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Surgical intervention for unruptured intracranial aneurysms (IAs) carries inherent health risks. The analysis of “patient-specific” IA geometric and computational fluid dynamics (CFD) simulated wall shear stress (WSS) data has been investigated to differentiate IAs at high and low risk of rupture to help clinical decision making. Yet, outcomes vary among studies, suggesting that novel analysis could improve rupture characterization. The authors describe a CFD analytic method to assess spatiotemporal characteristics of swirling flow vortices within IAs to improve characterization. CFD simulations were performed for 47 subjects harboring one medium-sized (4–10 mm) middle cerebral artery (MCA) aneurysm with available 3D digital subtraction angiography data. Alongside conventional indices, quantified IA flow vortex spatiotemporal characteristics were applied during statistical characterization. Statistical supervised machine learning using a support vector machine (SVM) method was run with cross-validation (100 iterations) to assess flow vortex-based metrics’ strength toward rupture characterization. Relying solely on vortex indices for statistical characterization underperformed compared with established geometric characteristics (total accuracy of 0.77 vs 0.80) yet showed improvements over wall shear stress models (0.74). However, the application of vortex spatiotemporal characteristics into the combined geometric and wall shear stress parameters augmented model strength for assessing the rupture status of middle cerebral artery aneurysms (0.85). This preliminary study suggests that the spatiotemporal characteristics of flow vortices within MCA aneurysms are of value to improve the differentiation of ruptured aneurysms from unruptured ones. more...

With the rate of cardiovascular diseases in the U.S increasing throughout the years, there is a need for developing more advanced treatment plans that can be tailored to specific patients and scenarios. The development of 3D printing is rapidly gaining acceptance into clinical cardiology. In this review, key technologies used in 3D printing are briefly summarized, particularly, the use of artificial intelligence (AI), open-source tools like MeshLab and MeshMixer, and 3D printing techniques such as fused deposition molding (FDM) and polyjet are reviewed. The combination of 3D printing, multiple image integration, and augmented reality may greatly enhance data visualization during diagnosis, treatment planning, and surgical procedures for cardiology. more...

In this work, a super-resolution approach based on generative adversary network (GAN) was used to interpolate (up-sample) ultrasound radio-frequency (RF) echo data along the lateral (perpendicular to the acoustic beam direction) direction before motion estimation. Our primary objective was to investigate the feasibility of using a GAN-based super-solution approach to improve lateral resolution in the RF data as a means of improving strain image quality in quasi-static ultrasound strain elastography (QUSE). Unlike natural scene photographs, axial (parallel to the acoustic beam direction) resolution is significantly higher than that of lateral resolution in ultrasound RF data. To better handle RF data, we first modified a super-resolution generative adversary network (SRGAN) model developed by the computer vision community. We named the modified SRGAN model as super-resolution radio-frequency neural network (SRRFNN) model. Our preliminary experiments showed that, compared with axial strain elastograms obtained using the original ultrasound RF data, axial strain elastograms using ultrasound RF data up-sampled by the proposed SRRFNN model were improved. Based on the Wilcoxon rank-sum tests, such improvements were statistically significant ($p more...

Although fluctuating hemodynamic wall stressors are known to impact intracranial aneurysms (IA) initiation, specificity of those stressors has not been evaluated. In this study, using human IA data, we investigated: (1) specificity of stressors in regions with and without IA eventual IA formation; and (2) how combinations of multiple stressors could improve IA formation prediction. 3D computational vasculatures were constructed based on angiographic images of 18 subjects having multiple closely-spaced IAs in the internal carotid artery. Two models were created: Model A with all IAs computationally removed, Model B which kept keep one IA. Computational fluid dynamics (CFD) simulated flow within models. Based on simulated flow fields, wall shear stress and its gradient (WSS, WSSG), oscillatory shear index (OSI), gradient oscillatory number (GON), aneurysm formation index (AFI), and mean number of swirling flow vortices (MV) were analysed. Multivariate logistic regression determined the accuracy of different combinations of those above-mentioned stressors. Overall, we found that combining hemodynamic stressors improves IA formation prediction over individual indices. Both Model A and Model B's parsimonious model was MV+WSS+GON: AUROC 0.88 and 0.83, respectively. Future studies are planned to understand biological meanings induced by fluctuating stressors. more...

Nonlinear mechanical properties of breast tissue can be employed to diagnose and differentiate breast tumors. To obtain such nonlinear mechanical properties, it is necessary to track tissue motion under large deformation. In this study, a multi-compression strategy was utilized to produce large tissue deformation and a method to estimate three-dimensional (3D) motion of tissue under large deformation was introduced. Given multiple volumes of ultrasound data, the proposed method first estimates volume-to-volume incremental displacements using a 3D region-growing motion-tracking method. Then, possible outliers among all incremental displacements are removed to avoid error accumulation. Once large displacement errors have been removed, all incremental displacements are registered together to obtain accumulated displacements under large tissue deformation (e.g. > 10%). The proposed method was tested with one set of in vivo tumor-bearing ultrasound data acquired from a human subject. A total of 10 small-strain deformation steps were performed to obtain the final accumulated displacement field, in which the breast lesion and its surrounding were deformed by approximately 6% and 16%, respectively. The contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) of the elasticity images obtained with the proposed method are all higher than those with a 2D tracking method. Furthermore, in three orthogonal views of accumulated axial strain images, the breast lesion was clearly visible with good correspondence between the axial strain and B-mode images. more...

