cells being present which take up the agent resulting in reduced signal at MRI. Gadobenate dimeglumine and gadoxetate disodium undergo both hepatic and renal excretion resulting in marked enhancement of functioning hepatocytes and are the dominant agents in Australia and New Zealand. When SPIO agents are employed for the characterisation of FNH,8 FNH shows marked uptake in 56.7% of cases and slight but definite uptake in the remainder in keeping with the presence of Kupffer cells. Intralesional characteristics such as the central scar and radiating septa are appreciated in up to 90% of lesions in the delayed phase. The remainder of the discussion is focused on Gadobenate dimeglumine and gadoxetate disodium. The scanning protocols using hepatocellular agents are similar to standard chelates and involve acquiring in and opposed phase T1-weighted images, fat-saturated T2-weighted images, a fat saturated pre-contrast T1 followed by arterial dominant, portal venous, equilibrium phase T1 and DWI images. A delayed phase T1 called the hepatobiliary phase (HPB) or hepatocyte-specific phase is then acquired. The timing of this phase depends on which agent is used and is dictated by the degree of
hepatic excretion. Gadobenate dimeglumine typically has delayed phase acquisitions performed between 1 and 3 hours after administration as only 4–5% of the agent is excreted by the liver. By comparison, 50% of gadoxetate disodium undergoes hepatic excretion allowing the HBP to be acquired 10–20 minutes postinjection. Agent choice is in part dictated by availability, cost and workflow decisions around acquiring the HBP. Because of the rapid contrast uptake by hepatocytes, soft tissue contrast between vessels and liver is less pronounced using gadoxetate disodium compared with gadobenate dimeglumine and standard gadolinium agents which is potentially a disadvantage when assessing vascular structures. Much of the diagnostic information gained by using HBCA is still the dynamic assessment (e.g. arterial and portal venous phases). The HBP can aid in lesion detection and provides information about cellular function, which, coupled with the dynamic components, increases diagnostic confidence. All sequences must be reviewed to reach a confident diagnosis, and the HBP should not be viewed in isolation. Sixty minutes post-injection of gadobenate dimeglumine 67% of FNH is hyperenhancing, 25% isoenhancing and 8% were slightly hypointense.10 These rates did not significantly change at 2 and 3 hours of delay. Of the FNH that were hyper to isointense at 3 hours, 56% were homogenous, 26% heterogenous and 18% had peripheral ring enhancement. A central scar was more likely to
a
c
e
b
d
f
g
h
Fig. 2. The four most common patterns of focal nodular hyperplasia (FNH) enhancement with hepatobiliary contrast agents. Arterial phase (a) shows a hyperenhancing lesion is homogenously hyperintense in the hepatobiliary phase (HBP) (b). Arterial lesion (c) is heterogenous in the HBP (d) with multiple small hypointense foci within it. Arterial phase lesion (e) has ring enhancement in the HPB (f). Arterial lesion (g) is homogenously isointense in the HBP (h).
52
© 2013 The Royal Australian and New Zealand College of Radiologists
MRI of FNH
Fig. 3. A ring enhancing variant. Notice that the lesion appears larger in the arterial phase (a) compared with the hepatobiliary phase (HBP) (b). Therefore, the lesion must have an isointense periphery. Comparing lesion size in the arterial and the HBP is vital to recognise this variant and avoid misdiagnosis.
a
be seen on delayed phase than on pre-contrast and dynamic images and was always hypointense at 3 hours. Using the hepatocyte-specific agent gadoxetate disodium at the 20-minute phase, 38% of FNH is hyperintense, 32% is isointense and only 2% is hypointense. The remaining 28% of lesions have mixed signal that typically comprises a hyperintense rim and an isointense to hypointense centre.13 This study also reported an accuracy of 88.1% for correctly differentiating FNH from other focal liver lesions. More recent studies report four enhancement patterns in the hepatocyte-specific phase14 (Fig. 2). These are (i) homogenously hyperintense (38%); (ii) heterogenously hyperintense with scattered 1–5 mm foci of hypointensity (15%); (iii) ring enhancing (23%) comprising a hypo or isointense centre and a hyperintense periphery; and (iv) isointense enhancement (19%). These enhancement patterns are the result of the intra-lesional bile duct type and the relative proportion of pre-existing bile ducts, ductular proliferation and ductular metaplasia.14 The degree of intralesional lymphocytic infiltration and fibrosis is also a factor. We have also encountered a fifth pattern of a ring with a hypointense centre with an isointense periphery (Fig. 3). It is vital to compare the size of the lesion in the arterial dominant phase to size in the HBP to recognise this pattern. It is worth remembering that, occasionally, FNH
Fig. 4. Irregular margin to this arterial phase (a) hyperenhancing lesion (arrow). It is slightly hypointense on the hepatobiliary phase (HBP) (arrow) (b). The lesion was resected, and pathological analysis revealed an focal nodular hyperplasia (FNH). Fortunately, hypoenhancing FNH in the HBP is uncommon.
