Diagnostic imaging of small HCC
in liver cirrhosis : The current
approach
Dr.Tony Loke
United Christian Hospital
Disclosure
No conflict of interest
Contents
•  Step wise progression of hepatocarcinogenesis
•  MR I can image this histhopathological process - Gadoxetic
en...
Multistep progression of Hepatocarcinogenesis

Kudo M Oncology 2010;78:87-93
Intranodular blood supplyunpaired arteries / portal tracts	

Tajima T AJR 2002:178;885
Histopathological pathway of Carcinogenesis	

•  Replacement of normal liver cells by abnormal liver
malignant cells -↓ OA...
Process of Hepatocarcinogenesis

Kudo M J gastroenterology and hepatology 2010;25:439-452
Diagnostic criteria for typical HCC

Bruix J, Sherman M Hepatology 2011;53:1020-1022
Definite HCC	
• Wash in (arterial phase hyperenhancement) /
Wash out– AASLD, EASL criteria (>1 cm) and
JSH (any size)
•  D...
↑ Sensitivity - Malignant liver nodules	
•  Absence of OATP8 expression / kupffer
cells
•  Liver specific contrast agents
...
Ancillary MRI criteria -

Malignant liver nodules	
•  T2W Hyperintensity
•  Capsular enhancement – LI RADS
•  T1 hypointen...
PRIMOVIST alone has higher sensitivity
-? Compromised specificity

•  Comparing primovist and magnevist,
•  Significant in...
Hypervascular nodule
Size does not matter!
Hypervascular nodule without washout

Primovist
Negative uptake

HCC

Positive ...
Hypovascular Nodule- size matters!
Hypovascular nodule

Primovist
Negative uptake

≥1.5cm
HCC – 98%
LGDN – 2%

Positive up...
PRIMOVIST (GD-EOB-DTPA)
GADOXETIC ACID

HCC-Hypointense at 20 min HBP (e)
DIFFUSION WEIGHTED MRI - ↑ Specificity
•  SI ratio significantly differentiates malignant and benign
lesions at all b-valu...
Classic HCC -SI ratio 1.83 for b600 (g)
Small HCC -No lesion seen on T1, T2 or enhanced MRI.
SI ratio=1.5 at b600
CURRENT APPROACH
•  Combined Primovist enhanced MRI
and Diffusion weighted imaging – able
to image the step wise pathogene...
COMBINED PRIMOVIST MRI AND DWI
•  Criteria for HCC
•  Hypervascular nodules with washout
•  Hypervascular nodules without ...
COMBINED PRIMOVIST AND DWI
	

Park MJ et al Radiology 2012:264;761-770
COMBINED PRIMOVIST AND DWI
	

Park MJ et al Radiology 2012:264;761-770
Typical small HCC

Small hypervascular HCC –DWI b=100, 800
Segment 6 hypervascular HCC < 1.5 CM
Atypical small HCC

Hypervascular HCC- hypointense on HBP but DWI normal
Hypervascular HCC
– and DN (DWI and HBP-Normal)
CT hypervascular lesionSegment 5 pseudolesion
Hypovascular HCC < 1.5 CM
Hypointense HBP + Hypertintense DWI
SEGMENT 2/3 HCC
Hypo/hypervascular component (HBP+DWI = +ve)
HGDN simulating HCC

