Jonathan M. Rubin

Elastography Assessment of Liver Fibrosis: Society of Radiologists in Ultrasound Consensus Conference Statement

The Society of Radiologists in Ultrasound convened a panel of specialists from radiology, hepatology, pathology, and basic science and physics to arrive at a consensus regarding the use of elastography in the assessment of liver fibrosis in chronic liver disease. The panel met in Denver, Colo, on October 21-22, 2014, and drafted this consensus statement. The recommendations in this statement are based on analysis of current literature and common practice strategies and are thought to represent a reasonable approach to the noninvasive assessment of diffuse liver fibrosis.

Doppler ultrasound color flow imaging in the study of breast cancer: Preliminary findings

A prospective study of the Doppler color flow features of 55 proved breast cancers was performed. On a three-level scale of low to marked vascularity, visual assessment of the color flow images classified 82% of the cancers as moderately or markedly vascular (minimal: 14%, moderate: 29%, marked: 53%). Four percent of the cancers had no detectable flow. In 29 women, a volume of tissue comparable to the cancer was scanned in the contralateral normal breast. Sixty-nine percent of the normal breasts had moderate or marked vascularity (minimal: 28%, moderate: 41%, marked: 28%), and 3% were avascular. There was poor distinction between normal tissues and cancer which suggests that more sensitive Doppler methods than were employed in this study may be needed in order to detect the small vessel flow reported to be rather specific for malignancy. The high, 82%, detection rate of tumor vessels in this study suggests the potential use of color flow Doppler for directing more specific but lengthy Doppler procedures.

3-D Correlation-Based Speckle Tracking

Widely-used 1-D/2-D speckle tracking techniques in elasticity imaging often experience significant speckle decorrelation in applications involving large elevational motion (i.e., out of plane motion). The problem is more pronounced for cardiac strain rate imaging (SRI) since it is very difficult to confine cardiac motion to a single image plane. Here, we present a 3-D correlation-based speckle tracking algorithm. Conceptually, 3-D speckle tracking is just an extension of 2-D phase-sensitive correlation-based speckle tracking. However, due to its high computational cost, optimization schemes, such as dynamic programming, decimation and two-path processing, are introduced to reduce the computational burden. To evaluate the proposed approach, a 3-D bar phantom under uniaxial compression was simulated for benchmark tests. A more sophisticated 3-D simulation of the left ventricle of the heart was also made to test the applicability of 3-D speckle tracking in cardiac SRI. Results from both simulations clearly demonstrated the feasibility of 3-D correlation-based speckle tracking. With the ability to follow 3-D speckle in 3-D space, 3-D speckle tracking outperforms lower-dimensional speckle tracking by minimizing decorrelation caused by pure elevational translation. In other words, 3-D tracking can push toward solely deformation-limited, decorrelation-optimized speckle tracking. Hardware implementation of the proposed 3-D speckle tracking algorithm using field programmable gate arrays (FPGA) is also discussed.

Methods for evaluating cardiac wall motion in three dimensions using bifurcation points of the coronary arterial tree.

An accurate three-dimensional (3D) representation of heart wall motion would be an important means of evaluating cardiac function. To accomplish this, we have developed an interactive computer graphics system designed to enter the time-dependent 3D positions of bifurcations of the coronary arterial tree. These bifurcations are precise markers of the epicardial surface, and their motions accurately represent the motion of the underlying heart wall. We demonstrate techniques for calculating local wall motion, including displacement and velocity, for determining a time-dependent center-of-contraction point towards which the epicardium tends to move and for tracking the mechanical contraction wave using cross-correlation methods. We have applied these techniques to study seven patients with normal left ventriculograms and coronary arteriograms. We have found these methods to be generally applicable and to provide information not obtainable without 3D analysis.