a
© 2013 The Royal Australian and New Zealand College of Radiologists
b
will be hypointense in the HBP (Fig. 4), and histologic sampling in these cases is usually required. A recent study by Gupta et al.15 retrospectively compared gadobenate dimeglumine and gadoxetate disodium for the diagnosis of FNH. They concluded that, qualitatively, lesion conspicuity was equivalent between agents in the arterial phase, was greater for gadoxetate disodium in the HPB and that the enhancement was more likely to be heterogenous with this agent. Depiction of the scar was equivalent between agents, and the scar was always hypointense with both when seen. The early phase enhancement characteristics of FNH may vary with hepatobiliary MRI contrast agents. For example, the central scar that typically enhances in the late portal venous phase may not enhance with agents such as gadoxetate disodium which may relate to rapid extraction of contrast by functioning hepatocytes. The potential for slight differences in the early phases needs to be remembered when using these agents. Despite these potential differences, the additional information gained by using liver-specific contrast agents increases the accuracy diagnosing FNH compared with other modalities, particularly in atypical FNH, and allows accurate differentiation from other hypervascular lesions such as hepatocellular adenoma. The appear-
b
53
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a
b
c
Fig. 5. Non-contrast T1 (a) in a 65-year-old male demonstrating a hypointense segment 6 mass (arrow). The lesion is heterogenously hypointense (arrow) in the portal venous phase (b) and is isointense (arrow) in the hepatobiliary phase (HBP) (c). Compare the intensity of liver (L) and pancreas (P) in the pre-contrast (a) and HBP (c), and note that there has been virtually no hepatic retention of contrast. This renders the HBP unreliable. Lesion was a pathologically proven adenocarcinoma.
ance of other hypervascular focal liver lesions using liver-specific contrast agents is described in Part 2 of this series.16 The intensity of the liver in the HPB should be compared with spleen or pancreas as a qualitative estimation of contrast retention/excretion. Patients with hepatic fibrosis, fatty liver, genetic polymorphisms in the OATP1B1 transporter and hepatic dysfunction may show reduced enhancement. This can result in pseudo hyper or isoenhancement in the HPB (Fig. 5). Recognition of poor contrast uptake is necessary for an accurate diagnosis. The signal intensity of the liver should be compared with the spleen and pancreas on pre-contrast images and should be substantially brighter than these organs in the HBP. If it is not brighter, the HBP is unreliable for diagnosis functional evaluation.
Conclusion FNH can have multiple appearances at hepatic MRI; however, MRI with hepatobiliary contrast agents is particularly accurate at differentiating FNH form other focal liver lesions.
References 1. Di Stasi M, Caturelli E, De Sio I, Salmi A, Buscarini E, Buscarini L. Natural history of focal nodular hyperplasia of the liver: an ultrasound study. J Clin Ultrasound 1996; 24: 345–50. 2. Kuo YH, Wang JH, Lu SN et al. Natural course of hepatic focal nodular hyperplasia: a long-term follow-up study with sonography. J Clin Ultrasound 2009; 37: 132–7. 3. Perrakis A, Demir R, Muller V et al. Management of the focal nodular hyperplasia of the liver: evaluation of the surgical treatment comparing with observation only. Am J Surg 2012; 204: 689–96.
