MR imaging of liver fibrosis: current state of the art

Abstract

Chronic liver disease is a major public health problem worldwide. Liver fibrosis, a common feature of almost all causes of chronic liver disease, involves the accumulation of collagen, proteoglycans, and other macromolecules within the extracellular matrix. Fibrosis tends to progress, leading to hepatic dysfunction, portal hypertension, and ultimately cirrhosis. Liver biopsy, the standard of reference for diagnosing liver fibrosis, is invasive, costly, and subject to complications and sampling variability. These limitations make it unsuitable for diagnosis and longitudinal monitoring in the general population. Thus, development of a noninvasive, accurate, and reproducible test for diagnosis and monitoring of liver fibrosis would be of great value. Conventional cross-sectional imaging techniques have limited capability to demonstrate liver fibrosis. In clinical practice, imaging studies are usually reserved for evaluation of the presence of portal hypertension or hepatocellular carcinoma in cases that have progressed to cirrhosis. In response to the rising prevalence of chronic liver diseases in Western nations, a number of imaging-based methods including ultrasonography-based transient elastography, computed tomography-based texture analysis, and diverse magnetic resonance (MR) imaging-based techniques have been proposed for noninvasive diagnosis and grading of hepatic fibrosis across its entire spectrum of severity. State-of-the-art MR imaging-based techniques in current practice and in development for noninvasive assessment of liver fibrosis include conventional contrast material-enhanced MR imaging, double contrast-enhanced MR imaging, MR elastography, diffusion-weighted imaging, and MR perfusion imaging.

Figure 10a

Dynamic enhancement patterns of fibrous versus neoplastic tissue after administration of a hepatobiliary gadolinium-based contrast agent. Axial 3D T1-weighted gradient-echo images (~4/1.5, flip angle = 15°), obtained at 3 T 20 seconds (a), 5 minutes (b), and 30 minutes (c) after intravenous injection of the hepatobiliary gadolinium-based contrast agent gadoxetate disodium, show a cirrhotic liver. Fibrotic scars are not well demonstrated in the arterial or late venous phase but are clearly visible as a meshwork of hypointense reticulations on the hepatocellular phase image (arrows in c). By comparison, a 4.2 × 4.1-cm HCC (*) in segment 6 enhances vividly in the arterial phase, washes out to hypointensity relative to the liver in the late venous phase, and remains hypointense to the liver in the hepatocellular phase. The tumor is surrounded by a fibrous capsule (arrow in a and b) and contains internal septa. Note the biliary excretion of contrast material on the 30-minute image.

Figure 10b

Dynamic enhancement patterns of fibrous versus neoplastic tissue after administration of a hepatobiliary gadolinium-based contrast agent. Axial 3D T1-weighted gradient-echo images (~4/1.5, flip angle = 15°), obtained at 3 T 20 seconds (a), 5 minutes (b), and 30 minutes (c) after intravenous injection of the hepatobiliary gadolinium-based contrast agent gadoxetate disodium, show a cirrhotic liver. Fibrotic scars are not well demonstrated in the arterial or late venous phase but are clearly visible as a meshwork of hypointense reticulations on the hepatocellular phase image (arrows in c). By comparison, a 4.2 × 4.1-cm HCC (*) in segment 6 enhances vividly in the arterial phase, washes out to hypointensity relative to the liver in the late venous phase, and remains hypointense to the liver in the hepatocellular phase. The tumor is surrounded by a fibrous capsule (arrow in a and b) and contains internal septa. Note the biliary excretion of contrast material on the 30-minute image.

Figure 10c

Dynamic enhancement patterns of fibrous versus neoplastic tissue after administration of a hepatobiliary gadolinium-based contrast agent. Axial 3D T1-weighted gradient-echo images (~4/1.5, flip angle = 15°), obtained at 3 T 20 seconds (a), 5 minutes (b), and 30 minutes (c) after intravenous injection of the hepatobiliary gadolinium-based contrast agent gadoxetate disodium, show a cirrhotic liver. Fibrotic scars are not well demonstrated in the arterial or late venous phase but are clearly visible as a meshwork of hypointense reticulations on the hepatocellular phase image (arrows in c). By comparison, a 4.2 × 4.1-cm HCC (*) in segment 6 enhances vividly in the arterial phase, washes out to hypointensity relative to the liver in the late venous phase, and remains hypointense to the liver in the hepatocellular phase. The tumor is surrounded by a fibrous capsule (arrow in a and b) and contains internal septa. Note the biliary excretion of contrast material on the 30-minute image.

Figure 11a

Synergy of SPIO and a gadolinium-based contrast agent for direct visualization of advanced fibrosis in a man with HCV-related cirrhosis. Axial unenhanced (a), gadolinium-enhanced (b), SPIO-enhanced (c), and double contrast-enhanced (SPIO plus gadolinium) (d) 2D T1-weighted (repetition time = 150 msec, flip angle = 70°) and T2*-weighted (echo time = 6 msec) gradient-echo images, obtained at 3 T within a 1-week period, show a cirrhotic liver with innumerable hyperintense reticulations surrounding hypointense regenerative nodules. Parenchymal alterations are poorly demonstrated on the unenhanced image. Gadolinium-based contrast agent accumulates in extracellular spaces within fibrotic tissue and enhances the signal of fibrotic reticulations. Iron oxides selectively accumulate within Kupffer cells and darken the background parenchyma. In combination, SPIO and a gadolinium-based contrast agent are synergistic and depict fibrotic reticulations (arrows in d) and regenerative nodules (arrowheads in d) with high clarity on the double contrast-enhanced image.

Figure 11b

Synergy of SPIO and a gadolinium-based contrast agent for direct visualization of advanced fibrosis in a man with HCV-related cirrhosis. Axial unenhanced (a), gadolinium-enhanced (b), SPIO-enhanced (c), and double contrast-enhanced (SPIO plus gadolinium) (d) 2D T1-weighted (repetition time = 150 msec, flip angle = 70°) and T2*-weighted (echo time = 6 msec) gradient-echo images, obtained at 3 T within a 1-week period, show a cirrhotic liver with innumerable hyperintense reticulations surrounding hypointense regenerative nodules. Parenchymal alterations are poorly demonstrated on the unenhanced image. Gadolinium-based contrast agent accumulates in extracellular spaces within fibrotic tissue and enhances the signal of fibrotic reticulations. Iron oxides selectively accumulate within Kupffer cells and darken the background parenchyma. In combination, SPIO and a gadolinium-based contrast agent are synergistic and depict fibrotic reticulations (arrows in d) and regenerative nodules (arrowheads in d) with high clarity on the double contrast-enhanced image.