Hypovascular DN- hypointense on HBP and DWI hyperintense
Segment 5 HGDN – Hypointense HBP (DWI-Normal)
DN > 1.5CM
HBP + DWI = negative
Summary - Current Approach
•  Nodule detected on USG
•  Dynamic CT
•  Hypervascular with washout (>1cm)
•  Atypical featur...
Conclusion - Current Approach
•  Combined Primovist and DWI
•  Higher diagnostic accuracy and sensitivity
•  Particularly ...
SEG 2/3 HYPERVASCULAR HCC WITH
PARADOXICAL UPTAKE (DWI-hyperintense)
SEGMENT 6 HCC WITH NORMAL ARTERIAL,
T2W AND DWI
FOCAL NODULAR LIVER LESIONS:
1994 INTERNATIONAL CLASSIFICATION	
•  Regenerative nodule
•  Cirrhotic nodule
•  Low grade dy...
DEVELOPMENT OF HCC IN
CIRRHOTIC LIVER 	
•  Temporal progression from regenerative nodules
to dysplastic nodules to well di...
PRIMOVIST MRI MOST SENSITIVE TECHNIQUE IN
DETECTING EARLY HEPATOCARCINOGENESIS
CONSENSUS STATEMENTSJAPAN SOCIETY OF HEPATOLOGY
•  Typical HCC can be diagnosed by imaging regardless
of the size if a typ...
CONSENSUS STATEMENTSJAPAN SOCIETY OF HEPATOLOGY
•  Sonazoid-enhanced ultrasound is more sensitive for
detection of intrano...
JAPAN SOCIETY OF HEPATOLOGY
JAPAN SOCIETY OF HEPATOLOGY
2ND INTERNATIONAL FORUM LIVER MRI
PRIMOVIST CONTRAST ENHANCED
MRI- PROTOCOL OPTIMIZATION AND
EVALUATION OF HEPATIC NODULES IN
LIVER CIRRHOSIS
Dr. Tony Loke
...
PRIMOVIST - GADOLINIUM-ETHOXYBENZYLDIETHYLENETRIAMINEPENTAACETIC ACID (GDEOB-DTPA)
•  Combined extracellular hepatobiliary...
PROTOCOL OPTIMIZATION - PHARMACOKINETIC
AND PHARMACODYNAMIC PROPERTIES OF
PRIMOVIST IN LIVER CIRRHOSIS.
•  Patients with a...
PROTOCOL OPTIMIZATION - PHARMACOKINETIC
AND PHARMACODYNAMIC PROPERTIES OF
PRIMOVIST IN LIVER CIRRHOSIS.
•  Patients with a...
PROTOCOL OPTIMIZATION – PRIMOVIST
ENHANCED MRI IN CIRRHOTIC LIVER
•  Problems with on-label approved dose Gd-EOB-DTPA of
0...
PROTOCOL OPTIMIZATION-SOLUTION FOR
ACHIEVING OPTIMAL ARTERIAL PHASE
•  Optimal arterial phase increases sensitivity for de...
PRIMOVIST PROTOCOL - DIFFERENCE WITH
CONVENTIONAL GD
UCH PROTOCOL - PRIMOVIST ENHANCED MRI
LIVER
• 

MRCP performed before contrast injection

• 

Bolus timing method is used
...
UCH PROTOCOL –
PRIMOVIST ENHANCED MRI LIVER
WHEN TO USE PRIMOVIST IN PATIENTS WITH
LIVER CIRRHOSIS
•  Primovist is routinely use in cirrhosis except for:
•  Assessmen...
IS PRIMOVIST BETTER FOR DETECTING HCC?
-COMPARED WITH OTHER AGENTS /IMAGING
MODALITIES

•  Combined dynamic and hepatocyte...
PRIMOVIST UPTAKE BY HEPATOCYTE BY OATP1
EXCRETION TO BILE JUICE REGULATED BY MRP2

Kudo M J gastroenterology and hepatolog...
Kudo M Oncology 2010;78:87-93
HCC (87 lesions)
Hepatobiliary phase

