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Unveiling the unreal: Comprehensive imaging review of hepatic pseudolesions

Open AccessPublished:September 17, 2021DOI:https://doi.org/10.1016/j.clinimag.2021.09.008

      Highlights

      • Hepatic pseudolesions are non-neoplastic focal abnormalities of the liver which can mimic or conceal liver lesions
      • It can be categorised in to focal parenchymal abnormalities, perfusion related lesions and pitfalls related pseudo lesions
      • It can both mimic and mask hypovascular and hypervascular neoplastic lesions.
      • It can also be a pointer for an underlying disease process like portal or hepatic arterial obstruction.

      Abstract

      Hepatic pseudolesions are defined as non-neoplastic focal abnormalities of the liver which can mimic or conceal true liver lesions. It is particularly common in liver due to its unique dual blood supply and the existence of multilevel anastomosis between them. Because of the recent advances in CT and MRI technology, they are being increasingly encountered in daily practice. Broadly they can be categorised in to (1) Focal parenchymal abnormalities like focal fatty change, focal fat sparing, focal confluent fibrosis, segmental hypertrophy and regenerative nodules, (2) Perfusion abnormalities which include transient hepatic parenchymal enhancement in portal vein obstruction, third inflow, intrahepatic shunts, hepatic arterial occlusion and hepatic venous obstruction, (3) Imaging pitfalls like parenchymal compression, unenhanced vessels and pseudolipoma. It is essential for the radiologists to be familiar with the typical and atypical imaging features of pseudolesions to avoid mistaking them for sinister pathologies and also to avoid overlooking underlying hidden pathologies.

      Keywords

      1. Introduction

      The anatomy of the liver, the complex blood supply and drainage, and the myriad pathologies that can affect this organ, make liver imaging challenging to even an experienced radiologist. A convincing liver lesion may actually represent a “pseudolesion”, far from being a hepatoma or metastasis. Hepatic pseudolesions are defined as non-neoplastic focal abnormalities of the liver which can mimic or conceal true liver lesions.
      • Lencioni R.
      • Cioni D.
      • Bartolozzi C.
      Focal Liver Lesions.
      • Yoshimitsu K.
      • Honda H.
      • Kuroiwa T.
      • et al.
      Unusual hemodynamics and pseudolesions of the noncirrhotic liver at CT.
      These are often caused by unusual hemodynamics, intrahepatic vascular compromise or shunting. Incidental detection of hepatic pseudolesions has increased due to availability of multidetector CT, dynamic MRI and single breath-hold faster imaging techniques. It is particularly important to diagnose pseudolesions because they may be misinterpreted as true pathological lesions and followed by unwanted investigations or inadvertently biopsied, may mask serious underlying disease or cause overestimation of lesion size.
      In this article, we classify and describe commonly and also rarely encountered hepatic pseudolesions, discuss their pathophysiology, familiarize their imaging features and highlight imaging clues to distinguish from true lesions.

      2. Pathophysiology

      The human liver has a unique dual blood supply, with 75% portal venous and 25% hepatic arterial supply, at pressures of approximately 7 mmHg and 100 mmHg respectively.
      • Torabi M.
      • Hosseinzadeh K.
      • Federle M.P.
      CT of nonneoplastic hepatic vascular and perfusion disorders.
      These, however, are not independent vascular systems. There are multilevel communications between the portal vein and hepatic arterial system, which include transsinusoidal (connections between the hepatic interlobular arterioles and portal venules), transvasal (through the vasa vasorum supplying the portal venous wall), transtumoral (through a tumor thrombus) and transplexal (peribiliary) shunts.
      • Quiroga S.
      • Sebastià C.
      • Pallisa E.
      • Castellà E.
      • Pérez-Lafuente M.
      • Alvarez-Castells A.
      Improved diagnosis of hepatic perfusion disorders: value of hepatic arterial phase imaging during helical CT.
      Any vascular compromise changes the volume and direction of blood flow through nervous or humoral compensatory mechanisms. For example, decreased portal vein flow from portal or hepatic vein thrombosis or extrinsic compression leads to compensatory increased hepatic arterial flow through the above-mentioned routes. This results in a segmental area of transient hepatic attenuation differences (THAD) in the arterial phase, becoming isodense on the portal venous phase CT, and a similar transient hepatic intensity difference (THID) on contrast enhanced MRI. An umbrella term of transient hepatic parenchymal enhancement (THPE) is used to describe these features. However, it is important to remember that a decrease in the arterial flow does not correspondingly increase portal venous flow, and may lead to hepatic ischemia.
      • Colagrande S.
      • Centi N.
      • La Villa G.
      • Villari N.
      Transient hepatic attenuation differences.
      A similar perfusion anomaly can be seen when there is increase in the hepatic arterial flow, such as in hypervascular tumors (hepatocellular carcinoma [HCC] and hemangioma) and acute inflammatory conditions such as cholecystitis, liver abscesses and pancreatitis. Interestingly, the resultant perfusion anomaly is not only due to increased arterial pressure in the regions of low portal perfusion, but also due to reduced dilution of the contrast-enhanced arterial blood by the unenhanced portal blood.
      • Chen W.P.
      • Chen J.H.
      • Hwang J.I.
      • et al.
      Spectrum of transient hepatic attenuation differences in biphasic helical CT.
      A “steal phenomenon” has also been described, which refers to perfusion differences arising from siphoning of the arterial blood by highly vascular tumors (such as HCC, neuroendocrine metastasis). The resultant effect can be arterial hypoperfusion or hyperperfusion of the segment which contains the liver lesion depending on the tumor location, degree of vascularity and blood flow mismatch between tumor and surrounding parenchyma.
      • Quiroga S.
      • Sebastià C.
      • Pallisa E.
      • Castellà E.
      • Pérez-Lafuente M.
      • Alvarez-Castells A.
      Improved diagnosis of hepatic perfusion disorders: value of hepatic arterial phase imaging during helical CT.
      • Itai Y.
      • Murata S.
      • Kurosaki Y.
      Straight border sign of the liver: spectrum of CT appearances and causes.
      Another interesting phenomenon is the third inflow. This refers to non-portal aberrant veins that independently enter the liver parenchyma, but communicate with the intrahepatic portal branches. These bring in systemic venous blood into the hepatic circulation hence focally reducing portal perfusion, and are another important cause of hepatic pseudolesions.
      • Yoshimitsu K.
      • Honda H.
      • Kuroiwa T.
      • et al.
      Unusual hemodynamics and pseudolesions of the noncirrhotic liver at CT.
      Considering the multitude of normal variants as well as pathologies causing hepatic pseudolesions, we systematically classify them, explain their causes and describe imaging appearances, so as to facilitate a better understanding of these lesions.