Aneurysms are malformations within the arterial vasculature brought on by the structural breakdown of the micro-architecture of the vessel wall, with aneurysms posing serious health risks in the event of their rupture. Blood flow within vessels is generally laminar with high, uni-directional wall shear stressors that modulate vascular endothelial cell functionality and regulate vascular smooth muscle cells. However, altered vascular geometry induced by bifurcations, significant curvature, stenosis, or clinical interventions can alter the flow, generating low stressor disturbed flow patterns. Disturbed flow is associated with altered cellular morphology, upregulated expression of proteins modulating inflammation, decreased regulation of vascular permeability, degraded extracellular matrix, and heightened cellular apoptosis. The understanding of the effects disturbed flow has on the cellular cascades which initiate aneurysms and promote their subsequent growth can further elucidate the nature of this complex pathology. This review summarizes the current knowledge about the disturbed flow and its relation to aneurysm pathology, the methods used to investigate these relations, as well as how such knowledge has impacted clinical treatment methodologies. This information can contribute to the understanding of the development, growth, and rupture of aneurysms and help develop novel research and aneurysmal treatment techniques. more...

Techniques aimed at the non-invasive characterization of soft tissues according to elastic properties are rapidly evolving. Virtual touch-based elastographic methods including acoustic radiation force imaging (ARFI) and optical elastography measure the peak axial displacement (PD) and time-to-peak-displacement (TTP) of tissue in response to a localized force. These measurements have been used clinically to differentiate tissues, albeit with mixed results. However, to date, the reason has not been fully understood. In this study, we apply a novel modeling approach to explore the mechanistic link between simplistic displacement measurements and tissue viscoelasticity in the application of virtual touch-based elastographic methods to staging chronic liver disease (CLD). To our knowledge, such a study has not been reported in the literature. Specifically, a numerical screening study was first conducted to identify factors that most strongly determine PD and TTP. Response surface experimental designs were then applied to these factors to produce meta-models of expected PD and TTP probability density functions (PDFs) as functions of identified factors. Results from the screening study suggest that both PD and TTP measurements are primarily influenced by three factors: the initial Young’s modulus of the tissue, the first viscoelastic Prony series time constant, and pre-compression ap- plied during acquisition. To investigate the implications of these results, stochastic inputs for these three factors associated were used to determine a robust response surface. The identified response surface methodology can be used to determine optimal cutoff values for PD and TTP that could be used in order to stage chronic liver disease. more...

Monte-Carlo ray tracing, which enables realistic simulation of ultrasound-tissue interactions such as soft shadows and fuzzy reflections, has been used to simulate ultrasound images. The main technical challenge presented with Monte-Carlo ray tracing is its computational efficiency. In this study, we investigated the use of a commercially-available ray-tracing engine (NVIDIA’s Optix 6.0), which provides a simple, recursive, and flexible pipeline for accelerating ray tracing algorithms. Our preliminary results show that our ultrasound simulation algorithm accelerated by the Optix engine can achieve a frame of 25 frames/second using an Nvidia RTX 2060 card. Furthermore, we compare ultrasound simulations built on the proposed Monte-Carlo ray-tracing algorithm with a deep-learning generative adversarial network (GANs)-based ultrasound simulator and a physics-based ultrasound simulator (Field II). The proposed ultrasound simulator was able to better visualize small-sized structures while the other two above-mentioned simulators could not. Our future work includes integration of our proposed simulator with a virtual reality platform and expansion to other ultrasound modalities such as elastography and flow imaging. more...

Ultrasound elastography is a modality that is uniquely suited to augment conventional B-mode ultrasound for various clinical applications. Motion tracking plays a critically important role during image formation for ultrasound elastography. In this study, the accuracy of four motion tracking methods tailored for acoustic radiation force-based elastography (e.g. acoustic radiation force imaging, shear wave elastography) is compared. In these elastography methods, external mechanical excitation results in small tissue displacements (i.e. 5-10 micrometers). This paper compares four published motion tracking methods: a quadratic sub-sample estimation method, a coupled sub-sample estimation method, a 2-D spline-based estimator, and a 2-D autocorrelation-based motion estimator. Those four methods are evaluated using computer-simulated and tissue-mimicking phantom data. Based on our preliminary data, we find that the autocorrelation-based method is the preferred estimator without considering the lateral displacement. Overall, the spline-based estimator is superior to the other two competitors when both axial and lateral displacements are estimated. Since the spline-based estimation algorithm is considerably time-intensive, the coupled sub-sample estimation method becomes a practical alternative. more...

Tissue motion tracking is a critically important step for many ultrasound elastography applications. In this study, we are particularly interested in evaluating motion tracking strategies for large deformation quasi-static elastography. In this study, Bayesian inference is incorporated into a region-growing motion estimation framework and we named the proposed tracking algorithm as a region-growing Bayesian motion tracking (RGBMT) algorithm. Basically, we replace signal correlation by a maximum posterior probability density function to perform motion tracking. Using a computer-simulated phantom and one set of human subject ultrasound data with pathologically-confirmed breast cancer, the proposed RGBMT algorithm was compared to the original region-growing motion tracking algorithm. Our preliminary data suggested that the addition of Bayesian inference is useful in terms of improving the accuracy of motion tracking. Results from both the numerical phantom and in vivo ultrasound data set showed that there are fewer tracking errors in axial displacement and strain images obtained from the proposed RGBMT algorithms. That explained why the contrast-to-noise (CNR) values were higher and the breast tumor on the reconstructed modulus image was better visualized. more...

Hepatocellular carcinoma and liver metastases are common hepatic malignancies presenting with high mortality rates. Minimally invasive microwave ablation (MWA) yields high success rates similar to surgical resection. However, MWA procedures require accurate image guidance during the procedure and for post-procedure assessments. Ultrasound electrode displacement elastography (EDE) has demonstrated utility for non-ionizing imaging of regions of thermal necrosis created with MWA in the ablation suite. Three strategies for displacement vector tracking and strain tensor estimation, namely coupled subsample displacement estimation (CSDE), a multilevel 2-D normalized cross-correlation method, and quality-guided displacement tracking (QGDT) have previously shown accurate estimations for EDE. This paper reports on a qualitative and quantitative comparison of these three algorithms over 79 patients after an MWA procedure. Qualitatively, CSDE presents sharply delineated, clean ablated regions with low noise except for the distal boundary of the ablated region. Multilevel and QGDT contain more visible noise artifacts, but delineation is seen over the entire ablated region. Quantitative comparison indicates CSDE with more consistent mean and standard deviations of region of interest within the mass of strain tensor magnitudes and higher contrast, while Multilevel and QGDT provide higher CNR. This fact along with highest success rates of 89% and 79% on axial and lateral strain tensor images for visualization of thermal necrosis using the Multilevel approach leads to it being the best choice in a clinical setting. All methods, however, provide consistent and reproducible delineation for EDE in the ablation suite. more...