In one study

Hypointense
92%

Isointense
6%

Hyperintense
2%

WDHCC (39 lesions)
He...
CRITERIA FOR HCC
•  Reading Hepatobiliary phase alone insufficient
•  Result in false positives and negatives
•  Hepatocyt...
CRITERIA FOR HCC DIAGNOSIS
•  A nodule with increased enhancement on arterial phase and washout on late venous or equilibr...
HYPOVASCULAR NODULE – SIZE MATTERS
•  Hypovascular nodules (on arterial phase) with
negative uptake on hepatobiliary phase...
DN > 1.5CM - POSITIVE UPTAKE
DN > 1.5 CM - POSITIVE UPTAKE
DN - NEGATIVE UPTAKE
SEGMENT 3 HCC
– LESION DEMARCATION BETTER
HYPERVASCULAR RECURRENT HCC
– OTHER DN +VE UPTAKE
SEG 2/3 HYPERVASCULAR HCC WITH
PARADOXICAL UPTAKE
HYPERVASCULAR SEG 7 DN - POSITIVE UPTAKE
HYPOVASCULAR < 1.5 CM HCC – T2/DWI BRIGHT
DN –NOT VISIBLE IN OTHER SEQUENCES EXCEPT
HEPATOCYTE PHASE
SEGMENT 6 HCC WITH NORMAL ARTERIAL,
T2W AND DWI
CT SEGMENT 6 HYPOENHANCING NODULE
- HCC IN HEPATOCYTE PHASE > 1.5 CM
CT HYPERVASCULAR LESIONS – SEG 5 HCC
SEGMENT 6 HCC < 1.5 CM
CT HYPERVASCULAR LESION – SEG 5
PSEUDOLESION
SMALL HYPERVASCULAR HCC
SEGMENT 6 HCC & 2 HEMANGIOMAS
SEGMENT 5 – DN FEATURES ON T1/2
SEGMENT 5 HCC – NEGATIVE UPTAKE
COMBINED PRIMOVIST AND DWI
	

Park MJ et al Radiology 2012:264;761-770
FALSE POSITIVE – HEPATOBILIARY PHASE
•  Hypointense lesions seen only on hepatobiliary phase (without arterial
enhancement...
FALSE NEGATIVE - HEPATOBILIARY PHASE
•  HCC which are T1 hyperintense may be isointense on
hepatobiliary phase.
•  Look fo...
SUMMARY- CRITERIA FOR HCC
•  Hypervascular nodules with washout – irrespective of delayed
phase
•  Hypervascular nodules a...
SUMMARY
•  Negative uptake in hypovascular lesions <1.5 cm can still be
HCC
•  FU required as 17% becomes hypervascular in...
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Abdominal imaging hcc t loke
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Abdominal imaging hcc t loke

