In Vivo Longitudinal Monitoring of Cardiac Remodeling in Murine Ischemia Models With Adaptive Bayesian Regularized Cardiac Strain Imaging: Validation Against Histology.

Adaptive Bayesian regularized cardiac strain imaging (ABR-CSI) uses raw radiofrequency signals to estimate myocardial wall contractility as a surrogate measure of relative tissue elasticity incorporating regularization in the Bayesian sense. We determined the feasibility of using ABR-CSI -derived strain for in vivo longitudinal monitoring of cardiac remodeling in a murine ischemic injury model (myocardial infarction [MI] and ischemia-reperfusion [IR]) and validated the findings against ground truth histology. We randomly stratified 30 BALB/CJ mice (17 females, 13 males, median age = 10 wk) into three surgical groups (MI = 10, IR = 12, sham = 8) and imaged pre-surgery (baseline) and 1, 2, 7 and 14 d post-surgery using a pre-clinical high-frequency ultrasound system (VisualSonics Vevo 2100). We then used ABR-CSI to estimate end-systolic and peak radial (er) and longitudinal (el) strain estimates. ABR-CSI was found to have the ability to serially monitor non-uniform cardiac remodeling associated with murine MI and IR non-invasively through temporal variation of strain estimates post-surgery. Furthermore, radial end-systole (ES) strain images and segmental strain curves exhibited improved discrimination among infarct, border and remote regions around the myocardium compared with longitudinal strain results. For example, the MI group had significantly lower (Friedman's with Bonferroni-Dunn test, p = 0.002) ES er values in the anterior middle (infarcted) region at day 14 (n = 9, 9.23 ± 7.39%) compared with the BL group (n = 9, 44.32 ± 5.49). In contrast, anterior basal (remote region) mean ES er values did not differ significantly (non-significant Friedman's test, χ2 = 8.93, p = 0.06) at day 14 (n = 6, 33.05 ± 6.99%) compared with baseline (n = 6, 34.02 ± 6.75%). Histology slides stained with Masson's trichrome (MT) together with a machine learning model (random forest classifier) were used to derive the ground truth cardiac fibrosis parameter termed histology percentage of myocardial fibrosis (PMF). Both radial and longitudinal strain were found to have strong statistically significant correlations with the PMF parameter. However, radial strain had a higher Spearman's correlation value (εresρ = -0.67, n = 172, p < 0.001) compared with longitudinal strain (εlesρ = -0.60, n = 172, p < 0.001). Overall, the results of this study indicate that ABR-CSI can reliably perform non-invasive detection of infarcted and remote myocardium in small animal studies.

Murine cardiac fibrosis localization using adaptive Bayesian cardiac strain imaging in vivo.

An adaptive Bayesian regularized cardiac strain imaging (ABR-CSI) algorithm for in vivo murine myocardial function assessment is presented. We report on 31 BALB/CJ mice (n = 17 females, n = 14 males), randomly stratified into three surgical groups: myocardial infarction (MI, n = 10), ischemia-reperfusion (IR, n = 13) and control (sham, n = 8) imaged pre-surgery (baseline- BL), and 1, 2, 7 and 14 days post-surgery using a high frequency ultrasound imaging system (Vevo 2100). End-systole (ES) radial and longitudinal strain images were used to generate cardiac fibrosis maps using binary thresholding. Percentage fibrotic myocardium (PFM) computed from regional fibrosis maps demonstrated statistically significant differences post-surgery in scar regions. For example, the MI group had significantly higher PFMRadial (%) values in the anterior mid region (p = 0.006) at Day 14 (n = 8, 42.30 ± 14.57) compared to BL (n = 12, 1.32 ± 0.85). A random forest classifier automatically detected fibrotic regions from ground truth Masson's trichrome stained histopathology whole slide images. Both PFMRadial (r = 0.70) and PFMLongitudinal (r = 0.60) results demonstrated strong, positive correlation with PFMHistopathology (p < 0.001).

