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Ultrasound for Liver Screening:

Rationale and Protocol

Mindy M. Horrow, MD, FACR, FAIUM, FSRUVice Chair of Radiology

Einstein Medical Center

Professor of Radiology Sidney Kimmel Medical School

Philadelphia, PA

May 15, 2019

No Relevant Personal

Disclosures

Jay C. Horrow (spouse) is an employee of Merck & Co.

Outline

Goals: Screening and Surveillance ultrasound to detect

(1) Parenchymal disease: steatosis, fibrosis, cirrhosis

(2) Hepatocellular carcinoma (HCC)- focal or infiltrative

US every 6 months

Requires standardized, meticulous detail(1) Ease of comparison (2) Decrease inter-observer variability

Different approach from scanning patients with pain

1. Static images and cine clips

2. Low and high frequency imaging

3. Liver/spleen and liver/kidney comparison

for texture and echogenicity

1. PV patency, direction, velocity

2. HA size, velocity

3. Varices

Gray scale Doppler

Parenchymal Disease:What are we looking for?

1. Increased echogenicity

a) Diffuse

b) Patchy

2. Coarse echotexture

a) Reticular echoes

b) Regenerating nodules

Echogenicity and echotexture

Contour and size

1. Overall length

2. Focal hypertrophy

3. Focal atrophy

4. Contour: wavy, nodular

1. Gray scale

a) Ascites, pleural effusion

b) Splenomegaly

2. Vascular

a) Varices

b) Direction portal flow

c) Velocity, waveforms in

HA, PV, HV

Signs of portal hypertension

Einstein Liver US ProtocolAdapted from ACR US LI-RADS

Longitudinal images

• Left lobe

• Left of midline

• At midline with aorta

• With IVC

• With LPV

• Right lobe

• With gallbladder

• With right kidney

• Include right

hemidiaphragm and

adjacent pleural space

• Far lateral

• MPV in B-mode, color and

spectral Doppler

• Common bile duct

Transverse images

• Dome with hepatic veins

• Right liver edge

• Left liver edge

• Left lobe

• With left portal vein

• Falciform ligament

(assess for patent

paraumbilical vein)

• Main portal vein bifurcation

• Right lobe

• With right portal vein

• With main portal vein

• With gallbladder

• With right kidney

• Near liver tip

Additional views:

• Wide FOV of liver

• Liver/spleen

comparison

• Spleen

measurement

• High frequency R

and L lobes for

contour and

parenchyma

• R and L lower

quadrants to assess

for ascites

Cine loops

• Sagittal left lobe midline to left liver edge

• Transverse subcostal through porta hepatis, superior to inferior

• Transverse right lobe superior to inferior

• High frequency linear transducer, left and right lobes

Large FOV cine loop sweeps

Sagittal left

Begin at patient midline

and scan to left liver

edge

Transverse subcostal

large FOV from below

heart through porta

hepatis

Transverse right

from diaphragm to

inferior aspect of liver

Benefits:1. Interpreting radiologist can search for focal abnormalities

2. Ease of comparison with CT and MRI

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Liver Spleen ComparisonFor echogenicity and echotexture

• Usually liver echogenicity is ≤

spleen and both have

homogeneous echotexture

• Even when enlarged 2° to portal

hypertension, splenic echogenicity

and echotexture usually normal

• Renal appearance may be

abnormal since patients with

chronic liver disease often have

altered renal function, thus renal

comparison may not be sensitive

• In most patients liver and spleen

are not adjacent (as in this

example)

• We use split screen technique

without changing machine settings

for liver spleen comparison

Left lobe hypertrophy in cirrhotic patient allows

Liver/spleen comparison in single image

Split screen technique in same patient

Liver

Spleen

Benefit of Liver spleen comparisonCompare echogenicity and echotexture in 4 different patients

