Robert M. Lerner

Imaging of the elastic properties of tissue--a review.

Recently, a number of methods have been developed that make it possible to image the elastic properties of soft tissues. Because certain types of tissues such as malignant lesions, for example, have elastic properties that are markedly different from surrounding tissues, elasticity imaging could provide a significant adjunct to current diagnostic ultrasonic methods. Further, elasticity imaging techniques could be used to augment the study of tissues that change their elastic properties, such as skeletal and cardiac muscle. In this paper, we survey some of the previous work done in the related field of biomechanics, and we review measurement techniques from the 1950s to the 1980s. Different approaches to elastic imaging and signal processing are then discussed and a lexicography for elastic imaging is introduced. It is hoped that this nomenclature will provide a meaningful categorization of various approaches and will make evident the inherent parameters displayed and conditions applied in deriving the resulting images. Key assumptions and signal processing approaches are also reviewed. Finally, directions for future work are suggested.

Sono-Elasticity: Medical Elasticity Images Derived from Ultrasound Signals in Mechanically Vibrated Targets

Cancers of the prostate have traditionally been detected by digital palpation which identifies increased stiffness (modulus of elasticity, hardness) of the abnormal tissue. Gray-scale ultrasound is insensitive to stiffness as an imaging parameter and often fails to reveal the extent or existence of a prostate cancer. Recent developments in technology and understanding have improved the diagnostic efficacy of transrectal ultrasound for detection of early prostate cancer, but even when coupled with digital rectal examination, a significant percentage of existing carcinomas may not be recognized. This statement is based on the lower detection rates for transrectal ultrasound and digital rectal examination in screening populations (0.1-4%) as compared to autopsy series prevalance rates of approximately 30%. Recent reports suggest that early cancers of the prostate may be characterized as hypoechoic areas in the peripheral zone of the prostate (1). Others suggest that the more advanced lesions have varied appearances ranging from hypo to hyperechoic with some even showing combinations of both (2,3). Our transrectal ultrasound experience from patients with palpable cancers (which include moderately to advanced disease), suggests a varied non-specific gray-scale appearance as well, despite the uniform impression that they are all firm on digital palpation.

Sonoelasticity of organs: shear waves ring a bell.

Sonoelasticity is the use of ultrasonography to visualize, in real time, the hardness of stiffness of tissues and organs by depicting the tissues motion in response to an applied vibration source. The applied vibration source is usually of low amplitude and low frequency (less than 0.1 mm displacement and less than 2000 Hz). Under these conditions, the natural vibration response of tissues and whole organs is revealed as a standing wave pattern determined by the low‐frequency elastic constants of the tissues and their boundary conditions, factors that are not related to the ultrasonic echogenicity. As a result, hard or dense isoechoic tumors that are undetectable by conventional ultrasonography often can be visualized in sonoelasticity imaging by virtue of their altered vibration response. In this report, we demonstrate the appearance of organs such as the breast, liver, and kidney during real‐time, in vivo sonoelasticity imaging. The results show that the shape and location of vibration patterns are dependent on the tissues and vibration frequencies; thus, information about the basic elastic properties of tissues should be obtainable.

Sonoelasticity imaging: Theory and experimental verification

Sonoelasticity is a rapidly evolving medical imaging technique for visualizing hard tumors in tissues. In this novel diagnostic technique, a low-frequency vibration is externally applied to excite internal vibrations within the tissue under inspection. A small stiff inhomogeneity in a surrounding tissue appears as a disturbance in the normal vibration eigenmode pattern. By employing a properly designed Doppler detection algorithm, a real-time vibration image can be made. A theory for vibrations, or shear wave propagation in inhomogeneous tissue has been developed. A tumor is modeled as an elastic inhomogeneity inside a lossy homogeneous elastic medium. A vibration source is applied at a boundary. The solutions for the shear wave equation have been found both for the cases with tumor (inhomogeneous case) and without tumor (homogeneous case). The solutions take into account varying parameters such as tumor size, tumor stiffness, shape of vibration source, lossy factor of the material, and vibration frequency. The problem of the lowest detectable change in stiffness is addressed using the theory, answering one of the most critical questions in this diagnostic technique. Some experiments were conducted to check the validity of the theory, and the results showed a good correspondence to the theoretical predictions. These studies provide basic understanding of the phenomena observed in the growing field of clinical Sonoelasticity imaging for tumor detection.

In-vivo measurements of ultrasound attenuation in normal or diseased liver

Ultrasonic attenuation coefficients of liver have been derived from echoes received by a modified commercial B-scan imaging instrument. Values have been measured from selected regions within liver scans of 59 individuals, of which 15 cases were presumed normal (based on medical histories), and the remainder were involved with diffuse liver disease such as alcoholic cirrhosis, chemotherapy toxicity, chronic hepatitis, and liver metastases. Medical histories on most individuals include the results of serum liver function enzymes, conventional B-scan examinations, and exposure to drugs and alcohol. The results of CT abdominal scans (N = 13) and/or liver biopsy (N = 12) were also available. The results show that normal attenuation values for human liver are 0.054 +/- 0.009 Np/cm-MHz (0.47 dB/cm-MHz) with a frequency dependence of fn, where n = 1.05 +/- 0.25, in agreement with in vitro studies of mammalian liver. In diffuse liver disease, no relationship was found between the attenuation coefficient and the results of CT or conventional ultrasonic examination. A trend towards higher attenuation with increased fibrosis and fat, as graded from liver biopsies, was noted, but the results were generally not statistically significant. However, a significant correlation was found between high values of attenuation and abnormal liver function tests. High attenuation is also found with ingestion of alcohol, chemotherapeutic agents, and steroids, all of which may affect liver composition.