  1. 1. Diagnostic imaging of small HCC in liver cirrhosis : The current approach Dr.Tony Loke United Christian Hospital
  2. 2. Disclosure No conflict of interest
  3. 3. Contents •  Step wise progression of hepatocarcinogenesis •  MR I can image this histhopathological process - Gadoxetic enhanced MRI + DWI •  Definite Criteria for HCC – Low sensitivity •  Gadoxetic enhanced MRI alone - ↑sensitivity •  Diffusion weighted MRI -↑ specificity •  Combined Ga MRI and DWI – current approach •  Proposed Algorithm – Best diagnostic accuracy
  4. 4. Multistep progression of Hepatocarcinogenesis Kudo M Oncology 2010;78:87-93
  5. 5. Intranodular blood supplyunpaired arteries / portal tracts Tajima T AJR 2002:178;885
  6. 6. Histopathological pathway of Carcinogenesis •  Replacement of normal liver cells by abnormal liver malignant cells -↓ OATP8 expression •  Hypointensity – HBP Primovist enhanced MRI •  Unpaired arteries ↑ + Portal tract ↓ •  Wash in/ Wash out – Dynamic CT and MRI •  Increased cell density with progressive undifferentiated nodules •  Hyperintensity - DWI
  7. 7. Process of Hepatocarcinogenesis Kudo M J gastroenterology and hepatology 2010;25:439-452
  8. 8. Diagnostic criteria for typical HCC Bruix J, Sherman M Hepatology 2011;53:1020-1022
  9. 9. Definite HCC • Wash in (arterial phase hyperenhancement) / Wash out– AASLD, EASL criteria (>1 cm) and JSH (any size) •  Dynamic MDCT, MRI (Primovist enhanced MRI), CEUS • Only 71% - have ‘wash in’ and ‘wash out’ on more than one test Marrero JA et al Liver Transpl 2005;11:281-289
  10. 10. ↑ Sensitivity - Malignant liver nodules •  Absence of OATP8 expression / kupffer cells •  Liver specific contrast agents •  Primovist MRI, SPIO-MRI, Sonazoid- CEUS •  Restricted diffusion •  Diffusion weighted MRI
  11. 11. Ancillary MRI criteria -
 Malignant liver nodules •  T2W Hyperintensity •  Capsular enhancement – LI RADS •  T1 hypointensity •  Lesion size •  Lesional fat •  Lesion growth on follow up •  ‘Nodule in nodule’ pattern
  12. 12. PRIMOVIST alone has higher sensitivity -? Compromised specificity •  Comparing primovist and magnevist, •  Significant increased sensitivity with primovist. •  Hepatocellular phase imaging with Primovist improves HCC detection. •  Primovist MRI has higher diagnostic accuracy (0.88 vs 0.74, p<. 001) and higher sensitivity (0.85 vs0.69, p<.001) than triple phase MDCT •  Particularly in smaller lesions (<2cm) •  MRI with primovist has equal accuracy as dual-contrast MRI for HCC detection •  Combined use of extracellular gadolinium and SPIO. Marin D et al Radiology 2009;251:85-95 Park G et al BJR 2010;83:1010-1016 Kim YK et al Invest Radiol 2010:45:740-746 Martino et al Radiology 2010;256:806
  13. 13. Hypervascular nodule Size does not matter! Hypervascular nodule without washout Primovist Negative uptake HCC Positive uptake Biopsy or Follow up Kudo M Oncology 2010;78:87-93
  14. 14. Hypovascular Nodule- size matters! Hypovascular nodule Primovist Negative uptake ≥1.5cm HCC – 98% LGDN – 2% Positive uptake <1.5cm ≥1.5cm <1.5cm Follow up Biopsy or FU Follow up 17% progress to HCC in 1 year HCC LGDN
  15. 15. PRIMOVIST (GD-EOB-DTPA) GADOXETIC ACID HCC-Hypointense at 20 min HBP (e)
  16. 16. DIFFUSION WEIGHTED MRI - ↑ Specificity •  SI ratio significantly differentiates malignant and benign lesions at all b-values. •  Optimal threshold b=600 •  SI ratio 1.25. •  For detection of HCC, DWI with b=600 has •  sensitivity of 95.2% compared to 80.6% for conventional MRI (p=0.023) •  specificity of 82.7% compared to 65.4% (p=0.064%). •  The improved accuracy was most beneficial for differentiating lesions smaller than 2cm. Vandecaveye V Eur Radiol 2009;may:1431