Normal: Liver slightly less echogenic than spleen

Homogeneous echotexture at low and high frequency

Bx proven steatohepatitis: Liver echogenicity = spleen,

slight heterogeneity, confirmed on high frequency

Moderate steatosis: Liver echogenicity > spleen in 2013

Liver = spleen in 2016 after RYGB and weight loss

Mild steatosis: Liver echogenicity > spleen;

cannot compare to kidney because renal

echogenicity is due to CRF

1 3

2 4 2013

2016

Echogenic liver at low frequency

echogenicity

sound attenuation

Smooth contour

echogenicity

reticular echoes

Smooth contour

Steatosis Hepatitis and fibrosis Cirrhosis

1 2 3

echogenicity

Regenerating nodules

Nodular contour

High frequency supports more specific diagnosis

Benefit of low frequency and wide field of

view for global contour abnormalities

Indentation of posterior inferior surface of R lobe at

level of R kidney 2°enlargement of caudate lobe and

atrophy of right

Interlobar atrophy and lateral segment hypertrophy

Low vs. high frequency imaging for contour

abnormalities in same patient

Global Surface

Inferior R lobe atrophy Caudate lobe

hypertrophy

Smooth anterior

R lobe

Nodular surface may have variable distribution

Interlobar atropy

Nodular posterior R

lobe and anterior L lobe

Cirrhosis: US-CT comparison 1

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Cirrhosis: US-CT comparison 2 Cirrhosis: US-CT comparison 3

High frequency static images and cine clips

help visualize regenerating nodules

Slightly nodular

contour

Homogeneous

echotexture

More confident interpretation of cirrhosis using these techniques

5-1 MHz

12-3 MHz

Nodular surface with multiple 1-2 mm regenerating

nodules

9-2 MHz

12-5 MHz

Slightly nodular

contour

Significant

heterogeneity

Regenerating nodules, definite nodular contour

Two different patients

Mild hepatic heterogeneity and

possible GB wall thickening

Is this cholecystitis?

GB wall thickening, nodular surface and

regenerating nodules;

Inter-lobar atrophy results in “naked GB”

Cirrhosis causes GB wall thickening!

12-5 MHz5 -1 MHz

Benefit of high frequency imagingRUQ US for abnormal

LFTs and pain

Progression of cirrhosis on 12-5 MHz imaging

2016 US and MR2013 US and CT 2014 US

Smooth contour

Normal echogenicityWavy contour

Heterogeneity

Nodular contour

Tiny hypoechoic regenerating

nodules on US with corresponding

hypointense foci on MRLiver BX 4/2014:

Chronic hepatitis with

Bridging fibrosis

Liver BX 10/2014:

Cirrhosis with

Extensive fibrosisT1W portal venous phase

Combination of techniquesWide field of view, high frequency

Standard 5-1 MHz: Increased echogenicity

Hepatosplenomegaly

Slightly heterogeneous echogenic liver

Wide FOV 12-5 MHz

Nodular surface

Nodular heterogeneity

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Benefit of high frequency imaging for diagnosis of

cirrhosis when liver surface is smooth

Slightly heterogeneous

echotexture with smooth contour

5-1 MHz

Though surface is smooth, regenerating

nodules suggest cirrhosis

12-5 MHz

Coronary varices

Smooth liver

Normal spleen

Biopsy proven

cirrhosis

Combination of low and high frequency, color Doppler

and cine clips allow more specific diagnosis

Nodular contour ?

What are these linear

echogenic bands ?

5-1 MHz 12-5 MHz

Definite nodular contour

Linear echogenic bands in

transverse

Superficial varices

Definitive cirrhosis and

portal HTN at 12 MHz

Narrow, thick walled CHD

Echogenic bands parallel to portal veins =

dilated sludge filled ducts

Primary Sclerosing

Cholangitis

Other findings related to cirrhosis

and portal hypertensionRight pleural effusion

Nephromegaly

SplenomegalyAscites with 3D surface rendering

2 different patients

Wall thickening of colon and jejunum

Colopathy and enteropathy

Sag R colon Sag jejunum in LUQ

Doppler changes with chronic

liver diseaseHepatic Artery Hepatic Veins Portal Vein

1. Variable changes

to R.I.