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4. Maillette de Buy Wenniger L, Terpstra V, Beuers U. Focal nodular hyperplasia and hepatic adenoma: epidemiology and pathology. Dig Surg 2010; 27: 24–31. 5. Buscarini E, Danesino C, Plauchu H et al. High prevalence of hepatic focal nodular hyperplasia in subjects with hereditary hemorrhagic telangiectasia. Ultrasound Med Biol 2004; 30: 1089–97. 6. Vilgrain V, Uzan F, Brancatelli G, Federle MP, Zappa M, Menu Y. Prevalence of hepatic hemangioma in patients with focal nodular hyperplasia: MR imaging analysis. Radiology 2003; 229: 75–9. 7. Mortele KJ, Praet M, Van Vlierberghe H, de Hemptinne B, Zou K, Ros PR. Focal nodular hyperplasia of the liver: detection and characterization with plain and dynamic-enhanced MRI. Abdom Imaging 2002; 27: 700–7. 8. Terkivatan T, van den Bos IC, Hussain SM, Wielopolski PA, de Man RA, IJzermans JN. Focal nodular hyperplasia: lesion characteristics on state-of-the-art MRI including dynamic gadolinium-enhanced and superparamagnetic iron-oxide-uptake sequences in a prospective study. J Magn Reson Imaging 2006; 24: 864–72. 9. Grazioli L, Morana G, Kirchin MA, Schneider G. Accurate differentiation of focal nodular hyperplasia from hepatic adenoma at gadobenate dimeglumine-enhanced MR imaging: prospective study. Radiology 2005; 236: 166–77. 10. Grazioli L, Morana G, Federle MP et al. Focal nodular hyperplasia: morphologic and functional information from MR imaging with gadobenate dimeglumine. Radiology 2001; 221: 731–9. 11. Ferlicot S, Kobeiter H, Tran Van Nhieu J et al. MRI of atypical focal nodular hyperplasia of the liver: radiology-pathology correlation. AJR Am J Roentgenol 2004; 182: 1227–31. 12. Sutherland T, Steele E, van Tonder F, Yap K. Solid focal liver lesion characterisation with © 2013 The Royal Australian and New Zealand College of Radiologists
MRI of FNH
apparent diffusion coefficient ratios. J Med Imaging Radiat Oncol 2013; doi: 10.1111/ 1754-9485.12087. 13. Zech CJ, Grazioli L, Breuer J, Reiser MF, Schoenberg SO. Diagnostic performance and description of morphological features of focal nodular hyperplasia in Gd-EOB-DTPA-enhanced liver magnetic resonance imaging: results of a multicenter trial. Invest Radiol 2008; 43: 504–11. 14. van Kessel CS, de Boer E, Kate FJ, Brosens LA, Veldhuis WB, van Leeuwen MS. Focal nodular hyperplasia: hepatobiliary enhancement patterns on
© 2013 The Royal Australian and New Zealand College of Radiologists
gadoxetic-acid contrast-enhanced MRI. Abdom Imaging 2013; 204: 689–96. 15. Gupta RT, Iseman CM, Leyendecker JR, Shyknevsky I, Merkle EM, Taouli B. Diagnosis of focal nodular hyperplasia with MRI: multicenter Retrospective study comparing gadobenate dimeglumine to gadoxetate disodium. AJR Am J Roentgenol 2012; 199: 35–43. 16. Sutherland T, Seale M, Yap K. Part 2: MRI of hypervascular focal liver lesions using liver specific contrast agents. J Med Imaging Radiat Oncol 2013. doi: 10.1111/1754-9485.12129.
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RADIOLO GY —P I CTO R I A L E SSAY
Part 1: MRI features of focal nodular hyperplasia with an emphasis on hepatobiliary contrast agents Tom Sutherland, Melanie Seale and Kelvin Yap Medical Imaging Department, St. Vincent’s Hospital, Fitzroy, Victoria, Australia
T Sutherland MBBS MMed FRANZCR; M Seale MBBS FRANZCR; K Yap MBBS MMed FRANZCR FRACP. Correspondence Dr Tom Sutherland, Medical Imaging Department, St. Vincent’s Hospital, 41 Victoria Pde, Fitzroy, Vic. 3065, Australia. Email: [email protected]
Summary Focal nodular hyperplasia (FNH) is the second most common benign liver tumour and typically do not require any treatment. An accurate non-invasive diagnosis is therefore vital to avoid unnecessary intervention and to reassure patients. This article discusses the demographics and pathology of FNH and reviews the appearance of FNH at MRI using liver-specific contrast agents. Key words: abdomen; hepatobiliary imaging; MRI.
Conflict of interest: All authors are in agreement with the text. No conflict of interest. Submitted 13 July 2013; accepted 26 September 2013. doi:10.1111/1754-9485.12130
The introduction of hepatobiliary contrast agents (HBCA) at MRI has revolutionised the non-invasive characterisation of focal liver lesions. The characteristics of focal nodular hyperplasia are outlined in Part 1 of this series, whereas the features of other hypervascular liver lesions are described in Part 2.
