This document discusses various methods for assessing liver fibrosis, including serum biomarkers and imaging techniques like elastography. It provides details on transient elastography (FibroScan), point shear wave elastography, and shear wave elastography. Transient elastography applies external vibration to generate shear waves while shear wave elastography uses acoustic radiation force. Measurements of shear wave speed allow calculation of liver stiffness as an indicator of fibrosis. Validation criteria and guidelines for elastography performance are also outlined.

1. Liver Fibrosis -Current
Perspectives
Dr Manoj K S MD RD DNB RD
Consultant Radiologist
KIMS HOSPITAL
PIONEER METRO SCANS

4. LABS
IMAGING
PATHOLOG
Y
platelet count, prothrombin time,
albumin level, total bilirubin level,
and serum aminotransferase levels,
to more sophisticated tests,
including levels of hyaluronic acid
and a2-macroglobulin. Direct
markers of fibrosis include levels of
procollagen (types I, III, and IV),
matrix metalloproteinases,
cytokines, and chemokines.
HEPASURE
FIBROSCORE
FINROMETRE
US ELASTOGRAPHY
MR ELASTOGRAPHY Ishak
METAVIR
Batts- Ludwig
systems
Liver Fibrosis assessment

6. Serum biomarkers for non-invasive evaluation of liver fibrosis
Fibrotest patented formula combining α-2-macroglobulin, γGT, apolipoprotein A1, haptoglobin, total bilirubin, age
and gender
Forns Index = 7.811 - 3.131 x ln(platelet count) + 0.781 x ln(GGT) + 3.467 x ln(age) - 0.014 x (cholesterol)
AST to Platelet Ratio (APRI) = AST (/ULN)/platelet (109/L) x 100
FibroSpectII patented formula combining α-2-macroglobulin, hyaluronate and TIMP-1
MP3 = 0.5903 x log(PIIINP [ng/ml]) - 0.1749 x log(MMP-1 [ng/ml])
Enhanced Liver Fibrosis score patented formula combining age, hyaluronate, MMP-3 and TIMP-1
Hepascore patented formula combining bilirubin, γGT, hyaluronate, α-2- macroglobulin, age and gender
Fibrometer patented formula combining platelet count, prothrombin index, AST, α-2-macroglobulin, hyaluronate,
urea and age
Fibroindex = 1.738 - 0.064 x (platelets [104/mm3]) + 0.005 x (AST [IU/L]) + 0.463 x (gamma globulin [g/dl])
HALT-C model = -3.66 - 0.00995 x platelets (103/ml) + 0.008 x serum TIMP-1 + 1.42 x log(hyaluronate) ]
NAFLD Fibrosis Score (NFS) =
= (-1.675 + 0.037 x age (yr) + 0.094 x BMI (kg/m2) + 1.13 x IFG/diabetes (yes = 1, no = 0) + 0.99 x AST/ ALT ratio -
0.013 x platelet count (x109/L) - 0.66 x albumin [g/dl])
BARD score (BMI ≥28 = 1; AST/ALT ratio ≥0.8 = 2; diabetes = 1; score ≥2, odds ratio for advanced fibrosis = 17)

8. TECHNIQUES
PATHOPHYSIOLOGICAL
CASES
PHYSICS

9. ELASTOGRAPHY

10. 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

11. Ultrasound is the propagation of a transient
density deformation. In soft tissues, it
travels at speeds in the range of 1350 –
1600 ms–1, whereas shear deformation
travels much slower, in the range of 1 – 10
ms–1 .
This speed difference means that
ultrasound may be used to measure tissue
displacements at precise phases of shear
deformation.

12. Elastography methods take advantage of the changed
elasticity of soft tissues resulting from specific
pathological or physiological processes .Fibrosis
associated with chronic liver diseases causes the liver
to become stiffer than normal tissues.
3 types of elastic moduli defined
by the method of deformation:
Young’s modulus (E), shear
modulus (G), bulk modulus (K).

15. Elastography produces a force coupled with a measurement
system for the deformities caused by the force
• There are several types of forces or applications:
• Static compression induced externally by manual
compression or internally by organ motion (heart, vessel,
breathing);
• Dynamic compression induced with a continuous
vibration at a given frequency
• Impulse compression(transient vibration):induced
externally by a transient mechanical impulse (FibroScan®
)
or internally by an ultrasound impulse (ARFI, SWE), both
compression types producing shear waves.