  17. 17. Classic HCC -SI ratio 1.83 for b600 (g)
  18. 18. Small HCC -No lesion seen on T1, T2 or enhanced MRI. SI ratio=1.5 at b600
  19. 19. CURRENT APPROACH •  Combined Primovist enhanced MRI and Diffusion weighted imaging – able to image the step wise pathogenesis of HCC •  Dynamic Primovist MRI - Wash in / Wash out •  Hepatobiliary phase Primovist enhanced MRI - OATP8 expression •  DWI - cell density •  Ancillary features
  20. 20. COMBINED PRIMOVIST MRI AND DWI •  Criteria for HCC •  Hypervascular nodules with washout •  Hypervascular nodules without washout, hypointense on HBP phase (irrespective of DWI) •  Hypervascular nodules without wash out, iso/hyperintense on HBP phase + Hyperintense DWI •  Hypovascular nodules, hypointense on HBP phase + Hyperintensity DWI •  Combined Primovist and DWI has better diagnostic accuracy and sensitivity (93.3%) in detection of HCC < 2cm •  False positive – HGDN Park MJ et al Radiology 2012:264;761-770
  21. 21. COMBINED PRIMOVIST AND DWI Park MJ et al Radiology 2012:264;761-770
  22. 22. COMBINED PRIMOVIST AND DWI Park MJ et al Radiology 2012:264;761-770
  23. 23. Typical small HCC Small hypervascular HCC –DWI b=100, 800
  24. 24. Segment 6 hypervascular HCC < 1.5 CM
  25. 25. Atypical small HCC Hypervascular HCC- hypointense on HBP but DWI normal
  26. 26. Hypervascular HCC – and DN (DWI and HBP-Normal)
  27. 27. CT hypervascular lesionSegment 5 pseudolesion
  28. 28. Hypovascular HCC < 1.5 CM Hypointense HBP + Hypertintense DWI
  29. 29. SEGMENT 2/3 HCC Hypo/hypervascular component (HBP+DWI = +ve)
  30. 30. HGDN simulating HCC Hypovascular DN- hypointense on HBP and DWI hyperintense
  31. 31. Segment 5 HGDN – Hypointense HBP (DWI-Normal)
  32. 32. DN > 1.5CM HBP + DWI = negative
  33. 33. Summary - Current Approach •  Nodule detected on USG •  Dynamic CT •  Hypervascular with washout (>1cm) •  Atypical features •  Combined Primovist enhanced MRI and DWI •  Hypervascular without washout, hypointense on HBP phase •  Hypervascular without washout, isointense on HBP phase + Hyperintense DWI •  Hypovascular nodules, hypointense on HBP phase + Hyperintensity DWI •  Ancillary features •  Higher diagnostic accuracy and sensitivity •  Particularly for HCC < 2cm •  False positive for HGDN
  34. 34. Conclusion - Current Approach •  Combined Primovist and DWI •  Higher diagnostic accuracy and sensitivity •  Particularly for HCC < 2cm •  false positive include HGDN •  Combined Primovist enhanced MRI and DWI •  Hypervascular without washout, hypointense on HBP phase •  Hypervascular nodules, isointense on HBP phase + Hyperintense DWI •  Hypovascular nodules, hypointense on HBP phase + Hyperintensity DWI
  35. 35. SEG 2/3 HYPERVASCULAR HCC WITH PARADOXICAL UPTAKE (DWI-hyperintense)
  36. 36. SEGMENT 6 HCC WITH NORMAL ARTERIAL, T2W AND DWI
  37. 37. FOCAL NODULAR LIVER LESIONS: 1994 INTERNATIONAL CLASSIFICATION •  Regenerative nodule •  Cirrhotic nodule •  Low grade dysplastic nodule (adenomatous hyperplasia) •  High grade dysplastic nodule (adenomatous hyperplasia with atypia) •  Dysplastic nodule with subfoci of HCC (early HCC) •  HCC (overt HCC) International Working Party. Hepatology 1995;22:983-993
  38. 38. DEVELOPMENT OF HCC IN CIRRHOTIC LIVER •  Temporal progression from regenerative nodules to dysplastic nodules to well differentiated HCC. •  HCC may develop independently of RN and DN.
  39. 39. PRIMOVIST MRI MOST SENSITIVE TECHNIQUE IN DETECTING EARLY HEPATOCARCINOGENESIS
