Further characterization of changes in axial strain elastograms due to the presence of slippery tumor boundaries.

Elastography measures tissue strain, which can be interpreted under certain simplifying assumptions to be representative of the underlying stiffness distribution. This is useful in cancer diagnosis where tumors tend to have a different stiffness to healthy tissue and has also shown potential to provide indication of the degree of bonding at tumor-tissue boundaries, which is clinically useful because of its dependence on tumor pathology. We consider the changes in axial strain for the case of a symmetrical model undergoing uniaxial compression, studied by characterizing changes in tumor contrast transfer efficiency (CTE), inclusion to background strain contrast and strain contrast generated by slip motion, as a function of Young's modulus contrast and applied strain. We present results from a finite element simulation and an evaluation of these results using tissue-mimicking phantoms. The simulation results show that a discontinuity in displacement data at the tumor boundary, caused by the surrounding tissue slipping past the tumor, creates a halo of "pseudostrain" across the tumor boundary. Mobile tumors also appear stiffer on elastograms than adhered tumors, to the extent that tumors that have the same Young's modulus as the background may in fact be visible as low-strain regions, or those that are softer than the background may appear to be stiffer than the background. Tumor mobility also causes characteristic strain heterogeneity within the tumor, which exhibits low strain close to the slippery boundary and increasing strain toward the center of the tumor. These results were reproduced in phantom experiments. In addition, phantom experiments demonstrated that when fluid lubrication is present at the boundary, these effects become applied strain-dependent as well as modulus-dependent, in a systematic and characteristic manner. The knowledge generated by this study is expected to aid interpretation of clinical strain elastograms by helping to avoid misinterpretation as well as provide additional diagnostic criteria stated in the paper and stimulate further research into the application of elastography to tumor mobility assessment.

Ultrasound Shear Wave Elastography of the Normal Prostate: Interobserver Reproducibility and Comparison with Functional Magnetic Resonance Tissue Characteristics.

The purpose of this study was to establish interobserver reproducibility of Young's modulus (YM) derived from ultrasound shear wave elastography (US-SWE) in the normal prostate and correlate it with multiparametric magnetic resonance imaging (mpMRI) tissue characteristics. Twenty men being screened for prostate cancer underwent same-day US-SWE (10 done by two blinded, newly-trained observers) and mpMRI followed by 12-core biopsy. Bland-Altman plots established limits of agreement for YM. Quantitative data from the peripheral zone (PZ) and the transitional zone (TZ) for YM, apparent diffusion coefficient (ADC, mm2/s from diffusion-weighted MRI), and Ktrans (volume transfer coefficient, min-1), Ve (extravascular-extracellular space, %), Kep (rate constant, /min), and initial area under the gadolinium concentration curve (IAUGC60, mmol/L/s) from dynamic contrast-enhanced MRI were obtained for slice-matched prostate sextants. Interobserver intraclass correlation coefficients were fair to good for individual regions (PZ = 0.57, TZ = 0.65) and for whole gland 0.67, (increasing to 0.81 when corrected for systematic observer bias). In the PZ, there were weak negative correlations between YM and ADC ( p = 0.008), and Ve ( p = 0.01) and a weak positive correlation with Kep ( p = 0.003). No significant intermodality correlations were seen in the TZ. Transrectal prostate US-SWE done without controlling manually applied probe pressure has fair/good interobserver reproducibility in inexperienced observers with potential to improve this to excellent by standardization of probe contact pressure. Within the PZ, increase in tissue stiffness is associated with reduced extracellular water (decreased ADC) and space (reduced Ve).

Multi-Channel Optical Coherence Elastography Using Relative and Absolute Shear-Wave Time of Flight.