Graphics methods for tracking three-dimensional heart wall motion

Abstract An analysis of heart wall motion requires that specific points on the wall be identified and their movements tracked in three dimensions over several heart beats. A method to reconstruct time-dependent 3D coordinates from any two or more perspective views has been developed. We have used this method to determine accurately the 3D dynamics of bifurcation points of the coronary arteries or surgically implanted markers by tracking their projections in both views of a biplane coronary cineangiogram. The tracking operation is aided by a sophisticated interactive computer system which superimposes an animated graphics display onto the film image. This allows entries to be checked and corrected immediately. The most powerful tool provided by the graphics system is the ability to display the backprojections of positions from one view as auxiliary lines across the other view on which the projection of the point of interest must lie. We provide some examples of cardiac wall motion measures we have made using this system.

Ultrasound Elasticity Imaging for Detecting Intestinal Fibrosis and Inflammation in Rats and Humans With Crohn's Disease

BACKGROUND Intestinal fibrosis causes many complications of Crohns disease (CD). Available biomarkers and imaging modalities lack sufficient accuracy to distinguish intestinal inflammation from fibrosis. Transcutaneous ultrasound elasticity imaging (UEI) is a promising, noninvasive approach for measuring tissue mechanical properties. We hypothesized that UEI could differentiate inflammatory from fibrotic bowel wall changes in both animal models of colitis and humans with CD. METHODS Female Lewis rats underwent weekly trinitrobenzene sulfonic acid enemas yielding models of acute inflammatory colitis (n = 5) and chronic intestinal fibrosis (n = 6). UEI scanning used a novel speckle-tracking algorithm to estimate tissue strain. Resected bowel segments were evaluated for evidence of inflammation and fibrosis. Seven consecutive patients with stenotic CD were studied with UEI and their resected stenotic and normal bowel segments were evaluated by ex vivo elastometry and histopathology. RESULTS Transcutaneous UEI normalized strain was able to differentiate acutely inflamed (-2.07) versus chronic fibrotic (-1.10) colon in rat models of inflammatory bowel disease (IBD; P = .037). Transcutaneous UEI normalized strain also differentiated stenotic (-0.87) versus adjacent normal small bowel (-1.99) in human CD (P = .0008), and this measurement also correlated well with ex vivo elastometry (r = -0.81). CONCLUSIONS UEI can differentiate inflammatory from fibrotic intestine in rat models of IBD and can differentiate between fibrotic and unaffected intestine in a pilot study in humans with CD. UEI represents a novel technology with potential to become a new objective measure of progression of intestinal fibrosis. Prospective clinical studies in CD are needed.

Registration of three-dimensional compound ultrasound scans of the breast for refraction and motion correction

Use of multiple look directions, that is, compound imaging, has been shown previously to increase detection of specular reflectors and averaging of speckle noise in gray-scale images, often at the expense of spatial resolution and other misregistration errors. In color flow imaging, additional view angles can fill in vessels missed due to Doppler angle dropout and increase quantitative and visual Doppler accuracy by triangulation or a simple peak-frequency-shift combination algorithm. Image registration and unwarping throughout multiple three-dimensional (3D) volume sets should correct for many refraction artifacts, motion between and during compounded image sets and even, possibly, positioning errors between image sets, acquired months apart, to display growth of abnormalities. The registration described here does not provide sufficient accuracy for formation of enhanced coherent apertures, but shows promise in some cases to provide superior compound images and possibly comparisons of current and prior studies. In this study, the breast is stabilized by mild compression between a flat plate and a scanning membrane. Registration and unwarping is performed retrospectively on two separate volumetric data sets by defining pairs of corresponding points and, in some cases, line and plane segments. Three-dimensional linear affine transforms are performed using identified points, lines and planes. 3D nonlinear warped transforms are also possible given adequate numbers of identifiable points. More than two data sets are registered by selecting one as the standard, and registering the remainder to match. The most appropriate algorithm, such as averaging or maximum amplitude, may be used to combine the data sets for display. Significant success has been achieved in compound display of a test object and of the breast in vivo, even when there was relative motion or warping between image sets. In pulse-echo imaging, homologous feature registration for compounding appears to have advantages over mechanically registered compounding methods previously employed in the breast and significant increases in lesion and structural conspicuity are noted due to a reduction in speckle noise. The improvements from compounding in 3D, surface-rendered Doppler imaging of vasculature are striking.

