Methods in 'Stroke Prevention in the Wisconsin Native American Population'.

Native American individuals are more frequently affected by cerebrovascular diseases including stroke and vascular cognitive decline. The aim of this study is to determine stroke risk factors that are most prevalent in Wisconsin Native Americans and to examine how education at the community and individual level as well as intensive health wellness coaching may influence modification of stroke risk factors. Additionally, we will investigate the role novel stroke biomarkers may play in stroke risk in this population. This paper details the aims and methods employed in the "Stroke Prevention in the Wisconsin Native American Population" (clinicaltrials.gov identifier: NCT04382963) study including participant health assessments, clinical ultrasound exam of the carotid arteries, cognitive testing battery and structure and execution of the coaching program.

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.

Carotid Plaque Strain Indices Were Correlated With Cognitive Performance in a Cohort With Advanced Atherosclerosis, and Traditional Doppler Measures Showed no Association.

OBJECTIVES: Traditional Doppler measures have been used to predict cognitive performance in patients with carotid atherosclerosis. Novel measures, such as carotid plaque strain indices (CPSIs), have shown associations with cognitive performance. We hypothesized that lower mean middle cerebral artery (MCA) velocities, higher bulb-internal carotid artery (ICA) velocities, the MCA pulsatility index (PI), and CPSIs would be associated with poorer cognitive performance in individuals with advanced atherosclerosis. METHODS: Neurocognitive testing, carotid ultrasound imaging, transcranial Doppler imaging, and carotid strain imaging were performed on 40 patients scheduled for carotid endarterectomy. Kendall tau correlations were used to examine relationships between cognitive tests and the surgical-side maximum peak systolic velocity (PSV; from the bulb, proximal, mid, or distal ICA), mean MCA velocity and PI, and maximum CPSIs (axial, lateral, and shear strain indices used to characterize plaque deformations with arterial pulsation). Cognitive measures included age-adjusted indices of verbal fluency, verbal and visual learning/memory, psychomotor speed, auditory attention/working memory, visuospatial construction, and mental flexibility. RESULTS: Participants had a median age of 71.0 (interquartile range, 9.75) years; 26 were male (65%), and 14 were female (35%). Traditional Doppler parameters, PSV, mean MCA velocity, and MCA PI did not predict cognitive performance (all P > .05). Maximum CPSIs were significantly associated with cognitive performance (P < .05). CONCLUSIONS: Traditional velocity measurements of the maximum bulb-ICA PSV, mean MCA velocity, and PI were not associated with cognitive performance in patients with advanced atherosclerotic disease; however, maximum CPSIs were associated with cognitive performance. These findings suggest that cognition may be associated with unstable plaque rather than blood flow.

Deep Learning for Carotid Plaque Segmentation using a Dilated U-Net Architecture.

Carotid plaque segmentation in ultrasound longitudinal B-mode images using deep learning is presented in this work. We report on 101 severely stenotic carotid plaque patients. A standard U-Net is compared with a dilated U-Net architecture in which the dilated convolution layers were used in the bottleneck. Both a fully automatic and a semi-automatic approach with a bounding box was implemented. The performance degradation in plaque segmentation due to errors in the bounding box is quantified. We found that the bounding box significantly improved the performance of the networks with U-Net Dice coefficients of 0.48 for automatic and 0.83 for semi-automatic segmentation of plaque. Similar results were also obtained for the dilated U-Net with Dice coefficients of 0.55 for automatic and 0.84 for semi-automatic when compared to manual segmentations of the same plaque by an experienced sonographer. A 5% error in the bounding box in both dimensions reduced the Dice coefficient to 0.79 and 0.80 for U-Net and dilated U-Net respectively.

Influence of Ultrasound System and Gain on Grayscale Median Values.