Figure 11c

Synergy of SPIO and a gadolinium-based contrast agent for direct visualization of advanced fibrosis in a man with HCV-related cirrhosis. Axial unenhanced (a), gadolinium-enhanced (b), SPIO-enhanced (c), and double contrast-enhanced (SPIO plus gadolinium) (d) 2D T1-weighted (repetition time = 150 msec, flip angle = 70°) and T2*-weighted (echo time = 6 msec) gradient-echo images, obtained at 3 T within a 1-week period, show a cirrhotic liver with innumerable hyperintense reticulations surrounding hypointense regenerative nodules. Parenchymal alterations are poorly demonstrated on the unenhanced image. Gadolinium-based contrast agent accumulates in extracellular spaces within fibrotic tissue and enhances the signal of fibrotic reticulations. Iron oxides selectively accumulate within Kupffer cells and darken the background parenchyma. In combination, SPIO and a gadolinium-based contrast agent are synergistic and depict fibrotic reticulations (arrows in d) and regenerative nodules (arrowheads in d) with high clarity on the double contrast-enhanced image.

Figure 11d

Synergy of SPIO and a gadolinium-based contrast agent for direct visualization of advanced fibrosis in a man with HCV-related cirrhosis. Axial unenhanced (a), gadolinium-enhanced (b), SPIO-enhanced (c), and double contrast-enhanced (SPIO plus gadolinium) (d) 2D T1-weighted (repetition time = 150 msec, flip angle = 70°) and T2*-weighted (echo time = 6 msec) gradient-echo images, obtained at 3 T within a 1-week period, show a cirrhotic liver with innumerable hyperintense reticulations surrounding hypointense regenerative nodules. Parenchymal alterations are poorly demonstrated on the unenhanced image. Gadolinium-based contrast agent accumulates in extracellular spaces within fibrotic tissue and enhances the signal of fibrotic reticulations. Iron oxides selectively accumulate within Kupffer cells and darken the background parenchyma. In combination, SPIO and a gadolinium-based contrast agent are synergistic and depict fibrotic reticulations (arrows in d) and regenerative nodules (arrowheads in d) with high clarity on the double contrast-enhanced image.

Figure 12a

Double contrast-enhanced MR imaging appearance of different stages of HCV-related liver fibrosis. Axial double contrast-enhanced (SPIO plus gadolinium) gradient-echo images (180/6, flip angle = 70°), obtained at 3 T in four HCV-infected patients with histologically confirmed stage F1 (a), F2 (b), F3 (c), and F4 (d) liver fibro-sis, show hyperintense reticulations in the liver. With increasing stage of fibrosis, there is a corresponding increase in the density and thickness of the reticulations and their signal intensity relative to that of the liver.

Figure 12b

Double contrast-enhanced MR imaging appearance of different stages of HCV-related liver fibrosis. Axial double contrast-enhanced (SPIO plus gadolinium) gradient-echo images (180/6, flip angle = 70°), obtained at 3 T in four HCV-infected patients with histologically confirmed stage F1 (a), F2 (b), F3 (c), and F4 (d) liver fibro-sis, show hyperintense reticulations in the liver. With increasing stage of fibrosis, there is a corresponding increase in the density and thickness of the reticulations and their signal intensity relative to that of the liver.

Figure 12c

Double contrast-enhanced MR imaging appearance of different stages of HCV-related liver fibrosis. Axial double contrast-enhanced (SPIO plus gadolinium) gradient-echo images (180/6, flip angle = 70°), obtained at 3 T in four HCV-infected patients with histologically confirmed stage F1 (a), F2 (b), F3 (c), and F4 (d) liver fibro-sis, show hyperintense reticulations in the liver. With increasing stage of fibrosis, there is a corresponding increase in the density and thickness of the reticulations and their signal intensity relative to that of the liver.

Figure 12d

Double contrast-enhanced MR imaging appearance of different stages of HCV-related liver fibrosis. Axial double contrast-enhanced (SPIO plus gadolinium) gradient-echo images (180/6, flip angle = 70°), obtained at 3 T in four HCV-infected patients with histologically confirmed stage F1 (a), F2 (b), F3 (c), and F4 (d) liver fibro-sis, show hyperintense reticulations in the liver. With increasing stage of fibrosis, there is a corresponding increase in the density and thickness of the reticulations and their signal intensity relative to that of the liver.

Figure 13a

Double contrast-enhanced MR imaging appearance of cirrhosis due to chronic HCV infection. Axial double contrast-enhanced (SPIO plus gadolinium) 2D gradient-echo images of the liver, obtained at 1.5 T (100/6, flip angle = 70°) (a) and 3 T (150/6, flip angle = 70°) (b) in two patients with HCV-related cirrhosis, show a diffuse meshwork of hyperintense fibrotic reticulations surrounding variable-sized, predominantly hypointense regenerative nodules (arrowheads). There is no normal parenchyma. Note the small, mildly hyperintense HCCs in each patient (arrows).

Figure 13b

Double contrast-enhanced MR imaging appearance of cirrhosis due to chronic HCV infection. Axial double contrast-enhanced (SPIO plus gadolinium) 2D gradient-echo images of the liver, obtained at 1.5 T (100/6, flip angle = 70°) (a) and 3 T (150/6, flip angle = 70°) (b) in two patients with HCV-related cirrhosis, show a diffuse meshwork of hyperintense fibrotic reticulations surrounding variable-sized, predominantly hypointense regenerative nodules (arrowheads). There is no normal parenchyma. Note the small, mildly hyperintense HCCs in each patient (arrows).

Figure 14a

Double contrast-enhanced MR imaging appearance of confluent fibrosis with perivascular sparing in a man with alcohol-induced cirrhosis. Axial double contrast-enhanced (SPIO plus gadolinium) 2D gradient-echo images (140/6, flip angle = 70°), obtained at 1.5 T and displayed from superior (a) to inferior (d), show several areas of hyperintense confluent fibrosis (black arrows) in the liver. There are halos of low signal intensity surrounding many vessels (straight white arrow in a–c), a finding suggestive of perivascular sparing. Note the pseudotumoral hypertrophy of portions of the right and left lobes (curved arrows in c and d).

