New Trends in Elasticity Imaging

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

Literatur

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