OBJECTIVES: The purpose of this study was to determine the reliability of grayscale median (GSM) measurements across different ultrasound (US) systems and effects of gain on GSM values. METHODS: Two vessels in a grayscale vascular phantom were imaged with 7 US systems at 3 gain settings. Two human participants were imaged at 3 gain settings. Each image was normalized, standardized, and segmented by expert and novice readers using grayscale analysis software. The concordance correlation coefficient (CCC) assessed agreement of GSM values for each system across gain settings and vessels and between readers. The intraclass correlation coefficient (ICC) assessed system-level reader concordance across gain settings and vessels. A general linear mixed model for repeated measures was used to assess within- and between-system mean GSM values. RESULTS: Grayscale median measurements performed on images from the same US system yielded excellent (CCC) (95% confidence intervals): 0.85 (0.75, 0.92) to 0.96 (0.92, 0.98). ICC per system were 0.94 to 0.98 for the expert reader and 0.85 to 0.95 for the novice reader. Gain adjustments above and below an optimal setting contributed to significantly different intrasystem GSM values on 4 of 7 systems in the near zone and 5 of 7 systems in the far zone (P < .05). Intersystem GSM values differed on 5 of 7 systems (P < .05). Images from the human participants showed differences in GSM values at optimum gain values ± 10 dB/%. CONCLUSIONS: Grayscale median measurements are highly reproducible when obtained from the same US system with similar gain settings. Grayscale median values differ significantly across gain values and between systems. Researchers should consider the impact of US system and gain settings on GSM values when working to minimize system- and operator-dependent factors.

Lagrangian carotid strain imaging indices normalized to blood pressure for vulnerable plaque.

OBJECTIVE: Ultrasound Lagrangian carotid strain imaging (LCSI) utilizes physiological deformation caused by arterial pressure variations to generate strain tensor maps of the vessel walls and plaques. LCSI has been criticized for the lack of normalization of magnitude-based strain indices to physiological stimuli, namely blood pressure. We evaluated the impact of normalization of magnitude-based strain indices to blood pressure measured immediately after the acquisition of radiofrequency (RF) data loops for LCSI. MATERIALS AND METHODS: A complete clinical ultrasound examination along with RF data loops for LCSI was performed on 50 patients (30 males and 20 females) who presented with >60% carotid stenosis and were scheduled for carotid endarterectomy. Cognition was assessed using the 60-minute neuropsychological test protocol. RESULTS: For axial strains correlation of maximum accumulated strain indices (MASI), cognition scores were -0.46 for non-normalized and -0.45, -0.49, -0.37, and -0.48 for systolic, diastolic, pulse pressure, and mean arterial pressure normalized data, respectively. The corresponding area under the curve (AUC) values for classifiers designed using maximum likelihood estimation of a binormal distribution with a median-split of the executive function cognition scores were 0.73, 0.70, 0.71, 0.70, and 0.71, respectively. CONCLUSIONS: No significant differences in the AUC estimates were obtained between normalized and non-normalized magnitude-based strain indices.

Lower Bound on Estimation Variance of the Ultrasonic Attenuation Coefficient Using the Spectral-Difference Reference-phantom Method.

Ultrasonic attenuation is one of the primary parameters of interest in Quantitative Ultrasound (QUS). Non-invasive monitoring of tissue attenuation can provide valuable diagnostic and prognostic information to the physician. The Reference Phantom Method (RPM) was introduced as a way of mitigating some of the system-related effects and biases to facilitate clinical QUS applications. In this paper, under the assumption of diffuse scattering, a probabilistic model of the backscattered signal spectrum is used to derive a theoretical lower bound on the estimation variance of the attenuation coefficient using the Spectral-Difference RPM. The theoretical lower bound is compared to simulated and experimental attenuation estimation statistics in tissue-mimicking (TM) phantoms. Estimation standard deviation (STD) of the sample attenuation in a region of interest (ROI) of the TM phantom is measured for various combinations of processing parameters, including Radio-Frequency (RF) data block length (i.e., window length) from 3 to 17 mm, RF data block width from 10 to 100 A-lines, and number of RF data blocks per attenuation estimation ROI from 3 to 10. In addition to the Spectral-Difference RPM, local attenuation estimation for simulated and experimental data sets was also performed using a modified implementation of the Spectral Fit Method (SFM). Estimation statistics of the SFM are compared to theoretical variance predictions from the literature.1 Measured STD curves are observed to lie above the theoretical lower bound curves, thus experimentally verifying the validity of the derived bounds. This theoretical framework benefits tissue characterization efforts by isolating processing parameter ranges that could provide required precision levels in estimation of the ultrasonic attenuation coefficient using Spectral Difference methods.

Segmental Analysis of Cardiac Short-Axis Views Using Lagrangian Radial and Circumferential Strain.