Marrow-Derived Autologous Stromal Cells for the Restoration of Salivary Hypofunction (MARSH): Study protocol for a phase 1 dose-escalation trial of patients with xerostomia after radiation therapy for head and neck cancer: MARSH: Marrow-Derived Autologous Stromal Cells for the Restoration of Salivary Hypofunction.

BACKGROUND: Xerostomia, or dry mouth, is a common side effect of head and neck radiation. Current treatment options for radiation-induced xerostomia are generally supportive in nature. Adult stem cells are the ultimate source for replenishment of salivary gland tissue. Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are a viable cell-based therapy for xerostomia. We have undertaken studies enabling U.S. Food and Drug Administration Investigational New Drug status, demonstrating the normal phenotype, intact functionality, and pro-growth secretome of interferon-γ (IFNγ)-stimulated BM-MSCs taken from patients with head and neck cancer who have undergone radiation ± chemotherapy. Here we present the protocol of MARSH, a first-in-human clinical trial of bone marrow-derived, IFNγ-activated BM-MSCs for the treatment of radiation-induced xerostomia. METHODS: This single-center phase 1 dose-escalation with expansion cohort, non-placebo-controlled study will assess the safety and tolerability of BM-MSCs for the treatment of radiation-induced xerostomia in patients who had head and neck cancer. The phase 1 dose-escalation study will be a 3 + 3 design with staggered enrollment. A total of 21 to 30 subjects (9 to 18 in phase 1 study, 12 in expansion cohort) will be enrolled. The primary endpoint is determining the recommended phase 2 dose (RP2D) of IFNγ-stimulated BM-MSCs to enable further studies on the efficacy of BM-MSCs. Patients' bone marrow will be aspirated, and BM-MSCs will be expanded, stimulated with IFNγ, and injected into the submandibular gland. The RP2D will be determined by dose-limiting toxicities occurring within 1 month of BM-MSC injection. Secondary outcomes of saliva amounts and composition, ultrasound of salivary glands, and quality of life surveys will be taken at 3-, 6-, 12-, and 24-month visits. DISCUSSION: Autotransplantation of IFNγ-stimulated BM-MSCs in salivary glands after radiation therapy or chemoradiation therapy may provide an innovative remedy to treat xerostomia and restore quality of life. This is the first therapy for radiation-induced xerostomia that may be curative. TRIAL REGISTRATION: World Health Organization International Clinical Trials Registry Platform: NCT04489732.

Bayesian Regularized Strain Imaging for Assessment of Murine Cardiac Function In vivo.

A cardiac strain imaging framework with adaptive Bayesian regularization (ABR) is proposed for in vivo assessment of murine cardiac function. The framework uses ultrasound (US) radio-frequency data collected with a high frequency (fc = 30MHz) imaging system and a multi-level block matching algorithm with ABR to derive inter-frame cardiac displacements. Lagrangian cardiac strain (radial, er and longitudinal, el) tensors were derived by segmenting the myocardial wall starting at the ECG R-wave and accumulating interframe deformations over a cardiac cycle. In vivo feasibility was investigated through a longitudinal study with two mice (one ischemia-perfusion (IR) injury and one sham) imaged at five sessions (pre-surgery (BL) and 1,2,7 and 14 days post-surgery). End-systole (ES) strain images and segmental strain curves were derived for quantitative evaluation. Both mice showed periodic variation of er and el strain at BL with segmental synchroneity. Infarcted regions of IR mouse at Day 14 were associated with reduced or sign reversed ES er and el values while the sham mouse had similar or higher strain than at BL. Infarcted regions identified in vivo were associated with increased collagen content confirmed with Masson's Trichrome stained ex vivo heart sections.Clinical Relevance-Higher quality cardiac strain images derived with RF data and Bayesian regularization can potentially improve the sensitivity and accuracy of non-invasive assessment of cardiovascular disease models.

Differential Imaging of Liver Tumors before and after Microwave Ablation with Electrode Displacement Elastography.