Continuum tissue models that were often used to simulate or analyze the mechanical properties of tissues being imaged may not be biologically realistic. Our primary objective was to establish the feasibility of using systems biology to construct biologically relevant tissue models linking tissue structure, composition and architecture to the ultrasound measurements directly. The first application was designated to model fibrotic liver tissues. The proposed liver tissue model leveraged established histopathology knowledge of fibrotic liver tissues. Particularly, rules of systems biology derived from molecular histopathology were first implemented into an agent-based software platform SPARK to reflect progressions of liver fibrosis with/without steatosis. Then, microscopic compositions of tissues (e.g. cellular components) were converted to computing grids (at the 50–100 μm scale) for wave simulations using an open-source K-Wave. To verify the physical soundness of the proposed model, virtual wave speed measurements (i.e. shear wave speed [SWS] and the speed of sound [SOS]) were performed. Our initial results demonstrated that the simulated SWS values increased with the progression of liver fibrosis (from 1.5 m/s [Fibrosis stage 1] to 4 m/s [Fibrosis stage 4]). Similarly, the simulated SOS values were within the range of clinical data (from 1575 m/s [Fibrosis stage 0–3] to 1594 m/s [Fibrosis stage 4]). In summary, we found that those systems biology simulated fibrotic liver tissues with and without steatosis can reflect spatial characteristics of relevant histology. Also, their mechanical characteristics (i.e. shear/compressional wave speed) were in good agreement with data reported in the clinical literature. more...

Accurate tracking of tissue motion is critically important for several ultrasound elastography methods including strain elastography, acoustic radiation impulse force imaging and shear wave elastography. In this study, we investigate the feasibility of using three published convolution neural network (CNN) models built for optical flow (hereafter referred to CNN-based tracking) by the computer vision community for breast ultrasound strain elastography. Elastographic data sets produced by finite element and ultrasound simulations were used to retrain three published CNN models: FlowNet-CSS, PWC-Net, and LiteFlowNet. After retraining, the three improved CNN models were evaluated using computer-simulated and tissue-mimicking phantoms, and in vivo breast ultrasound data. CNN-based tracking results were compared to two published 2D speckle tracking methods: coupled tracking and GLobal Ultrasound Elastography (GLUE) methods. Our preliminary results showed that, after retraining, all three CNN models significantly outperformed the coupled tracking method in a simulated single-inclusion phantom. Retraining was effective for in vivo cases as well. The mean CNR values of axial strain using those three original models among 31 in vivo cases were 0.65 [FlowNet], 0.67 [PWC-Net] and 0.49 [LiteFlowNet], respectively, whereas the mean CNR values were improved to 0.94 [Retrained-FlowNet], 1.28 [Retrained-PWC-Net] and 0.79 [Retrained-LiteFlowNet], respectively. Overall, based on the Wilcoxon rank sum tests, the improvements due to retraining were statistically significant (p < 0.05) for all three CNN models. We also found that the PWC-Net model was the best neural network model for data investigated and its overall performance was on par with the coupled tracking method. CNR values estimated from in vivo axial and lateral strain elastograms showed that the GLUE algorithm outperformed both the retrained PWC-Net model and the coupled tracking method, though the GLUE algorithm exhibited some biases. The PWC-Net model was also able to achieve approximately 45 frames/second for 2D speckle tracking for data investigated. more...

This paper presents an artificial intelligence-based ultrasound simulator suitable for medical simulation and clinical training. Particularly, we propose a machine learning approach to realistically simulate ultrasound images based on generative adversarial networks (GANs). Using B-mode ultrasound images simulated by a known ultrasound simulator, Field II, an "image-to-image" ultrasound simulator was trained. Then, through evaluations, we found that the GAN-based simulator can generate B-mode images following Rayleigh scattering. Our preliminary study demonstrated that ultrasound B-mode images from anatomies inferred from magnetic resonance imaging (MRI) data were feasible. While some image blurring was observed, ultrasound B- mode images obtained were both visually and quantitatively comparable to those obtained using the Field II simulator. It is also important to note that the GAN-based ultrasound simulator was computationally efficient and could achieve a frame rate of 15 frames/second using a regular laptop computer. In the future, the proposed GAN-based simulator will be used to synthesize more realistic looking ultrasound images with artifacts such as shadowing. more...

Viscoelasticity Imaging (VEI) has been proposed to measure relaxation time constants for characterization of in vivo breast lesions. In this technique, an external compression force on the tissue being imaged is maintained for a fixed period of time to induce strain creep. A sequence of ultrasound echo signals is then utilized to generate time-resolved strain measurements. Relaxation time constants can be obtained by fitting local time-resolved strain measurements to a viscoelastic tissue model (e.g., a modified Kevin-Voigt model). In this study, our primary objective is to quantitatively evaluate the contrast transfer efficiency (CTE) of VEI, which contains useful information regarding image interpretations. Using an open-source simulator for virtual breast quasi-static elastography (VBQE), we conducted a case study of contrast transfer efficiency of VEI. In multiple three-dimensional (3D) numerical breast phantoms containing various degrees of heterogeneity, finite element (FE) simulations in conjunction with quasi-linear viscoelastic constitutive tissue models were performed to mimic data acquisition of VEI under freehand scanning. Our results suggested that there were losses in CTE, and the losses could be as high as −18 dB. FE results also qualitatively corroborated clinical observations, for example, artifacts around tissue interfaces. more...