Figure 14b

Double contrast-enhanced MR imaging appearance of confluent fibrosis with perivascular sparing in a man with alcohol-induced cirrhosis. Axial double contrast-enhanced (SPIO plus gadolinium) 2D gradient-echo images (140/6, flip angle = 70°), obtained at 1.5 T and displayed from superior (a) to inferior (d), show several areas of hyperintense confluent fibrosis (black arrows) in the liver. There are halos of low signal intensity surrounding many vessels (straight white arrow in a–c), a finding suggestive of perivascular sparing. Note the pseudotumoral hypertrophy of portions of the right and left lobes (curved arrows in c and d).

Figure 14c

Double contrast-enhanced MR imaging appearance of confluent fibrosis with perivascular sparing in a man with alcohol-induced cirrhosis. Axial double contrast-enhanced (SPIO plus gadolinium) 2D gradient-echo images (140/6, flip angle = 70°), obtained at 1.5 T and displayed from superior (a) to inferior (d), show several areas of hyperintense confluent fibrosis (black arrows) in the liver. There are halos of low signal intensity surrounding many vessels (straight white arrow in a–c), a finding suggestive of perivascular sparing. Note the pseudotumoral hypertrophy of portions of the right and left lobes (curved arrows in c and d).

Figure 14d

Double contrast-enhanced MR imaging appearance of confluent fibrosis with perivascular sparing in a man with alcohol-induced cirrhosis. Axial double contrast-enhanced (SPIO plus gadolinium) 2D gradient-echo images (140/6, flip angle = 70°), obtained at 1.5 T and displayed from superior (a) to inferior (d), show several areas of hyperintense confluent fibrosis (black arrows) in the liver. There are halos of low signal intensity surrounding many vessels (straight white arrow in a–c), a finding suggestive of perivascular sparing. Note the pseudotumoral hypertrophy of portions of the right and left lobes (curved arrows in c and d).

Figure 15a

MR elastography of HCV-related fibrosis. MR elastographic wave images (left) and color-coded elastograms (right), obtained at 3 T in three patients with chronic HCV infection, show biopsy-proved stage F0 (a), F2 (b), and F4 (c) fibrosis. Propagation of shear waves through the liver is adequate in all three patients. The elastograms show progressively greater liver stiffness in the three patients, a finding that corresponds to increases in histologic fibrosis stage.

Figure 15b

MR elastography of HCV-related fibrosis. MR elastographic wave images (left) and color-coded elastograms (right), obtained at 3 T in three patients with chronic HCV infection, show biopsy-proved stage F0 (a), F2 (b), and F4 (c) fibrosis. Propagation of shear waves through the liver is adequate in all three patients. The elastograms show progressively greater liver stiffness in the three patients, a finding that corresponds to increases in histologic fibrosis stage.

Figure 15c

MR elastography of HCV-related fibrosis. MR elastographic wave images (left) and color-coded elastograms (right), obtained at 3 T in three patients with chronic HCV infection, show biopsy-proved stage F0 (a), F2 (b), and F4 (c) fibrosis. Propagation of shear waves through the liver is adequate in all three patients. The elastograms show progressively greater liver stiffness in the three patients, a finding that corresponds to increases in histologic fibrosis stage.

Figure 16a

Diffusion-weighted imaging and ADC values in a patient with alcohol- and HCV-related cirrhosis (stage F4). (a–f) Diffusion-weighted MR images with b values of 0 (a), 100 (b), 250 (c), 500 (d), 750 (e), and 1000 (f) sec/mm², obtained in a single breath hold at 3 T, show a progressive reduction in signal intensity of the cirrhotic liver with increasing b values; however, the reduction is less pronounced than in noncirrhotic patients. At a b value of 1000 sec/mm², the liver silhouette remains visible. (g) Corresponding ADC map of the abdomen, generated under the assumption of monoexponential decay, shows that the liver has a mean ADC of ~0.9 × 10⁻³ mm²/sec.

Figure 16b

Diffusion-weighted imaging and ADC values in a patient with alcohol- and HCV-related cirrhosis (stage F4). (a–f) Diffusion-weighted MR images with b values of 0 (a), 100 (b), 250 (c), 500 (d), 750 (e), and 1000 (f) sec/mm², obtained in a single breath hold at 3 T, show a progressive reduction in signal intensity of the cirrhotic liver with increasing b values; however, the reduction is less pronounced than in noncirrhotic patients. At a b value of 1000 sec/mm², the liver silhouette remains visible. (g) Corresponding ADC map of the abdomen, generated under the assumption of monoexponential decay, shows that the liver has a mean ADC of ~0.9 × 10⁻³ mm²/sec.

Figure 16c

Diffusion-weighted imaging and ADC values in a patient with alcohol- and HCV-related cirrhosis (stage F4). (a–f) Diffusion-weighted MR images with b values of 0 (a), 100 (b), 250 (c), 500 (d), 750 (e), and 1000 (f) sec/mm², obtained in a single breath hold at 3 T, show a progressive reduction in signal intensity of the cirrhotic liver with increasing b values; however, the reduction is less pronounced than in noncirrhotic patients. At a b value of 1000 sec/mm², the liver silhouette remains visible. (g) Corresponding ADC map of the abdomen, generated under the assumption of monoexponential decay, shows that the liver has a mean ADC of ~0.9 × 10⁻³ mm²/sec.

Figure 16d

Diffusion-weighted imaging and ADC values in a patient with alcohol- and HCV-related cirrhosis (stage F4). (a–f) Diffusion-weighted MR images with b values of 0 (a), 100 (b), 250 (c), 500 (d), 750 (e), and 1000 (f) sec/mm², obtained in a single breath hold at 3 T, show a progressive reduction in signal intensity of the cirrhotic liver with increasing b values; however, the reduction is less pronounced than in noncirrhotic patients. At a b value of 1000 sec/mm², the liver silhouette remains visible. (g) Corresponding ADC map of the abdomen, generated under the assumption of monoexponential decay, shows that the liver has a mean ADC of ~0.9 × 10⁻³ mm²/sec.