Liver cancer is a leading cause of cancer-related deaths; however, primary treatment options such as surgical resection and liver transplant may not be viable for many patients. Minimally invasive image-guided microwave ablation (MWA) provides a locally effective treatment option for these patients with an impact comparable to that of surgery for both cancer-specific and overall survival. MWA efficacy is correlated with accurate image guidance; however, conventional modalities such as B-mode ultrasound and computed tomography have limitations. Alternatively, ultrasound elastography has been used to demarcate post-ablation zones, yet has limitations for pre-ablation visualization because of variability in strain contrast between cancer types. This study attempted to characterize both pre-ablation tumors and post-ablation zones using electrode displacement elastography (EDE) for 13 patients with hepatocellular carcinoma or liver metastasis. Typically, MWA ablation margins of 0.5-1.0 cm are desired, which are strongly correlated with treatment efficacy. Our results revealed an average estimated ablation margin inner quartile range of 0.54-1.21 cm with a median value of 0.84 cm. These treatment margins lie within or above the targeted ablative margin, indicating the potential to use EDE for differentiating index tumors and ablated zones during clinical ablations. We also obtained a high correlation between corresponding segmented cross-sectional areas from contrast-enhanced computed tomography, the current clinical gold standard, when compared with EDE strain images, with r2 values of 0.97 and 0.98 for pre- and post-ablation regions.

Adaptation of Dictionary Learning for Electrode Displacement Elastography.

Microwave ablation has become a common treatment method for liver cancers. Unfortunately, microwave ablation success is correlated with clinician's ability for proper electrode placement and assess ablative margins, requiring accurate imaging of liver tumors and ablated zones. Conventionally, ultrasound and computed tomography are utilized for this purpose, yet both have their respective drawbacks. As an alternate approach, electrode displacement elastography offers promise but is still plagued by decorrelation artifacts reducing lesion depiction and visualization. A recent filtering method, namely dictionary representation, has improved contrast-to-noise ratios without reducing delineation contrast. As a supplement to this recent work, this paper evaluates adaptations on this initial dictionary-learning algorithm and applies them to an EDE phantom and 15 in-vivo patient datasets. Two new adaptations of dictionary representations were evaluated, namely a combined dictionary and magnitude-based dictionary representation. When comparing numerical results, the combined dictionary representation algorithm outperforms the previous developed dictionary representation in signal-to-noise (1.54 dB) and contrast-to-noise (0.67 dB) ratios, while a magnitude dictionary representation produces higher noise levels, but improves visualized strain tensor resolution.

Interstitial diffuse optical probe with spectral fitting to measure dynamic tumor hypoxia.

Understanding the dynamic nature of tumor hypoxia is vital for cancer therapy. The presence of oxygen within a tumor during radiation therapy increases the likelihood of local control. We used a novel interstitial diffuse optical probe to make real-time measurements of blood volume fraction and hemoglobin oxygen saturation within a tumor at a high temporal resolution. This device was initially characterized and benchmarked using a customized vessel designed to control hemoglobin oxygen saturation and blood volume in a solution of blood with different concentrations of an oxygen scavenger, tetrakis (hydroxymethyl) phosphonium chloride. The optical device was found to consistently monitor the changes in oxygen saturation and these changes correlated to the concentration of the oxygen scavenger added. In near-simultaneous measurements of blood volume and oxygen saturation in tumor-bearing mice, the changes in blood volume fraction and oxygen saturation measured with the interstitial diffuse optical probe were benchmarked against photoacoustic imaging system to track and compare temporal dynamics of oxygen saturation and blood volume in a patient-derived xenograft model of hypopharyngeal carcinoma. Positive correlations between our device and photoacoustic imaging in measuring blood volume and oxygen saturation were observed.

Physiological Motion Reduction Using Lagrangian Tracking for Electrode Displacement Elastography.