Elastography, the imaging of elastic properties of soft tissues, is well developed for macroscopic clinical imaging of soft tissues and can provide useful information about various pathological processes which is complementary to that provided by the original modality. Scaling down of this technique should ply the field of cellular biology with valuable information with regard to elastic properties of cells and their environment. This paper evaluates the potential to develop such a tool by modifying a commercial optical coherence tomography (OCT) device to measure the speed of shear waves propagating in a three-dimensional (3D) medium. A needle, embedded in the gel, was excited to vibrate along its long axis and the displacement as a function of time and distance from the needle associated with the resulting shear waves was detected using four M-mode images acquired simultaneously using a commercial four-channel swept-source OCT system. Shear-wave time of arrival (TOA) was detected by tracking the axial OCT-speckle motion using cross-correlation methods. Shear-wave speed was then calculated from inter-channel differences of TOA for a single burst (the relative TOA method) and compared with the shear-wave speed determined from positional differences of TOA for a single channel over multiple bursts (the absolute TOA method). For homogeneous gels the relative method provided shear-wave speed with acceptable precision and accuracy when judged against the expected linear dependence of shear modulus on gelatine concentration (R2 = 0.95) and ultimate resolution capabilities limited by 184µm inter-channel distance. This overall approach shows promise for its eventual provision as a research tool in cancer cell biology. Further work is required to optimize parameters such as vibration frequency, burst length and amplitude, and to assess the lateral and axial resolutions of this type of device as well as to create 3D elastograms.

Ultrasound Tomography Evaluation of Breast Density: A Comparison With Noncontrast Magnetic Resonance Imaging.

OBJECTIVES: Ultrasound tomography (UST) is an emerging whole-breast 3-dimensional imaging technique that obtains quantitative tomograms of speed of sound of the entire breast. The imaged parameter is the speed of sound which is used as a surrogate measure of density at each voxel and holds promise as a method to evaluate breast density without ionizing radiation. This study evaluated the technique of UST and compared whole-breast volume averaged speed of sound (VASS) with MR percent water content from noncontrast magnetic resonance imaging (MRI). MATERIALS AND METHODS: Forty-three healthy female volunteers (median age, 40 years; range, 29-59 years) underwent bilateral breast UST and MRI using a 2-point Dixon technique. Reproducibility of VASS was evaluated using Bland-Altman analysis. Volume averaged speed of sound and MR percent water were evaluated and compared using Pearson correlation coefficient. RESULTS: The mean ± standard deviation VASS measurement was 1463 ± 29 m s (range, 1434-1542 m s). There was high similarity between right (1464 ± 30 m s) and left (1462 ± 28 m s) breasts (P = 0.113) (intraclass correlation coefficient, 0.98). Mean MR percent water content was 35.7% ± 14.7% (range, 13.2%-75.3%), with small but significant differences between right and left breasts (36.3% ± 14.9% and 35.1% ± 14.7%, respectively; P = 0.004). There was a very strong correlation between VASS and MR percent water density (r = 0.96, P < 0.0001). CONCLUSIONS: Ultrasound tomography holds promise as a reliable and reproducible 3-dimensional technique to provide a surrogate measure of breast density and correlates strongly with MR percent water content.

In Vivo response to compression of 35 breast lesions observed with a two-dimensional locally regularized strain estimation method.

The objective of this study was to assess the in vivo performance of our 2-D locally regularized strain estimation method with 35 breast lesions, mainly cysts, fibroadenomas and carcinomas. The specific 2-D deformation model used, as well as the method's adaptability, led to an algorithm that is able to track tissue motion from radiofrequency ultrasound images acquired in clinical conditions. Particular attention was paid to strain estimation reliability, implying analysis of the mean normalized correlation coefficient maps. For all lesions examined, the results indicated that strain image interpretation, as well as its comparison with B-mode data, should take into account the information provided by the mean normalized correlation coefficient map. Different trends were observed in the tissue response to compression. In particular, carcinomas appeared larger in strain images than in B-mode images, resulting in a mean strain/B-mode lesion area ratio of 2.59 ± 1.36. In comparison, the same ratio was assessed as 1.04 ± 0.26 for fibroadenomas. These results are in agreement with those of previous studies, and confirm the interest of a more thorough consideration of size difference as one parameter discriminating between malignant and benign lesions.