On estimating the amplitude of harmonic vibration from the Doppler spectrum of reflected signals

The Doppler spectrum of echoes from a sinusoidally vibrating scatterer has discrete spectral lines weighted by Bessel functions of the first kind. Because the signal and spectrum are complicated functions of the vibration amplitude, a number of different approaches have been tried in the past to estimate the vibration amplitude, given a received signal. Here, a new and simple relationship between the spread (or variance) of the Doppler spectrum and the vibration amplitude is derived. A method of estimating the vibration amplitude is proposed based on this relation and a noise compensation procedure is also demonstrated. The performance of the estimators is studied through simulations. High accuracy is predicted under proper sampling conditions even when the signal‐to‐noise ratio is poor. Slight deviations from single‐frequency oscillation, as would be caused by nonlinear or nonideal medium or source effects, are found to have little contribution to the total estimation error.

A particulate contrast agent with potential for ultrasound imaging of liver

Ultrasonic backscatter and attenuation coefficients of a medium can be increased by the addition of solid, micron sized inhomogeneities. A potentially useful agent for ultrasonic contrast of liver images has been identified. Iodipamide ethyl ester (IDE) particles can be produced in the form of dense, relatively incompressible solids with high impedance mismatch to water. The chemical, biomechanical, and pharmacological properties of the small, uniform diameter IDE particles permit safe intravenous injection followed by rapid accumulation by reticuloendothelial (RE) cells of the liver and spleen, and later elimination from these organs. Since the particles are phagocytized by RE cells, present in normal liver but not in tumors and many lesions, the selective enhancement of ultrasonic backscatter should improve detectability of lesions which are hypo- or iso-echoic compared to surrounding tissue. The mechanisms of particle-ultrasound interaction may be described by relative motion attenuation, and scattering from a cloud of dense, incompressible spheres for the case of IDE particles in agar. Thus, values of attenuation and backscatter can be controlled by choice of ultrasound frequency and particle concentration and size. When the particles are accumulated in rat livers, additional mechanisms induce attenuation and backscatter in excess of that predicted by IDE in agar. This preliminary work demonstrates that solid, biocompatible particles may be useful as an ultrasonic contrast agent.

Elastography in the management of liver disease.

Normal liver tissue is soft and pliable. With inflammation, however, many of the cells die and are replaced by collagenous fibrils and the tissue gets stiffer. The progress is often slow-extending over decades in many cases. When liver stiffness increases by a factor of about five, the condition is called cirrhosis, a disease with serious medical implications. After the onset of cirrhosis, the probability of developing hepatic cancer increases at the rate of about 5% per year. Precise, noninvasive measurement of liver stiffness, a simple application of elastography, promises to be a safe, inexpensive method to monitor the progress of liver patients, improve outcome, save many lives and much suffering and reduce the cost of medical care.

Time domain Doppler estimators of the amplitude of vibrating targets

Five basic algorithms using time domain techniques are described in this paper to estimate the amplitude and frequency of relatively low‐frequency vibration of a target that is interrogated with a relatively high‐frequency wave. The estimations are based on the Doppler shift generated by the vibrating target, which produces a frequency modulated echo. All algorithms presented here use only a small fraction of the low‐frequency vibration cycle to obtain the estimated parameters; therefore, real‐time imaging of vibration can be made in many applications. The described algorithms complement each other to cover a wide range of the estimated parameters and different sampling, scanning, and imaging criteria. Simulations show that these time domain algorithms have good noise performance and low sensitivity to nonlinearities of the vibration that may be present in nonideal conditions.

Color doppler ultrasound compared to a radionuclide scanning of spermatic cord torsion in a canine model

High resolution color doppler ultrasound can simultaneously display blood flow superimposed on detailed gray scale anatomic images. Using a single-blind study design, nine adult male dogs underwent intravaginal spermatic cord torsion and subsequent evaluation with technetium 99M-pertechnetate radionuclide, and color doppler ultrasound imaging techniques. Torsions of 90 to 720 degrees were created surgically, followed by examination with each modality at one hour (four animals), and four hours (five animals) following the procedure. Testicular torsion was diagnosed if perfusion was absent or markedly diminished on color doppler imaging or radionuclide scan. In all cases of 360 degrees or greater, torsion was diagnosed by either modality at both one and four hour time delays. If observers did not diagnose torsion, they were asked to assess the relative testicular perfusion. Color doppler ultrasound and radionuclide scanning were without error in correctly detecting a relative decrease in perfusion in each of these instances. Furthermore, color doppler imaging with spectral analysis was able to detect an enhancement of the diastolic component of the arterial signal at 180 degrees of torsion. This spectral pattern coupled with a relative decrease in blood flow allowed presumptive diagnosis at one hour of partial torsion that was subsequently apparent as absent perfusion only after 4 hours on radionuclide and repeat color doppler ultrasound. Color doppler ultrasound proved to be superior to radionuclide scanning in detecting diminished perfusion in this experiment. The detailed information provided by spectral and anatomic display with color doppler ultrasound recommends it for the evaluation of acute scrotal pathology of uncertain etiology.