  40. 40. CONSENSUS STATEMENTSJAPAN SOCIETY OF HEPATOLOGY •  Typical HCC can be diagnosed by imaging regardless of the size if a typical vascular pattern is obtained on dynamic CT, dynamic MRI, CEUS or a combination of CTHA and CTAP. •  Different from Western guidelines, only one dynamic study showing the typical pattern is sufficient to diagnose HCC. •  The typical imaging pattern include hypervascularity in the arterial phase and washes-out in the portal venous phase.
  41. 41. CONSENSUS STATEMENTSJAPAN SOCIETY OF HEPATOLOGY •  Sonazoid-enhanced ultrasound is more sensitive for detection of intranodular hypervascularity than MDCT or dynamic MRI. Therefore to confirm true hypovascularity, sonazoid-enhanced CEUS is recommended. •  Nodules with hypovascularity and negative findings on SPIO-MRI, Kupffer imaging of Sonazoid CEUS, primovist MRI are likely to be benign. They can be followed up without treatment.
  42. 42. JAPAN SOCIETY OF HEPATOLOGY
  43. 43. JAPAN SOCIETY OF HEPATOLOGY
  44. 44. 2ND INTERNATIONAL FORUM LIVER MRI
  45. 45. PRIMOVIST CONTRAST ENHANCED MRI- PROTOCOL OPTIMIZATION AND EVALUATION OF HEPATIC NODULES IN LIVER CIRRHOSIS Dr. Tony Loke Consultant Radiologist United Christian Hospital
  46. 46. PRIMOVIST - GADOLINIUM-ETHOXYBENZYLDIETHYLENETRIAMINEPENTAACETIC ACID (GDEOB-DTPA) •  Combined extracellular hepatobiliary gadolinium based contrast agents with liver specific properties •  Multihance and Primovist •  These agents able to assess both vascularity and hepatocellular function.
  47. 47. PROTOCOL OPTIMIZATION - PHARMACOKINETIC AND PHARMACODYNAMIC PROPERTIES OF PRIMOVIST IN LIVER CIRRHOSIS. •  Patients with advanced cirrhosis, three important differences are present. •  Diminished and delayed liver parenchyma enhancement •  diminished parenchymal enhancement in the hepatocyte phase •  time to peak enhancement may be delayed. •  Diminished and delayed biliary excretion. •  In the noncirrhotic liver, primovist produces intense biliary tree enhancement beginning as early as 5 minutes after contrast injection. •  Enhancement of bile ducts in the cirrhotic liver is delayed and of limited intensity
  48. 48. PROTOCOL OPTIMIZATION - PHARMACOKINETIC AND PHARMACODYNAMIC PROPERTIES OF PRIMOVIST IN LIVER CIRRHOSIS. •  Patients with advanced cirrhosis, three important differences are present. •  Prolonged blood pool enhancement. •  50% of primovist is cleared by the liver and 50% via the kidneys. •  Patients with advanced cirrhosis, the hepatic elimination pathway is impaired and the blood vessels appear hyperintense for a longer duration. •  The relatively low contrast enhancement in portal and hepatic veins is relevant because it reduces the sensitivity for detecting venous obstruction and invasion.
  49. 49. PROTOCOL OPTIMIZATION – PRIMOVIST ENHANCED MRI IN CIRRHOTIC LIVER •  Problems with on-label approved dose Gd-EOB-DTPA of 0.025mmol/kg. •  Selecting the appropriate scan delay is difficult from low dose and small amount of on-label approved dose •  Studies have shown the signal intensity of vessels in the arterial phase is less with primovist than extracellular gadolinium-based agents using on-label approved dose. •  Standard dose provide low sensitivity for detection of hypervascular HCC/lesions despite its higher T1 relaxivitiy Cruite I et al AJR 2010;195:29-41