Determination of scan-plane motion using speckle decorrelation: Theoretical considerations and initial test

The correlation function of the echo signal intensities at a fixed region on a series of B‐mode images is directly related to the change of speckle patterns between these images. An indication is given here of how the rate of the change of that correlation function can be used to estimate the scan‐plane motion in any direction relative to the imaged tissue or other material. In this first implementation it is assumed that the statistical properties of the echo signals follow those of a complex circular Gaussian, and the case is considered of diffusely scattering tissue with many fine particles per resolution cell and with no phase distortion. The method is applied to data from a one‐dimensional linear array and initial results are presented for scanning a tissue‐mimicking phantom in the elevational direction of the transducer. Experimental results are in good agreement with the predictions. The current method should provide a good indication of the local rate of scan‐head motion in those tissues in which the normalized correlation function of the echo signal intensities behaves, or can be made to behave, as it would for a medium with uniform acoustic properties and containing many, randomly distributed, pointlike scatterers, although application might be made to other situations where a deterministic condition exists for the correlation between images taken at differing locations within a volume.

Quantitative assessment of cartilage surface roughness in osteoarthritis using high frequency ultrasound

Osteoarthritis (OA) is a common disease which affects nearly 50% of people over age 60. Histologic evaluation suggests that fibrillations approximately 20-150 microns are among the earliest changes in the articular cartilage. We propose a technique to quantify these surface fibrillatory changes in osteoarthritic articular cartilage by considering the angular distribution of the envelope-detected backscattered pressure field from an incident 30-MHz focused transducer. The angular distribution of the scattered acoustic field from an inosonifying source will directly relate to the distribution of surface fibrillatory changes. Data are presented for three different grades (400, 500 and 600 grit) of commercially available emory paper and three samples of osteoarthritic femoral head articular cartilage, which were visually assessed as having smooth, intermediate and rough surfaces, respectively. Our preliminary results indicate a probable monotonic relationship between articular cartilage roughening and the degree of broadening in the angle-dependent pressure amplitude. When applied to the emory paper, the technique indicates sensitivity to differences as small as approximately 5-10 microns in mean roughness. This procedure may provide an extremely sensitive and reproducible means of quantifying and following the cartilage changes observed in early osteoarthritis.

Noninvasive Ultrasound Elasticity Imaging (UEI) of Crohn's Disease: Animal Model

Inflammation occurs in episodic flares in Crohns disease, which are part of the waxing and waning course of the disease. Healing between flares allows the intestine to reconstitute its epithelium, but this healing results in the deposition of fibrotic scar tissue as part of the healing process. Repeated cycles of flares and healing often lead to clinically significant fibrosis and stenosis of the intestine. Patients are treated empirically with steroids, with their many side effects, in the hope that they will respond. Many patients would be better treated with surgery if we could identify which patients truly have intestinal fibrosis. Ultrasound elasticity imaging (UEI) offers the potential to radically improve the diagnosis and management of local tissue elastic property, particularly intestinal fibrosis. This method allows complete characterization of local intestine tissue with high spatial resolution. The feasibility of UEI on Crohns disease is demonstrated by directly applying this technique to an animal model of inflammatory bowel disease (IBD). Five female Lewis rats (150-180g) were prepared with phosphate buffered solution (PBS) as a control group and six were prepared with repeated intrarectal administration of trinitrobenzenesulfonic acid (TNBS) as a disease group. Preliminary strain measurements differentiate the diseased colons from the normal colons (p < 0.0002) and compared well with direct mechanical measurements and histology (p < 0.0005). UEI provides a simple and accurate assessment of local severity of fibrosis. The preliminary results on an animal model also suggest the feasibility of translating this imaging technique directly to human subjects for both diagnosis and monitoring.