Shear Wave Sonoelastography in Pediatric Liver Fibrosis

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 elasticity.

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).

Inclusion Criteria:

- 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.

Exclusion Criteria:

- 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.