Reliable methods of evaluating liver fibrosis using noninvasive techniques in the pediatric
population are limited and inconclusive. Liver biopsy remains the gold standard; however, it
requires sedation in pediatric patients, has a risk of hemorrhage, and provides unreliable
results secondary to sampling error. Sonoelastography is a new method of evaluating liver
disease that eliminates these pitfalls. There are 3 types of quantitative sonoelastography
currently in use.
Transient elastography is a non-imaging based technique used in adults to measure liver
fibrosis in which a mechanical vibrator creates a low-frequency wave causing shear stress in
the liver at a fixed depth. This technique does not work in small livers and, therefore, is
not appropriate for pediatric patients.
Acoustic Radiation Force Impulse Imaging (ARFI) and Shear Wave Imaging (SWE) use real-time
ultrasonography and administer focused high-intensity, short-duration pulses to produce
shear waves in the liver tissue. ARFI calculates the degree of tissue displacement and
creates an elastogram or measurement of the stiffness of the sampled liver tissue without
corresponding images. It is limited since only a small sample or region of interest (ROI)
can be obtained, and it is unable to provide a corresponding elasticity map of the tissue.
SWE is the newest elastography technique. It measures tiny displacements of tissue in a
larger ROI with corresponding ultrasound images which provides a side by side image of the
liver and color-coded elasticity map of the sampled tissue. Advantages include a larger ROI
and simultaneous viewing of the selected region of interest which provides better anatomic
detail with a corresponding color map of the tissue elasticity which may result in more
accurate scoring of the stage of fibrosis.
There are a few studies of ARFI in the pediatric population. Studies using SWE for
evaluation of liver fibrosis are also few, and, all but one in adults. However, these
studies have shown it to be an accurate method for liver fibrosis staging. Use of SWE in
assessing liver fibrosis in pediatric patients may represent an accurate noninvasive
alternative to liver biopsy in evaluating liver fibrosis as well as avoid the use of
The evaluation of pediatric liver disease continues to be a major focus of research both in
well-characterized liver diseases and in liver fibrosis secondary to obesity. The degree of
fibrosis is generally well-accepted as both a measurement of disease severity and a
prognostic indicator. Unfortunately, the current gold standard to assess fibrosis remains a
liver biopsy, which, in addition to anesthesia risks and sampling errors, can result in
profound hemorrhage, infections, and even mortality. Standard and reliable noninvasive
biomarkers of hepatic fibrosis in the pediatric population are greatly needed.
Sonoelastography has emerged as a method of evaluating liver disease. Three methods of
quantitative sonoelastography are currently in use.
Transient elastography is an M-mode based sonographic technique in which a mechanical
vibrator creates a low-frequency wave causing shear stress in the tissue at a fixed depth in
the target tissue. It has gained widespread use in evaluation of liver fibrosis in the adult
population (Fibroscan); however, its use has great limitations in the pediatric population
as it does not use real-time ultrasonography (B mode) and has a fixed depth in which the
measurement is taken. The lack of real-time imaging makes it impossible to accurately select
an area for appropriate sampling, and the fixed depth is not appropriate for very young
children with smaller livers. Also, the shock wave that is administered has not been
tailored for use in young children. Furthermore, this technique is very unreliable in
patients that are obese or who have ascites.
Other methods of sonoelastography include Acoustic Radiation Force Impulse Imaging (ARFI)
and Shear Wave Elastography (SWE). The latter is also known as supersonic shear wave
imaging. Both of these techniques use real-time ultrasonography and administer focused
high-intensity, short-duration (acoustic radiation) pulses to produce shear waves in the
target tissue. Neither technique is limited by the presence of ascites as the shear waves
propagate through the fluid. ARFI uses a single pushing beam to generate the shear waves,
and the propagation of those shear waves are monitored using conventional pulse-echo
ultrasound at various off-axis lateral locations. The speed of the shear wave in the tissue
is determined by collecting the displacement through time. This principle of elastography is
based on the Young modulus using the formula: E=3ρѴ2 (E elasticity's modulus, Ѵ speed, ρ
density of the tissue). The degree of tissue displacement is then used to create an
elastogram. Limitations of ARFI include a small selected region of interest (ROI) (10 mm x 5
mm), it is a 1-dimensional technique, and it is unable to provide a corresponding elasticity
map of the tissue. The latter also prevents retrospective evaluations of the tissue
SWE is the newest elastography technique. It works by generating a localized radiation force
that travels faster down the acoustic axis than the shear wave speed producing tiny, almost
simultaneous, displacements in the tissues at all positions along the acoustic axis. The
generated shear wave is shaped like a cone or fan, known as the Mach cone. An ultrafast
sonography is then performed which provides a side-by-side greyscale image and color-coded
elasticity map of the tissue in the ROI. The ROI is displayed in real time B-mode imaging
and, thus, represents a 2-dimensional technique. Advantages include a larger, fan-shaped ROI
(up to 50mm x 50mm), and the acquisition of a quantitative map of liver tissue stiffness
with corresponding greyscale ultrasound image. As a result, simultaneous viewing of the
selected region of interest provides better anatomic detail with a corresponding color map
of the tissue elasticity which may result in more accurate scoring of the stage of fibrosis.
The presence of a color map also allows for retrospective analysis.
Only a few studies have begun to use ARFI to analyze liver fibrosis in the pediatric
population. Studies using SWE for evaluation of liver fibrosis are also limited and all but
one have been performed in adults; however, early studies have shown it to be an accurate
method for liver fibrosis staging. Tutar, et al safely performed a study using SWE in
pediatric patients in Turkey. No dedicated pediatric studies have been performed in the
United States, as the technology was just recently approved for use in adults by the FDA.
The use of this device in pediatrics represents an off-label use. That being said, SWE has
safety considerations that are similar to Doppler mode which is a standard ultrasound
technology performed in pediatric patients of all ages. While it has a higher thermal index
than routine B-mode ultrasound, it is measured to be within the safety limits set by the
American Institute of Ultrasound in Medicine (AIUM).
- Any pediatric patient (0-18 years of age) with known liver disease with plans to
undergo a liver biopsy within 1 month of ultrasound exam. Underlying diagnoses
include biliary atresia, congenital fibrosis-cholestasis, Alagille syndrome, Caroli's
disease, choledochal cyst, alpha-1-antitrypsin deficiency, progressive familial
intrahepatic cholestasis (PFIC), viral hepatitis, glycogenosis, fructosemia, Wilson
disease, cystic fibrosis, autosomal recessive polycystic kidney disease (ARPCKD),
mesenterico-caval shunt, post liver transplant, and nonalcoholic steatohepatitis
(NASH). Written informed consent from parent or legal guardian. Written informed
assent from the child.
- Inconclusive biopsy results. Patient not cooperative for the ultrasound exam. Failure
to give informed consent. No biopsy results within allotted time frame. Poor acoustic
window in which to perform sonoelastography.