Evangelos Chartampilas Bioclinic Hospital Thessaloniki, Greece - - PowerPoint PPT Presentation

Evangelos Chartampilas Bioclinic Hospital Thessaloniki, Greece

Hepatospecific contrast agents

MOAT: multispecific organic anion transporter OATP: organic anion transporting polypeptides

Gadobenate dimeglumine (Multihance) Gadoxetic acid (Primovist) 3-5% liver uptake 50% liver uptake Hepatobiliary phase: 2h Hepatobiliary phase: 20min Transported via MOAT Transported via OATP(B1,B3) Relaxivity r1 : 6,3 [l mmol-1 s] Relaxivity r1: 6,9 [l mmol-1 s] Dosage: 0.1 mmol/kg (0.2 mL/kg) Dosage:0.025 mmol/kg (0.1 mL/kg)

Transport mechanism for Gd-EOB-DTPA

Choi Y, BJR 2015

Uses of hepatospecific contrast agents

As they are taken up by functioning hepatocytes (and

then excreted in the bile), they can be used to:

1.

Evaluate liver function

• In cirrhosis, fibrosis and reduced number of functioning

hepatocytes decrease contrast uptake

2.

Identify early hepatocellular carcinoma (HCC)

• During hepatocarcinogenesis, the ability to take up the

contrast is gradually lost

3.

To differentiate FNH from adenoma

4.

To depict the biliary tree (eg possible leaks)

5.

To detect metastases

Evaluation of liver function

Reduced liver enhancement in cirrhosis may be caused by

Decrease in the number of functioning hepatocytes Impairment of transport mechanism

Slight decrease in OATP1 activity in cirrhotic rats and Significant up-regulation of MRP2 activity, leading to elimination

• f the drug

Tsuda N, Radiology 2010

Ways to evaluate liver function I

1.

Direct measurement of liver signal intensity

• Liver to spleen ratio
• Liver to muscle ratio
• Relative enhancement (SIpost –SIpre )/SIpre
• Liver to spleen ratio and liver volume

(

• ) Correlation with indocyanin green clearance, hepatic

function parameters, Child-Pugh score and MELD score was found

Motosugi U, JMRI 2009 Yamada A, Radiology 2011 Verloh N, Eur Radiol 2014 Lee S, JMRI 2016

(─) Non absolute, non comparable measurements

Direct measurement of liver signal intensity

Lee S, JMRI 2016

Normal liver

Verloh N, Sci Rep 2015

Ishak 6 (cirrhosis)

Ways to evaluate liver function II

2.

MR perfusion (DCE-MRI) – labor intensive

3.

MR relaxometry

• Measurement of T1 relaxation time (ms)
• T1 values significantly longer in cirrhosis on gadoxetate

enhanced MRI

(

• )Absolute values,

independent of technical factors

(─) Technically

demanding method

Evaluate cirrhotic nodule-early HCC

Arterial Portal

Typical pattern of arterial enhancement and portal

washout is absent in 20-50% in HCC<3cm

Arterial enhancement absent in 15-25% Portal washout absent in 40-60% The smaller the lesion, the higher the probability for

atypical vascular kinetics

Diagnosis of early HCC is associated with longer

time to recurrence and a higher 5-year survival rate

Early HCC -definition

Clinically: <2cm (very early) or <3cm and <3 in

number (early)[Barcelona stage 0 & A]

Both hypervascular in arterial phase (classic

HCC)

Pathologically: < 2cm, in an early stage of

carcinogenesis

Vascular invasion or intrahepatic metastasis

extremely rare

Well differentiated HCC is not necessarily early

HCC!

Early HCC pathological

Small HCC <2cm Grows by replacing and not expansively Fatty change is common No fibrous capsule Well differentiated Unpaired arteries poorly developed

Not easily seen in arterial phase

May retain some portal venous supply

Not easily seen in portal phase

Vaguely nodular (early)

Distinctly nodular (not early)

Hytiroglou P,

• Gastroent. Clin. N. Am

2007

Vascular kinetics and hepatospecific contrast uptake

Kitao et al, Eur Radiol 2011 Early HCC

Role of Gd-EOB-DTPA in diagnosis I

Loss of metabolic function might precede

development of neoangiogenesis

Bartolozzi, Abdom Imaging 2013

More than 90% of early HCCs showed no or decreased

expression of OATP1B3 transporters

Hypointensity on hepatobiliary phase

Ichikawa T, Liver Cancer 2014

With the use of Gd-EOB-DTPA, diagnostic accuracy of

HCC is ≥95%

Sano K, Radiology 2011 Kitao A, Eur Radiol 2011

(Kudo Μ, Dig Dis 2011) Borderline HCC

Role of Gd-EOB-DTPA in diagnosis II

Role of Gd-EOB-DTPA in diagnosis III

Comparison to other techniques

Ichikawa T, Liver Cancer 2014

SPIR DWI T1 pre-Gd Arterial HB

60-year-old man with cirrhosis

Hypointense nodules I

Not all hypointense nodules are early HCC; some represent

dysplastic nodules

However even if early HCC is ruled out on biopsy, there is high

probability this nodule will transform to hypervascular, typical HCC, especially when large (>10mm)