Figure 16e

Diffusion-weighted imaging and ADC values in a patient with alcohol- and HCV-related cirrhosis (stage F4). (a–f) Diffusion-weighted MR images with b values of 0 (a), 100 (b), 250 (c), 500 (d), 750 (e), and 1000 (f) sec/mm², obtained in a single breath hold at 3 T, show a progressive reduction in signal intensity of the cirrhotic liver with increasing b values; however, the reduction is less pronounced than in noncirrhotic patients. At a b value of 1000 sec/mm², the liver silhouette remains visible. (g) Corresponding ADC map of the abdomen, generated under the assumption of monoexponential decay, shows that the liver has a mean ADC of ~0.9 × 10⁻³ mm²/sec.

Figure 16f

Diffusion-weighted imaging and ADC values in a patient with alcohol- and HCV-related cirrhosis (stage F4). (a–f) Diffusion-weighted MR images with b values of 0 (a), 100 (b), 250 (c), 500 (d), 750 (e), and 1000 (f) sec/mm², obtained in a single breath hold at 3 T, show a progressive reduction in signal intensity of the cirrhotic liver with increasing b values; however, the reduction is less pronounced than in noncirrhotic patients. At a b value of 1000 sec/mm², the liver silhouette remains visible. (g) Corresponding ADC map of the abdomen, generated under the assumption of monoexponential decay, shows that the liver has a mean ADC of ~0.9 × 10⁻³ mm²/sec.

Figure 16g

Diffusion-weighted imaging and ADC values in a patient with alcohol- and HCV-related cirrhosis (stage F4). (a–f) Diffusion-weighted MR images with b values of 0 (a), 100 (b), 250 (c), 500 (d), 750 (e), and 1000 (f) sec/mm², obtained in a single breath hold at 3 T, show a progressive reduction in signal intensity of the cirrhotic liver with increasing b values; however, the reduction is less pronounced than in noncirrhotic patients. At a b value of 1000 sec/mm², the liver silhouette remains visible. (g) Corresponding ADC map of the abdomen, generated under the assumption of monoexponential decay, shows that the liver has a mean ADC of ~0.9 × 10⁻³ mm²/sec.

Figure 1a

Progression of fibrosis in viral hepatitis. Photomicrographs (original magnification, ×40; trichrome stains) of histologic sections from liver biopsy specimens show the progression of fibrosis in viral hepatitis: normal portal triads with no signs of fibrosis (stage F0) (a), portal fibrous expansion (stage F1) (b), thin fibrous septa emanating from portal triads (stage F2) (c), fibrous septa bridging portal triads and central veins (stage F3) (d), and cirrhosis (stage F4) (e), which appears as nodules of liver parenchyma separated by thick fibrous bands.

Figure 1b

Progression of fibrosis in viral hepatitis. Photomicrographs (original magnification, ×40; trichrome stains) of histologic sections from liver biopsy specimens show the progression of fibrosis in viral hepatitis: normal portal triads with no signs of fibrosis (stage F0) (a), portal fibrous expansion (stage F1) (b), thin fibrous septa emanating from portal triads (stage F2) (c), fibrous septa bridging portal triads and central veins (stage F3) (d), and cirrhosis (stage F4) (e), which appears as nodules of liver parenchyma separated by thick fibrous bands.

Figure 1c

Progression of fibrosis in viral hepatitis. Photomicrographs (original magnification, ×40; trichrome stains) of histologic sections from liver biopsy specimens show the progression of fibrosis in viral hepatitis: normal portal triads with no signs of fibrosis (stage F0) (a), portal fibrous expansion (stage F1) (b), thin fibrous septa emanating from portal triads (stage F2) (c), fibrous septa bridging portal triads and central veins (stage F3) (d), and cirrhosis (stage F4) (e), which appears as nodules of liver parenchyma separated by thick fibrous bands.

Figure 1d

Progression of fibrosis in viral hepatitis. Photomicrographs (original magnification, ×40; trichrome stains) of histologic sections from liver biopsy specimens show the progression of fibrosis in viral hepatitis: normal portal triads with no signs of fibrosis (stage F0) (a), portal fibrous expansion (stage F1) (b), thin fibrous septa emanating from portal triads (stage F2) (c), fibrous septa bridging portal triads and central veins (stage F3) (d), and cirrhosis (stage F4) (e), which appears as nodules of liver parenchyma separated by thick fibrous bands.

Figure 1e

Progression of fibrosis in viral hepatitis. Photomicrographs (original magnification, ×40; trichrome stains) of histologic sections from liver biopsy specimens show the progression of fibrosis in viral hepatitis: normal portal triads with no signs of fibrosis (stage F0) (a), portal fibrous expansion (stage F1) (b), thin fibrous septa emanating from portal triads (stage F2) (c), fibrous septa bridging portal triads and central veins (stage F3) (d), and cirrhosis (stage F4) (e), which appears as nodules of liver parenchyma separated by thick fibrous bands.

Figure 2a

Mixed micro- and macronodular cirrhosis in an explanted cirrhotic liver from a patient with end-stage primary biliary cirrhosis who underwent liver transplantation for hepatic decompensation. Oblique axial T1-weighted three-dimensional (3D) gradient-echo (a) and T2-weighted two-dimensional (2D) spin-echo (b) ex vivo MR images obtained at 3 T show innumerable regenerative nodules throughout the liver. The nodules are hyperintense on the T1- weighted image and hypointense on the T2-weighted image and range in size from less than 0.3 mm to 2.5 cm (arrow). Histologic analysis of the largest nodules demonstrated that they were benign regenerative nodules.

Figure 2b

Mixed micro- and macronodular cirrhosis in an explanted cirrhotic liver from a patient with end-stage primary biliary cirrhosis who underwent liver transplantation for hepatic decompensation. Oblique axial T1-weighted three-dimensional (3D) gradient-echo (a) and T2-weighted two-dimensional (2D) spin-echo (b) ex vivo MR images obtained at 3 T show innumerable regenerative nodules throughout the liver. The nodules are hyperintense on the T1- weighted image and hypointense on the T2-weighted image and range in size from less than 0.3 mm to 2.5 cm (arrow). Histologic analysis of the largest nodules demonstrated that they were benign regenerative nodules.

