3. Epidemiology
According to the Centers for Disease Control and Prevention ,an
estimated 240 million people in the world have chronic hepatitis B virus
infection, including as many as 1.4 million people in the United States.
An estimated 160 million individuals worldwide have hepatitis C,
including approximately 3.2 million U.S. residents .
The prevalence of nonalcoholic fatty liver disease (directly linked to
obesity, diabetes, and dyslipidemia) is estimated to be 27%–34% in
the United States .
Overall, an estimated 30 million Americans have chronic liver disease
4. At present, global prevalence of NAFLD is estimated as
about 9% in the developing countries and 30% in the
developed countries. Indeed, NAFLD is the most common
cause of chronic liver disease in the industrialised world.
5. NAFLD is seen in approximately 25%, of population with more
than 80 million individuals affected in the United States alone.
There are similar rates in Asia, with an estimated pooled
prevalence rate of 27.4% (95% confidence interval [CI],
23.3%–31.9%) observed.17
Both the prevalence of NAFLD and stage of liver disease
appear to increase with age
The overall prevalence of NAFLD appears to be higher in men,
however, the prevalence of NASH with more advanced stages
of fibrosis appears to be somewhat increased in women.
6. It is estimated that between 17–46% of European adults
have NAFLD (on average, around 25%)
Up to 90% of patients with NAFLD have simple steatosis,
which carries a relatively benign prognosis, with no overall
increase in mortality. However, approximately 10– 30% have
the potentially progressive form of NAFLD, non-alcoholic
steatohepatitis (NASH), which is associated with
hepatocellular injury and inflammation.
Approximately 25– 40% of patients with NASH will
develop progressive liver fibrosis, ultimately resulting in
cirrhosis in 20– 30%.
7. It is estimated that 16-32% of general population in India
(nearly 120 million) has NAFLD and among them nearly
31% are diagnosed with NASH.
Industrialization and change in lifestyle and diet with less
physical activity and increased calorie rich food are
contributing to the increased prevalence of NAFLD in Indian
population.
It is also estimated that 63 million Indians are Type 2
diabetic, and among them 70% are having NAFLD (44
million). And one third of the NAFLD population is estimated
to have NASH (13 million). It is also probable that 5% of
people with NASH (650,000) may develop liver cancer.
13. Limitations of liver biopsy
Sampling error: Only 1/50000 of the whole liver tissue is sampled
during a liver biopsy, for which sampling error is of concern
Inter- and intra-observer variability: Inter- and intra-observer
variability also presents a serious problem for the pathological
diagnosis of NAFLD
Risk and complications: Regarding the complications of liver biopsy,
the incidence of pain is reportedly 20%
The incidence of serious complications and mortality has been
reported to be 0.3%-0.57% and 0.01%,
14. Although histologic evaluation of a liver biopsy sample has
been considered the reference standard for staging liver
fibrosis, it is an imperfect reference standard.
In addition to its invasive nature, some degree of sampling
variability is inevitable because of the irregular distribution of
fibrosis in chronic liver disease
18. The elasticity of a material describes its tendency to resume its
original size and shape after being subjected to a deforming force
or stress. The change in size or shape is known as the strain.
The force acting on unit area is known as the stress.
Elastography refers to an imaging technique that images
and/or quantifies elasticity (mechanical properties) of
biologic tissues. Mechanical properties reflecting tissue
organization, physiologic findings, and pathologic conditions
can be quantified with elastography .
Tissues are considered viscoelastic in their mechanical
properties. Elastographic techniques assess the stiffness of the
tissue on the basis of many mechanical assumptions
19. Many disease processes alter the mechanical
properties of tissue and induce changes in its
elasticity, and are therefore detectible by
elastography.
In hepatic fibrosis, for example, abnormal
accumulation of collagen fibers
decreases the elasticity of the affected tissue,
allowing for detection and quantification by
elastography
. In order to measure elasticity, a mechanical
stimulus or stress is applied to the target tissue and
its response is measured.