On the potential of ultrasound elastography for pressure ulcer early detection.

PURPOSE: Pressure ulcers are areas of soft tissue breakdown induced by a sustained mechanical stress that damages the skin and underlying tissues. They represent a considerable burden to the society in terms of health care and cost. Yet, techniques for prevention and detection of pressure ulcers still remain very limited. In this article, the authors investigated the potential of ultrasound elastography for pressure ulcer early detection. Elastography is an imaging technique providing local information on biological tissue mechanical properties. It is relevant for pressure ulcer detection as this pathology is associated with a gradual stiffening of damaged tissues, beginning in the deeper tissues and progressing toward the skin surface. METHODS: A 2D ultrasound elastography method was proposed and its ability in terms of pressure ulcer detection was validated through numerical simulations and physical acquisitions on pressure ulcer mimicking phantoms. In vivo experiments on a rat model are also reported. A maintained pressure was applied on the animal thigh, with a view to generate a pressure ulcer, and ultrasound data were acquired and processed before and after application of this pressure. RESULTS: Numerical simulations demonstrated that a pressure ulcer can theoretically be detected at a very early stage with ultrasound elastography. Even when the ulcer region was characterized by a low stiffening (ratio of 1.8 relative to normal tissues), the corresponding elastogram clearly underlined the pathological area. This observation was confirmed by the results obtained on a physical phantom mimicking a pressure ulcer at an early stage. Computed elastograms showed strain differences between areas mimicking healthy and pathological tissues. Results corresponding to in vivo experiments revealed a difference in the way tissues behaved before and after the pressure was applied on the animal thigh, which strongly suggests the presence of a pathological area. CONCLUSIONS: Experiments demonstrated that ultrasound elastography is a promising technique for pressure ulcer detection, especially at an early stage of the pathology, when the disease is still visually undetectable. In the absence of any gold standard method, this is also a first step toward the development of a quantitative technique.

A compensative model for the angle-dependence of motion estimates in noninvasive vascular elastography.

PURPOSE: Atherosclerosis of peripheral cerebral arteries can lead to stroke either by stenosis formation or plaque rupture. This pathology is initiated by the alteration of arterial wall mechanical properties shown to be assessable by ultrasound elastography. Recently, noninvasive vascular elastography (NIVE) was introduced for noninvasive imaging of the mechanical properties of superficial arteries as markers of vulnerable plaques. However, NIVE motion estimates are angle-dependent, with optimal scanning angle being represented by the alignment of tissue motion with ultrasound beam orientation. The objective of this study was to introduce a model that compensates for such angle-dependence in order to reduce the bias on strain estimates, namely, when investigating longitudinal vessel segments. METHODS: The model is based on the Lagrangian speckle model estimator (LSME) because the LSME assesses the 2D-deformation matrix required to compute the scanning angle. RESULTS: Experiments on vessel-mimicking phantoms indicated that such a model enables the estimation of scanning angle with less than 3-degrees error. The method was also validated in vivo in human carotid arteries where less than 4-degrees error was observed. In both cases, the compensative model estimated the inclination angles with low variability. CONCLUSION: Angle-dependence may be an important factor to consider in avoiding potentially distort clinical diagnoses. Results, reported in this article, suggest that the LSME-based compensative model might be considered as a very interesting and promising clinical tool for NIVE applications.

A new method for the acquisition of ultrasonic strain image volumes.

This article presents a new method for acquiring three-dimensional (3-D) volumes of ultrasonic axial strain data. The method uses a mechanically-swept probe to sweep out a single volume while applying a continuously varying axial compression. Acquisition of a volume takes 15-20 s. A strain volume is then calculated by comparing frame pairs throughout the sequence. The method uses strain quality estimates to automatically pick out high quality frame pairs, and so does not require careful control of the axial compression. In a series of in vitro and in vivo experiments, we quantify the image quality of the new method and also assess its ease of use. Results are compared with those for the current best alternative, which calculates strain between two complete volumes. The volume pair approach can produce high quality data, but skillful scanning is required to acquire two volumes with appropriate relative strain. In the new method, the automatic quality-weighted selection of image pairs overcomes this difficulty and the method produces superior quality images with a relatively relaxed scanning technique.

