The assessment of tissue elasticity has gained significant interest in medicine due
to the availability of this technology in the clinical environment. Elasticity is
one of the most important physical parameters we experience from the very beginning
of our life. We explore each object by touching and squeezing it in order to estimate
its stiffness. As we already know, the more force we need in order to generate a certain
amount of deformation, the stiffer we say the material is. In medicine, elasticity
or stiffness is an important characteristic of tissues that has been linked not only
to malignancy but also to disease processes related to diffuse disorders.
Efforts to estimate tissue elasticity using ultrasound have been under development
for a few decades. Methods have progressed from simple M–mode data acquisition and
simple motion tracking to sophisticated 3D/4D systems with quantitative estimates
of elastic moduli on an absolute scale. Elasticity imaging methods combine some forms
of tissue excitation with methods for detection of tissue response. All ultrasound–based
elasticity estimation methods have the same principle consisting in acquiring a map
of tissue anatomy before and after some type of deformation. In conventional ultrasound
elastography, biologic structures are compressed slightly. Normally, <1% deformation
is recommended. Different methods of displacement and strain estimation have been
proposed using radio frequency ultrasound data pre– and post–compression, aiming to
improve the smoothness of strain field, speed up the calculation, increase the strain
image contrast and/or achieve robustness against de-correlation during compression.
However, few methods have been implemented in commercialized ultrasound machines for
real–time elasticity imaging.
Transient Elastography, is considered among the first clinical applications of elastography
in medicine. Fibroscan (Echosens, Paris, France) has been successfully used for liver
fibrosis assessment, being completely non–invasive. It uses an A–mode ultrasound with
a very high frame rate to monitor shear wave propagation generated by a vibration
source. A 5-MHz ultrasound transducer probe mounted on the axis of a vibrator is used.
The vibrator generates a completely painless vibration (with a frequency of 50 Hz
and amplitude of 2 mm) which produces an elastic share wave propagating through the
skin and the subcutaneous tissue to the liver [1]. Liver stiffness is compared to the fibrosis stage obtained by liver biopsy. The
wave propagation speed of the shear wave is used to calculate tissue modulus [2]. While it can provide a quantitative measure for the elasticity, the device cannot
provide a real–time B–mode image for localization and guiding. Thus, the operator
does not know the exact portion of liver being tested.
Instead, Real-Time Elastography (RTE) is an ultrasound imaging method that overlays
traditional B–mode imaging with a colored graphical representation of tissue elasticity.
Using strain ratio assessment, RTE provides additional information about a lesion’s
characteristics. RTE has been reported to be useful for the diagnosis and differentiation
of many tumors, which are usually harder than normal surrounding tissues, for e.g.
in assessing breast and thyroid cancer diagnosis (Fig. [1]), or in guiding minimally invasive treatment of prostate cancer [3], [4]. Recently, transabdominal RTE was proposed as a new method for non-invasive staging
of liver fibrosis (Fig. [2]) [5].
Fig. 1 Real-time elastography of (A) breast calcified fibroadenoma and malignant nodule
of thyroid gland (B)
Fig. 2 Real-time elastography of the liver: (A) fatty liver disease, (B) chronic viral
C hepatitis and (C) cirrhosis.
Furthermore, different solid tumors situated near the gastrointestinal tract might
be also visualized by endoscopic ultrasound (EUS) RTE and potentially characterized
by this technique. EUS elastography was already used in several studies for Fig. 2
Real-time elastography of the liver: (A) fatty liver disease, (B) chronic viral C
hepatitis and (C) cirrhosis. the characterization and differentiation of benign and
malignant lymph nodes, with variable sensitivity, specificity, and accuracy [6]. Furthermore, the value of EUS elastography was tested in focal pancreatic lesions
in large multicentric studies with good results (Fig. [3]).
Fig. 3 Endoscopic ultrasound real-time elastography of pancreatic cancer (A) and mediastinal
malignant lymph node (B).
Because of the inherent bias induced by selection of images from a dynamic sequence
of elastography, different authors reported on the utility of using computer-aided
diagnosis by averaging images from a dynamic sequence and calculating hue histograms,
as a better way to describe, semiquantitatively, elastography movies [7]. The new advances incorporated in newer ultrasound systems allow this analysis in
real-time, using the software of the device (Strain Histogram Measurement, Hitachi,
Japan) shortening in this way, the diagnosis timing and offering a quantitative assessment
of the structures.
Acoustic Radiation Force Impulse (ARFI) is a suitable technology for the evaluation
of deep tissues, not accessible by superficial compression elastography. Virtual Touch
Imaging software (Siemens, Europe) provides a qualitative gray scale map of relative
stiffness for a user defined region of interest. Using this method, stiff tissue may
be differentiated from soft tissue even if they appear isoechoic in conventional ultrasound
imaging. ARFI imaging technology involves the mechanical excitation of tissue using
short-duration acoustic pulses (push pulses) in a region of interest chosen by the
examiner, producing shear waves that spread away from the region of interest, perpendicularly
to the acoustic push pulse, generating localized, micron-scale displacements in the
tissue.
It provides accurate numerical measurements related to tissue stiffness at user-defined
anatomical locations [8]. ARFI technology quantifies stiffness without manual compression, the tissue being
compressed by acoustic energy. Furthermore, effective tumor localization and intra–procedural
monitoring are critical to treatment success during thermal ablation. ARFI imaging
showed great potential in determining the size and shape of the ablated area (protein
denaturation and water vaporization increase the tissue elastic modulus).
Magnetic Resonance Elastography (MRE), a non–invasive MR–based approach, is very well–suited
to obtain patient–specific biomechanical properties of tumoral tissue. It can directly
visualize and quantitatively measure propagating mechanical shear waves in biological
tissues. An important advantage of MRE is the possibility of measuring displacements
accurately in all three directions. The technique spatially maps and measures the
shear wave displacement patterns [9]. The wave images are processed to generate local quantitative values of shear modulus
of tissues in maps. It can provide relevant pre–operative information on the consistency
of the tumor and surrounding healthy tissue. MRE has recently been shown to be useful
for non-invasive assessment of liver fibrosis. Studies have demonstrated that MRE
can be used to differentiate normal liver from fibrotic liver with a very high degree
of accuracy. In other applications, MRE has been found to have promising results for
differentiating benign breast and brain lesions from malignant tumors.
The Supersonic Shear Imaging (SSI) technique is based on the radiation force induced
by a conventional ultrasonic probe to generate a planar shear wave deep into tissue.
The shear wave propagation throughout the medium is caught in real–time due to an
ultrafast ultrasound scanner (up to 5000 frames/s). Using modified sequences and post–processing,
this technique is implemented with curved arrays in order to get a larger field of
view of liver tissue. This real–time elasticity mapping using an ultrasonic curved
probe offers better signal–to–noise ratio than linear arrays and a larger area in
the patient‘s liver [10]. This gives more confidence about the accuracy of the diagnosis of the fibrosis
stage. Furthermore, the elasticity parameters obtained with SSI give access to the
shear wave group velocity and the phase velocity. As a consequence, the SSI assessment
of liver stiffness could potentially give more information on the viscoelasticity
properties of the liver.
In conclusion, elastography has become an efficient and easy-to-perform component
of the ultrasound examination with a rapidly increasing number of clinical applications.
New techniques, including 3D and 4D elastography, as well as fusion imaging, are currently
tested in research laboratories in order to discover the real potential of elasticity
imaging.
Dan Ionut Gheonea, Adrian Saftoiu
Research Center of Gastroenterology and Hepatology
University of Medicine and Pharmacy, Craiova, Romania