17. Strain elastography can be further subdivided by
the excitation method:
I The operator exerts manual compression on the tissue
with the ultrasound transducer. Manual compression
works fairly well for superficial organs such as the breast
and thyroid but is challenging for assessing elasticity in
deeper located organs such as the liver.
II In excitation method, the ultrasound transducer is held
steady, and tissue displacement is generated by internal
physiologic motion (e.g. cardiovascular, respiratory).
Since this method is not dependent on superficially
applied compression, it may be used to assess deeper
located organs

20. The ARFI technique
On a conventional gray-
scale US image (oblique
scan including the right
kidney and the lowest
portion of the right lobe of
the liver), acoustic push
pulses (curved lines) are
generated together with the
main US beam. From the
push pulses originate shear
waves (dashed horizontal
lines) propagating
perpendicular to the main
US beam, which are
sampled by tracking beams
(arrows) parallel to the main
beam.

21. Point shear wave elastography
In this technique, ARFI is used to induce tissue displacement in the n
Unlike ARFI strain imaging, the tissue displacement itself is not meas
Instead, a portion of the longitudinal waves generated by ARFI is intr
The speed of the shear waves perpendicular to the plane of excitatio

22. 1D Transient Elastography
• The Fibroscanprobe is a single device that contains both an
ultrasound transducer and a mechanical vibrating device.
Although 1D-TE is an US-based technique, it is used without
direct B-mode image guidance.
• The operator selects the imaging area using time-motion
ultrasound (based on multiple A-mode lines in time at different
proximal locations assembled to form a low quality image) to
locate a liver portion 2.5 – 6.5 cm below the skin surface and
free of large vascular structures.
• The mechanical vibrating device then exerts a controlled
vibrating external “punch” on the body surface to generate
shear waves which propagate through the tissue.
• The same probe then uses A-mode US to measure the shear
wave speed and Young’s modulus E is calculated .
Measurements assess a tissue volume of approximately 1 cm
wide x 4 cm long, which is >100 times larger than the average
volume of a biopsy sample

25. Transient elastography (TE):
shear wave elastometry
An automated movement of a piston, which is also
a disc-shaped ultrasound transducer, applies a
single cycle 50 Hz push to the body surface with
controlled applied force.
The transient shear deformation created in this
way, propagates into the tissue.
Its near constant speed for about 4 cm in the liver
(before being rendered non-detectable due to
attenuation) is measured by a straight line
automatically fitted to the displacement M-mode

26. Criteria for validation
(1) at least 10 valid measurements,
(2) ratio of number of valid
measurements to the total number of
measurements is ≥ 60%,
(3) interquartile range (IQR), which
reflects the variability of measurements,
is less than 30% of the median value of
liver stiffness measurements

27. Point shear wave elastography
ARFI is used to induce tissue displacement in the normal
direction in a single focal location, similar to ARFI strain
imaging. Unlike ARFI strain imaging, the tissue
displacement itself is not measured.
Instead, a portion of the longitudinal waves generated by
ARFI is intra-converted to shear waves through the
absorption of acoustic energy .
The speed of the shear waves perpendicular to the plane of
excitation cs are measured, which are either directly reported
or converted Young’s modulus E and reported to provide a
quantitative estimate of tissue elasticity .

28. Shear Wave Elastography(SWE)
It is based on the generation of a radiation force in the tissue to
create the shear wave. 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 captured by the very rapid acquisition of ultrasound
images (up to 20,000 images per second), called UltraFast
Imaging.

29. Shear Wave Elastography(SWE)
The acquisition takes only a few milliseconds, thus the patient or
operator movement does not impact the result. A high- speed
acquisition is necessary to capture the shear wave as it moves at
a speed in the order of 1 to 10 m/s.
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).