      3. Classification

      Hepatic pseudolesions may be classified as (1) Focal parenchymal abnormalities, which include focal fatty infiltration (FFI), focal fat sparing (FFS), focal confluent fibrosis, segmental hypertrophy and regenerative nodules, (2) Perfusion related pseudolesions, which include transient hepatic parenchymal enhancement (THPE) in portal vein obstruction, third inflow, intrahepatic shunts, and those related to hepatic arterial occlusion and hepatic venous obstruction, (3) A third category of pseudolesions due to technical and interpretation pitfalls, which include those caused by parenchymal compression, unenhanced vessels, pericaval and Glisson capsule pseudolipoma
      • Colagrande S.
      • Centi N.
      • Galdiero R.
      • Ragozzino A.
      Transient hepatic intensity differences: part 2, those not associated with focal lesions.
      • Colagrande S.
      • Centi N.
      • Galdiero R.
      • Ragozzino A.
      Transient hepatic intensity differences: part 1, those associated with focal lesions.
      • Kanematsu M.
      • Kondo H.
      • Semelka R.C.
      • et al.
      Early-enhancing non-neoplastic lesions on gadolinium-enhanced MRI of the liver.
      (Table 1).
      Table 1Classification of hepatic pseudolesions.
      Parenchymal pseudolesionsPerfusion related pseudolesionsPitfalls related pseudolesions
      • Focal fat sparing (FFS)
      • Focal fat infiltration (FFI)
      • Focal confluent fibrosis
      • Segmental hypertrophy
      • Regenerative nodules
      • Portal venous obstruction and Transient hepatic parenchymal enhancement
      • Arterioportal shunts
      • Arteriovenous shunts
      • Portosystemic venous shunts
      • Passive hepatic congestion
      • Hepatic venous obstruction
      • Hepatic arterial occlusion
      • Third inflow
      • Parenchymal compression
      • Unenhanced vessels
      • Pericaval and Glisson capsule pseudolipoma

      3.1 Focal parenchymal abnormalities

      3.1.1 Focal fatty infiltration (FFI) and focal fat sparing (FFS)

      FFI has an incidence of approximately 30–40%, with 10% involving a single region of the liver, and 20–30% being multifocal.
      • Lencioni R.
      • Cioni D.
      • Bartolozzi C.
      Focal Liver Lesions.
      Typical locations are at the porta hepatis (segment 4), the gall bladder fossa, adjacent to the falciform ligament (20% cases) and subcapsular regions of liver. A geographic or perivascular pattern may also occur. There are varied patterns of FFI, such as segmental, focal, multifocal, perivascular and subcapsular.
      • Vilgrain V.
      • Lagadec M.
      • Ronot M.
      Pitfalls in liver imaging.
      The pathophysiology of FFI is related to focal areas of decreased portal venous flow leading to nutritional ischemia, aberrant vascular supply (third inflow), and hypoxia. Most commonly located in the posterior part of the segment 4, focal fat infiltration or fat sparing in this area is due to abnormal venous drainage; i.e. instead of the portal vein, this region may be supplied by the gastric veins or the duodenopancreatic venous arcade. Supporting this theory is that this segment shows relative hypoenhancement during the portal venous phase.
      • Gabata T.
      • Matsui O.
      • Kadoya M.
      • et al.
      Aberrant gastric venous drainage in a focal spared area of segment IV in fatty liver: demonstration with color doppler sonography.
      • Hashimoto M.
      • Heianna J.
      • Tate E.
      • Nishii T.
      • Iwama T.
      • Ishiyama K.
      Small veins entering the liver.
      Owing to a higher concentration of insulin in the duodenopancreatic veins, a higher fat deposition is observed, whereas a venous drainage from aberrant right gastric veins carrying much lesser insulin causes FFS in this area (“insulin theory”). Insulin converts glucose to fatty acids (lipogenetic effect) hence leading to hepatic steatosis. Similarly, FFS around the gall bladder fossa is caused by the same reason, that the cystic veins draining directly into segment 4 contain lesser insulin levels. It has been observed that patients with a cholecystectomy much less commonly have FFS in this region, supporting this hypothesis.
      • Vilgrain V.
      • Lagadec M.
      • Ronot M.
      Pitfalls in liver imaging.
      • Aubin B.
      • Denys A.
      • Lafortune M.
      • Déry R.
      • Breton G.
      Focal sparing of liver parenchyma in steatosis: role of the gallbladder and its vessels.
      Other common locations of FFS are the dorsomedial portion of the medial segment where supply to the hepatic parenchyma may derive from systemic veins such as the cystic vein of the gallbladder or an aberrant right gastric vein, rather than from the portal vein. FFS can also occur adjacent to a tumor due to the presence of an arterioportal shunt or as a rim around an expansively growing tumor.
      The characteristic location, absence of mass effect and non-distortion of intrahepatic vessels usually indicates the diagnosis. MRI can depict the presence or absence of fat within these areas using fat saturated T1/T2 sequences and chemical shift (in and out-of-phase) imaging. FFI may demonstrate variable enhancement patterns. Post contrast T1 gradient echo sequences demonstrate these areas as slightly hypointense focal abnormalities, while liver specific contrast agents depict iso to hypointense areas (phenomenon termed ‘hepatocyte ballooning’).
      • Schneider G.
      • Martin D.R.
      • Grazioli L.
      • et al.
      MRI of the Liver: Imaging Techniques, Contrast Enhancement, Differential Diagnosis.
      No restriction is observed on diffusion weighted imaging (DWI)
      • Vilgrain V.
      • Ronot M.
      • Abdel-Rehim M.
      • et al.
      Hepatic steatosis: a major trap in liver imaging.
      (Fig. 1, Fig. 2).
      Fig. 1
      Fig. 1Focal fatty infiltration in a 26-year-old woman.
      (a) Ultrasound with color flow shows subcapsular well circumscribed echogenic lesion in the anterior part of left lobe with no internal vascularity (arrow). (b) Axial T2W MRI shows ill-defined mild T2 hyperintense lesion in segment 4 adjacent to falciform ligament (arrow) corresponding to the ultrasound. Lesion appears isointense on axial T1W in-phase (c) with signal drop (arrow) on the out-of-phase image (d) suggesting intravoxel fat. Lesion appears mildly hypointense on axial precontrast fat saturated T1W MRI (e) and shows mild hypoenhancement on the dynamic post contrast fat saturated T1W MRI in the arterial (f), portal venous (g) and delayed (h) phases (arrows).
      Fig. 2
      Fig. 2Multifocal areas of fat sparing in a 57-year-old man.
      (a) Ultrasound shows diffuse fatty liver with multiple indeterminate hypoechoic focal lesions. Axial T1 in-phase (b) and Out-of-phase (c) MRI show diffuse drop in signal suggesting fatty liver with multiple T1 hyperintense lesions in right lobe of liver (arrows) seen only in out-of-phase images. These lesions show mild T2 hyperintensity on axial fat saturated T2W MRI (d) and isointensity on axial precontrast fat saturated T1W MRI (e). On dynamic post contrast fat saturated T1W MRI, lesions show no hypervascularity in the arterial phase (f) with severe celiac origin stenosis (long arrow) and post stenotic dilatation of common hepatic artery (short arrow). Mild enhancement seen in the portal venous phase (g) (arrows). (h) Coronal reformatted maximum intensity projection image shows collateral between hepatic and superior mesenteric artery (arrows). Altered perfusion to the liver with collaterals can be a contributing factor in diffuse fatty liver with focal areas of fat sparing. Lesions are stable on 2 years follow up.
      Cases of ‘pseudotumoral nodular steatosis’, comprising several nodular fatty deposits in the liver, simulating metastasis have been described. These lesions are typically seen as multiple hyperechoic nodules at ultrasonography, hypoattenuating during all CT phases, with an enhancement that is typical of focal steatosis. These are usually small (less than 2 cm in size) and may depict a very specific sign of a more fatty border at the periphery. Chemical shift MRI is useful in demonstrating fat content by signal drop on the out-of-phase (Fig. 3).Of note, fat containing tumors such as hepatocellular carcinoma also contain fat within them; however, other imaging features such as high T2 signal, enhancement pattern, diffusion restriction, pseudocapsule around the lesion and intratumoral necrosis or hemorrhage are usually seen
      • Schneider G.
      • Martin D.R.
      • Grazioli L.
      • et al.
      MRI of the Liver: Imaging Techniques, Contrast Enhancement, Differential Diagnosis.
      • Vilgrain V.
      • Ronot M.
      • Abdel-Rehim M.
      • et al.
      Hepatic steatosis: a major trap in liver imaging.
      (Fig. 4).
      Fig. 3
      Fig. 3Multifocal nodular hepatic steatosis in a 46-year-old man.
      (a) Axial non-contrast CT shows multiple small hypodense lesions in both lobes of liver. Few small incidental calcific foci also seen. Axial contrast enhanced CT in the arterial (b) and portal venous (c) shows persistent hypodense lesions with no hypervascularity or delayed enhancement.
      All these lesions appears isointense on axial T1W in-phase (d) with signal drop on the out-of-phase MRI (e) suggesting multifocal nodular hepatic steatosis.
      Fig. 4
      Fig. 4Multifocal fat containing hepatocellular carcinoma (HCC) in an 83-year-old man with history of partial right hepatectomy for HCC. (a) Axial T2W MRI shows numerous small T2 hyperintense lesions in both lobes of liver with background morphological changes of cirrhosis. Axial T1 in-phase (b) and Out-of-phase (c) MRI show significant drop in signal in all these lesions suggesting multifocal fat containing nodules. These lesions appear hypointense on axial precontrast fat saturated T1W MRI (d) and show moderate enhancement in the arterial phase (d) and wash out in the venous phase (e). Ultrasound guided biopsy confirmed the diagnosis of multifocal disseminated fat containing HCC.
      Initially thought to be due to FFI, a focal area of hypoattenuation around the anterior aspect of the falciform ligament (segment 4) seen in about 20% of CT or MRI is actually due to an inferior vein of Sappey draining blood from the anterior abdominal wall into the liver. It is most pronounced on the portal venous phase at CT or MRI, rarely seen on the equilibrium phase and measures an average of 9 mm. One study showed FFI as the cause only in 14% and rest of the 86% showed only altered perfusion without focal fat deposition
      • Macari M.
      • Yeretsian R.
      • Babb J.
      Assessment of low signal adjacent to the falciform ligament on contrast-enhanced MRI.
      (Fig. 1).