Figure 3a

Hepatic parenchymal alterations at unenhanced MR imaging in a man with HCV-related cirrhosis. Unenhanced T1-weighted 2D gradient-echo image (repetition time msec/echo time msec = 180/2.3, flip angle = 70°) (a) and T2-weighted respiratory triggered fat-saturated fast spin-echo image (5000/80) (b), obtained at 3 T, show fibrotic septa and bridges as reticulations throughout the liver parenchyma. The reticulations (arrows) are hypointense on the T1-weighted image and hyperintense on the T2-weighted image. Note the innumerable regenerative nodules (arrowheads), which are iso- to hyperintense on the T1-weighted image and iso- to hypointense on the T2-weighted image.

Figure 3b

Hepatic parenchymal alterations at unenhanced MR imaging in a man with HCV-related cirrhosis. Unenhanced T1-weighted 2D gradient-echo image (repetition time msec/echo time msec = 180/2.3, flip angle = 70°) (a) and T2-weighted respiratory triggered fat-saturated fast spin-echo image (5000/80) (b), obtained at 3 T, show fibrotic septa and bridges as reticulations throughout the liver parenchyma. The reticulations (arrows) are hypointense on the T1-weighted image and hyperintense on the T2-weighted image. Note the innumerable regenerative nodules (arrowheads), which are iso- to hyperintense on the T1-weighted image and iso- to hypointense on the T2-weighted image.

Figure 4a

Fibrotic scars devoid of fat in a patient with end-stage liver disease due to cystic fibrosis. The patient underwent liver transplantation for hepatic decompensation; ex vivo MR imaging of the explanted cirrhotic liver was performed. (a) Fat fraction map shows the percentage of fat according to proton density in each voxel of the image. The map was obtained by generating multiple gradient echoes at serial out-of-phase and in-phase echo times. As described by Bydder et al (26) and Yokoo et al (27), the signal intensity is modeled as a function of echo time. The modeling takes into account the interference effects between water and fat and also between the various fat moieties while correcting for exponential T2* decay. Most of the liver parenchyma has intermediate signal intensity, with pixel values ranging from 5% to 10% fat content. Several fibrotic scars course through the parenchyma and carve the liver into 1–1.5-cm regenerative nodules. The fibrotic scars have low signal intensity (arrows), which indicates that they are devoid of fat. The gallbladder fossa (gbf) and falciform ligament (FL) contain adipose tissue with very high fractional fat content and therefore appear markedly hyperintense. (b) T2 map shows that the fibrotic scars (arrows) have prolonged T2 relaxation. FL = falciform ligament, gbf = gallbladder fossa.

Figure 4b

Fibrotic scars devoid of fat in a patient with end-stage liver disease due to cystic fibrosis. The patient underwent liver transplantation for hepatic decompensation; ex vivo MR imaging of the explanted cirrhotic liver was performed. (a) Fat fraction map shows the percentage of fat according to proton density in each voxel of the image. The map was obtained by generating multiple gradient echoes at serial out-of-phase and in-phase echo times. As described by Bydder et al (26) and Yokoo et al (27), the signal intensity is modeled as a function of echo time. The modeling takes into account the interference effects between water and fat and also between the various fat moieties while correcting for exponential T2* decay. Most of the liver parenchyma has intermediate signal intensity, with pixel values ranging from 5% to 10% fat content. Several fibrotic scars course through the parenchyma and carve the liver into 1–1.5-cm regenerative nodules. The fibrotic scars have low signal intensity (arrows), which indicates that they are devoid of fat. The gallbladder fossa (gbf) and falciform ligament (FL) contain adipose tissue with very high fractional fat content and therefore appear markedly hyperintense. (b) T2 map shows that the fibrotic scars (arrows) have prolonged T2 relaxation. FL = falciform ligament, gbf = gallbladder fossa.

Figure 5a

Dynamic enhancement patterns in fibrous versus neoplastic tissue after administration of a gadolinium-based contrast agent. Axial 3D T1-weighted spoiled gradient-echo images (~4/1.5, flip angle = 15°) of the cirrhotic liver, obtained at 3 T before (a) and 20 seconds (b), 80 seconds (c), and 5 minutes (d) after intravenous injection of a gadolinium-based contrast agent, show fibrotic reticulations in the liver parenchyma. The reticulations enhance progressively after contrast agent administration. Although some of the reticulations are enhanced at the arterial phase, most are not enhanced until the more delayed images (black arrows in c and d). A 2.0 × 1.8-cm exophytic HCC (*) arises from segment 6. A fibrous capsule (white arrow in c and d) surrounds the tumor. The fibrous capsule enhances progressively, with a temporal pattern similar to that of the parenchymal fibrotic reticulations. By comparison, the HCC enhances vividly on the arterial phase image, then washes out to hypointensity relative to the fibrotic reticulations on the venous phase images.

Figure 5b

Dynamic enhancement patterns in fibrous versus neoplastic tissue after administration of a gadolinium-based contrast agent. Axial 3D T1-weighted spoiled gradient-echo images (~4/1.5, flip angle = 15°) of the cirrhotic liver, obtained at 3 T before (a) and 20 seconds (b), 80 seconds (c), and 5 minutes (d) after intravenous injection of a gadolinium-based contrast agent, show fibrotic reticulations in the liver parenchyma. The reticulations enhance progressively after contrast agent administration. Although some of the reticulations are enhanced at the arterial phase, most are not enhanced until the more delayed images (black arrows in c and d). A 2.0 × 1.8-cm exophytic HCC (*) arises from segment 6. A fibrous capsule (white arrow in c and d) surrounds the tumor. The fibrous capsule enhances progressively, with a temporal pattern similar to that of the parenchymal fibrotic reticulations. By comparison, the HCC enhances vividly on the arterial phase image, then washes out to hypointensity relative to the fibrotic reticulations on the venous phase images.

Figure 5c

Dynamic enhancement patterns in fibrous versus neoplastic tissue after administration of a gadolinium-based contrast agent. Axial 3D T1-weighted spoiled gradient-echo images (~4/1.5, flip angle = 15°) of the cirrhotic liver, obtained at 3 T before (a) and 20 seconds (b), 80 seconds (c), and 5 minutes (d) after intravenous injection of a gadolinium-based contrast agent, show fibrotic reticulations in the liver parenchyma. The reticulations enhance progressively after contrast agent administration. Although some of the reticulations are enhanced at the arterial phase, most are not enhanced until the more delayed images (black arrows in c and d). A 2.0 × 1.8-cm exophytic HCC (*) arises from segment 6. A fibrous capsule (white arrow in c and d) surrounds the tumor. The fibrous capsule enhances progressively, with a temporal pattern similar to that of the parenchymal fibrotic reticulations. By comparison, the HCC enhances vividly on the arterial phase image, then washes out to hypointensity relative to the fibrotic reticulations on the venous phase images.