Thermal ablation therapy is a minimally invasive technique with the potential to allow eradication of tumors utilizing highly localized heating. Protein coagulation induced by heating is thought to induce a change at the microscopic level, thereby manifesting itself as measurable macroscopic changes of the tissue's viscoelastic properties. The objective of this study was to determine the relationship between clinically relevant thermal doses and a novel biomechanical parameter measurable using ultrasound. Ex vivo porcine liver tissue samples were administered clinically relevant thermal doses via a temperature-controlled double immersive water bath. Stress and strain data obtained from unconfined uniaxial compression and stress-relaxation tests were fit to a Kelvin-Voigt fractional derivative (KVFD) model of tissue viscoelasticity. In the KVFD model, the alpha parameter is the order of the fractional derivative $(0 < \alpha < 1)$ and may represent the amount of collagen microstructure change due to protein coagulation. An analysis of experimental results suggests a predictable correlation between thermal dose received during a simulated thermal ablation therapy and the increase of the alpha parameter. In short, the relationship between thermal dose and the viscoelastic biomechanical parameters of thermally treated tissue may be used to develop new imaging techniques to reliably delineate ablated tissues and prevent damage to healthy surrounding tissues during thermal ablation therapies. In the future, ultrasound elastography techniques allowing for the measurement of the proposed alpha parameter in vivo will be determined since the correlation between thermal dosage and the alpha parameter has now been demonstrated. more...

With the availability of 3D whole breast ultrasound data (WBUS), a lot of recent research efforts are devoted to 3D ultrasound strain elastography. We propose a software post-processing strategy that can be used to further improve ultrasonically-tracked displacements, particularly, off-axis components of ultrasonically-tracked displacements. A correlation-based speckle tracking algorithm was first used to obtain relatively accurate 3D displacement fields. Then, three different denoising algorithms were applied and evaluated. The first denoising algorithm is a partial differential equation (PDE)-based algorithm and tissue incompressibility was enforced through iterative optimization. The second method utilizes radial basis function (RBF) also to enforce tissue incompressibility, while the third method is a non-local median filter method. Based on data investigated, the PDE-based algorithm achieved the lowest incompressibility among three different algorithms. As compared to the raw displacement estimates, reduction rates of incompressibility were approximately 95%, 50% and 63% after three denoising algorithms had been applied, respectively. The analysis of 3D ultrasound data acquired using a clinical scanner (Acuson S2000 ABVS, Siemens Medical Solution (USA) Inc., Mountain View, CA) demonstrated that the PDE-based denoising algorithm can provide most consistent lateral strain images. In conclusion, our preliminary results demonstrated that denoising can significantly improve non-axial displacement estimates. more...

Accurate tracking of tissue motion is critically important for several ultrasound elastography methods including strain elastography and shear wave elastography. In this study, we investigate the feasibility of using a convolution neural network (CNN)-based speckle tracking method for elastographic applications. Additional data sets produced by finite element simulations were used to train an existing Flownet 2.0 model. After training, the improved network was evaluated using computer-simulated and tissue-mimicking phantoms, and in vivo breast ultrasound data. Our preliminary results were compared to a published 2D high-quality speckle tracking method by our group. Our preliminary results showed that the improved CNN outperformed the original Flownet 2.0. More specifically, in a tissue-mimicking phantom and one set of in vivo breast ultrasound data, the proposed CNN-based method achieved higher contrast-to-noise ratios (0.64 vs 1.05 and 1.16 vs. 1.40, respectively), as compared with the original Flownet 2.0 model. However, the improved CNN was still inferior to the coupled tracking algorithm. Currently, the inference process after the training of the proposed CNN can achieve approximately 60 frames/second for 2D speckle tracking under the NVIDIA TensorRT™ framework. Overall, we conclude that applying the proposed CNN-based speckle tracking method is feasible and good-quality strain elastography data can be obtained in TM phantoms and in vivo breast data. Our future work includes applying this technique to in vivo 3D whole breast ultrasound data. more...

Purpose: Quasistatic ultrasound elastography (QUE) is being used to augment in vivo characterization of breast lesions. Results from early clinical trials indicated that there was a lack of confidence in image interpretation. Such confidence can only be gained through rigorous imaging tests using complex, heterogeneous but known media. The objective of this study is to build a virtual breast QUE simulation platform in the public domain that can be used not only for innovative QUE research but also for rigorous imaging tests. Methods: The main thrust of this work is to streamline biomedical ultrasound simulations by leveraging existing open source software packages including Field II (ultrasound simulator), VTK (geometrical visualization and processing), FEBio [finite element (FE) analysis], and Tetgen (mesh generator). However, integration of these open source packages is nontrivial and requires interdisciplinary knowledge. In the first step, a virtual breast model containing complex anatomical geometries was created through a novel combination of image-based landmark structures and randomly distributed (small) structures. Image-based landmark structures were based on data from the NIH Visible Human Project. Subsequently, an unstructured FE-mesh was created by Tetgen. In the second step, randomly positioned point scatterers were placed within the meshed breast model through an octree-based algorithm to make a virtual breast ultrasound phantom. In the third step, an ultrasound simulator (Field II) was used to interrogate the virtual breast phantom to obtain simulated ultrasound echo data. Of note, tissue deformation generated using a FE-simulator (FEBio) was the basis of deforming the original virtual breast phantom in order to obtain the postdeformation breast phantom for subsequent ultrasound simulations. Using the procedures described above, a full cycle of QUE simulations involving complex and highly heterogeneous virtual breast phantoms can be accomplished for the first time. Results: Representative examples were used to demonstrate capabilities of this virtual simulation platform. In the first set of three ultrasound simulation examples, three heterogeneous volumes of interest were selected from a virtual breast ultrasound phantom to perform sophisticated ultrasound simulations. These resultant B-mode images realistically represented the underlying complex but known media. In the second set of three QUE examples, advanced applications in QUE were simulated. The first QUE example was to show breast tumors with complex shapes and/or compositions. The resultant strain images showed complex patterns that were normally seen in freehand clinical ultrasound data. The second and third QUE examples demonstrated (deformation-dependent) nonlinear strain imaging and time-dependent strain imaging, respectively. Conclusions: The proposed virtual QUE platform was implemented and successfully tested in this study. Through show-case examples, the proposed work has demonstrated its capabilities of creating sophisticated QUE data in a way that cannot be done through the manufacture of physical tissue-mimicking phantoms and other software. This open software architecture will soon be made available in the public domain and can be readily adapted to meet specific needs of different research groups to drive innovations in QUE. more...