  50. 50. PROTOCOL OPTIMIZATION-SOLUTION FOR ACHIEVING OPTIMAL ARTERIAL PHASE •  Optimal arterial phase increases sensitivity for detection of hypervascular lesions •  Perform consecutive arterial phase data sets. •  Administer the agent at a higher off-label dose (0.0375 – 0.05 mmol/kg). •  This is 50%-100% higher than the approved dose. •  Injecting all 10ml (20ml if patient exceeds the dose rate calculation) -rounded up to the nearest bottle •  For patients with estimated GFR of less than 60mL/min, a weightadjusted dose is administered without rounding. •  Inject contrast at slower rate of 1cc/second followed by 20ml of saline chaser at 2cc/second. •  2cc/sec with higher dose
  51. 51. PRIMOVIST PROTOCOL - DIFFERENCE WITH CONVENTIONAL GD
  52. 52. UCH PROTOCOL - PRIMOVIST ENHANCED MRI LIVER •  MRCP performed before contrast injection •  Bolus timing method is used •  Contrast seen at LVOT or ascending aorta, patient asked to take 2 breath holds (8 -10 seconds) and 2 consecutive arterial phases imaging is acquired using 3D VIBE (15 seconds). •  late arterial phase is performed after 2 breath holds. •  Hepatic phase is performed after another 2 breath holds •  Equilibrium phase is performed at 120 minutes. •  Diffusion weighted imaging and 2D axial SPAIR is performed while waiting for delayed 20 mins hepatocyte phase. •  Hepatocyte phase - 20 minutes delay. •  Hepatocyte phase - 40 minutes delay •  if hepatic veins and portal veins not cleared •  contrast not visible in biliary tree. •  Hepatocyte phase - 60 minutes delay may be necessary.
  53. 53. UCH PROTOCOL – PRIMOVIST ENHANCED MRI LIVER
  54. 54. WHEN TO USE PRIMOVIST IN PATIENTS WITH LIVER CIRRHOSIS •  Primovist is routinely use in cirrhosis except for: •  Assessment of ablated lesions for residual or recurrent disease. •  Reduced vascularity •  Patients whose bilirubin is above 3 mg/dL. •  Sensitivity for lesion detection reduced from diminished liver enhancement •  Evaluation of vascular patency •  PV and HV remains hyperintense from prolonged blood pool •  Evaluation of hemangiomas •  Appearance same as HCC
  55. 55. IS PRIMOVIST BETTER FOR DETECTING HCC? -COMPARED WITH OTHER AGENTS /IMAGING MODALITIES •  Combined dynamic and hepatocyte phase of Primovist has greater diagnoctic accuracy for HCC detection than either dynamic or MDCT alone •  Comparing primovist and magnevist, significant increase in sensitivity was achieved with primovist. •  Hepatocellular phase imaging with Primovist improves HCC detection compared with conventional extracellular gadolinium chelates. •  MRI with primovist has equal accuracy as dual-contrast MRI for HCC detection (simultaneous use of conventional extracellular gadolinium and superparamagnetic iron oxide agent). Marin D et al Radiology 2009;251:85-95 Park G et al BJR 2010;83:1010-1016 Kim YK et al Invest Radiol 2010:45:740-746
  56. 56. PRIMOVIST UPTAKE BY HEPATOCYTE BY OATP1 EXCRETION TO BILE JUICE REGULATED BY MRP2 Kudo M J gastroenterology and hepatology 2010;25:439-452
  57. 57. Kudo M Oncology 2010;78:87-93
  58. 58. HCC (87 lesions) Hepatobiliary phase In one study Hypointense 92% Isointense 6% Hyperintense 2% WDHCC (39 lesions) Hepatobiliary phase Another study Hypointense 35 Isointense 2 Hyperintense 2 DN (8) Hypointense 3 Isointense 3 Hyperintense 2 Kudo M J gastroenterology and hepatology 2010;25:439-452
  59. 59. CRITERIA FOR HCC •  Reading Hepatobiliary phase alone insufficient •  Result in false positives and negatives •  Hepatocyte phase •  Post contrast EOB ratio •  Read the whole exam •  T1 (hypointense) •  T2 (hyperintense) •  Dynamic contrast (hypervascularity +/- washout) •  DWI (restricted diffusion)
  60. 60. CRITERIA FOR HCC DIAGNOSIS •  A nodule with increased enhancement on arterial phase and washout on late venous or equilibrium phase •  A nodule with arterial enhancement and hyperintensity on T2WI (and/or DWI) •  A nodule with isointensity during contrast enhanced arterial phase, hyperintensity on T2WI (and/or DWI) and no uptake of contrast on hepatobiliary phase (even < 1.5cm) •  Nodule > 1.5cm with no uptake of contrast agent on hepatobiliary phase images.