      3.1.2 Focal confluent fibrosis

      Focal confluent fibrosis typically occurs in patients with alcoholic cirrhosis (most common, in up to 15% of advanced cases), autoimmune hepatitis and primary sclerosing cholangitis. These are usually wedge or band shaped, associated with overlying capsular retraction or flattening, commonly seen in medial segments of right and left lobe (specifically segments 4, 7 and 8) and demonstrate delayed enhancement. Trapped and crowded vessels may be seen within the lesion in 15% of cases.
      • Brancatelli G.
      • Baron R.L.
      • Federle M.P.
      • Sparacia G.
      • Pealer K.
      Focal confluent fibrosis in cirrhotic liver: natural history studied with serial CT.
      They are usually hypodense on unenhanced and portal venous CT, and are moderately hyperintense on T2 weighted MRI due to edema within. Very rarely, these may enhance on the arterial phase when there is associated inflammation or reduction in portal flow, in which case may resemble a hepatocellular carcinoma. Biopsy may be helpful in these cases. Owing to the presence of fibrous tissue and lack of hepatocytes, leads to the characteristic imaging features of delayed (equilibrium) phase enhancement on CT and MRI
      • Ohtomo K.
      • Baron R.L.
      • Dodd III, G.D.
      • Federle M.P.
      • Ohtomo Y.
      • Confer S.R.
      Confluent hepatic fibrosis in advanced cirrhosis: evaluation with MR imaging.
      (Fig. 5).
      Fig. 5
      Fig. 5Focal confluent fibrosis in a 40-year-old man with history of alcoholic cirrhosis.
      (a) Axial fat saturated T2W MRI shows subcapsular ill-defined wedge shaped mildly T2 hyperintense area (arrow) in the right lobe of liver with right lobe atrophy. Contrast enhanced MRI in the (b) arterial and (c) portal venous phase reveal subtle enhancement of the lesion with more definite enhancement (arrow) in the delayed phase (d).
      The common imaging differentials are 1) segmental fatty liver, which, although appears similarly wedge shaped and hypo-attenuating, demonstrates no capsular retraction and chemical shift MRI is useful in demonstrating its fat content 2) hepatic infarction, which does not enhance even in the delayed phase, 3) infiltrative sclerosing hepatocellular carcinoma, which depicts typical arterial phase hypervascularity, contrast wash out in the subsequent phases, and a pseudocapsule, 4) cholangiocarcinoma is one of the closest differential and at times practically difficult to distinguish as it can show capsular retraction and lack of hypervascularity similar to focal confluent fibrosis. Mass-like appearance and associated biliary dilatation favours cholangiocarcinoma.
      • Baron R.L.
      • Peterson M.S.
      From the RSNA refresher courses: screening the cirrhotic liver for hepatocellular carcinoma with CT and MR imaging: opportunities and pitfalls.

      3.1.3 Segmental hypertrophy

      A commonly observed imaging finding in cirrhosis of liver is volume redistribution, with selective atrophy of the right lobe and segment 4, and hypertrophy of the left lobe and caudate. This atrophy-hypertrophy complex can lead to a pseudotumorous appearance, with the hypertrophied segment simulating a hepatic mass.
      • Vilgrain V.
      • Lagadec M.
      • Ronot M.
      Pitfalls in liver imaging.
      Congenital hepatic fibrosis also leads to a cirrhosis like volume-redistribution, however, with preservation or hypertrophy of the segment 4.
      • Zeitoun D.
      • Brancatelli G.
      • Colombat M.
      • et al.
      Congenital hepatic fibrosis: CT findings in 18 adults.
      A portal cavernoma subsequent to extrahepatic portal venous obstruction leads to hypertrophy of the central liver (segment 4 and caudate) with atrophy of the peripheral liver. A similar appearance is seen with primary sclerosing cholangitis.
      • Vilgrain V.
      • Condat B.
      • Bureau C.
      • et al.
      Atrophy-hypertrophy complex in patients with cavernous transformation of the portal vein: CT evaluation.
      In Budd-Chiari syndrome, the caudate and the segments uninvolved by venous obstruction show hypertrophy.
      Interestingly, the hypertrophied segments may demonstrate hyperattenuation on unenhanced CT or hyperintensity on T1 weighted MRI with often mild T2 hypointensity due to high cellularity. A major diagnostic clue to avoid mistaking a hypertrophied liver segment for a mass, is liver-like enhancement of the former, with identification of normal undistorted intrahepatic vessels within the hypertrophied segment
      • Gryspeerdt S.
      • Van Hoe L.
      • Marchal G.
      • Baert A.L.
      Evaluation of hepatic perfusion disorders with double-phase spiral CT.
      (Fig. 6).
      Fig. 6
      Fig. 6Segmental hypertrophy in a 20-year-old man with Congenital hepatic fibrosis.
      Axial fat saturated precontrast T1W MRI (a) and T2W MRI (b) shows pseudotumoral hypertrophy of caudate lobe (arrows) and medial segments showing mild T1 hyperintensity and T2 hypointensity due to densely packed cells. Contrast enhanced MRI in the (c) arterial and (d) portal venous phase shows mild patchy enhancement in the arterial phase (arrows) with relative hypoenhancement (arrows) in the portal venous phase with preserved intrahepatic vessels (long arrow). Associated splenomegaly with incidental large cystic lesion (asterisk).