The objective of this study was to use image-based computational fluid dynamics (CFD) techniques to analyze the impact that multiple closely spaced intracranial aneurysm (IAs) of the supra-clinoid segment of the internal carotid artery (ICA) have on each other's hemodynamic characteristics. The vascular geometry of fifteen (15) subjects with 2 IAs was gathered using a 3D digital subtraction angiography clinical system. Two groups of computer models were created for each subject's vascular geometry: both IAs present (model A) and after removal of one IA (model B). Models were separated into two groups based on IA separation: tandem (one proximal and one distal) and adjacent (aneurysms directly opposite on a vessel). Simulations using a pulsatile velocity waveform were solved by a commercial CFD solver. Proximal IAs altered flow into distal IAs (5 of 7), increasing flow energy and spatial-temporally averaged wall shear stress (STA-WSS: 3–50% comparing models A to B) while decreasing flow stability within distal IAs. Thus, proximal IAs may “protect” a distal aneurysm from destructive remodeling due to flow stagnation. Among adjacent IAs, the presence of both IAs decreased each other's flow characteristics, lowering WSS (models A to B) and increasing flow stability: all changes statistically significant (p more...

Minimally invasive procedures such as microwave ablation (MWA) are growing in popularity as a substitute for surgical resection of hepatocellular carcinomas. Ultrasound electrode displacement elastography (EDE) has demonstrated the potential to provide a feasible non-ionizing approach for monitoring the region of thermal necrosis. We present results on a comparison of the contrast, signal-to-noise (SNR) and contrast-to-noise (CNR) ratios for two displacement estimation algorithms; namely the Quality-Guided Displacement Tracking (QGDT) and the Coupled Subsample Displacement Estimation (CSDE) methods. Twenty patients with EDE strain images estimated from the same radiofrequency frame pair using both algorithms are presented. CSDE depicts well delineated ablated regions, while QGDT in many instances depicts noisy boundaries. Quantitatively, the SNR, contrast, and CNR obtained using CSDE were higher than those obtained with QGDT. The axial SNR, contrast, and CNR for QGDT were found to be 34.6 ± 11.9 dB, 7.8 ± 4.2 dB, and 2.7 ± 6.4 dB, while the CSDE presented with values of 56.9 ± 20.4 dB, 22.5 ± 12.3, and 3.8 ± 2.5 dB, respectively. This study indicates that EDE using CSDE provides improved strain images however, both approaches produced reproducible results. more...

Shear wave elastography (SWE) has been used to measure viscoelastic properties for characterization of fibrotic livers. In this technique, external mechanical vibrations or acoustic radiation forces are first transmitted to the tissue being imaged to induce shear waves. Ultrasonically measured displacement/velocity is then utilized to obtain elastographic measurements related to shear wave propagation. Using an open-source wave simulator, k-Wave, we conducted a case study of the relationship between plane shear wave measurements and the microstructure of fibrotic liver tissues. Particularly, three different virtual tissue models (i.e., a histology-based model, a statistics-based model, and a simple inclusion model) were used to represent underlying microstructures of fibrotic liver tissues. We found underlying microstructures affected the estimated mean group shear wave speed (SWS) under the plane shear wave assumption by as much as 56%. Also, the elastic shear wave scattering resulted in frequency-dependent attenuation coefficients and introduced changes in the estimated group SWS. Similarly, the slope of group SWS changes with respect to the excitation frequency differed as much as 78% among three models investigated. This new finding may motivate further studies examining how elastic scattering may contribute to frequency-dependent shear wave dispersion and attenuation in biological tissues. more...

Obtaining accurate ultrasonically estimated displacements along both axial (parallel to the acoustic beam) and lateral (perpendicular to the beam) directions is an important task for various clinical elastography applications (e.g., modulus reconstruction and temperature imaging). In this study, a partial differential equation (PDE)–based regularization algorithm was proposed to enhance motion tracking accuracy. More specifically, the proposed PDE-based algorithm, utilizing two-dimensional (2D) displacement estimates from a conventional elastography system, attempted to iteratively reduce noise contained in the original displacement estimates by mathematical regularization. In this study, tissue incompressibility was the physical constraint used by the above-mentioned mathematical regularization. This proposed algorithm was tested using computer-simulated data, a tissue-mimicking phantom, and in vivo breast lesion data. Computer simulation results demonstrated that the method significantly improved the accuracy of lateral tracking (e.g., a factor of 17 at 0.5% compression). From in vivo breast lesion data investigated, we have found that, as compared with the conventional method, higher quality axial and lateral strain images (e.g., at least 78% improvements among the estimated contrast-to-noise ratios of lateral strain images) were obtained. Our initial results demonstrated that this conceptually and computationally simple method could be useful for improving the image quality of ultrasound elastography with current clinical equipment as a post-processing tool. more...

Supersonic shear imaging (SSI) is evaluated as a means of visualizing changes in regional tendon elasticity caused by partial tears in a porcine model. Thirty digital flexor tendons were cut to 25% (n = 10), 50% (n = 10) and 75% (n = 10) of the tendon thickness along the deep surface. Tendon elasticity was mapped left of, centered on and right of the tear site before and after tearing from 0% to 2% strain. Shear wave speed increased at 1% (p more...