33. When tissue is displaced posteriorly by focused ultrasound
beams from the probe, the restorative force of the tissue
propagates laterally, generating shear waves.
Focused US pulses are used to generate a transverse wave
(shear wave) at specific depths within the liver, as selected by
the operator.
Tracking US pulses are then used to measure the velocity of
these shear waves as they travel through the liver parenchyma.
The velocity of propagation of the shear waves is proportional
to the square root of the tissue stiffness or elasticity, thus
enabling estimation of fibrosis.
34. The principle underlying SSI involves the combination of a
radiation force induced in tissues by focused ultrasonic
beams and a very high frame rate ultrasound imaging
sequence able to capture the propagation of resulting shear
waves in real time.
The ultrasound system captures the generated shear waves.
To capture them in sufficient detail, frame rates of a few
thousands of images per second are needed.
This ultrafast imaging mode acquires raw radiofrequency
data at a very high frame rate, up to 5000 frames/s. Shear
wave speed is then estimated by a Doppler-like acquisition
over a region of interest.
SSI
35. The ultrasound probe of the device produces a very localized radiation
force deep in the tissue of interest. This acoustic radiation force/push
induces a shear wave, which then propagates from this focal point.
Several focal points are then generated almost simultaneously, in a line
perpendicular to the surface of the patient’s skin. This creates a conical
shear wave front, which sweeps the image plane, on both sides of the
focal point.
The progression of the shear wave is capturedby the very rapid
acquisition of ultrasound images (up to 20,000 images per second),
called UltraFastTM Imaging.
The acquisition takes only a few milliseconds, thus the patient or operator
movement does not impact the result. A highspeed acquisition is
necessary to capture the shear wave as it moves at a speed in the order
of 1 to 10 m/s.
SSI
36. A comparison of two consecutive ultrasound images allows
the measurement of displacements induced by the shear
wave and creates a ‘‘movie’’ showing the propagation of the
shear wave whose local speed is intrinsically linked to
elasticity.
The propagation speed of the shear wave is then estimated
from the movie that is created and a two-dimensional color
map is displayed, for which each color codes either the shear
wave speed in meters per second (m/s), or the elasticity of
the medium in kilopascals (kPa).
SSI
37. This color map is accompanied by an anatomic reference gray
scale (or B-mode) image. This quantitative imaging technique
is a real-time imaging mode.
Quantitative measurements can be performed in the color
window by positioning one or more ROI (regions of interest)
called Q-Box. The Q-Boxes are variable in size (from 3 mm2 to
700 mm2). Measurements can be performed retrospectively
from the saved image or cineloop.
The measurements provided by Q-Box are the mean, standard
deviation, and minimum and maximum elastography values.
Results are given in m/s or kPa
SSI
39. Toshiba, Philips and Mindray seem to have implemented a
conventional ARFI pushing method similar to Siemens.
Mindray employs highly parallel receive beam-forming and a
zoned transmit wave to sample the travelling shear wave at more
than 1000 frames per second within areas up to 4 cm wide.
Philips also employs highly parallel processing, allowing free-
running 2DSWE over areas up to 5 cm high by 7 cm wide with an
abdominal curved array transducer at a frame rate of 0.4 – 1.6Hz,
while the underlying B-mode runs at 20 Hz for visual guidance .
GE has implemented the “comb push” technique , which
pushes along a number of ARFI lines simultaneously
42. 1. Patients should fast at least 4 hours before the
examination
2. Measurement should be taken at an intercostal
space with the patient in the supine or slight lateral
decubitus (30°) position with right arm in extension
43. 3. Measurements should be taken at neutral
breathing during a breath hold
4. Measurement should be taken at least 15–20 mm
below liver capsule in pSWE
5. The 2D SWE region of interest can be positioned
closer to the liver capsule, if reverberation artifacts
are avoided; however, the measurement
box should be positioned at least 15–20 mm below
the liver capsule
44. 6. Results can be reported in meters per second or
in kilopascals
7. In most systems, the maximum ARFI push pulse
is at 4–4.5 cm from the transducer, which is the
optimal location for obtaining measurements.