Figure 5d

Dynamic enhancement patterns in fibrous versus neoplastic tissue after administration of a gadolinium-based contrast agent. Axial 3D T1-weighted spoiled gradient-echo images (~4/1.5, flip angle = 15°) of the cirrhotic liver, obtained at 3 T before (a) and 20 seconds (b), 80 seconds (c), and 5 minutes (d) after intravenous injection of a gadolinium-based contrast agent, show fibrotic reticulations in the liver parenchyma. The reticulations enhance progressively after contrast agent administration. Although some of the reticulations are enhanced at the arterial phase, most are not enhanced until the more delayed images (black arrows in c and d). A 2.0 × 1.8-cm exophytic HCC (*) arises from segment 6. A fibrous capsule (white arrow in c and d) surrounds the tumor. The fibrous capsule enhances progressively, with a temporal pattern similar to that of the parenchymal fibrotic reticulations. By comparison, the HCC enhances vividly on the arterial phase image, then washes out to hypointensity relative to the fibrotic reticulations on the venous phase images.

Figure 6a

Increased conspicuity of liver fibrosis after SPIO administration in a patient with liver cirrhosis and HCC (same patient as in Fig 5). Axial 2D T2*-weighted gradient-echo images (200/8, flip angle = 35°) of the cirrhotic liver, obtained at 3 T before (a) and after (b) a 30-minute infusion of SPIO, show that fibrotic reticulations are not well demonstrated on the unenhanced image. After injection, SPIO particles accumulate in the liver owing to uptake by Kupffer cells and cause the liver to darken. Fibrotic reticulations have diminished Kupffer cell density, do not accumulate iron oxides, and hence appear relatively hyperintense (arrows in b). Note the 2.0 × 1.8-cm exophytic HCC (*) arising from segment 6. Similarly to the fibrotic reticulations, the carcinoma has low Kupffer cell density and appears relatively hyperintense on the SPIO-enhanced image.

Figure 6b

Increased conspicuity of liver fibrosis after SPIO administration in a patient with liver cirrhosis and HCC (same patient as in Fig 5). Axial 2D T2*-weighted gradient-echo images (200/8, flip angle = 35°) of the cirrhotic liver, obtained at 3 T before (a) and after (b) a 30-minute infusion of SPIO, show that fibrotic reticulations are not well demonstrated on the unenhanced image. After injection, SPIO particles accumulate in the liver owing to uptake by Kupffer cells and cause the liver to darken. Fibrotic reticulations have diminished Kupffer cell density, do not accumulate iron oxides, and hence appear relatively hyperintense (arrows in b). Note the 2.0 × 1.8-cm exophytic HCC (*) arising from segment 6. Similarly to the fibrotic reticulations, the carcinoma has low Kupffer cell density and appears relatively hyperintense on the SPIO-enhanced image.

Figure 7a

Dynamic enhancement patterns of confluent fibrosis versus active inflammation after administration of a gadolinium-based contrast agent in a woman with biliary cirrhosis complicated by acute cholangitis. The biliary cirrhosis was due to a long-standing benign stricture of the common bile duct. Axial 3D T1-weighted gradient-echo images (~4/1.5, flip angle = 15°), obtained at 3 T before (a) and 20 seconds (b), 80 seconds (c), and 5 minutes (d) after intravenous injection of a gadolinium-based contrast agent, show a liver with lobulated contours. The right lobe is atrophic, and the left lobe is large. At the junction of the left and right lobes, a wedge-shaped area of confluent fibrosis (black arrows) radiates from the portal hilum, contacts and retracts the liver capsule (white arrow), and causes focal volume loss. The confluent fibrosis is hypointense on the unenhanced image and enhances progressively after contrast agent administration. Similarly, thickened fibrotic walls of intrahepatic biliary radicles enhance progressively (arrowheads in c and d). By comparison, patchy areas of liver parenchyma are hyperenhanced on the arterial phase image, then fade to isointensity relative to background liver tissue. These patchy areas of arterial hypervascularity probably reflect hyperemia due to active inflammation and, in the setting of chronic biliary obstruction, suggest acute cholangitis.

Figure 7b

Dynamic enhancement patterns of confluent fibrosis versus active inflammation after administration of a gadolinium-based contrast agent in a woman with biliary cirrhosis complicated by acute cholangitis. The biliary cirrhosis was due to a long-standing benign stricture of the common bile duct. Axial 3D T1-weighted gradient-echo images (~4/1.5, flip angle = 15°), obtained at 3 T before (a) and 20 seconds (b), 80 seconds (c), and 5 minutes (d) after intravenous injection of a gadolinium-based contrast agent, show a liver with lobulated contours. The right lobe is atrophic, and the left lobe is large. At the junction of the left and right lobes, a wedge-shaped area of confluent fibrosis (black arrows) radiates from the portal hilum, contacts and retracts the liver capsule (white arrow), and causes focal volume loss. The confluent fibrosis is hypointense on the unenhanced image and enhances progressively after contrast agent administration. Similarly, thickened fibrotic walls of intrahepatic biliary radicles enhance progressively (arrowheads in c and d). By comparison, patchy areas of liver parenchyma are hyperenhanced on the arterial phase image, then fade to isointensity relative to background liver tissue. These patchy areas of arterial hypervascularity probably reflect hyperemia due to active inflammation and, in the setting of chronic biliary obstruction, suggest acute cholangitis.

Figure 7c

Dynamic enhancement patterns of confluent fibrosis versus active inflammation after administration of a gadolinium-based contrast agent in a woman with biliary cirrhosis complicated by acute cholangitis. The biliary cirrhosis was due to a long-standing benign stricture of the common bile duct. Axial 3D T1-weighted gradient-echo images (~4/1.5, flip angle = 15°), obtained at 3 T before (a) and 20 seconds (b), 80 seconds (c), and 5 minutes (d) after intravenous injection of a gadolinium-based contrast agent, show a liver with lobulated contours. The right lobe is atrophic, and the left lobe is large. At the junction of the left and right lobes, a wedge-shaped area of confluent fibrosis (black arrows) radiates from the portal hilum, contacts and retracts the liver capsule (white arrow), and causes focal volume loss. The confluent fibrosis is hypointense on the unenhanced image and enhances progressively after contrast agent administration. Similarly, thickened fibrotic walls of intrahepatic biliary radicles enhance progressively (arrowheads in c and d). By comparison, patchy areas of liver parenchyma are hyperenhanced on the arterial phase image, then fade to isointensity relative to background liver tissue. These patchy areas of arterial hypervascularity probably reflect hyperemia due to active inflammation and, in the setting of chronic biliary obstruction, suggest acute cholangitis.