Minimally invasive treatments such as microwave ablation (MWA) have been growing in popularity for extending liver cancer survival rates in patients, when surgery is not an option. As a non-ionizing, real-time alternative to contrast-enhanced computed tomography, electrode displacement elastography (EDE) has shown promise as an imaging modality for MWA. Despite imaging efficacy, motion artifacts caused by physiological motion result in unintended speckle pattern variance, thereby inhibiting consistent and accurate ablated region visualization. To combat these unavoidable motion artifacts, a Lagrangian deformation tracking (LDT) approach based on freehand EDE was developed to track tissue movement and better define tissue properties. For validating LDT efficacy, a spherical inclusion phantom as well as seven in vivo data sets were processed, and strain tensor images were compared with identical time sampled images estimated using a traditional Eulerian approach. In vivo results revealed greater consistency among visualized LDT strain tensor images, with segmented ablated regions exhibiting standard deviation reductions of up to 98% when compared with Eulerian strain tensor images. Additionally, Lagrangian strain tensor images provided Dice coefficient improvements up to 25%, and success rates improved from approximately 50% to nearly 100% for ablated region visualization.

Two-dimensional ultrasound-computed tomography image registration for monitoring percutaneous hepatic intervention.

PURPOSE: Deformable registration of ultrasound (US) and contrast enhanced computed tomography (CECT) images are essential for quantitative comparison of ablation boundaries and dimensions determined using these modalities. This comparison is essential as stiffness-based imaging using US has become popular and offers a nonionizing and cost-effective imaging modality for monitoring minimally invasive microwave ablation procedures. A sensible manual registration method is presented that performs the required CT-US image registration. METHODS: The two-dimensional (2D) virtual CT image plane that corresponds to the clinical US B-mode was obtained by "virtually slicing" the 3D CT volume along the plane containing non-anatomical landmarks, namely points along the microwave ablation antenna. The initial slice plane was generated using the vector acquired by rotating the normal vector of the transverse (i.e., xz) plane along the angle subtended by the antenna. This plane was then further rotated along the ablation antenna and shifted along with the direction of normal vector to obtain similar anatomical structures, such as the liver surface and vasculature that is visualized on both the CT virtual slice and US B-mode images on 20 patients. Finally, an affine transformation was estimated using anatomic and non-anatomic landmarks to account for distortion between the colocated CT virtual slice and US B-mode image resulting in a final registered CT virtual slice. Registration accuracy was measured by estimating the Euclidean distance between corresponding registered points on CT and US B-mode images. RESULTS: Mean and SD of the affine transformed registration error was 1.85 ± 2.14 (mm), computed from 20 coregistered data sets. CONCLUSIONS: Our results demonstrate the ability to obtain 2D virtual CT slices that are registered to clinical US B-mode images. The use of both anatomical and non-anatomical landmarks result in accurate registration useful for validating ablative margins and comparison to electrode displacement elastography based images.

A kernel smoothing algorithm for ablation visualization in ultrasound elastography.

Three-dimensional visualization of tumor ablation procedures have significant clinical value because the ability to accurately visualize ablated volumes can help clinicians gauge the extent of ablated tissue necrosis and plan future treatment steps. Better control over ablation volume can prevent recurrence of tumors treated using ablative procedures. This paper presents a kernel based smoothing algorithm called MatérnSmooth to reconstruct shear wave velocity maps from data acquired through ultrasound electrode vibration elastography. Shear wave velocity estimates are acquired on several intersecting imaging planes that share a common axis of intersection collinear with the ablation needle. An objective method of choosing smoothing parameters from underlying data is outlined through simulations. Experimental validation was performed on data acquired from a tissue mimicking phantom. Volume estimates were found to be within 20% of the true value.

Comparison of Displacement Tracking Algorithms for in Vivo Electrode Displacement Elastography.

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.

Dictionary Representations for Electrode Displacement Elastography.