Accurate description of myocardial deformation in the left ventricle is a three-dimensional problem, requiring three normal strain components along its natural axis, that is, longitudinal, radial, and circumferential strains. Although longitudinal strains are best estimated from long-axis views, radial and circumferential strains are best depicted in short-axis views. An algorithm that utilizes a polar grid for short-axis views previously developed in our laboratory for a Lagrangian description of tissue deformation is utilized for radial and circumferential displacement and strain estimation. Deformation of the myocardial wall, utilizing numerical simulations with ANSYS, and a finite-element analysis-based canine heart model were adapted as the input to a frequency-domain ultrasound simulation program to generate radiofrequency echo signals. Clinical in vivo data were also acquired from a healthy volunteer. Local displacements estimated along and perpendicular to the ultrasound beam propagation direction are then transformed into radial and circumferential displacements and strains using the polar grid based on a pre-determined centroid location. Lagrangian strain variations demonstrate good agreement with the ideal strain when compared with Eulerian results. Lagrangian radial and circumferential strain estimation results are also demonstrated for experimental data on a healthy volunteer. Lagrangian radial and circumferential strain tracking provide accurate results with the assistance of the polar grid, as demonstrated using both numerical simulations and in vivo study.

Slope Estimation in Noisy Piecewise Linear Functions.

This paper discusses the development of a slope estimation algorithm called MAPSlope for piecewise linear data that is corrupted by Gaussian noise. The number and locations of slope change points (also known as breakpoints) are assumed to be unknown a priori though it is assumed that the possible range of slope values lies within known bounds. A stochastic hidden Markov model that is general enough to encompass real world sources of piecewise linear data is used to model the transitions between slope values and the problem of slope estimation is addressed using a Bayesian maximum a posteriori approach. The set of possible slope values is discretized, enabling the design of a dynamic programming algorithm for posterior density maximization. Numerical simulations are used to justify choice of a reasonable number of quantization levels and also to analyze mean squared error performance of the proposed algorithm. An alternating maximization algorithm is proposed for estimation of unknown model parameters and a convergence result for the method is provided. Finally, results using data from political science, finance and medical imaging applications are presented to demonstrate the practical utility of this procedure.

Mean scatterer spacing estimation in normal and thermally coagulated ex vivo bovine liver.

The liver has been hypothesized to have a unique arrangement of microvasculature that presents as an arrangement of quasiperiodic scatterers to an interrogating ultrasound pulse. The mean scatterer spacing (MSS) of these quasiperiodic scatterers has been proposed as a useful quantitative ultrasound biomarker for characterizing liver tissue. Thermal ablation is an increasingly popular method for treating hepatic tumors, and ultrasonic imaging approaches for delineating the extent of thermal ablation are in high demand. In this work, we examine the distribution of estimated MSS in thermally coagulated bovine liver and normal untreated bovine liver ex vivo. We estimate MSS by detecting local maxima in the spectral coherence function of radio frequency echoes from a clinical transducer, the Siemens VFX 9L4 transducer operating on an S2000 scanner. We find that normal untreated bovine liver was characterized by an MSS of approximately 1.3 mm. We examined regions of interest 12 mm wide laterally, and ranging from 12 mm to 18 mm axially, in 2 mm increments. Over these parameters, the mode of the MSS estimates was between 1.25 and 1.37 mm. On the other hand, estimation of MSS in thermally coagulated liver tissue yields a distribution of MSS estimates whose mode varied between 0.45 and 1.0 mm when examining regions of interest over the same sizes. We demonstrate that the estimated MSS in thermally coagulated liver favors small spacings because the randomly positioned scatterers in this tissue are better modeled as aperiodic scatterers. The submillimeter spacings result from the fact that this was the most probable spacing to be estimated if the discretely sampled spectral coherence function was a uniformly random two-dimensional function.

Lumen segmentation using a Mask R-CNN in carotid arteries with stenotic atherosclerotic plaque.