      3.1.4 Regenerative nodules and related conditions

      Liver is well known to show significant regenerative response to various forms of injury at molecular level and can be detected on imaging. Nodular regenerative hyperplasia (NRH), large regenerative nodules (LRN) and Focal nodular hyperplasia (FNH) like lesions are the three main types of benign regenerative lesions.
      • Yoneda N.
      • Matsui O.
      • Kitao A.
      • et al.
      Benign hepatocellular nodules: hepatobiliary phase of gadoxetic acid-enhanced MR imaging based on molecular background.
      Although it can be argued that these are true lesions and not pseudolesions, they are included here for two reasons: (1) It can mimic hypervascular malignant lesions like hepatoma and metastasis (2) pathologically these are cluster of hyperplastic normal hepatocytes and hence can be considered as pseudolesions. Common associated conditions include organ transplantation, post chemotherapy, rheumatologic diseases, myeloproliferative syndromes and various immunosuppresants.
      • Brancatelli G.
      • Federle M.P.
      • Grazioli L.
      • Golfieri R.
      • Lencioni R.
      Benign regenerative nodules in budd-chiari syndrome and other vascular disorders of the liver: radiologic-pathologic and clinical correlation.
      • Özcan H.N.
      • Karçaaltıncaba M.
      • Seber T.
      • et al.
      Hepatocyte-specific contrast-enhanced MRI findings of focal nodular hyperplasia-like nodules in the liver following chemotherapy in pediatric cancer patients.
      NRH is an uncommon liver lesion and typically occurs in normal liver with no background cirrhosis. It is characterized by small 1–3 mm diffuse or few discrete nodules with little or no fibrosis. Often these nodules are not detected on imaging and identified on histopathology. Typical imaging features described include isointensity on T1 and T2, no arterial hyperenhancement, variable enhancement in the portal venous phase and isointensity on delayed phase. Liver specific contrast can show peripheral hyperintensity (dough nut like) with central hypointensity due to portal tracts in sizable lesions
      • Yoneda N.
      • Matsui O.
      • Kitao A.
      • et al.
      Benign hepatocellular nodules: hepatobiliary phase of gadoxetic acid-enhanced MR imaging based on molecular background.
      • Ames J.T.
      • Federle M.P.
      • Chopra K.
      Distinguishing clinical and imaging features of nodular regenerative hyperplasia and large regenerative nodules of the liver.
      (Fig. 7).
      Fig. 7
      Fig. 7Nodular regenerative hyperplasia (NRH) in a 51-year-old man with history of renal transplantation 10 years ago.
      (a) Axial T1W and (b) axial T2W MRI show nodular outline along the left lobe. (c) Axial diffusion weighted MRI shows no focal lesion. Contrast enhanced MRI shows no hypervascular lesion in the arterial phase (d) and venous phase (e) and multiple small hyperintense lesions (arrows) in delayed hepatobiliary phase (f) with liver specific contrast. Patient had normal liver function with esophageal varices suggesting idiopathic portal hypertension and liver biopsy showed regenerative nodules with no fibrosis consistent with NRH.
      LRN are hyperplastic nodules measuring 5 mm to 5 cm, larger than the usual regenerative nodules seen in cirrhosis. It is classically seen in Budd-Chiari syndrome and can be seen rarely in cirrhosis as well. It is important to differentiate from hepatoma as these lesions show arterial hyperenhancement; however, it shows iso to mild hyperintensity on portal venous and isointensity on delayed phases with no wash out
      • Brancatelli G.
      • Federle M.P.
      • Grazioli L.
      • Golfieri R.
      • Lencioni R.
      Benign regenerative nodules in budd-chiari syndrome and other vascular disorders of the liver: radiologic-pathologic and clinical correlation.
      • Ames J.T.
      • Federle M.P.
      • Chopra K.
      Distinguishing clinical and imaging features of nodular regenerative hyperplasia and large regenerative nodules of the liver.
      (Fig. 8).
      Fig. 8
      Fig. 8Large regenerative noduleshyperplasia (LRN) in a 31-year-old man with Budd-Chiari syndrome related to Paroxysmal nocturnal hemoglobinuria.
      (a) Axial T2W MRI show enlarged liver with heterogeneous signal intensity and nodular outline. (b) Axial T1W MRI small mildly hyperintense lesion in posterior left lobe (arrow). Contrast enhanced MRI shows two hypervascular lesions (short arrows) in the arterial phase (c) and venous phase (d) becoming isointense on delayed phase (e) with no wash out. Note the occluded hepatic veins (long arrows).
      FNH like nodules show imaging features very similar to classical FNH. It is often multiple and often discovered incidentally in childhood cancer survivors on followup imaging. Due to their hypervascular nature and prior history of malignancy, it leads to diagnostic dilemma of metastasis and second malignancy. Demonstrating the absence of washout in delayed phase with conventional gadolinium contrast or iso to hyperintensity on delayed hepatobiliary phase with liver specific contrast helps to confirm the diagnosis of FNH thereby avoiding biopsy
      • Özcan H.N.
      • Karçaaltıncaba M.
      • Seber T.
      • et al.
      Hepatocyte-specific contrast-enhanced MRI findings of focal nodular hyperplasia-like nodules in the liver following chemotherapy in pediatric cancer patients.
      • Yoo S.Y.
      • Kim J.H.
      • Eo H.
      • Jeon T.Y.
      • Sung K.W.
      • Kim H.S.
      Dynamic MRI findings and clinical features of benign hypervascular hepatic nodules in childhood-cancer survivors.
      (Fig. 9).
      Fig. 9
      Fig. 9Multiple FNH like nodules in a 60-year-old woman with history of childhood leukemia.
      (a) Axial T1W MRI shows ill-defined mildly hypointense lesion in right lobe of liver (arrow). (b) Axial T2W MRI shows ill-defined mildly hyperintense lesion in right lobe of liver (arrow). Contrast enhanced MRI shows multiple hypervascular lesions (arrows) in the arterial phase (c and d). Largest lesion in the right lobe shows persistent hyperintensity (arrow) in the venous phase (e) and shows mild hyperintensity with central scar (arrow) in the delayed hepatobiliary phase (f) with liver specific contrast.
      Another closely related condition is pseudo cirrhosis seen predominantly in breast cancer patients with liver metastasis post treatment. Imaging features like heterogeneous signal intensity, nodular hepatic outline, capsular retraction and atrophic changes mimic cirrhosis, however pathological examination show no typical findings of cirrhosis and hence termed ‘Pseudo cirrhosis’.
      • Qayyum A.
      • Lee G.K.
      • Yeh B.M.
      • Allen J.N.
      • Venook A.P.
      • Coakley F.V.
      Frequency of hepatic contour abnormalities and signs of portal hypertension at CT in patients receiving chemotherapy for breast cancer metastatic to the liver.
      The underlying mechanism can be either due to fibrosis from infiltrating metastasis or regenerative response to toxic anti-cancer drugs. Detection of pseudo cirrhosis is essential for two reasons: (1) It can both mimic hepatic metastasis and hamper the optimal detection of metastasis (2) In severe stages, it can lead to portal hypertension and its related complications.
      • Lee S.L.
      • Chang E.D.
      • Na S.J.
      • et al.
      Pseudocirrhosis of breast cancer metastases to the liver treated by chemotherapy.
      Imaging has limited role due to cirrhotic background making lesion detection a difficult task. Interpretation of imaging can be improved by knowing the detailed clinical history of prior malignancy, chemotherapy, radiotherapy and appearance of lesions before treatment so that it can be compared to current examination. If there is strong suspicion of recurrence by clinical and laboratory parameters, biopsy should be performed to detect occult metastasis
      • Jha P.
      • Poder L.
      • Wang Z.J.
      • Westphalen A.C.
      • Yeh B.M.
      • Coakley F.V.
      Radiologic mimics of cirrhosis.
      • Young S.T.
      • Paulson E.K.
      • Washington K.
      • Gulliver D.J.
      • Vredenburgh J.J.
      • Baker M.E.
      CT of the liver in patients with metastatic breast carcinoma treated by chemotherapy: findings simulating cirrhosis.
      (Fig. 10).
      Fig. 10
      Fig. 10Pseudo cirrhosis in a 58-year-old woman with history of treatment for hepatic metastasis from breast cancer.
      Axial (a) and coronal (b) contrast enhanced CT in the portal venous phase shows enlarged liver with significant surface nodularity involving the left lobe with heterogenous enhancement pattern (arrows). Although no discrete lesions are not seen, due to heterogenous liver parenchyma underlying recurrent or residual metastasis cannot be excluded and should be correlated with clinical data.