Recent developments in medical imaging and advanced computer modeling simulations) now enable studies designed to correlate either simulated or measured "patient-specific" parameters with the natural history of intracranial aneurysm i.e., ruptured or unruptured. To achieve significance, however, these studies require rigorous comparison of large amounts of data from large numbers of aneurysms, many of which are quite dissimilar anatomically. In this study, we present a method that can likely facilitate such studies as its application could potentially simplify an objective comparison of surface-based parameters of interest such as wall shear stress and blood pressure using large multi-patient, multi-institutional data sets. Based on the concept of harmonic function/field, we present a unified and simple approach for mapping the surface of an aneurysm onto a unit disc. Requiring minimal human interactions the algorithm first decomposes the vessel geometry into 1) target aneurysm and 2) parent artery and any adjacent branches; it, then, maps the segmented aneurysm surface onto a unit disk. In particular, the decomposition of the vessel geometry quantitatively exploits the unique combination of three sets of information regarding the shape of the relevant vasculature: 1) a distance metric defining the spatially varying deviation from a tubular characteristic (i.e., cylindrical structure) of a normal parent artery, 2) local curvatures and 3) local concavities at the junction/interface between an aneurysm and its parent artery. These three sets of resultant shape/geometrical data are then combined to construct a linear system of the Laplacian equation with a novel shape-sensitive weighting scheme. The solution to such a linear system is a shape-sensitive harmonic function/field whose iso-lines will densely gather at the border between the normal parent artery and the aneurysm. Finally, a simple ranking system is utilized to select the best candidate among all possible iso-lines. Quantitative analysis using “patient-specific” aneurysm geometries taken from our internal database demonstrated that the technique is robust. Similar results were obtained from aneurysms having widely different geometries (bifurcation, terminal and lateral aneurysms). Application of our method should allow for meaningful, reliable and reproducible model-to-model comparisons of surface-based physiological and hemodynamic parameters. more...

We reconstruct the in vivo spatial distribution of linear and nonlinear elastic parameters in ten patients with benign (five) and malignant (five) tumors. The mechanical behavior of breast tissue is represented by a modified Veronda-Westmann model with one linear and one nonlinear elastic parameter. The spatial distribution of these elastic parameters is determined by solving an inverse problem within the region of interest (ROI). This inverse problem solution requires the knowledge of the displacement fields at small and large strains. The displacement fields are measured using a free-hand ultrasound strain imaging technique wherein, a linear array ultrasound transducer is positioned on the breast and radio frequency echo signals are recorded within the ROI while the tissue is slowly deformed with the transducer. Incremental displacement fields are determined from successive radio-frequency frames by employing cross-correlation techniques. The rectangular regions of interest were subjectively selected to obtain low noise displacement estimates and therefore were variables that ranged from 346 to 849.6 mm2 . It is observed that malignant tumors stiffen at a faster rate than benign tumors and based on this criterion nine out of ten tumors were correctly classified as being either benign or malignant. more...

The feasibility of using ultrasound-based elastic modulus imaging to visualize thermal ablation zones in an in vivo porcine model is reported. Elastic modulus images of soft tissues are estimated as an inverse optimization problem. Ultrasonically measured displacement data are utilized as inputs to determine an elastic modulus distribution that provides the best match to this displacement field. A total of 14 in vivo thermal ablation zones were investigated in this study. To determine the accuracy of delineation of each thermal ablation zone using elastic modulus imaging, the dimensions (lengths of long and short axes) and the area of each thermal ablation zone obtained from an elastic modulus image were compared to the corresponding gross pathology photograph of the same ablation zone. Comparison of elastic modulus imaging measurements and gross pathology measurements showed high correlation with respect to the area of thermal ablation zones (Pearson coefficient = 0.950 and p < 0.0001). The radiological-pathological correlation was slightly lower (correlation = 0.853, p < 0.0001) for strain imaging among these 14 in vivo ablation zones. We also found that, on average, elastic modulus imaging can more accurately depict thermal ablation zones, when compared to strain imaging (14.7% versus 22.3% absolute percent error in area measurements, respectively). Furthermore, elastic modulus imaging also provides higher (more than a factor of 2) contrast-to-noise ratios for evaluating these thermal ablation zones than those on corresponding strain images, thereby reducing inter-observer variability. Our preliminary results suggest that elastic modulus imaging might potentially enhance the ability to visualize thermal ablation zones, thereby improving assessment of ablative therapies. more...

Purpose: Percutaneous thermal ablation is increasingly being used to destroy hepatic tumorsin situ. The success of ablative techniques is highly dependent on adequate ablation zone monitoring, and ultrasound-based strain imaging could become a convenient and cost-effective means to delineate ablation zone boundaries. This study investigates in vivo electrode displacement-based strain imaging for monitoring hepatic ablation procedures that are difficult to perform with conventional elastography. Methods: In our method, minute displacements (less than a millimeter) are applied to the unconstrained end of the ablation electrode, resulting in localized tissue deformation within the ablation zone that provides the mechanical stimuli required for strain imaging. This article presents electrode displacement strain images of radiofrequency ablation zones created in porcine liver in vivo (n=13). Results: Cross-sectional area measurements from strain images of these ablation zones were obtained using manual and automated segmentation. Area measurements from strain images were highly correlated with areas measured on histopathology images, quantitated using linear regression (R=0.894, P more...

Accurate determination of the complex shear modulus of soft tissues and soft-tissue-like materials in the 10–300 Hz frequency range is very important to researchers in MR elastography and acoustic radiation force impulse (ARFI) imaging. A variety of instruments for making such measurements has been reported, but none of them is easily reproduced, and none have been tested to conform to causality via the Kramers–Kronig (K-K) relations. A promising linear oscillation instrument described in a previous brief report operates between 20 and 160 Hz, but results were not tested for conformity to the K-K relations. We have produced a similar instrument with our own version of the electronic components and have also accounted for instrumental effects on the data reduction, which is not addressed in the previous report. The improved instrument has been shown to conform to an accurate approximation of the K-K relations over the 10–300 Hz range. The K-K approximation is based on the Weichert mechanical circuit model. We also found that the sample thickness must be small enough to obtain agreement with a calibrated commercial rheometer. A complete description of the improved instrument is given, facilitating replication in other labs. more...