In patients at high risk for ischemic stroke, clinical carotid ultrasound is often used to grade stenosis, determine plaque burden and assess stroke risk. Analysis currently requires a trained sonographer to manually identify vessel and plaque regions, which is time and labor intensive. We present a method for automatically determining bounding boxes and lumen segmentation using a Mask R-CNN network trained on sonographer assisted ground-truth carotid lumen segmentations. Automatic lumen segmentation also lays the groundwork for developing methods for accurate plaque segmentation, and wall thickness measurements in cases with no plaque. Different training schemes are used to identify the Mask R-CNN model with the highest accuracy. Utilizing a single-channel B-mode training input, our model produces a mean bounding box intersection over union (IoU) of 0.81 and a mean lumen segmentation IoU of 0.75. However, we encountered errors in prediction when the jugular vein is the most prominently visualized vessel in the B-mode image. This was due to the fact that our dataset has limited instances of B-mode images with both the jugular vein and carotid artery where the vein is dominantly visualized. Additional training datasets are anticipated to mitigate this issue.

Transrectal quantitative shear wave elastography in the detection and characterisation of prostate cancer.

BACKGROUND: Shear wave imaging (SWI) is a new ultrasound technique whose application facilitates quantitative tissue elasticity assessment during transrectal ultrasound biopsies of the prostate gland. The aim of this study was to determine whether SWI quantitative data can differentiate between benign and malignant areas within prostate glands in men suspected of prostate cancer (PCa). METHODS: We conducted a protocol-based, prospective, prebiopsy quantitative SWI of prostate glands in 50 unscreened men suspected of prostate cancer between July 2011 and May 2012. The ultrasound image of whole prostate gland was arbitrarily divided into 12 zones for sampling biopsies, as is carried out in routine clinical practice. Each region was imaged by grey scale and SWI imaging techniques. Each region was further biopsied irrespective of findings of grey scale or SWI on ultrasound. Additional biopsies were taken if SWI abnormal area was felt to be outside of these 12 zones. Quantitative assessment of SWI abnormal areas was obtained in kilopascals (kPa) from abnormal regions shown by SWI and compared with histopathology. Sensitivity, specificity, positive and negative predictive values, and likelihood ratios were calculated for SWI (histopathology was a reference standard). RESULTS: Fifty patients, with a mean age of 69 ± 6.2 years, were recruited into the study. Thirty-three (66%) patients were diagnosed with PCa, while an additional 4 (8%) had atypia in at least one of the 12 prostate biopsies. Thirteen (26%) patients had a benign biopsy. Data analysed per core for SWI findings showed that for patients with PSA <20 µg/L, the sensitivity and specificity of SWI for PCa detection were 0.9 and 0.88, respectively, while in patients with PSA >20 µg/L, the sensitivity and specificity were 0.93 and 0.93, respectively. In addition, PCa had significantly higher stiffness values compared to benign tissues (p <0.05), with a trend toward stiffness differences in different Gleason grades. CONCLUSION: SWI provides quantitative assessment of the prostatic tissues and, in our preliminary observation, provides better diagnostic accuracy than grey-scale ultrasound imaging.

In Vivo Adaptive Bayesian Regularized Lagrangian Carotid Strain Imaging for Murine Carotid Arteries and Its Associations With Histological Findings.

OBJECTIVES: Non-invasive methods for monitoring arterial health and identifying early injury to optimize treatment for patients are desirable. The objective of this study was to demonstrate the use of an adaptive Bayesian regularized Lagrangian carotid strain imaging (ABR-LCSI) algorithm for monitoring of atherogenesis in a murine model and examine associations between the ultrasound strain measures and histology. METHODS: Ultrasound radiofrequency (RF) data were acquired from both the right and left common carotid artery (CCA) of 10 (5 male and 5 female) ApoE tm1Unc/J mice at 6, 16 and 24 wk. Lagrangian accumulated axial, lateral and shear strain images and three strain indices-maximum accumulated strain index (MASI), peak mean strain of full region of interest (ROI) index (PMSRI) and strain at peak axial displacement index (SPADI)-were estimated using the ABR-LCSI algorithm. Mice were euthanized (n = 2 at 6 and 16 wk, n = 6 at 24 wk) for histology examination. RESULTS: Sex-specific differences in strain indices of mice at 6, 16 and 24 wk were observed. For male mice, axial PMSRI and SPADI changed significantly from 6 to 24 wk (mean axial PMSRI at 6 wk = 14.10 ± 5.33% and that at 24 wk = -3.03 ± 5.61%, p < 0.001). For female mice, lateral MASI increased significantly from 6 to 24 wk (mean lateral MASI at 6 wk = 10.26 ± 3.13% and that at 24 wk = 16.42 ± 7.15%, p = 0.048). Both cohorts exhibited strong associations with ex vivo histological findings (male mice: correlation between number of elastin fibers and axial PMSRI: rs = 0.83, p = 0.01; female mice: correlation between shear MASI and plaque score: rs = 0.77, p = 0.009). CONCLUSION: The results indicate that ABR-LCSI can be used to measure arterial wall strain in a murine model and that changes in strain are associated with changes in arterial wall structure and plaque formation.