      3.2 Perfusion related pseudolesions

      3.2.1 Portal venous obstruction and THPE

      Portal venous obstruction is one of the common causes of altered perfusion pattern in the liver parenchyma. As detailed in the section on pathophysiology, any decrease in the portal flow is compensated by increased arterial inflow leading to THPE. Common causes include (1) thrombosis (bland and malignant thrombosis) which can be seen in cirrhosis, HCC, acute inflammation, hypercoagulable states (2) Compression or invasion by benign and malignant hepatic lesions.
      • Virmani V.
      • Ramanathan S.
      • Virmani V.S.
      • Kielar A.
      • Sheikh A.
      • Ryan J.
      Non-neoplastic hepatic vascular diseases: spectrum of CT and MRI appearances.
      Although THPE is classically described in portal vein obstruction, it is a nonspecific finding and can be seen in other conditions like increased arterial inflow from hypervascular tumors, arterio portal shunts, arterio venous shunts and acute inflammation. THPE can be classified based on morphological appearances as lobar multisegmental, sectorial, polymorphous, and diffuse.
      • Quiroga S.
      • Sebastià C.
      • Pallisa E.
      • Castellà E.
      • Pérez-Lafuente M.
      • Alvarez-Castells A.
      Improved diagnosis of hepatic perfusion disorders: value of hepatic arterial phase imaging during helical CT.
      • Colagrande S.
      • Centi N.
      • La Villa G.
      • Villari N.
      Transient hepatic attenuation differences.
      The sectorial type of THPE occurs in the portal vein distribution, and appears as classical wedge shaped sharply demarcated areas (straight border sign typical of portal dichotomy) (Fig. 11). It is caused due to portal hypoperfusion in cases where is an associated focal lesion (tumor or abscess), or due to portal or hepatic vein thrombosis, biliary obstruction, and arterioportal shunts with no associated focal lesions. A sectorial THPE with no obvious cause apparent on imaging, must prompt search for a hidden neoplasm.
      • Brink J.A.
      Increased CT contrast enhancement of "normal" hepatic parenchyma may herald "occult" metastases.
      Fig. 11
      Fig. 11Pseudolesion due to acute portal vein thrombosis in a 35-year-old man with small hepatic abscess.
      (a) Axial T2W MRI shows small hepatic abscess in segment 6 of right lobe of liver (long arrow) and reactive gallbladder wall edema (short arrow). (b) Axial diffusion weighted image shows restriction within the small hepatic abscess (arrow). (c) Contrast enhanced MRI in the arterial phase shows wedge shaped hyperenhancement (short arrow) around the abscess (long arrow). (d and e) Contrast enhanced MRI in the venous phase shows wedge shaped hypoenhancement (short arrow) around the abscess with thrombosis of peripheral portal vein branch (long arrow) at its apex. (f) Contrast enhanced MRI in the delayed phase shows wedge shaped area becoming isointense to surrounding liver suggesting transient hepatic parenchymal enhancement (THPE) or transient hepatic intensity difference (THID) (short arrow).
      The lobar multisegmental variant occurs in the arterial distribution, when there is a global increase in the hepatic arterial inflow (‘sump’ or ‘siphoning’ effect) and is usually associated with a focal lesion. Examples are focal hypervascular liver lesions, inflammation, or aberrant arterial supply. Typically, they do not demonstrate straight borders.
      • Colagrande S.
      • Centi N.
      • Galdiero R.
      • Ragozzino A.
      Transient hepatic intensity differences: part 1, those associated with focal lesions.
      The polymorphous type, as the name suggests follows no particular distribution and has a variable morphology. Causes are varied, such as hepatic parenchymal compression (by ribs or diaphragmatic slips), hepatic trauma, iatrogenic injury, and aberrant blood supply (arterial or venous). These reactions may also be seen in the vicinity of percutaneous injections or biopsy sites.
      • Chen W.P.
      • Chen J.H.
      • Hwang J.I.
      • et al.
      Spectrum of transient hepatic attenuation differences in biphasic helical CT.
      • Colagrande S.
      • Centi N.
      • Galdiero R.
      • Ragozzino A.
      Transient hepatic intensity differences: part 2, those not associated with focal lesions.
      The diffuse variant may demonstrate a patchy, peripheral or peribiliary pattern and are caused by a more proximal portal or hepatic venous obstruction. These may be seen in Budd Chiari syndrome, cirrhosis and biliary obstruction. The latter causes an obstruction to the peribiliary venules, hence an increased arterial inflow to the peribiliary parenchyma and resultant THPE.
      • Lencioni R.
      • Cioni D.
      • Bartolozzi C.
      Focal Liver Lesions.
      • Schneider G.
      • Martin D.R.
      • Grazioli L.
      • et al.
      MRI of the Liver: Imaging Techniques, Contrast Enhancement, Differential Diagnosis.