30. Shear Wave Elastography
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)
The ROI are variable in size (from 3 mm2
to 700 mm2
).
Measurements can be performed retrospectively from the
saved image or cineloop. The measurements provided are the
mean, standard deviation, and minimum and maximum
elastography values. Results are given in m/s or kPa

36. Pathophysiology
correlation

46. SW Elastography Study -KIMS

48. The main clinical indication for liver elastography is
staging of chronic liver disease
The main objective is determining the presence or
absence of advanced fibrosis
For the clinician, the most important question in a
patient with chronic liver disease is whether or not the
patient has cirrhosis

49. Best Practice for Performance of US-based
Elastography
Fasting for 4–6 hours
Specific positioning
Supine or slight (30°) left lateral decubitus position
Right arm elevated above the head Shallow breath hold
ROI placement in the right lobe of liver (typically segment VII or
VIII) about 2 cm beneath the Glisson capsule, perpendicular to
the liver capsuleROI placement to avoid large liver vessels
and/or bile ducts and rib shadows
Ten measurements obtained in the same location

56. MR Elastography

58. MR Elastographic Technique

59. MR Elastographic Technique
Mechanical shear waves used to determine liver
stiffness with MR elastography are created by a wave
generator located outside the MR imaging room .
60-Hz mechanical waves are most commonly used.
Mechanical waves are transmitted through a flexible
plastic tube to a passive driver.
The passive driver transmits acoustic pressure into the
abdominal wall and liver as shear waves. The passive
driver is placed directly over the liver on the upper
abdomen or lower chest and is held securely in place
with a soft elastic strap.

60. The most commonly used MR elastography sequence
is a two- dimensional gradient-echo sequence that
uses motion-encoding gradients . Four phase offsets
between the wave and the motion- encoding gradients
are used to obtain displacement information.
Tissue displacements on the order of nanometers or
micrometers are then measured with the MR
elastography sequence
Two sets of raw-data images that carry the
information about propagating shear waves: the
magnitude images and the phase images.
MR Elastographic Technique

61. MR Elastographic Technique
The magnitude images and the phase images are analyzed with
an automated “inversion algorithm,” which produces several
postprocessed images
The mechanical property measured with the inversion algorithm
is the “magnitude of the complex shear modulus.” This
measurement accounts for the properties of both tissue
elasticity and tissue viscosity.
Images produced with the inversion algorithm include (a) the
two-dimensional displacement map called the “wave image,”
and (b) a two-dimensional gray or color-coded map of liver
stiffness in units of kilopascals that is called an “elastogram “

62. MR Elastographic Technique
The 2D-GRE MRE sequence is performed at 60Hz
and 4 slices of 10mm thickness is prescribed over the
region of liver with the largest cross-section.
This is usually near the dome of the liver but the dome
should be avoided as there may be breath hold
artifacts.
The slices are obtained in expiration to ensure
reproducibility of the position of the liver.
Typical sequence parameters are as follows:
repetition time/echo time (TR/TE) = 50/18.4 to 26ms;
matrix = 256 ×64; band width = 33 KHz; flip angle of
30, 4 phase offsets and NEX=1

63. MR Elastographic Technique

65. Correlation between MR Elastographic
Stiffness and the Stage of Fibrosis
MR Elastographic
Stiffness (kPa)
Less than 2.5
2.5–2.9
2.9–3.5
4.0–5.0
Stage of Fibrosis
Normal
Normal or chronic inflammation
Stage 1–2
Stage 3–4
Normal liver stiffness is usually less than 2.5 kPa
most studies have reported normal liver stiffness within a range of 1.54 to 2.87kPa

66. MRE Accuracy
Multiple published studies have concluded that MRE has
a high diagnostic performance in detection and staging of
liver fibrosis.
MRE can differentiate normal livers from fibrotic livers
with an accuracy of ≥ 90% using a cut off of >2.4kPa
MRE can also detect liver fibrosis when anatomical
features of fibrosis and cirrhosis are absent .
The accuracy of MRE for detecting clinically significant
fibrosis and cirrhosis are >95% and 98% respectively
The high performance of MRE has been demonstrated in
chronic liver diseases of different etiologies.

67. Patient-related Factors
influencing Liver Stiffness
Patient-related Factor Effect on Tissue Stiffness

68. Patient-related Factors
influencing Liver Stiffness
Patient-related Factor Effect on Tissue Stiffness

71. THANKS
CITY CHAPTER IRIA
DR MADHU SASIDHARAN
DR RACHEL
DR HANAN
DR SURESH BABU
DR MADHAVAN UNNI
DR VENKATESH
DR MALINI
DR SEBASTIAN
DR SREERAJ