Changes in carotid artery texture by ultrasound and elastin features in a murine model.

Objective: In humans, arterial grayscale ultrasound texture features independently predict adverse cardiovascular disease (CVD) events and change with medical interventions. We performed this study to examine how grayscale ultrasound texture features and elastin fibers change in plaque-free segments of the arterial wall in a murine model prone to atherosclerosis. Methods: A total of 10 Apoetm1Unc/J mice (n = 5 male, n = 5 female) were imaged at 6, 16, and 24 weeks of age. Two mice were euthanized at 6 and 16 weeks and the remaining mice at 24 weeks. Texture features were extracted from the ultrasound images of the distal 1.0 mm of the common carotid artery wall, and elastin measures were extracted from histology images. Two-way analysis of variance was used to evaluate associations between week, sex, and grayscale texture features. Texture feature and elastin number comparisons between weeks were conducted using the sex-by-week two-way interaction contrasts. Sex-specific correlations between the number of elastin fibers and grayscale texture features were analyzed by conducting non-parametric Spearman's rank correlation analyses. Results: Arterial wall homogeneity changed significantly in male mice from 6 to 24 weeks, with a mean (SD) of 0.14 (0.03) units at 6 weeks and 0.18 (0.03) units at 24 weeks (p = 0.026). Spatial gray level dependence matrices-homogeneity (SGLD-HOM) also correlated with carotid artery plaque score (rs = 0.707, p = 0.033). Elastin fibers in the region of interest decreased from 6 to 24 weeks for both male and female mice, although only significantly in male mice. The mean (SD) number of elastin fibers for male mice was 5.32 (1.50) at 6 weeks and 3.59 (0.38) at 24 weeks (p = 0.023). For female mice, the mean (SD) number of elastin fibers was 3.98 (0.38) at 6 weeks and 3.46 (0.19) at 24 weeks (p = 0.051). Conclusion: Grayscale ultrasound texture features that are associated with increased risk for CVD events in humans were used in a murine model, and the grayscale texture feature SGLD-HOM was shown to change in male mice from 6 weeks to 24 weeks. Structural alterations of the arterial wall (change in elastin fiber number) were observed during this time and may differ by sex.

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.

Lagrangian displacement tracking using a polar grid between endocardial and epicardial contours for cardiac strain imaging.

PURPOSE: Accurate cardiac deformation analysis for cardiac displacement and strain imaging over time requires Lagrangian description of deformation of myocardial tissue structures. Failure to couple the estimated displacement and strain information with the correct myocardial tissue structures will lead to erroneous result in the displacement and strain distribution over time. METHODS: Lagrangian based tracking in this paper divides the tissue structure into a fixed number of pixels whose deformation is tracked over the cardiac cycle. An algorithm that utilizes a polar-grid generated between the estimated endocardial and epicardial contours for cardiac short axis images is proposed to ensure Lagrangian description of the pixels. Displacement estimates from consecutive radiofrequency frames were then mapped onto the polar grid to obtain a distribution of the actual displacement that is mapped to the polar grid over time. RESULTS: A finite element based canine heart model coupled with an ultrasound simulation program was used to verify this approach. Segmental analysis of the accumulated displacement and strain over a cardiac cycle demonstrate excellent agreement between the ideal result obtained directly from the finite element model and our Lagrangian approach to strain estimation. Traditional Eulerian based estimation results, on the other hand, show significant deviation from the ideal result. An in vivo comparison of the displacement and strain estimated using parasternal short axis views is also presented. CONCLUSIONS: Lagrangian displacement tracking using a polar grid provides accurate tracking of myocardial deformation demonstrated using both finite element and in vivo radiofrequency data acquired on a volunteer. In addition to the cardiac application, this approach can also be utilized for transverse scans of arteries, where a polar grid can be generated between the contours delineating the outer and inner wall of the vessels from the blood flowing though the vessel.