2. ↑ velocities reflect

shift to more

arterial flow as

portal HTN

worsens and PV

flow decreases

3. Dilatation

1. Decreasing phasicity1

a. a wave ↓ baseline

b. Ultimately

monophasic

2. Spectral broadening:

loss of normal spectral

window

3. Diminutive size

1. Slow flow, < 16 cm/sec

2. Abnormal direction

a. Complete or partial

hepatofugal

3. Absent

a. Stasis

b. Benign thrombus

c. Malignant thrombus

4. Dilatation1 Obtain waveform during mild inspiration

Valsalva maneuver can reduce phasicity

NORMALa

PV

VaricesParaumbilical

Coronary

Spleno-renalCavernous transformation

after chronic PV thrombosis

Gallbladder varices due to chronic PV thrombus

T1W post contrast

TRV

Elevated hepatic

artery velocity 2°

increased arterial flow

PV direction remains

hepatopetal with normal

velocity

Para-umbilical varix

Loss of phasicity in

hepatic veins due

to stiff liver

Doppler in patient with cirrhosis

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Beware:

Diffusely ↑ size of intrahepatic arteries can have appearance similar

to biliary dilatation in gray scale images

Hepatofugal flow in

Splenic V and MPV

Splenorenal varices

Trv splenic vein

Doppler in patient with cirrhosis

Low velocity hepatopetal

flow in main PV

Reversed flow in left PV

“No flow” in PV at routine

PRF settings

Patent PV with slow flow at

lower PRF

Low velocity in PV

Intermittently reversed flow

Hepatofugal

Hepatopetal

Doppler in 3 different patients with cirrhosisSubtle and variable reversals of portal flow, low velocities

HCC: Diffuse and FocalACR US LI-RADS

• Terminology: Recommend use of “Observation” for any

focal region that differs from background parenchyma in

echogenicity and echotexture

• US Scores for:

– Detection

1. Negative- No observation or definitely benign

2. Sub-threshold- Observation <10mm or not definitely benign

3. Positive- Observation ≥ 10mm, not definitely benign, new thrombus in PV

– Visualization: extent of heterogeneity, ability to adequately

penetrate to diaphragm

A. Minimal limitations

B. Moderate limitations

C. Severe limitations

Remember: US LI-RADS is for detection of “Observations”

Contrast CT/MRI and Contrast US are tests

for definitive diagnosis and characterization of HCC

Importance of R and L lobe comparison

to appreciate diffuse HCC

Typical cirrhosis:

1. Nodular contour

2. Coarse echotexture

3. Normal population

of vessels

Infiltrative HCC =

“Adenomyosis of the Liver”

1. Considerable

heterogeneity

2. “Venetian blind” shadowing

3. Indistinct echogenic

nodularity

4. Absent vessels

STOP

Evaluate

vessels!

Same

patient

Uterus with adenomyosis

R L

Diffuse portal “tumor in vein” confirms

suspicion of diffuse HCC (US LI-RADS 3)

Branching pattern of echogenic “nodules”

more easily appreciated as tumor in vein

by using cine clips

Expanded R PV filled with tumor that

demonstrates arterial flow

Same patient

Localized infiltrative HCCPoorly defined region of tumor with corresponding PV tumor in vein

PV thrombus in same

region as infiltrative tumor(note how tumor bulges capsule!)