Figure 7d

Dynamic enhancement patterns of confluent fibrosis versus active inflammation after administration of a gadolinium-based contrast agent in a woman with biliary cirrhosis complicated by acute cholangitis. The biliary cirrhosis was due to a long-standing benign stricture of the common bile duct. Axial 3D T1-weighted gradient-echo images (~4/1.5, flip angle = 15°), obtained at 3 T before (a) and 20 seconds (b), 80 seconds (c), and 5 minutes (d) after intravenous injection of a gadolinium-based contrast agent, show a liver with lobulated contours. The right lobe is atrophic, and the left lobe is large. At the junction of the left and right lobes, a wedge-shaped area of confluent fibrosis (black arrows) radiates from the portal hilum, contacts and retracts the liver capsule (white arrow), and causes focal volume loss. The confluent fibrosis is hypointense on the unenhanced image and enhances progressively after contrast agent administration. Similarly, thickened fibrotic walls of intrahepatic biliary radicles enhance progressively (arrowheads in c and d). By comparison, patchy areas of liver parenchyma are hyperenhanced on the arterial phase image, then fade to isointensity relative to background liver tissue. These patchy areas of arterial hypervascularity probably reflect hyperemia due to active inflammation and, in the setting of chronic biliary obstruction, suggest acute cholangitis.

Figure 8a

Atypical enhancement pattern of confluent fibrosis after administration of a gadolinium-based contrast agent in a man with HCV- and alcohol-related cirrhosis. Axial 3D T1-weighted gradient-echo images (~4/1.5, flip angle = 15°) (a–c) and 2D T1- and T2*-weighted gradient-echo image (180/6, flip angle = 70°) (d), obtained at 3 T after intravenous infusion of SPIO and before (a) and 20 seconds (b), 80 seconds (c), and 4 minutes (d) after intravenous injection of a gadolinium-based contrast agent, show a wedge-shaped area of confluent fibrosis (straight arrows) in segment 5 of the liver. The confluent fibrosis radiates from the portal hilum, contacts and retracts the liver capsule, and causes focal volume loss. The fibrosis is hypointense before contrast agent administration but hyperenhances heterogeneously in the arterial phase. The enhancement persists and becomes more homogeneous in the venous phases. Arterial hyperenhancement is atypical of confluent fibrosis, and the differential diagnosis includes HCC. However, the persistent enhancement, homogeneity in the late venous phase, and characteristic morphologic features favor the diagnosis of confluent fibrosis. Note the fine fibrotic reticulations surrounding hypointense regenerative nodules on the late venous phase image. The reticulations are most pronounced in the atrophic right and left lobes, with relative sparing in the hypertrophic caudate lobe (C in c and d). Also note the subcapsular fibrosis (arrowhead in d) and the long fibrous scar at the caudate lobe–segment 6 junction (curved arrow in d).

Figure 8b

Atypical enhancement pattern of confluent fibrosis after administration of a gadolinium-based contrast agent in a man with HCV- and alcohol-related cirrhosis. Axial 3D T1-weighted gradient-echo images (~4/1.5, flip angle = 15°) (a–c) and 2D T1- and T2*-weighted gradient-echo image (180/6, flip angle = 70°) (d), obtained at 3 T after intravenous infusion of SPIO and before (a) and 20 seconds (b), 80 seconds (c), and 4 minutes (d) after intravenous injection of a gadolinium-based contrast agent, show a wedge-shaped area of confluent fibrosis (straight arrows) in segment 5 of the liver. The confluent fibrosis radiates from the portal hilum, contacts and retracts the liver capsule, and causes focal volume loss. The fibrosis is hypointense before contrast agent administration but hyperenhances heterogeneously in the arterial phase. The enhancement persists and becomes more homogeneous in the venous phases. Arterial hyperenhancement is atypical of confluent fibrosis, and the differential diagnosis includes HCC. However, the persistent enhancement, homogeneity in the late venous phase, and characteristic morphologic features favor the diagnosis of confluent fibrosis. Note the fine fibrotic reticulations surrounding hypointense regenerative nodules on the late venous phase image. The reticulations are most pronounced in the atrophic right and left lobes, with relative sparing in the hypertrophic caudate lobe (C in c and d). Also note the subcapsular fibrosis (arrowhead in d) and the long fibrous scar at the caudate lobe–segment 6 junction (curved arrow in d).

Figure 8c

Atypical enhancement pattern of confluent fibrosis after administration of a gadolinium-based contrast agent in a man with HCV- and alcohol-related cirrhosis. Axial 3D T1-weighted gradient-echo images (~4/1.5, flip angle = 15°) (a–c) and 2D T1- and T2*-weighted gradient-echo image (180/6, flip angle = 70°) (d), obtained at 3 T after intravenous infusion of SPIO and before (a) and 20 seconds (b), 80 seconds (c), and 4 minutes (d) after intravenous injection of a gadolinium-based contrast agent, show a wedge-shaped area of confluent fibrosis (straight arrows) in segment 5 of the liver. The confluent fibrosis radiates from the portal hilum, contacts and retracts the liver capsule, and causes focal volume loss. The fibrosis is hypointense before contrast agent administration but hyperenhances heterogeneously in the arterial phase. The enhancement persists and becomes more homogeneous in the venous phases. Arterial hyperenhancement is atypical of confluent fibrosis, and the differential diagnosis includes HCC. However, the persistent enhancement, homogeneity in the late venous phase, and characteristic morphologic features favor the diagnosis of confluent fibrosis. Note the fine fibrotic reticulations surrounding hypointense regenerative nodules on the late venous phase image. The reticulations are most pronounced in the atrophic right and left lobes, with relative sparing in the hypertrophic caudate lobe (C in c and d). Also note the subcapsular fibrosis (arrowhead in d) and the long fibrous scar at the caudate lobe–segment 6 junction (curved arrow in d).