      3.2.2 Intrahepatic shunts

      3.2.2.1 Arterioportal shunts (APS)

      These are the commonest intrahepatic shunts and may occur at the transsinusoidal, transvasal and transtumoral levels. Often microscopic, sometimes they may be macroscopic and visualized directly at imaging. They can be classified as non-tumorous APS usually associated with portal vein thrombosis, cirrhosis, prior inflammation, trauma, post intervention and tumorous APS such as hemangioma, hepatocellular carcinoma and angiosarcoma.
      • Schneider G.
      • Martin D.R.
      • Grazioli L.
      • et al.
      MRI of the Liver: Imaging Techniques, Contrast Enhancement, Differential Diagnosis.
      The etiopathogenesis of these shunts is an obliteration of the microscopic hepatic venules (as is the case in cirrhosis), leading to chemical mediator-related shunting and retrograde filling of the portal vein by the hepatic artery.
      • Motosugi U.
      • Ichikawa T.
      • Sou H.
      • et al.
      Distinguishing hypervascular pseudolesions of the liver from hypervascular hepatocellular carcinomas with gadoxetic acid-enhanced MR imaging.
      Any obstruction to the portal vein opens up the APS and creates perfusion abnormalities. Both portal venous obstruction and APS share similar clinical and imaging features as the underlying pathophysiology is shunting of arterial blood to portal system at microscopic or macroscopic levels.
      • Chen W.P.
      • Chen J.H.
      • Hwang J.I.
      • et al.
      Spectrum of transient hepatic attenuation differences in biphasic helical CT.
      At imaging, there is THPE seen at arterial phase in the involved segment similar to seen in portal venous obstruction. In addition because of the pressure difference between hepatic arterial and portal venous system, there is inversion of portal flow with early peripheral portal venous enhancement of the corresponding area (before the main portal vein enhances). Sometimes, the main portal vein and intrahepatic branches may enhance prior to the superior mesenteric and splenic veins.
      • Chen J.H.
      • Chai J.W.
      • Huang C.L.
      • Hung H.C.
      • Shen W.C.
      • Lee S.K.
      Proximal arterioportal shunting associated with hepatocellular carcinoma: features revealed by dynamic helical CT.
      • Matsuo M.
      • Kanematsu M.
      • Kondo H.
      • et al.
      Arterioportal shunts mimicking hepatic tumors with hyperintensity on T2-weighted MR images.
      In clinical practice, APS are commonly seen in cirrhosis and often mimic small HCC. APS are usually isointense on unenhanced CT or MRI, as well as diffusion weighted MRI. These are usually less than 1.5 cm, and the resultant areas of THPE are often polymorphous. It is important to differentiate these from HCC; the T2 hyperintense morphology, diffusion restriction, and the typical pattern of venous/delayed phase washout of HCC help in diagnosis.
      • Motosugi U.
      • Ichikawa T.
      • Sou H.
      • et al.
      Distinguishing hypervascular pseudolesions of the liver from hypervascular hepatocellular carcinomas with gadoxetic acid-enhanced MR imaging.
      • Matsuo M.
      • Kanematsu M.
      • Kondo H.
      • et al.
      Arterioportal shunts mimicking hepatic tumors with hyperintensity on T2-weighted MR images.
      Rarely, they may be nodular with mild hyperintensity on T2 weighted MRI likely due to sinusoidal congestion (or the Zahn's infarct) and due to increased extravasation of fluid into the perisinusoidal space of Disse.
      • Kanematsu M.
      • Kondo H.
      • Semelka R.C.
      • et al.
      Early-enhancing non-neoplastic lesions on gadolinium-enhanced MRI of the liver.
      In difficult cases, liver specific contrast agents (which are typically not taken up by HCC) may help. A small percentage (5 to 15%) of these shunts remain hypointense during the hepatocyte phase; this signal intensity is only modestly low compared with the profoundly low signal of HCC.
      • Motosugi U.
      • Ichikawa T.
      • Sou H.
      • et al.
      Distinguishing hypervascular pseudolesions of the liver from hypervascular hepatocellular carcinomas with gadoxetic acid-enhanced MR imaging.
      Alternatively, a short interval follow up at 3 to 6 months may be recommended. The cause of these lesions may not be apparent even after various imaging techniques in up to 26% of cases
      • Kanematsu M.
      • Kondo H.
      • Semelka R.C.
      • et al.
      Early-enhancing non-neoplastic lesions on gadolinium-enhanced MRI of the liver.
      (Fig. 12).
      Fig. 12
      Fig. 12Arterioportal shunt in a 55-year-old man with Hepatitis B related cirrhosis.
      (a) Axial T1W and (b) axial T2W MRI show morphological changes of cirrhosis with nodular outline. (c) Axial diffusion weighted MRI shows faintly hyperintense lesion (arrow) in segment 7 subcapsular location. Contrast enhanced MRI shows hypervascularity of the subcapsular wedge shaped lesion (arrow) in the arterial phase (d), persisting in the venous phase (e) and becoming isointense in the delayed phase (f) with no wash out.
      In cirrhosis, APS may occur even in the absence of HCC (in 28% of cases), and arteriovenous shunts occur in about 2.8%. These shunts cause a hepatofugal flow and are a relative contraindication for performing transarterial chemoembolization, due to the risk of non-targeted splanchnic embolization.
      • Lencioni R.
      • Cioni D.
      • Bartolozzi C.
      Focal Liver Lesions.
      • Sunnapwar A.
      • Katre R.
      • Prasad S.R.
      • Chintapalli K.
      • Philips S.
      Spectrum of multidetector computed tomography/magnetic resonance imaging findings in intrahepatic vascular shunts: classification, characterization, and management.

      3.2.2.2 Arteriovenous shunts (AVS)

      These refer to direct communications between the hepatic artery and hepatic veins, and are primarily observed in pathologies such as HCC, hemangioma, hemangioendothelioma or sometimes in focal nodular hyperplasia.
      • Ngan H.
      • Peh W.C.
      Arteriovenous shunting in hepatocellular carcinoma: its prevalence and clinical significance.
      These are seen at imaging as early enhancement of the hepatic vein in the segment containing the tumor, prior to the opacification of the portal vein. The hepatic veins may also demonstrate arterialized flow with increased velocities, and loss of the usual triphasic pattern on Doppler study
      • Sunnapwar A.
      • Katre R.
      • Prasad S.R.
      • Chintapalli K.
      • Philips S.
      Spectrum of multidetector computed tomography/magnetic resonance imaging findings in intrahepatic vascular shunts: classification, characterization, and management.
      • Wu J.S.
      • Saluja S.
      • Garcia-Tsao G.
      • Chong A.
      • Henderson K.J.
      • White Jr., R.I.
      Liver involvement in hereditary hemorrhagic telangiectasia: CT and clinical findings do not correlate in symptomatic patients.
      (Fig. 13).
      Fig. 13
      Fig. 13(a) Intrahepatic portosystemic venous shunt in a 54-year-old asymptomatic man. Axial contrast enhanced CT in the venous phase shows small peripheral vascular shunt (arrow) between portal and hepatic venous branch in the left lobe of liver.
      (b and c) Arteriovenous shunt in a 35-year-old woman with focal nodular hyperplasia.
      (b) Contrast enhanced MRI in the arterial phase shows lobulated hypervascular lesion (short arrow) in the right lobe of liver with small arterial feeder (long arrow). (c) Contrast enhanced MRI in the venous phase shows persistent enhancement of the lesion with no wash out (short arrow) with draining vein (long arrow).

      3.2.2.3 Intrahepatic portosystemic venous shunts

      These refer to either congenital or acquired communications between the intrahepatic branches of the portal vein with the hepatic and perihepatic systemic veins. Congenital shunting is due to persistent embryonic connections between the tributaries of the vitelline vein. Causes of acquired shunts include cirrhosis, trauma, or ruptured portal vein aneurysm. Complications such as fibrosis, hepatic encephalopathy or high output cardiac failure may ensue. These can be easily demonstrated on color Doppler and cross sectional imaging as direct communication between dilated portal and hepatic venous branch
      • Virmani V.
      • Ramanathan S.
      • Virmani V.S.
      • Kielar A.
      • Sheikh A.
      • Ryan J.
      Non-neoplastic hepatic vascular diseases: spectrum of CT and MRI appearances.
      • Sunnapwar A.
      • Katre R.
      • Prasad S.R.
      • Chintapalli K.
      • Philips S.
      Spectrum of multidetector computed tomography/magnetic resonance imaging findings in intrahepatic vascular shunts: classification, characterization, and management.
      • Remer E.M.
      • Motta-Ramirez G.A.
      • Henderson J.M.
      Imaging findings in incidental intrahepatic portal venous shunts.
      (Fig. 13).

      3.2.3 Passive hepatic congestion

      Cardiac conditions increasing the right heart pressure, such as congestive heart failure, constrictive pericarditis, valvular heart disease and cardiomyopathy may cause congestive changes in the liver.
      • Giallourakis C.C.
      • Rosenberg P.M.
      • Friedman L.S.
      The liver in heart failure.
      This is evident with dilated hepatic veins and IVC and early enhancement of the hepatic veins due to tricuspid reflux. The liver is typically enlarged with perivenous edema and demonstrates heterogeneous enhancement due to non-uniform perfusion, known as the nutmeg liver. The periphery of the liver may demonstrate hypoenhancement due to poor perfusion. Ascites may be present. Chronic congestive changes may lead to hepatocellular damage and irreversible cardiac cirrhosis
      • Torabi M.
      • Hosseinzadeh K.
      • Federle M.P.
      CT of nonneoplastic hepatic vascular and perfusion disorders.
      (Fig. 14).
      Fig. 14
      Fig. 14Passive hepatic congestion in an 64-year-old woman presenting with congestive cardiac failure. (a) and (b) Axial contrast-enhanced CT image in the venous phase reveals pericardial and right pleural effusion (asterisk) with inhomogeneous hepatic parenchymal enhancement (nutmeg liver) (short arrow) with dilatation of the IVC (long arrow).