Ultrasound electrode displacement elastography (EDE) has demonstrated the potential to monitor ablated regions in human patients after minimally invasive microwave ablation procedures. Displacement estimation for EDE is commonly plagued by decorrelation noise artifacts degrading displacement estimates. In this paper, we propose a global dictionary learning approach applied to denoising displacement estimates with an adaptively learned dictionary from EDE phantom displacement maps. The resulting algorithm is one that represents displacement patches sparsely if they contain low noise and averages remaining patches thereby denoising displacement maps while retaining important edge information. The results of dictionary-represented displacements presented with a higher signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) with improved contrast, as well as improved phantom inclusion delineation when compared to initial displacements, median-filtered displacements, and spline smoothened displacements, respectively. In addition to visualized noise reduction, dictionary-represented displacements presented with the highest SNR, CNR, and improved contrast with values of 1.77, 4.56, and 4.35 dB, respectively, when compared to axial strain tensor images estimated using the initial displacements. Following EDE phantom imaging, we utilized dictionary representations from in vivo patient data, further validating efficacy. Denoising displacement estimates are a newer application for dictionary learning producing strong ablated region delineation with little degradation from denoising.

Delineation of Post-Procedure Ablation Regions with Electrode Displacement Elastography with a Comparison to Acoustic Radiation Force Impulse Imaging.

We compared a quasi-static ultrasound elastography technique, referred to as electrode displacement elastography (EDE), with acoustic radiation force impulse imaging (ARFI) for monitoring microwave ablation (MWA) procedures on patients diagnosed with liver neoplasms. Forty-nine patients recruited to this study underwent EDE and ARFI with a Siemens Acuson S2000 system after an MWA procedure. On the basis of visualization results from two observers, the ablated region in ARFI images was recognizable on 20 patients on average in conjunction with B-mode imaging, whereas delineable ablation boundaries could be generated on 4 patients on average. With EDE, the ablated region was delineable on 40 patients on average, with less imaging depth dependence. Study of tissue-mimicking phantoms revealed that the ablation region dimensions measured on EDE and ARFI images were within 8%, whereas the image contrast and contrast-to-noise ratio with EDE was two to three times higher than that obtained with ARFI. This study indicated that EDE provided improved monitoring results for minimally invasive MWA in clinical procedures for liver cancer and metastases.

Monitoring Microwave Ablation of Ex Vivo Bovine Liver Using Ultrasonic Attenuation Imaging.

Thermal ablation of soft tissue changes the tissue microstructure and, consequently, induces changes in its acoustic properties. Although B-mode ultrasound provides high-resolution and high-frame-rate images of ablative therapeutic procedures, it is not particularly effective at delineating boundaries of ablated regions because of poor contrast in echogenicity between ablated and surrounding normal tissue. Quantitative ultrasound techniques can provide quantitative estimates of acoustic properties, such as backscatter and attenuation coefficients, and differentiate ablated and unablated regions more effectively, with the potential for monitoring minimally invasive thermal therapies. In this study, a previously introduced attenuation estimation method was used to create quantitative attenuation coefficient maps for 11 microwave ablation procedures performed on refrigerated ex vivo bovine liver. The attenuation images correlate well with the pathologic images of the ablated region. The mean attenuation coefficient for regions of interest drawn inside and outside the ablated zones were 0.9 (±0.2) and 0.45 (±0.15) dB/cm/MHz, respectively. These estimates agree with reported values in the literature and establish the usefulness of non-invasive attenuation imaging for monitoring therapeutic procedures in the liver.

Efficient 3-D Reconstruction in Ultrasound Elastography via a Sparse Iteration Based on Markov Random Fields.

Percutaneous needle-based liver ablation procedures are becoming increasingly common for the treatment of small isolated tumors in hepatocellular carcinoma patients who are not candidates for surgery. Rapid 3-D visualization of liver ablations has potential clinical value, because it can enable interventional radiologists to plan and execute needle-based ablation procedures with real time feedback. Ensuring the right volume of tissue is ablated is desirable to avoid recurrence of tumors from residual untreated cancerous cells. Shear wave velocity (SWV) measurements can be used as a surrogate for tissue stiffness to distinguish stiffer ablated regions from softer untreated tissue. This paper extends the previously reported sheaf reconstruction method to generate complete 3-D visualizations of SWVs without resorting to an approximate intermediate step of reconstructing transverse C planes. The noisy data are modeled using a Markov random field, and a computationally tractable reconstruction algorithm that can handle grids with millions of points is developed. Results from simulated ellipsoidal inclusion data show that this algorithm outperforms standard nearest neighbor interpolation by an order of magnitude in mean squared reconstruction error. Results from the phantom experiments show that it also provides a higher contrast-to-noise ratio by almost 2 dB and better signal-to-noise ratio in the stiff inclusion by over 2 dB compared with nearest neighbor interpolation and has lower computational complexity than linear and spline interpolation.