Because ablation therapy alters the elastic modulus of tissues, emerging strain imaging methods may enable clinicians for the first time to have readily available, cost-effective, real-time guidance to identify the location and boundaries of thermal lesions. Electrode displacement elastography is a method of strain imaging tailored specifically to ultrasound-guided electrode-based ablative therapies (e.g., radio-frequency ablation). Here tissue deformation is achieved by applying minute perturbations to the unconstrained end of the treatment electrode, resulting in localized motion around the end of the electrode embedded in tissue. In this article, we present a method for three-dimensional (3D) elastographic reconstruction from volumetric data acquired using the C7F2 fourSight four-dimensional ultrasound transducer, provided by Siemens Medical Solutions USA, Inc. (Issaquah, WA, USA). Lesion reconstruction is demonstrated for a spherical inclusion centered in a tissue-mimicking phantom, which simulates a thermal lesion embedded in a normal tissue background. Elastographic reconstruction is also performed for a thermal lesion created in vitro in canine liver using radio-frequency ablation. Postprocessing is done on the acquired raw radio-frequency data to form surface-rendered 3D elastograms of the inclusion. Elastographic volume estimates of the inclusion compare reasonably well with the actual known inclusion volume, with 3D electrode displacement elastography slightly underestimating the true inclusion volume. more...

This paper presents a new method for forming high-quality ultrasonic strain images. To achieve this goal, three radiofrequency echo frames are selected by an automated performance assessment method and used to generate two parent strain images located in the same physical grid from which a high quality composite strain image may be calculated by averaging. The automatic performance evaluation method combines the consistency among the two parent strain images and the accuracy of motion tracking into a single summary "displacement quality measure." The proposed algorithm is evaluated with datasets acquired from in vivo breast tissue data. Our results show that that the proposed strain formation method shows substantial potential to outperform other methods available in the literature. more...

Two equivalent anthropomorphic breast phantoms were constructed, one for use in ultrasound elastography and the other in magnetic resonance (MR) elastography. A complete description of the manufacturing methods is provided. The materials used were oil-in-gelatin dispersions, where the volume percent oil differentiates the materials, primarily according to Young’s moduli. Values of Young’s moduli are in agreement with in vitro ranges for the corresponding normal and abnormal breast tissues. Ultrasound and nuclear magnetic resonance (NMR) properties are reasonably well represented. Phantoms of the type described promise to aid researchers who are developing hardware and software for elastography. Examples of ultrasound and MR elastograms of the phantoms are included to demonstrate the utility of the phantoms. Also, the level of stability of elastic properties of the component materials is quantified over a 15-month period. Such phantoms can serve as performance-assessing intermediaries between simple phantoms (consisting, for example, of homogeneous cylindrical inclusions in a homogeneous background) and a full-scale clinical trial. Thus, premature clinical trials may be avoided. more...

Ultrasound-based Elastography is being used to augment in vivo characterization of breast lesions. Results from a meta-analysis of all clinical trials (up to 2011) indicated a lack of confidence in image interpretation. Such confidence can only be gained through rigorous imaging tests using complex, heterogeneous but known media. Our objective of this study is to build a virtual breast phantom lab in the public domain that can be used for rigorous imaging testing of this kind. Main thrust of this work is to streamline biomedical ultrasound simulations in conjunction with anatomically complex (software) phantoms by leveraging existing open source software packages including K-wave or Field II (acoustic simulation), VTK (data visualization and processing), FEBio (biomechanical deformation) and Tetgen (mesh generation). The integration of these four open source packages was based on a simple message-passing scheme to facilitate its use among imaging scientists. more...

According to the US National Institute of Neurological Disorders and Stroke, incidence of reported intracranial aneurysm (IA) rupture is about 0.001%. In other words, there are thus about 27,000 people who may suffer stroke from ruptured cerebral aneurysms each year. The origin and natural history of IAs are closely associated with disturbed hemodynamics though exact mechanisms are unknown.[1, 2] Consequently, blood flow parameters measured from phase-contrast magnetic resonance imaging (PC-MRI) [3, 4] may provide insight not only into factors relevant to the development and progression of IAs but also into their short and long term responses to therapeutic interventions (e.g. coil embolization and stent deployment).Copyright © 2013 by ASME more...

Breast cancer is currently the second leading cause of cancer deaths in women. Early detection and accurate classification of suspicious masses as benign or malignant is important for arriving at an appropriate treatment plan. In this article, we present classification results for features extracted from ultrasound-based, axial-strain and axial-shear images of breast masses. The breast-mass stiffness contrast, size ratio, and a normalized axial-shear strain area feature are evaluated for the classification of in vivo breast masses using a leave-one-out classifier. Radiofrequency echo data from 123 patients were acquired using Siemens Antares or Elegra clinical ultrasound systems during freehand palpation. Data from four different institutions were analyzed. Axial displacements and strains were estimated using a multilevel, pyramid-based two-dimensional cross-correlation algorithm, with final processing block dimensions of 0.385 mm × 0.507 mm (three A-lines). Since mass boundaries on B-mode images for 21 patients could not be delineated (isoechoic), the combined feature analysis was only performed for 102 patients. Results from receiver operating characteristic (ROC) demonstrate that the area under the curve was 0.90, 0.84, and 0.52 for the normalized axial-shear strain, size ratio, and stiffness contrast, respectively. When these three features were combined using a leave-one-out classifier and support vector machine approach, the overall area under the curve improved to 0.93. more...