      3.2.4 Hepatic arterial occlusion

      Hepatic infarction is uncommon due to dual hepatic blood supply and collateral system. When it occurs, it is often associated with underlying portal vein compromise. The common causes include iatrogenic injury, post traumatic, following liver transplantation, chemo-embolization, hypercoagulability and infection. The resultant ischemic insult to the liver appears as a rounded area if the central branches are involved, or wedge shaped and tubular when peripheral subcapsular arteries are affected. The affected area parallels the bile duct distribution, reflecting the arterial supply to the liver.
      • Torabi M.
      • Hosseinzadeh K.
      • Federle M.P.
      CT of nonneoplastic hepatic vascular and perfusion disorders.
      Imaging clues are low density on CT, with a low T1 and high T2 signal on MRI with no associated mass effect. Post contrast images reveal relative hypoattenuation on all phases due to underlying necrosis, hemorrhage or fibrous changes. There may be patchy enhancement of the involved segment or lobe due to collaterals. Typically, preserved vessels course through the lesions due to absence of mass effect, unlike other conditions like abscess or biloma. Partly viable or revascularized hepatic tissue may appear isodense on the portal venous or delayed phases. Complications of biliary necrosis including bile lakes and intrahepatic gas formation may occur.
      • Holbert B.L.
      • Baron R.L.
      • Dodd 3rd., G.D.
      Hepatic infarction caused by arterial insufficiency: spectrum and evolution of CT findings.
      Although hepatic infarct per se is not a pseudo lesion, it needs to be differentiated from neoplastic lesions to avoid unwarranted biopsy and its associated complications (Fig. 15).
      Fig. 15
      Fig. 15Hepatic infarction in a 33-year-old woman with hypercoagulability.
      (a) Axial T2W MRI shows heterogeneous predominantly cystic lesion (short arrow) in the right lobe of liver. (b) Axial precontrast T1W MRI shows iso to mild hyperintense lesion in the right lobe of liver (short arrow). (c) Contrast enhanced MRI in the arterial (c) and venous phase (d) shows nonenhancement of the lesion in keeping with hepatic infarct (short arrows), Note the celiac axis occlusive thrombus (black arrow) and partial thrombosis in the main portal vein (long white arrow). Associated complete splenic infarction (asterisk) also seen.

      3.2.5 Hepatic venous occlusion

      Budd Chiari syndrome (BCS) is the prototype of hepatic venous occlusion which may occur at the level of small or large hepatic veins, the intra- or suprahepatic IVC. It may be congenital due to venous webs or diaphragms, or secondary to hypercoagulable states and myeloproliferative disorders. The increased sinusoidal pressures lead to decreased portal venous inflow and a compensatory increase in the hepatic arterial flow and transsinusoidal APS, culminating in perfusion abnormalities. The portal vein becomes the draining vein instead of supplying vein for the liver (functional portal flow elimination), in cases of acute hepatic venous obstruction. The obstruction is usually confined to a few segments, leading to diversion to patent venous pathways in the vicinity and veno-venous collaterals, in subacute to chronic cases. Eventually, there is atrophy of the involved segment and hypertrophy of the uninvolved segments and the caudate, as the latter drains directly into the IVC.
      • Lencioni R.
      • Cioni D.
      • Bartolozzi C.
      Focal Liver Lesions.
      On imaging, acute BCS presents as an enlarged hypoattenuating liver with heterogeneous enhancement. Hyperdense clot may be seen in the thrombosed hepatic vein or IVC. There is early enhancement of the caudate and central liver at arterial phase, with hypoattenuation more peripherally, owing to sinusoidal congestion, hepatic steatosis and necrosis. However on the portal venous phase, the central liver washes out while the periphery gradually enhances deriving blood supply from capsular vessels, descriptive of the typical ‘flip-flop pattern’ of enhancement in BCS.
      • Virmani V.
      • Ramanathan S.
      • Virmani V.S.
      • Kielar A.
      • Sheikh A.
      • Ryan J.
      Non-neoplastic hepatic vascular diseases: spectrum of CT and MRI appearances.
      • Bansal V.
      • Gupta P.
      • Sinha S.
      • et al.
      Budd-chiari syndrome: imaging review.
      Transient hepatic enhancement is also seen in such cases due to increased arterial flow; however, the apex of the typically wedge-shaped perfusion anomaly points towards the inferior vena cava, in contrast to the apex pointing to the hepatic hilum in cases of portal vein obstruction.
      • Itai Y.
      • Murata S.
      • Kurosaki Y.
      Straight border sign of the liver: spectrum of CT appearances and causes.
      Chronic cases culminate in caudate hypertrophy and peripheral atrophy, veno-venous collaterals, mosaic pattern of enhancement, and regenerative nodules. The latter may demonstrate arterial hypervascularity similar to HCC; however, they tend to remain mildly hyperenhancing on the portal venous CT or MRI, unlike HCC which washes out. Typical of BCS are the intrahepatic veno-venous collaterals, which may be comma shaped or tortuous hepatic vein to hepatic vein shunts, spider-web like, or drain into the inferior vena cava or subcapsular veins
      • Brancatelli G.
      • Federle M.P.
      • Grazioli L.
      • Golfieri R.
      • Lencioni R.
      Benign regenerative nodules in budd-chiari syndrome and other vascular disorders of the liver: radiologic-pathologic and clinical correlation.
      • Brancatelli G.
      • Vilgrain V.
      • Federle M.P.
      • et al.
      Budd-chiari syndrome: spectrum of imaging findings.
      (Fig. 16).
      Fig. 16
      Fig. 16Veno venous shunt in a 58-year-old man with chronic Budd-Chiari syndrome
      (a) Axial contrast enhanced MRI in the venous phase shows large shunt between the middle and left hepatic vein (arrow). (b) Coronal contrast enhanced MRI in the venous phase shows severe narrowing of intrahepatic IVC (arrow) with splenomegaly (asterisk).