Post-Procedure Evaluation of Microwave Ablations of Hepatocellular Carcinomas Using Electrode Displacement Elastography.

Microwave ablation has been used clinically as an alternative to surgical resection. However, lack of real-time imaging to assess treated regions may compromise treatment outcomes. We previously introduced electrode displacement elastography (EDE) for strain imaging and verified its feasibility in vivo on porcine animal models. In this study, we evaluated EDE on 44 patients diagnosed with hepatocellular carcinoma, treated using microwave ablation. The ablated region was identified on EDE images for 40 of the 44 patients. Ablation areas averaged 13.38 ± 4.99 cm2 on EDE, compared with 7.61 ± 3.21 cm2 on B-mode imaging. Contrast and contrast-to-noise ratios obtained with EDE were 232% and 98%, respectively, significantly higher than values measured on B-mode images (p < 0.001). This study indicates that EDE is feasible in patients and provides improved visualization of the ablation zone compared with B-mode ultrasound.

Relative Elastic Modulus Imaging Using Sector Ultrasound Data for Abdominal Applications: An Evaluation of Strategies and Feasibility.

We reconstruct the elastic modulus distribution for one tissue mimicking (TM) phantom and two in vivo biopsy-confirmed liver tumors using curvilinear ultrasound echo data. Spatial distribution of the relative elastic modulus values is determined by solving an inverse problem within a region of interest (ROI). This inverse problem solution requires knowledge of the ultrasonically measured displacement field in a uniform rectilinear grid to ensure that the resolution on the resultant relative elastic modulus elastogram will be uniform over the entire ROI. Taking advantage of a new speckle tracking algorithm, two different displacement tracking strategies are investigated: 1) sector-shaped ultrasound data were converted to ultrasound data on a rectilinear grid prior to speckle tracking and 2) axial and lateral displacements directly obtained from sector-shaped data were converted to vertical and horizontal displacements on a rectilinear grid after speckle tracking. Compared with strain elastography (SE), TM phantom results show that relative elastic modulus imaging (REMI) using Strategy 2 provided higher contrast-to-noise ratios (>300% and 25% increases compared with SE and REMI using Strategy 1, respectively). Furthermore, in phantoms, REMI using Strategy 2 more accurately (a 1.3% difference to shear wave elastography measurements) estimated the elastic contrast ratio between the target and the background, compared with both SE (20%-25%) and REMI using Strategy 1 (4.1%). It was also observed that relative modulus elastograms were more consistent with anatomical structures visualized on corresponding B-mode images for the two in vivo liver cases. Overall, we conclude that applying REMI is feasible for abdominal organs such as the liver. Strategy 2 offered improved and consistent results for the data investigated.

Comparison of three dimensional strain volume reconstructions using SOUPR and wobbler based acquisitions: A phantom study.

PURPOSE: Ultrasound strain imaging is a relatively low cost and portable modality for monitoring percutaneous thermal ablation of liver neoplasms. However, a 3D strain volume reconstruction from existing 2D strain images is necessary to fully delineate the thermal dose distribution. Tissue mimicking (TM) phantom experiments were performed to validate a novel volume reconstruction algorithm referred to as sheaf of ultrasound planes reconstruction (SOUPR), based on a series of 2D rotational imaging planes. METHODS: Reconstruction using SOUPR was formulated as an optimization problem with constraints on data consistency with 2D strain images and data smoothness of the volume data. Reconstructed ablation inclusion dimensions, volume, and elastographic signal to noise ratio (SNRe) and contrast to noise ratio (CNRe) were compared with conventional 3D ultrasound strain imaging based on interpolating a series of quasiparallel 2D strain images with a wobbler transducer. RESULTS: Volume estimates of the phantom inclusion were in a similar range for both acquisition approaches. SNRe and CNRe obtained with SOUPR were significantly higher on the order of 250% and 166%, respectively. The mean error of the inclusion dimension reconstructed with a wobbler transducer was on the order of 10.4%, 3.5%, and 19.0% along the X, Y, and Z axes, respectively, while the error with SOUPR was on the order of 2.6%, 2.8%, and 9.6%. A qualitative comparison of SOUPR and wobbler reconstruction was also performed using a thermally ablated region created in ex vivo bovine liver tissue. CONCLUSIONS: The authors have demonstrated using experimental evaluations with a TM phantom that the reconstruction results obtained with SOUPR were superior when compared with a conventional wobbler transducer in terms of inclusion shape preservation and detectability.