Noninvasive vascular ultrasound elastography applied to the characterization of experimental aneurysms and follow-up after endovascular repair.

Experimental and simulation studies were conducted to noninvasively characterize abdominal aneurysms with ultrasound (US) elastography before and after endovascular treatment. Twenty three dogs having bilateral aneurysms surgically created on iliac arteries with venous patches were investigated. In a first set of experiments, the feasibility of elastography to differentiate vascular wall elastic properties between the aneurismal neck (healthy region) and the venous patch (pathological region) was evaluated on six dogs. Lower strain values were found in venous patches (p < 0.001). In a second set of experiments, 17 dogs having endovascular repair (EVAR) by stent graft (SG) insertion were examined three months after SG implantation. Angiography, color Doppler US, examination of macroscopic sections and US elastography were used. The value of elastography was validated with the following end points by considering a solid thrombus of a healed aneurysm as a structure with small deformations and a soft thrombus associated with endoleaks as a more deformable tissue: (1) the correlation between the size of healed organized thrombi estimated by elastography and by macroscopic examinations; (2) the correlation between the strain amplitude measured within vessel wall elastograms and the leak size; and (3) agreement on the presence and size of endoleaks as determined by elastography and by combined reference imaging modalities (angiography + Doppler US). Mean surfaces of solid thrombi estimated with elastography were found correlated with those measured on macroscopic sections (r = 0.88, p < 0.001). Quantitative strain values measured within the vessel wall were poorly linked with the leak size (r = 0.12, p = 0.5). However, the qualitative evaluation of leak size in the aneurismal sac was very good, with a Kappa agreement coefficient of 0.79 between elastography and combined reference imaging modalities. In summary, complementing B-scan and color Doppler, noninvasive US elastography was found to be potentially a relevant tool for aneurismal follow-up after EVAR, provided it allows geometrical and mechanical characterizations of the solid thrombus within the aneurismal sac. This elasticity imaging technique might help detecting potential complications during follows-up subsequent to EVAR.

Characterization of atherosclerotic plaques and mural thrombi with intravascular ultrasound elastography: a potential method evaluated in an aortic rabbit model and a human coronary artery.

Plaque rupture is correlated with the plaque morphology, composition, mechanical properties, and with the blood pressure. Whereas the geometry can accurately be assessed with intravascular ultrasound (IVUS) imaging, intravascular elastography (IVE) is capable of extracting information on the plaque local mechanical properties and composition. This paper reports additional IVE validation data regarding reproducibility and potential to characterize atherosclerotic plaques and mural thrombi. In a first investigation, radio frequency (RF) data were acquired from the abdominal aorta of an atherosclerotic rabbit model. In a second investigation, IVUS RF data were recorded from the left coronary artery of a patient referred for angioplasty. In both cases, Galaxy IVUS scanners (Boston Scientific, Freemont, CA), equipped with 40 MHz Atlantis catheters, were used. Elastograms were computed using two methods, the Lagrangian speckle model estimator (LSME) and the scaling factor estimator (SFE). Corroborated with histology, the LSME and the SFE both clearly detected a soft thrombus attached to the vascular wall. Moreover, shear elastograms, only available with the LSME, confirmed the presence of the thrombus. Additionally, IVE was found reproducible with consistent elastograms between cardiac cycles (CCs). Regarding the human dataset, only the LSME was capable of identifying a plaque that presumably sheltered a lipid core. Whereas such an assumption could not be certified with histology, radial shear and tangential strain LSME elastograms enabled the same conclusion. It is worth emphasizing that this paper reports the first ever in vivo tangential strain elastogram with regards to vascular imaging, due to the LSME. It is concluded that the IVE was reproducible exhibiting consistent strain patterns between CCs. The IVE might provide a unique tool to assess coronary wall lesions.