Figure 8d

Atypical enhancement pattern of confluent fibrosis after administration of a gadolinium-based contrast agent in a man with HCV- and alcohol-related cirrhosis. Axial 3D T1-weighted gradient-echo images (~4/1.5, flip angle = 15°) (a–c) and 2D T1- and T2*-weighted gradient-echo image (180/6, flip angle = 70°) (d), obtained at 3 T after intravenous infusion of SPIO and before (a) and 20 seconds (b), 80 seconds (c), and 4 minutes (d) after intravenous injection of a gadolinium-based contrast agent, show a wedge-shaped area of confluent fibrosis (straight arrows) in segment 5 of the liver. The confluent fibrosis radiates from the portal hilum, contacts and retracts the liver capsule, and causes focal volume loss. The fibrosis is hypointense before contrast agent administration but hyperenhances heterogeneously in the arterial phase. The enhancement persists and becomes more homogeneous in the venous phases. Arterial hyperenhancement is atypical of confluent fibrosis, and the differential diagnosis includes HCC. However, the persistent enhancement, homogeneity in the late venous phase, and characteristic morphologic features favor the diagnosis of confluent fibrosis. Note the fine fibrotic reticulations surrounding hypointense regenerative nodules on the late venous phase image. The reticulations are most pronounced in the atrophic right and left lobes, with relative sparing in the hypertrophic caudate lobe (C in c and d). Also note the subcapsular fibrosis (arrowhead in d) and the long fibrous scar at the caudate lobe–segment 6 junction (curved arrow in d).

Figure 9a

Infiltrative HCC as a differential diagnosis for confluent fibrosis in a man with HCV-related cirrhosis. Axial 3D T1-weighted gradient-echo images (~4/1.5, flip angle = 15°) (a–c) and 2D T1- and T2*-weighted gradient-echo image (180/6, flip angle = 70°) (d), obtained at 3 T after intravenous infusion of SPIO and before (a) and 20 seconds (b), 80 seconds (c), and 4 minutes (d) after intravenous injection of a gadolinium-based contrast agent, show a wedge-shaped conglomerate mass in the liver. The mass involves the entire right lobe, bulges the capsule, and expands the liver volume; it enhances heterogeneously on the arterial phase image (arrowheads in b). The dissipation of the contrast agent is nonuniform, causing the mass to have heterogeneous signal intensity in the late venous phase. The mass invades the right hepatic vein (white arrow in c) and a portal vein branch (black arrow in c). Although the wedge shape of the mass suggests a benign process, the volume expansion, nonuniform dissipation of contrast material, and delayed phase heterogeneity favor the diagnosis of carcinoma. Vascular invasion by the tumor, which was an HCC, clinches the diagnosis of malignancy.

Figure 9b

Infiltrative HCC as a differential diagnosis for confluent fibrosis in a man with HCV-related cirrhosis. Axial 3D T1-weighted gradient-echo images (~4/1.5, flip angle = 15°) (a–c) and 2D T1- and T2*-weighted gradient-echo image (180/6, flip angle = 70°) (d), obtained at 3 T after intravenous infusion of SPIO and before (a) and 20 seconds (b), 80 seconds (c), and 4 minutes (d) after intravenous injection of a gadolinium-based contrast agent, show a wedge-shaped conglomerate mass in the liver. The mass involves the entire right lobe, bulges the capsule, and expands the liver volume; it enhances heterogeneously on the arterial phase image (arrowheads in b). The dissipation of the contrast agent is nonuniform, causing the mass to have heterogeneous signal intensity in the late venous phase. The mass invades the right hepatic vein (white arrow in c) and a portal vein branch (black arrow in c). Although the wedge shape of the mass suggests a benign process, the volume expansion, nonuniform dissipation of contrast material, and delayed phase heterogeneity favor the diagnosis of carcinoma. Vascular invasion by the tumor, which was an HCC, clinches the diagnosis of malignancy.

Figure 9c

Infiltrative HCC as a differential diagnosis for confluent fibrosis in a man with HCV-related cirrhosis. Axial 3D T1-weighted gradient-echo images (~4/1.5, flip angle = 15°) (a–c) and 2D T1- and T2*-weighted gradient-echo image (180/6, flip angle = 70°) (d), obtained at 3 T after intravenous infusion of SPIO and before (a) and 20 seconds (b), 80 seconds (c), and 4 minutes (d) after intravenous injection of a gadolinium-based contrast agent, show a wedge-shaped conglomerate mass in the liver. The mass involves the entire right lobe, bulges the capsule, and expands the liver volume; it enhances heterogeneously on the arterial phase image (arrowheads in b). The dissipation of the contrast agent is nonuniform, causing the mass to have heterogeneous signal intensity in the late venous phase. The mass invades the right hepatic vein (white arrow in c) and a portal vein branch (black arrow in c). Although the wedge shape of the mass suggests a benign process, the volume expansion, nonuniform dissipation of contrast material, and delayed phase heterogeneity favor the diagnosis of carcinoma. Vascular invasion by the tumor, which was an HCC, clinches the diagnosis of malignancy.

Figure 9d

Infiltrative HCC as a differential diagnosis for confluent fibrosis in a man with HCV-related cirrhosis. Axial 3D T1-weighted gradient-echo images (~4/1.5, flip angle = 15°) (a–c) and 2D T1- and T2*-weighted gradient-echo image (180/6, flip angle = 70°) (d), obtained at 3 T after intravenous infusion of SPIO and before (a) and 20 seconds (b), 80 seconds (c), and 4 minutes (d) after intravenous injection of a gadolinium-based contrast agent, show a wedge-shaped conglomerate mass in the liver. The mass involves the entire right lobe, bulges the capsule, and expands the liver volume; it enhances heterogeneously on the arterial phase image (arrowheads in b). The dissipation of the contrast agent is nonuniform, causing the mass to have heterogeneous signal intensity in the late venous phase. The mass invades the right hepatic vein (white arrow in c) and a portal vein branch (black arrow in c). Although the wedge shape of the mass suggests a benign process, the volume expansion, nonuniform dissipation of contrast material, and delayed phase heterogeneity favor the diagnosis of carcinoma. Vascular invasion by the tumor, which was an HCC, clinches the diagnosis of malignancy.