Branching of PV with tumor in

vein and subtle difference in

echotexture of tumor more

easily appreciated with cine

clip Arterial enhancement in

PV tumor, difficult to

appreciate

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Focal Observation ≥ 1cm at screeninghistory of Hepatitis C and Cirrhosis

Cine helps categorize Couinaud

segment and assess

relationship to vessels and

ducts

Arterial MRI

Delayed MRI

CT/MRI LI-RADS 5: Classic HCC

Recommend

multiphase

contrast study

(Look carefully on cine for second “observation”)

US LI-RADS Category 3

Small observation on screening US

Solitary 8.4 mm lobulated

echogenic nodule visible

on low and high frequency

MRI arterial phase

hyperenhancement

MRI delayed phase washout

with capsule

MRI was

performed

US LI-RADS Category 2

Sub-thresholdCT/MRI LI-RADS 4

Note: There is shift

towards US rather than

CT/MRI F/U for sub cm

observations to decrease

false positive rate of US

screening and due to size

(< 1 cm does not meet

criteria for LI-RADS 5)

Small observation on screening US

7 mm hypoechoic observation

in left lobe

MRI T1 pre

T1 arterial phase

T1 delayed

What to do

when not

visible

on MRI ?

Resume US screening

US LI-RADS Category 2,

Sub-threshold

Note: There is shift

towards US rather than

CT/MRI F/U for sub cm

observations to decrease

false positive rate of US

screening . Observation

< 1 cm does not meet

criteria for LI-RADS 5.

New 1.4 cm observation on surveillance US

not visible on MRI

Arterial phaseSag L lobe

Portal venous phase 5 minutes

CEUS LI-RADS 3

No washout

Small component enhances similar to

liver, no arterial hyperenhancement

Isoenhancing

Contrast US

Resume US screening

Pitfalls and other issues

• Be wary of making dx of PV thrombosis unless

thrombus is visualized in gray scale

• Multiple tiny regenerating nodules: when to

become concerned for a focal lesion?

– We suggest >5mm

• Lack of correlation between US and MR/CT

– If observation only visualized on US continue US

screening and/or contrast enhanced US

• When is US insufficient for screening/surveillance?

– If unable to penetrate adequately 2º severe steatosis or

extreme heterogeneity

Troubleshooting and Pitfalls

Visualization improved!

C5 R lobe

supine

Poor visualization 2°

obesity

Wavy contour L lobe, Cirrhosis?

Nodularity often not uniform

Check contour both lobes!

Poor visualization 2°

steatosis

C5 penetration

LPO positioning

C5 penetration

When steatosis is severe

and cannot visualize

diaphragm, US is limited

Check R lobe

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• Dedicated screening and surveillance liver US is a highly

specialized imaging technique which benefits from

attention to detail using: – Standardized technique in routine order

– High and low frequency imaging

– Liver/spleen comparison

– Cine clips

• Doppler: Even if formal spectral Doppler is not ordered,

check direction of PV flow and search for varices

• HCC screening– Use wide FOV, compare echotexture of lobes and look for PV thrombus

as clue to infiltrative HCC

Tips from Einstein radiologists:1. “Adenomyosis” of liver may be clue to infiltrative HCC

2. “Naked gallbladder” is a useful sign of inter-lobar atrophy

3. If no color flow in “anechoic” PV on routine settings, make PRF sensitive to R/O thrombus

Summary References

1. Colli A, et al. Severe Liver Fibrosis or Cirrhosis: Accuracy of US for

Detection – Analysis of 300 Cases. Radiology 2003; 227:89-94

2. Hirooka M, et al. Nonalcoholic Fatty Liver Disease: Portal hypertension due

to outflow block in patients without cirrhosis. Radiology 2015; 274: 597- 604

3. Kelly EM, et al. Sonography predicts liver steatosis in patients with chronic

hepatitis B. J Ultrasound Med 2017; 36: 925-932

4. McNaughton DA, Abu-Yousef MM. Doppler US of the Liver Made Simple.

Radiographics 2011;31:161-188

5. Morgan TA, et al. US LI-RADS: ultrasound liver imaging reporting and data

system for screening and surveillance of hepatocellular carcinoma. Abdom

Radiol (2017) DOI: 10.1007/s00261-017-1317-7