Introduction Focal nodular hyperplasia (FNH) is, after haemagioma, the second most common benign tumour of liver and is most commonly asymptomatic incidental discoveries. An MRI using liver-specific contrast agents provides both anatomical and functional information, allowing an accurate diagnosis. An understanding of the imaging features of FNH using these agents is important to enable an accurate diagnosis to reassure the patient and avoid unnecessary intervention. The demographic, pathologic and imaging features are outlined below.
Demographics FNH is most frequently solitary, can range in size from subcentimetre to over 10 cm and occur over a wide age 50
range. They are more common in women. With respect to size, the majority of FNH will remain stable over time;1,2 however, up to 10% may increase in size.3 Unlike the known association of oral contraceptive (OCP) use in hepatic adenomas, there is no known relationship between OCP and FNH. The risk of haemorrhage and malignant transformation is extremely rare allowing conservative management.
Pathology Pathologically, FNH is divided into ‘classic’ and ‘nonclassic’ varieties with classic varieties characterised by the following: (i) abnormal nodular architecture; (ii) malformed vessels; and (iii) proliferation of small bile ducts. The non-classical variety conforms to point (iii), but features (i) and (ii) may be absent or atypical or with cellular atypia.4 A stellate central scar comprising fibrous tissue and malformed vessels of thick walled arteries may have fibrous septa radiating from it, and an inflammatory infiltrate around proliferative bile ducts may occur. Kupffer cells are present and can often be imaged along with the sequalae of the small bile duct proliferation allowing accurate characterisation of FNH. © 2013 The Royal Australian and New Zealand College of Radiologists
MRI of FNH
a
b
d
e
c
Fig. 1. T2-weighted MRI (a) demonstrating an isointense focal nodular hyperplasia (FNH) with a hyperintense scar (arrow), and on T1 (b) is isointense with a hypointense scar (arrow). Standard gadolinium shows the lesion is hyperenhancing in the arterial dominant phase (c) apart from the scar, is subtly hyperintense on the portal venous phase (d) with scar still seen, whereas in the 3-minute delay phase, (e) the lesion is now isoenhancing with interval scar enhancement so it is no longer well seen.
It is thought that FNH forms as a localised reaction to hepatic vascular disturbance. This is because of the higher than expected rate of co-existing haemangiomas and the high incidence of FNH in patients with hereditary haemorrhagic telangectasia.5,6
Magnetic resonance imaging with standard extracellular chelates The features of FNH on MRI have been well defined.7–10 They are typically homogenous on T1- and T2-weighted images. When seen on T1, they are hypo to isointense in over 90% of cases, whereas on T2, 60–73% are slightly hyperintense with the remainder being isointense. On T2, they maintain this signal on both long and short TE sequences. Non-contrast visualisation of the central scar varies widely between studies (18–78% on T1 and 25–69% on T2). When seen, it is always hypointense on T1 and is usually hyperintense on T2 with only 4% being hypointense. It may be eccentrically positioned. Using standard extracellular gadolinium chelates produces intense homogenous enhancement in the arterial phase in over 95% of lesions with 46–64% maintaining hyperenhancement into the portal venous phase and 30–40% remaining slightly hyperenhancing in the equilibrium phase. It is rare for an FNH to washout. When seen in the arterial phase, the central scar is typically © 2013 The Royal Australian and New Zealand College of Radiologists
hypoenhancing. In the portal venous phase, the central scar is hyperenhancing in around 95% of cases. Based on the above findings, six features are required to confidently diagnose a typical FNH at MRI using extracellular contrast agents. These are (i) iso or hypointensity on T1 and iso or hyperintensity on T2; (ii) homogenous intensity; (iii) central T2 hyperintense scar; (iv) marked contrast enhancement; (v) delayed phase scar enhancement; and (vi) the absence of a capsule11 (Fig. 1). It is worth remembering that the pre-contrast signal of a lesion will depend on background liver signal. TI images are frequently fat saturated, and so, in fatty liver, FNH may appear hyperintense or as areas of fatty sparing on opposed phase T1. Heterogeneity and high T1 signal can be seen with intralesional fat or haemorrhage, whereas stellate areas are less likely to be seen in small lesions.11 The absence of typical features can reduce diagnostic confidence. Diffusion-weighted imaging (DWI) does not have a significant role as it is unable to accurately differentiate solid malignant lesions from solid benign lesions.12
Magnetic resonance imaging with hepatocyte-specific chelates Hepatocyte-specific contrast agents have been a major addition to the diagnostic algorithm when characterising 51
T Sutherland et al.