      3.2.6 Third inflow

      This refers to non-portal aberrant veins that independently enter the liver parenchyma, but communicate with the intrahepatic portal branches. They can be classified region-wise as i) the paraumbilical (around the falciform ligament), ii) the parabiliary, involving segments 4 and 3, iii) the cholecystic, around the gall bladder in segments 4 and 5, and iv) diaphragmatic, involving the subcapsular aspect of right lobe.
      • Itai Y.
      • Matsui O.
      'Nonportal' splanchnic venous supply to the liver: abnormal findings on CT, US and MRI.
      Third inflow pseudolesions may be seen as focal hyperattenuating areas in the arterial phase because of earlier inflow compared with the rest of the liver receiving blood from the splanchnic circulation. They may also lead to differential fat sparing (due to lower concentration of fatty acids) or to FFI, which is likely due to altered metabolism from nutritional elements or hormones.
      • Yoon K.H.
      • Matsui O.
      • Kadoya M.
      • Yoshigawa J.
      • Gabata T.
      • Arai K.
      Pseudolesion in segments II and III of the liver on CT during arterial portography caused by aberrant right gastric venous drainage.
      The parabiliary non-portal venous drainage to the liver comprises of aberrant right gastric venous drainage coursing through the hepatoduodenal ligament, and the pancreaticoduodenal venous drainage. They usually cause perfusion abnormalities in the dorsum of left lateral segment and caudate lobe, and the dorsum of the medial segment
      • Gabata T.
      • Matsui O.
      • Kadoya M.
      • et al.
      Aberrant gastric venous drainage in a focal spared area of segment IV in fatty liver: demonstration with color doppler sonography.
      • Itai Y.
      • Matsui O.
      'Nonportal' splanchnic venous supply to the liver: abnormal findings on CT, US and MRI.
      (Fig. 17).
      Fig. 17
      Fig. 17Pseudolesions due to third inflow.
      (a, b and c) Pseudolesions in superior vena cava obstruction in three different patients with lung cancer.
      (a) Axial contrast-enhanced CT in the arterial phase shows focal hypervascularity in segment IV (long arrow) with abdominal wall collaterals (short arrows).
      (b) Axial contrast-enhanced CT in the arterial phase shows subcapsular wedge shaped hypervascularity adjacent to falciform ligament (long arrow) with abdominal wall collaterals (short arrows). Note the early intense opacification of middle hepatic vein and IVC (black arrows).
      (c) Axial contrast-enhanced CT in the arterial phase shows subcapsular wedge shaped hypervascularity in the right lobe (long arrow) with abdominal wall collaterals (short arrows). Note the early intense opacification of IVC (black arrows).
      (d and e) Pseudolesions due to parabiliary third inflow.
      (d) Axial contrast-enhanced CT in the venous phase shows subcapsular ill-defined enhancing area in segment 3 (arrow). (e) Axial contrast-enhanced CT in the venous phase shows associated aberrant venous channel (arrow).
      In chronic superior vena cava (SVC) obstruction, several cavoportal collaterals open up to divert blood flow towards the portal vein through the paraumbilical and diaphragmatic collateral pathways as described above.
      • Kapur S.
      • Paik E.
      • Rezaei A.
      • Vu D.N.
      Where there is blood, there is a way: unusual collateral vessels in superior and inferior vena cava obstruction.
      These may lead to increased enhancement in the corresponding segments of the liver in up to 29%, leading to a misinterpretation as a focal hypervascular liver lesion. Most common locations are the anterior part of segment 4 and the subdiaphragmatic liver, with other clues visible on imaging such as SVC obstruction and collaterals
      • Sheth S.
      • Ebert M.D.
      • Fishman E.K.
      Superior vena cava obstruction evaluation with MDCT.
      • Siegel Y.
      • Schallert E.
      Prevalence and etiology of focal liver opacification in patients with superior vena cava obstruction.
      (Fig. 17).

      3.3 Pseudolesions due to imaging pitfalls

      These are neither true lesions, nor the classical pseudolesions described above and occur due to technical factor in the acquisition or due to interpretation error. Parenchymal compression, unopacified vessels and pericaval lipoma are included under this category.

      3.3.1 Parenchymal compression

      These occur in cases of hepatic parenchymal compression typically by ribs or diaphragmatic slips. Other causes include intra or extrahepatic masses, perihepatic and subcapsular metastatic deposits, pseudomyxoma peritonei. It may cause a decrease in portal pressure with or without evident arterial flow alteration (usually a mild compensatory increase in the arterial flow). It appears as ill-defined subcapsular hypodensity with concave hepatic surface in portal venous phase. Usually there is no abnormality in precontrast, arterial and delayed phases. Typically, they disappear with different inspiration levels, and the cause of compression is eliminated
      • Gryspeerdt S.
      • Van Hoe L.
      • Marchal G.
      • Baert A.L.
      Evaluation of hepatic perfusion disorders with double-phase spiral CT.
      • Yoshimitsu K.
      • Honda H.
      • Kuroiwa T.
      • et al.
      Pseudolesions of the liver possibly caused by focal rib compression: analysis based on hemodynamic change.
      (Fig. 18).
      Fig. 18
      Fig. 18Pseudolesions due to imaging pitfalls.
      (a) Pseudolesion due to parenchymal compression. Axial contrast-enhanced CT in the venous phase shows subtle subcapsular hypodensity in the hepatic dome with concave surface due to diaphragmatic compression.
      (b) Pericaval lipoma. Axial contrast-enhanced CT in the venous phase shows small fat density lesion inseparable from intrahepatic IVC representing pericaval lipoma simulating thrombus (arrow).
      (c and d) Pseudolesion due to unenhanced vessel.
      (c) Axial contrast-enhanced CT in the venous phase shows small hypodense lesion (arrow).
      (d) Axial contrast enhanced CT in the delayed phase reveals the lesion as continuous with the hepatic vein (arrow).

      3.3.2 Unenhanced vessels

      Unenhanced vessels (portal and hepatic veins) can mimic a hypodense liver lesion when seen end-on or dilated biliary duct on inplane view. Careful attention to the phase of imaging and comparison with delayed phase along with anatomical location can help in diagnosis
      • Vilgrain V.
      • Lagadec M.
      • Ronot M.
      Pitfalls in liver imaging.
      (Fig. 18).

      3.3.3 Pseudolipoma

      Pericaval and Glisson capsule pseudolipoma are seen as focal fat around the intrahepatic IVC and liver capsule respectively. They are considered normal variants and are seen more frequently with obesity and chronic liver disease. They may mimic fat containing tumor or thrombus. Evaluation of contiguous slices and multiplanar reformats help in accurate assessment of these lesions
      • Lencioni R.
      • Cioni D.
      • Bartolozzi C.
      Focal Liver Lesions.
      • Han B.K.
      • Im J.G.
      • Jung J.W.
      • Chung M.J.
      • Yeon K.M.
      Pericaval fat collection that mimics thrombosis of the inferior vena cava: demonstration with use of multi-directional reformation CT.
      (Fig. 18).

      4. Conclusion

      Hepatic pseudolesions are no longer a rare entity and are increasingly encountered in daily practice of General and abdominal radiologists. Broadly it can be categorised in to focal parenchymal abnormalities, perfusion related lesions and pseudo lesions due to imaging pitfalls. It is important to familiarize the typical imaging features of these pseudo lesions for two main reasons: (1) It can mimic hypovascular and hypervascular neoplastic lesions (2) It can be a pointer for an underlying disease process like portal vein or hepatic arterial obstruction. Hence it is not a completely innocuous lesion as it can be a manifestation of an underlying serious disease like arterioportal shunt in HCC or mosaic enhancement in Budd-Chiari syndrome. Both overcalling and underreporting of these lesions by radiologists should be avoided as it can initiate unnecessary chain of investigations or hinder appropriate patient management respectively. Their morphology, typical location, absence of mass effect and characteristic enhancement pattern helps to clinch the diagnosis in a majority of patients. Keen attention to the various phases of image acquisition is essential in making the correct diagnosis. In difficult cases DWI imaging, chemical shift imaging, and/or MRI with hepatocyte specific contrast can be helpful to narrow down the differential diagnosis. Short interval follow up can be considered in indeterminate cases with rational use of biopsy in selected indications.

      Funding

      Open access funding supported by Qatar national library.

      Research involving human participants and/or animals

      All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

      Informed consent

      This is a retrospective study involving collection of anonymized radiological images without patient information or identifiers. Hence they are exempted from formal consent process.

      CRediT authorship contribution statement

      Conceptualization: Subramaniyan Ramanathan, Sree Harsha Tirumani
      Draft Writing: Subramaniyan Ramanathan, Vineetha Raghu
      Draft review: Vivek Virmani, Adnan Sheikh
      Draft editing: Mahmoud Heidous

      Declaration of competing interest

      All the authors declare that they have no financial or non-financial conflicts of interest.

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