Other risk factors: presence of fat, restricted diffusion, T2

hyperintensity

Incidence rates are approximately 18%, 25% and 30% at 1, 2 and

3 years respectively

Suh CH, AJR 2017 Joishi D, Magn Reson Med Sci. 2013 Kim, Radiology 2012

Hypointense nodules II

Whether HCC or HGDN, the hypovascular, hypointense

lesion is suspicious (especially if large, ↑T2, ↑DWI or has intralesional fat) but not urgent

Management

Follow up? Biopsy? CEUS?

Benefit from intervention in early HCC?

RFA: despite lower local progression, similar OS and PFS with

hypervascular (overt)HCC [Lee DH, Radiology 2017]

Surgery: marginal survival benefit [Midorikawa Y, J Hepatol 2013]

Hypovascular hypointense HCC

Τ2 HB DWI Art

Hyperintense HCC

A significant percentage (9-20%) of typical

hypervascular HCC show paradoxical gadoxetate uptake (iso/hyperintense in hepatobiliary phase)

Overexpression of OATP1B3 transporters Less aggressive biological behaviour Less frequent portal vein invasion Lower recurrence rate compared to hypointense

Choi JW, Radiology 2013

Greater lipiodol uptake post TACE

Kim JW, Eur J Radiol 2017

Hyperintense HCC & histology

Are hyperintense HCCs better differentiated?

Although controversial, most evidence suggests that

there is an association between degree of enhancement

• n HB phase and degree of differentiation

Jin YJ, Medicine 2017; Tong H, Clin Imaging 2017 Grade I Grade IV

T2 SPIR T1 Art HB

Well differentiated HCC

Hyperintense HCC & differential

DDx:

Dysplastic nodules Regenerative nodules FNH like nodules Focal defect in uptake, hypointense rim, nodule-in-

nodule appearance , portal washout→ HCC

Suh JY, AJR 2011

HCC DN

Hyperintense HCC & differential

DDx:

Dysplastic nodules Regenerative nodules FNH like nodules Focal defect in uptake, hypointense rim, nodule-in-

nodule appearance , portal washout→ HCC

Suh JY, AJR 2011

HCC DN

Regenerative nodules

Hyperintense HCC & differential

DDx:

Dysplastic nodules Regenerative nodules FNH like nodules Focal defect in uptake, hypointense rim, nodule-in-

nodule appearance , portal washout→ HCC

Suh JY, AJR 2011

HCC DN

Regenerative nodules

Pre Art PV

FNH

HB

KimWJ, JMRI 2016

50-year-old man with cirrhosis

1,5 years later

DWI T1 FS DWI HB ART T1 FS ART HB

Typical HCC characteristics but the lesion unchanged in size!

Additional features with Gd-EOB-DTPA

Detection of microscopic vascular invasion

Seen as a hypointense halo in HB phase (Nishie A, J Gastroenterol Hepatol 2014)

Pitfalls with Gd-EOB-DTPA imaging

Genetic polymorphisms in the expression of OATP

transporters may lead to reduced hepatic enhancement

Cirrhosis is associated with reduced liver enhancement

Bilirubin, PT activity, MELD score, indocyanine green

clearance correlate with degree of HB enhancement

Patients with compromised liver function may not

benefit from hepatospecific agent use

Acute transient dyspnea (14% with Gd-EOB-DTPA vs

5% with Gd-BOPTA)

Davenport MS, Radiology 2013

Overall performance of Gd-EOB-DTPA

When the nodule is enhancing in the arterial phase

and is hypointense in the HB→ 100% specificity

Wang YC, PLOS ONE 2017; Golfieri, JMRI 2012

Excellent sensitivity (79–95%) and specificity (89–

92%) for lesions ≤ 2cm

Suboptimal performance for lesions ≤ 1cm

Arterial hyperenhancement and HB hypointensity most

common pattern

Apply ancillary imaging features

38-year-old man with HBV cirrhosis

US Art HB CT post TACE

30

Same patient, 4 years later

US DWI T2 T1 pre Art Portal Images courtesy of Dr Michailidis N

Conclusions

Hepatospecific contrast agents are useful for the

assessment of liver fibrosis

They have achieved a major breakthrough for diagnosis of

early HCC

Closely follow-up hypovascular, HB hypointense nodules Diagnosis of HCC is based on all sequences (T1, T2, DWI) HCC may appear hyperintense in HB phase; associated

with better prognosis

Thank you!

Zongolopoulos “Umbrellas”,Thessaloniki