In most systems, the ARFI push pulse is attenuated
by 6–7 cm, limiting adequate shear wave generation
45. 8. Major potential confounding factors include liver
severe inflammation indicated by AST and/or ALT
elevation greater than five times upper normal limits,
obstructive cholestasis, liver congestion, acute
hepatitis, and infiltrative liver disease (these all lead
to overestimation of the stage of fibrosis)
9. Ten measurements should be obtained with
pSWE, and the final result should be expressed as
the median together with the IQR/M
46. 10. Fewer than 10 measurements with pSWE can
be obtained (at least five); however, the IQR/M
should be within the recommended range
11. For 2D SWE, five measurements should be
obtained when the manufacturer’s quality criteria are
available, and the final result should be
expressed as the median together with the IQR/M
47. 12. The most important reliability criterion is an
IQR/M of </30% of the 10 measurements (pSWE) or
five measurements (2D SWE) for kilopascals and
</15% for measurements in velocity (in meters per
second)
13. Adequate B-mode liver imaging is a prerequisite
for point and 2D SWE as shear waves are tracked
with B-mode
57. Studies have shown that the level of variability
between consecutive acquisitions, assessed by
means of the IQR/M, is the
most important quality criterion.
When this ratio is higher than 30% (for measurements given
in kilopascals ), the accuracy of the technique is reduced.
If the IQR/M values are greater than 30% in kilopascals
or 15% in meters per second, the measurement of liver
stiffness should be judged as unreliable.
58. Shearwave elastography techniques have excellent
reproducibility,provided the recommendations of the
manufacturer or expert recommendations are
followed.
For all systems,intra-observer reproducibility
assessed with the intra-class correlation
coefficient(ICC) was>0.90,and inter-observer
reproducibility was>0.80
59. Confounding Factors
Acute hepatitis -alcoholic hepatitis
Liver inflammation - transaminitis flares with alanine
aminotransferase value more than five times the upper limit
of normal
Obstructive cholestasis
Hepatic congestion -CCF,Edema, ascites
infiltrative liver diseases such as amyloidosis, lymphoma, or
extramedullary hematopoiesis
60. Confounding Factors
• Obesity -SCT thickness >25mm
• Non fasting status
• Interfering vessels or bile ducts
• Rib shadows and narrow intercostal spaces
• Increased probe pressure
• Angled insonation
61. Society of Radiologists in Ultrasound Liver
Elastography Consensus
The consensus panel proposes a vendor-neutral “rule of four” (5, 9,
13, 17 kPa) for the ARFI techniques for viral etiologies and NAFLD:
Liver stiffness of 5 kPa (1.3 m/sec) or less has high probability of being
normal; liver stiffness less than 9 kPa (1.7 m/sec), in the absence of
other known clinical signs, rules out cACLD;
values between 9 kPa (1.7 m/sec) and 13 kPa (2.1 m/sec) are
suggestive of cACLD but may need further test for confirmation;
and values greater than 13 kPa (2.1 m/sec) are highly suggestive of
cACLD
114. • Acquisition technique: B-mode & SWE entanglement,
transducer frequency, posterior elastographic
shadowing artifact, mirrored elastogram artifact, “vertical
striped” artifact, resolution limits in SWE, non-
equivalence of elastographic devices
• Medium: SWE in liquid medium, “black hole
phenomenon”, pseudo-liquid lesions, musculotendinous
anisotropy, intrinsic stiffness variations of tendons and
muscles, depth of analysis, movement artifacts
• Operator: Region of interest compression, acquisition
and measurement parameters (ROI size, ROI location,
elastogram acquisition time)
115.
116.
117.
118.
119.
120. where the size and diameter of the ROI is limited by
vessel pulsation, vessel drop- out and an
acoustic shadow to the right of the image as seen on B-mode