hypervascular focal liver lesions. The three main agents are superparamagnetic iron oxide (SPIO), gadobenate dimeglumine (Multihance; Bracco Imaging, Milan, Italy) and gadoxetate disodium (Primovist (Eovist in the United States); Bayer Schering Pharma, Berlin, Germany). SPIO is dependent upon Kupffer cells being present which take up the agent resulting in reduced signal at MRI. Gadobenate dimeglumine and gadoxetate disodium undergo both hepatic and renal excretion resulting in marked enhancement of functioning hepatocytes and are the dominant agents in Australia and New Zealand. When SPIO agents are employed for the characterisation of FNH,8 FNH shows marked uptake in 56.7% of cases and slight but definite uptake in the remainder in keeping with the presence of Kupffer cells. Intralesional characteristics such as the central scar and radiating septa are appreciated in up to 90% of lesions in the delayed phase. The remainder of the discussion is focused on Gadobenate dimeglumine and gadoxetate disodium. The scanning protocols using hepatocellular agents are similar to standard chelates and involve acquiring in and opposed phase T1-weighted images, fat-saturated T2-weighted images, a fat saturated pre-contrast T1 followed by arterial dominant, portal venous, equilibrium phase T1 and DWI images. A delayed phase T1 called the hepatobiliary phase (HPB) or hepatocyte-specific phase is then acquired. The timing of this phase depends on which agent is used and is dictated by the degree of
hepatic excretion. Gadobenate dimeglumine typically has delayed phase acquisitions performed between 1 and 3 hours after administration as only 4–5% of the agent is excreted by the liver. By comparison, 50% of gadoxetate disodium undergoes hepatic excretion allowing the HBP to be acquired 10–20 minutes postinjection. Agent choice is in part dictated by availability, cost and workflow decisions around acquiring the HBP. Because of the rapid contrast uptake by hepatocytes, soft tissue contrast between vessels and liver is less pronounced using gadoxetate disodium compared with gadobenate dimeglumine and standard gadolinium agents which is potentially a disadvantage when assessing vascular structures. Much of the diagnostic information gained by using HBCA is still the dynamic assessment (e.g. arterial and portal venous phases). The HBP can aid in lesion detection and provides information about cellular function, which, coupled with the dynamic components, increases diagnostic confidence. All sequences must be reviewed to reach a confident diagnosis, and the HBP should not be viewed in isolation. Sixty minutes post-injection of gadobenate dimeglumine 67% of FNH is hyperenhancing, 25% isoenhancing and 8% were slightly hypointense.10 These rates did not significantly change at 2 and 3 hours of delay. Of the FNH that were hyper to isointense at 3 hours, 56% were homogenous, 26% heterogenous and 18% had peripheral ring enhancement. A central scar was more likely to
a
c
e
b
d
f
g
h
Fig. 2. The four most common patterns of focal nodular hyperplasia (FNH) enhancement with hepatobiliary contrast agents. Arterial phase (a) shows a hyperenhancing lesion is homogenously hyperintense in the hepatobiliary phase (HBP) (b). Arterial lesion (c) is heterogenous in the HBP (d) with multiple small hypointense foci within it. Arterial phase lesion (e) has ring enhancement in the HPB (f). Arterial lesion (g) is homogenously isointense in the HBP (h).
52
© 2013 The Royal Australian and New Zealand College of Radiologists
MRI of FNH
Fig. 3. A ring enhancing variant. Notice that the lesion appears larger in the arterial phase (a) compared with the hepatobiliary phase (HBP) (b). Therefore, the lesion must have an isointense periphery. Comparing lesion size in the arterial and the HBP is vital to recognise this variant and avoid misdiagnosis.