On the potential of the lagrangian estimator for endovascular ultrasound elastography: in vivo human coronary artery study.

Diagnosis and prognosis of coronary artery atherosclerosis evolution currently rely on plaque morphology and vessel stenosis degree. Such information can accurately be assessed with intravascular ultrasound (IVUS) imaging. A severe complication of coronary artery atherosclerosis is thrombosis, a consequence of plaque rupture or fissure, which might lead to myocardial infarction and sudden ischemic death. Plaque rupture is a complicated mechanical process, correlated with the plaque morphology, composition, mechanical properties and with the blood pressure. Extracting information on the plaque local mechanical properties may reveal relevant features about plaque vulnerability. Accordingly, endovascular elastography (EVE) was introduced to complement IVUS for investigating coronary artery diseases. In this article, in vivo elastographic data are reported for three patients (patient 1, patient 2 and patient 3) who were diagnosed with severe coronary artery stenoses. Time-sequence radio-frequency (RF) data were acquired, in the minutes preceding angioplasty, using an ultrasound scanner working with a 30 MHz mechanical rotating single-element transducer. The elastograms of the radial strain and radial shear distributions within the vessel wall were computed from pairs of successive RF images using the Lagrangian estimator (LE). A hard atherosclerotic plaque (low radial strain and shear) was identified in patient 1. High radial strain and shear values in the plaque areas for patient 2 and patient 3 suggested the presence of lipid cores (soft materials), known to be prone-to-rupture sites when located close to the lumen. To conclude, EVE allowing radial strain and shear images is an improvement over existing EVE methods that may assist IVUS in preoperative vessel lesion assessments and in endovascular therapy planning.

Estimation of polyvinyl alcohol cryogel mechanical properties with four ultrasound elastography methods and comparison with gold standard testings.

Tissue-mimicking phantoms are very useful in the field of tissue characterization and essential in elastography for the purpose of validating motion estimators. This study is dedicated to the characterization of polyvinyl alcohol cryogel (PVA-C) for these types of applications. A strict fabrication procedure was defined to optimize the reproducibility of phantoms having a similar elasticity. Following mechanical stretching tests, the phantoms were used to compare the accuracy of four different elastography methods. The four methods were based on a one-dimensional (1-D) scaling factor estimation, on two different implementations of a 2-D Lagrangian speckle model estimator (quasistatic elastography methods), and on a 1-D shear wave transient elastography technique (dynamic method). Young's modulus was investigated as a function of the number of freeze-thaw cycles of PVA-C, and of the concentration of acoustic scatterers. Other mechanical and acoustic parameters-such as the speed of sound, shear wave velocity, mass density, and Poisson's ratio-also were assessed. The Poisson's ratio was estimated with good precision at 0.499 for all samples, and the Young's moduli varied in a range of 20 kPa for one freeze-thaw cycle to 600 kPa for 10 cycles. Nevertheless, above six freeze-thaw cycles, the results were less reliable because of sample geometry artifacts. However, for the samples that underwent less than seven freeze-thaw cycles, the Young's moduli estimated with the four elastography methods showed good matching with the mechanical tensile tests with a regression coefficient varying from 0.97 to 1.07, and correlations R2 varying from 0.93 to 0.99, depending on the method.

Characterization of PVA cryogel for intravascular ultrasound elasticity imaging.

The present study characterizes the mechanical properties of polyvinyl alcohol (PVA) cryogel in order to show its utility for intravascular elastography. PVA cryogel becomes harder with an increasing number of freeze-thaw cycles, and Young's modulus and Poisson's ratio are measured for seven samples. Mechanical tests were performed on cylindrical samples with a pressure column and on a hollow cylinder with the calculation of an intravascular elastogram. An image of the Young's modulus was obtained from the elastogram using cylinder geometry properties. Results show the mechanical similitude of PVA cryogel with the biological tissues present in arteries. A good agreement between Young's modulus obtained from pressure column and from elastogram was also observed.