Visualizing ex vivo radiofrequency and microwave ablation zones using electrode vibration elastography.

PURPOSE: Electrode vibration elastography is a new shear wave imaging technique that can be used to visualize thermal ablation zones. Prior work has shown the ability of electrode vibration elastography to delineate radiofrequency ablations; however, there has been no previous study of delineation of microwave ablations or radiological-pathological correlations using multiple observers. METHODS: Radiofrequency and microwave ablations were formed in ex vivo bovine liver tissue. Their visualization was compared on shear wave velocity and maximum displacement images. Ablation dimensions were compared to gross pathology. Elastographic imaging and gross pathology overlap and interobserver variability were quantified using similarity measures. RESULTS: Elastographic imaging correlated with gross pathology. Correlation of area estimates was better in radiofrequency than in microwave ablations, with Pearson coefficients of 0.79 and 0.54 on shear wave velocity images and 0.90 and 0.70 on maximum displacement images for radiofrequency and microwave ablations, respectively. The absolute relative difference in area between elastographic imaging and gross pathology was 18.9% and 22.9% on shear wave velocity images and 16.0% and 23.1% on maximum displacement images for radiofrequency and microwave ablations, respectively. CONCLUSIONS: Statistically significant radiological-pathological correlation was observed in this study, but correlation coefficients were lower than other modulus imaging techniques, most notably in microwave ablations. Observers provided similar delineations for most thermal ablations. These results suggest that electrode vibration elastography is capable of imaging thermal ablations, but refinement of the technique may be necessary before it can be used to monitor thermal ablation procedures clinically.

Displacement and strain estimation for evaluation of arterial wall stiffness using a familial hypercholesterolemia swine model of atherosclerosis.

PURPOSE: To track variations in the deformation of the arterial wall noninvasively by estimating the accumulated displacement and strain over a cardiac cycle may provide useful indicators of vascular health. METHODS: In this paper, we propose an approach to track a region of interest (ROI) locally and estimate arterial stiffness variation in a familial hypercholesterolemic swine model of spontaneous atherosclerosis that allows for systematic and reproducible study of progression of the disease mechanism. RESULTS: Strain and displacement indices may be derived from the variations of the accumulated displacement and accumulated strain (obtained from the gradient of the accumulated displacement) over a cardiac cycle to predict not only the likelihood of developing vascular diseases, but also the sites where they may occur. Currently, an ROI thickness value of less than one mm within the arterial wall is necessary for the axial accumulated displacement and strain to obtain reproducible estimates. CONCLUSIONS: Accumulated axial displacement and strain estimation on the artery wall shown in this paper indicate the repeatability of these measurements over several cardiac cycles and over five familial hypercholesterolemic swine. Our results also demonstrate the need for a small region of interest within the arterial walls for accurate and robust estimates of arterial function.

A novel saline infusion sonohysterography-based strain imaging approach for evaluation of uterine abnormalities in vivo: preliminary results.

In this article, we demonstrate the feasibility of saline infusion sonohysterography-based strain imaging for the determination of stiffness variations in uterine masses in vivo. Strain images are estimated using a 2-dimensional multilevel hybrid algorithm developed for sector array ultrasound transducers. Coarse displacements are initially estimated using envelope echo signals, followed by a guided finer displacement estimation using window lengths on the order of 6 wavelengths and 7 A-lines on radiofrequency data. Strain images are obtained by estimating displacement slopes using least squares estimation. In this prospective study, we show that stiffer masses such as fibroids appear darker or as regions with low strain on strain images and are thus clearly differentiated when compared to normal uterine tissue. A high strain boundary around stiffer masses referred to as a "halo" due to increased slipping or sliding of the mass during the applied deformation is also visualized. Uterine polyps, on the other hand, are visualized as masses that are brighter or regions with high strain when compared to the background myometrium, indicating the presence of a softer mass. Axial strain images provide additional new information that may supplement current clinical B-mode imaging used for the diagnosis of uterine abnormalities. Our results show the feasibility of improving clinical diagnosis based on strain imaging.

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).