Ultrasound Doppler (UD) velocity measurements are commonly used to quantify blood flow velocities in vivo. The aim of our work was to investigate the accuracy of in vivo spectral Doppler measurements of velocity waveforms. Waveforms were derived from spectral Doppler signals and corrected for intrinsic spectral broadening errors by applying a previously published algorithm. The method was tested in a canine aneurysm model by determining velocities in small arteries (3–4 mm diameter) near the aneurysm where there was moderately disturbed flow. Doppler results were compared to velocity measurements in the same arteries acquired with a rapid volumetric phase contrast MR angiography technique named phase contrast vastly undersampled isotropic projection reconstruction magnetic resonance angiography (PC-VIPR MRA). After correcting for intrinsic spectral broadening, there was a high degree of correlation between velocities obtained by the real-time UD and the accelerated PC-MRA technique. The peak systolic velocity yielded a linear correlation coefficient of r = 0.83, end diastolic velocity resulted in r = 0.81, and temporally averaged mean velocity resulted in r = 0.76. The overall velocity waveforms obtained by the two techniques were also highly correlated (r = 0.89 ± 0.06). There were, however, only weak correlations for the pulsatility index (PI: 0.25) and resistive index (RI: 0.14) derived from the two techniques. Results demonstrate that to avoid overestimations of peak systolic velocities, the results for UD must be carefully corrected to compensate for errors caused by intrinsic spectral broadening. more...

The etiology and progression of intracranial aneurysms (IAs) are closely associated with complex patterns of disturbed blood flow. [1] Consequently, blood flow imaging [2] and CFD simulations in realistic geometries [3, 4] are of clinical interests because flow information obtained by such techniques can provide insight not only into the development and progression of IAs but also into their responses to therapeutic interventions (e.g. coil embolization and stent deployment).Copyright © 2010 by ASME more...

This article reports the use of a two-dimensional (2-D) capacitive micro-machined ultrasound transducer (CMUT) to acquire radio-frequency (RF) echo data from relatively large volumes of a simple ultrasound phantom to compare three-dimensional (3-D) elasticity imaging methods. Typical 2-D motion tracking for elasticity image formation was compared with three different methods of 3-D motion tracking, with sum-squared difference (SSD) used as the similarity measure. Differences among the algorithms were the degree to which they tracked elevational motion: not at all (2-D search), planar search, combination of multiple planes and plane independent guided search. The cross-correlation between the predeformation and motion-compensated postdeformation RF echo fields was used to quantify motion tracking accuracy. The lesion contrast-to-noise ratio was used to quantify image quality. Tracking accuracy and strain image quality generally improved with increased tracking sophistication. When used as input for a 3-D modulus reconstruction, high quality 3-D displacement estimates yielded accurate and low noise modulus reconstruction. more...

Radiofrequency (RF) ablation is the most common minimally invasive therapy used in the United States to treat primary (hepatocellular carcinoma) and metastatic liver cancers. The ability to accurately evaluate the thermal ablation zone while a patient is undergoing radiofrequency ablation may help reduce the high recurrence rates (as high as 55%) following radiofrequency ablation therapy. In this paper we demonstrate the feasibility of performing ultrasound-based elastic modulus imaging (EMI) to evaluate thermal ablation zones in a porcine model. more...

Previous work has demonstrated improved diagnostic performance of highly trained breast radiologists when provided with B-mode plus elastography images over B-mode images alone. In those studies we have observed that elasticity imaging can be difficult to perform if there is substantial motion of tissue out of the image plane. So we are extending our methods to 3D/4D elasticity imaging with 2D arrays. Further, we have also documented the fact that some breast tumors change contrast with increasing deformation and those observations are consistent with in vitro tissue measurements. Hence, we are investigating imaging tissue stress-strain nonlinearity. These studies will require relatively large tissue deformations (e.g., > 20%) which will induce out of plane motion further justifying 3D/4D motion tracking. To further enhance our efforts, we have begun testing the ability to perform modulus reconstructions (absolute elastic parameter) imaging of in vivo breast tissues. The reconstructions are based on high quality 2D displacement estimates from strain imaging. Piecewise linear (secant) modulus reconstructions demonstrate the changes in elasticity image contrast seen in strain images but, unlike the strain images, the contrast in the modulus images approximates the absolute modulus contrast. Nonlinear reconstructions assume a reasonable approximation to the underlying constitutive relations for the tissue and provide images of the (near) zero-strain shear modulus and a nonlinearity parameter that describes the rate of tissue stiffening with increased deformation. Limited data from clinical trials are consistent with in vitro measurements of elastic properties of tissue samples and suggest that the nonlinearity of invasive ductal carcinoma exceeds that of fibroadenoma and might be useful for improving diagnostic specificity. This work is being extended to 3D. more...

The incidence of primary and secondary liver tumors has increased significantly over the last two decades. Due to poor liver function and/or distribution of lesions, surgery is often not an option for affected patients. An alternative to surgical resection, percutaneous radiofrequency ablation is often used to thermally destroy the tumor in situ. Radiofrequency ablation is evolving into one of the more popular minimally-invasive treatments for hepatic tumors. Monitoring the treated region is an important factor in the success of radiofrequency ablation, and ultrasound elastography could become a convenient, cost-effective means to delineate the thermal lesion boundaries for clinical personnel during the procedure. This study assesses “electrode displacement” strain imaging for monitoring abdominal radiofrequency ablation procedures. We present results utilizing a novel approach of displacing the ablation electrode itself to introduce the mechanical stimuli required for strain imaging. Utilizing a Siemens Antares clinical ultrasound scanner equipped with a research interface, ultrasound radiofrequency data were acquired immediately following radiofrequency ablation of porcine liver. The porcine liver was excised following the procedure, and the dimensions of the thermal lesion in the imaging plane measured by slicing though the lesion. Strain images of the lesions were produced offline using axial guidance based block-matching and multi-level motion tracking algorithms. The area of the lesion on the strain image was compared to the area of the lesion in pathology images obtained from eight separate lesions. The estimated linear correlation coefficient between the pathology image and the strain image was r = 0.961 (p ≪ .001) for manual segmentation using 4 observers. The area of the lesion in the strain image slightly underestimates the area of the lesion in the pathology image for all slices, agreeing with earlier ex-vivo experiments. more...