  61. 61. HYPOVASCULAR NODULE – SIZE MATTERS •  Hypovascular nodules (on arterial phase) with negative uptake on hepatobiliary phase are thought to represent DN or WDHCC •  Lesion > 1.5 will progress to hypervascular nodules in 80% in 1 year •  Lesion < 1.5 will progress to hypervascular nodules in 17% in 1 year Kudo M Oncology 2010;78:87-93
  62. 62. DN > 1.5CM - POSITIVE UPTAKE
  63. 63. DN > 1.5 CM - POSITIVE UPTAKE
  64. 64. DN - NEGATIVE UPTAKE
  65. 65. SEGMENT 3 HCC – LESION DEMARCATION BETTER
  66. 66. HYPERVASCULAR RECURRENT HCC – OTHER DN +VE UPTAKE
  67. 67. SEG 2/3 HYPERVASCULAR HCC WITH PARADOXICAL UPTAKE
  68. 68. HYPERVASCULAR SEG 7 DN - POSITIVE UPTAKE
  69. 69. HYPOVASCULAR < 1.5 CM HCC – T2/DWI BRIGHT
  70. 70. DN –NOT VISIBLE IN OTHER SEQUENCES EXCEPT HEPATOCYTE PHASE
  71. 71. SEGMENT 6 HCC WITH NORMAL ARTERIAL, T2W AND DWI
  72. 72. CT SEGMENT 6 HYPOENHANCING NODULE - HCC IN HEPATOCYTE PHASE > 1.5 CM
  73. 73. CT HYPERVASCULAR LESIONS – SEG 5 HCC
  74. 74. SEGMENT 6 HCC < 1.5 CM
  75. 75. CT HYPERVASCULAR LESION – SEG 5 PSEUDOLESION
  76. 76. SMALL HYPERVASCULAR HCC
  77. 77. SEGMENT 6 HCC & 2 HEMANGIOMAS
  78. 78. SEGMENT 5 – DN FEATURES ON T1/2
  79. 79. SEGMENT 5 HCC – NEGATIVE UPTAKE
  80. 80. COMBINED PRIMOVIST AND DWI Park MJ et al Radiology 2012:264;761-770
  81. 81. FALSE POSITIVE – HEPATOBILIARY PHASE •  Hypointense lesions seen only on hepatobiliary phase (without arterial enhancement and T2 hyperintensity) can either be WDHCC or Cirrhotic nodules •  HCC tend to be larger(>1.5cm) than benign nodules(0.5-1.2cm) •  Lesions <1.5cm seen on hepatobiliary phase can still be well-differentiated HCC and should not be ignored. •  Close monitoring, biopsy or resected in patients with coexisting overt HCC. •  Hypervascular pseudolesions •  15% shows negative uptake on hepatobiliary phase •  13% showed T2 hyperintensity •  DWI normal
  82. 82. FALSE NEGATIVE - HEPATOBILIARY PHASE •  HCC which are T1 hyperintense may be isointense on hepatobiliary phase. •  Look for hypervascularity on arterial phase, T2/DWI hyperintensity •  Hepatic dysfunction or hyperbilirubinemia reduces hepatic uptake of the contrast agent •  lesion conspicuity on hepatobiliary phase images is decreased, although false-negative cases can occur in patients with normal bilirubin level. •  Lesions are less conspicuous in fatty liver •  do 20 min delay without fat sat •  Paradoxical uptake – Green hepatomas •  2.5 to 8.5% of HCC appear iso/hyperintense •  Altered transporter mechanism
  83. 83. SUMMARY- CRITERIA FOR HCC •  Hypervascular nodules with washout – irrespective of delayed phase •  Hypervascular nodules and hyperintensity on T2WI (and/or DWI) – irrespective of delayed phase •  Isointense nodule (arterial phase) with hyperintensity on T2WI (and/or DWI) and negative uptake of contrast on hepatobiliary phase (even < 1.5cm) •  Nodule > 1.5cm with no uptake of Primovist on hepatobiliary phase images– irrespective of vascularity
  84. 84. SUMMARY •  Negative uptake in hypovascular lesions <1.5 cm can still be HCC •  FU required as 17% becomes hypervascular in 1 year •  Positive uptake can still be HCC •  DWI (+/- hepatocyte SI ratio) to exclude pseudolesion •  Hypointense rim and/or focal defect on delayed phase •  Nodule in nodule and internal septation helps •  FU(+/-biopsy) necessary
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