a
be seen on delayed phase than on pre-contrast and dynamic images and was always hypointense at 3 hours. Using the hepatocyte-specific agent gadoxetate disodium at the 20-minute phase, 38% of FNH is hyperintense, 32% is isointense and only 2% is hypointense. The remaining 28% of lesions have mixed signal that typically comprises a hyperintense rim and an isointense to hypointense centre.13 This study also reported an accuracy of 88.1% for correctly differentiating FNH from other focal liver lesions. More recent studies report four enhancement patterns in the hepatocyte-specific phase14 (Fig. 2). These are (i) homogenously hyperintense (38%); (ii) heterogenously hyperintense with scattered 1–5 mm foci of hypointensity (15%); (iii) ring enhancing (23%) comprising a hypo or isointense centre and a hyperintense periphery; and (iv) isointense enhancement (19%). These enhancement patterns are the result of the intra-lesional bile duct type and the relative proportion of pre-existing bile ducts, ductular proliferation and ductular metaplasia.14 The degree of intralesional lymphocytic infiltration and fibrosis is also a factor. We have also encountered a fifth pattern of a ring with a hypointense centre with an isointense periphery (Fig. 3). It is vital to compare the size of the lesion in the arterial dominant phase to size in the HBP to recognise this pattern. It is worth remembering that, occasionally, FNH
Fig. 4. Irregular margin to this arterial phase (a) hyperenhancing lesion (arrow). It is slightly hypointense on the hepatobiliary phase (HBP) (arrow) (b). The lesion was resected, and pathological analysis revealed an focal nodular hyperplasia (FNH). Fortunately, hypoenhancing FNH in the HBP is uncommon.
a
© 2013 The Royal Australian and New Zealand College of Radiologists
b
will be hypointense in the HBP (Fig. 4), and histologic sampling in these cases is usually required. A recent study by Gupta et al.15 retrospectively compared gadobenate dimeglumine and gadoxetate disodium for the diagnosis of FNH. They concluded that, qualitatively, lesion conspicuity was equivalent between agents in the arterial phase, was greater for gadoxetate disodium in the HPB and that the enhancement was more likely to be heterogenous with this agent. Depiction of the scar was equivalent between agents, and the scar was always hypointense with both when seen. The early phase enhancement characteristics of FNH may vary with hepatobiliary MRI contrast agents. For example, the central scar that typically enhances in the late portal venous phase may not enhance with agents such as gadoxetate disodium which may relate to rapid extraction of contrast by functioning hepatocytes. The potential for slight differences in the early phases needs to be remembered when using these agents. Despite these potential differences, the additional information gained by using liver-specific contrast agents increases the accuracy diagnosing FNH compared with other modalities, particularly in atypical FNH, and allows accurate differentiation from other hypervascular lesions such as hepatocellular adenoma. The appear-
b
53
T Sutherland et al.
a
b
c
Fig. 5. Non-contrast T1 (a) in a 65-year-old male demonstrating a hypointense segment 6 mass (arrow). The lesion is heterogenously hypointense (arrow) in the portal venous phase (b) and is isointense (arrow) in the hepatobiliary phase (HBP) (c). Compare the intensity of liver (L) and pancreas (P) in the pre-contrast (a) and HBP (c), and note that there has been virtually no hepatic retention of contrast. This renders the HBP unreliable. Lesion was a pathologically proven adenocarcinoma.
ance of other hypervascular focal liver lesions using liver-specific contrast agents is described in Part 2 of this series.16 The intensity of the liver in the HPB should be compared with spleen or pancreas as a qualitative estimation of contrast retention/excretion. Patients with hepatic fibrosis, fatty liver, genetic polymorphisms in the OATP1B1 transporter and hepatic dysfunction may show reduced enhancement. This can result in pseudo hyper or isoenhancement in the HPB (Fig. 5). Recognition of poor contrast uptake is necessary for an accurate diagnosis. The signal intensity of the liver should be compared with the spleen and pancreas on pre-contrast images and should be substantially brighter than these organs in the HBP. If it is not brighter, the HBP is unreliable for diagnosis functional evaluation.
Conclusion FNH can have multiple appearances at hepatic MRI; however, MRI with hepatobiliary contrast agents is particularly accurate at differentiating FNH form other focal liver lesions.
References 1. Di Stasi M, Caturelli E, De Sio I, Salmi A, Buscarini E, Buscarini L. Natural history of focal nodular hyperplasia of the liver: an ultrasound study. J Clin Ultrasound 1996; 24: 345–50. 2. Kuo YH, Wang JH, Lu SN et al. Natural course of hepatic focal nodular hyperplasia: a long-term follow-up study with sonography. J Clin Ultrasound 2009; 37: 132–7. 3. Perrakis A, Demir R, Muller V et al. Management of the focal nodular hyperplasia of the liver: evaluation of the surgical treatment comparing with observation only. Am J Surg 2012; 204: 689–96.
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