The relationship between carotid artery plaque stability and white matter ischemic injury.

Higher local carotid artery strain has previously been shown to be a characteristic of unstable carotid plaques. These plaques may be characterized by microvascular changes that predispose to intraplaque hemorrhage, increasing the likelihood of embolization. Little is known however, about how these strain indices correspond with imaging markers of brain health and metrics of brain structure. White matter hyperintensities (WMHs), which are bright regions seen on T2-weighted brain MRI imaging, are postulated to result from cumulative ischemic vascular injury. Consequently, we hypothesized that plaques that are more prone to microvascular changes and embolization, represented by higher strain indices on ultrasound, would be associated with an increased amount of WMH lesion volume. This relationship would suggest not only emboli as a cause for the brain degenerative changes, but more importantly, a common microvascular etiology for large and small vessel contributions to this process. Subjects scheduled to undergo a carotid endarterectomy were recruited from a neurosurgery clinic. Prior to surgery, participating subjects underwent both ultrasound strain imaging and brain MRI scans as part of a larger clinical study on vascular health and cognition. A linear regression found that maximum absolute strain and peak to peak strain in the surgical side carotid artery were predictive of WMH burden. Furthermore, the occurrence of microembolic signals monitored using transcranial Doppler (TCD) ultrasound examinations also correlated with increasing lesion burden. It is becoming increasingly recognized that cognitive decline is often multifactorial in nature. One contributing extra-brain factor may be changes in the microvasculature that produce unstable carotid artery plaques. In this study, we have shown that higher strain indices in carotid artery plaques are significantly associated with an increased WMH burden, a marker of vascular mediated brain damage.

Dynamic and quasi-static mechanical testing for characterization of the viscoelastic properties of human uterine tissue.

Ultrasound elastography is envisioned as an optional modality to augment standard ultrasound B-mode imaging and is a promising technique to aid in detecting uterine masses which cause abnormal uterine bleeding in both pre- and post-menopausal women. In order to determine the effectiveness of strain imaging, mechanical testing to establish the elastic contrast between normal uterine tissue and stiffer masses such as leiomyomas (fibroids) and between softer pathologies such as uterine cancer and adenomyosis has to be performed. In this paper, we evaluate the stiffness of normal uterine tissue, leiomyomas, and endometrial cancers using a EnduraTEC ElectroForce (ELF) system. We quantify the viscoelastic characteristics of uterine tissue and associated pathologies globally by using two mechanical testing approaches, namely a dynamic and a quasi-static (ramp testing) approach. For dynamic testing, 21 samples obtained from 18 patients were tested. The testing frequencies were set to 1, 10, 20, and 30 Hz. We also report on stiffness variations with pre-compression from 1% to 6% for testing at 2%, 3%, and 4% strain amplitude. Our results show that human uterine tissue stiffness is both dependent on percent pre-compression and testing frequencies. For ramp testing, 20 samples obtained from 14 patients were used. A constant strain rate of 0.1% was applied and comparable results to dynamic testing were obtained. The mean modulus contrast at 2% amplitude between normal uterine tissue (the background) and leiomyomas was 2.29 and 2.17, and between the background and cancer was 0.47 and 0.39 for dynamic and ramp testing, respectively.