A Hybrid Deep Learning Approach to Identify Preventable Childhood Hearing Loss.

OBJECTIVE: Childhood hearing loss has well-known, lifelong consequences. Infection-related hearing loss disproportionately affects underserved communities yet can be prevented with early identification and treatment. This study evaluates the utility of machine learning in automating tympanogram classifications of the middle ear to facilitate layperson-guided tympanometry in resource-constrained communities. DESIGN: Diagnostic performance of a hybrid deep learning model for classifying narrow-band tympanometry tracings was evaluated. Using 10-fold cross-validation, a machine learning model was trained and evaluated on 4810 pairs of tympanometry tracings acquired by an audiologist and layperson. The model was trained to classify tracings into types A (normal), B (effusion or perforation), and C (retraction), with the audiologist interpretation serving as reference standard. Tympanometry data were collected from 1635 children from October 10, 2017, to March 28, 2019, from two previous cluster-randomized hearing screening trials (NCT03309553, NCT03662256). Participants were school-aged children from an underserved population in rural Alaska with a high prevalence of infection-related hearing loss. Two-level classification performance statistics were calculated by treating type A as pass and types B and C as refer. RESULTS: For layperson-acquired data, the machine-learning model achieved a sensitivity of 95.2% (93.3, 97.1), specificity of 92.3% (91.5, 93.1), and area under curve of 0.968 (0.955, 0.978). The model's sensitivity was greater than that of the tympanometer's built-in classifier [79.2% (75.5, 82.8)] and a decision tree based on clinically recommended normative values [56.9% (52.4, 61.3)]. For audiologist-acquired data, the model achieved a higher AUC of 0.987 (0.980, 0.993), had an equivalent sensitivity of 95.2 (93.3, 97.1), and a higher specificity of 97.7 (97.3, 98.2). CONCLUSIONS: Machine learning can detect middle ear disease with comparable performance to an audiologist using tympanograms acquired either by an audiologist or a layperson. Automated classification enables the use of layperson-guided tympanometry in hearing screening programs in rural and underserved communities, where early detection of treatable pathology in children is crucial to prevent the lifelong adverse effects of childhood hearing loss.

Combined ARFI and Shear Wave Imaging of Prostate Cancer: Optimizing Beam Sequences and Parameter Reconstruction Approaches.

This study demonstrates the implementation of a shear wave reconstruction algorithm that enables concurrent acoustic radiation force impulse (ARFI) imaging and shear wave elasticity imaging (SWEI) of prostate cancer and zonal anatomy. The combined ARFI/SWEI sequence uses closely spaced push beams across the lateral field of view and simultaneously tracks both on-axis (within the region of excitation) and off-axis (laterally offset from the excitation) after each push beam. Using a large number of push beams across the lateral field of view enables the collection of higher signal-to-noise ratio (SNR) shear wave data to reconstruct the SWEI volume than is typically acquired. The shear wave arrival times were determined with cross-correlation of shear wave velocity signals in two dimensions after 3-D directional filtering to remove reflection artifacts. To combine data from serially interrogated lateral push locations, arrival times from different pushes were aligned by estimating the shear wave propagation time between push locations. Shear wave data acquired in an elasticity lesion phantom and reconstructed using this algorithm demonstrate benefits to contrast-to-noise ratio (CNR) with increased push beam density and 3-D directional filtering. Increasing the push beam spacing from 0.3 to 11.6 mm (typical for commercial SWEI systems) resulted in a 53% decrease in CNR. In human in vivo data, this imaging approach enabled high CNR (1.61-1.86) imaging of histologically-confirmed prostate cancer. The in vivo images had improved spatial resolution and CNR and fewer reflection artifacts as a result of the high push beam density, the high shear wave SNR, the use of multidimensional directional filtering, and the combination of shear wave data from different push beams.

Radiological Society of North America/Quantitative Imaging Biomarker Alliance Shear Wave Speed Bias Quantification in Elastic and Viscoelastic Phantoms.

OBJECTIVES: To quantify the bias of shear wave speed (SWS) measurements between different commercial ultrasonic shear elasticity systems and a magnetic resonance elastography (MRE) system in elastic and viscoelastic phantoms. METHODS: Two elastic phantoms, representing healthy through fibrotic liver, were measured with 5 different ultrasound platforms, and 3 viscoelastic phantoms, representing healthy through fibrotic liver tissue, were measured with 12 different ultrasound platforms. Measurements were performed with different systems at different sites, at 3 focal depths, and with different appraisers. The SWS bias across the systems was quantified as a function of the system, site, focal depth, and appraiser. A single MRE research system was also used to characterize these phantoms using discrete frequencies from 60 to 500 Hz. RESULTS: The SWS from different systems had mean difference 95% confidence intervals of ±0.145 m/s (±9.6%) across both elastic phantoms and ± 0.340 m/s (±15.3%) across the viscoelastic phantoms. The focal depth and appraiser were less significant sources of SWS variability than the system and site. Magnetic resonance elastography best matched the ultrasonic SWS in the viscoelastic phantoms using a 140 Hz source but had a - 0.27 ± 0.027-m/s (-12.2% ± 1.2%) bias when using the clinically implemented 60-Hz vibration source. CONCLUSIONS: Shear wave speed reconstruction across different manufacturer systems is more consistent in elastic than viscoelastic phantoms, with a mean difference bias of < ±10% in all cases. Magnetic resonance elastographic measurements in the elastic and viscoelastic phantoms best match the ultrasound systems with a 140-Hz excitation but have a significant negative bias operating at 60 Hz. This study establishes a foundation for meaningful comparison of SWS measurements made with different platforms.

Semi-automated weak annotation for deep neural network skin thickness measurement.

Correctly calculating skin stiffness with ultrasound shear wave elastography techniques requires an accurate measurement of skin thickness. We developed and compared two algorithms, a thresholding method and a deep learning method, to measure skin thickness on ultrasound images. Here, we also present a framework for weakly annotating an unlabeled dataset in a time-effective manner to train the deep neural network. Segmentation labels for training were proposed using the thresholding method and validated with visual inspection by a human expert reader. We reduced decision ambiguity by only inspecting segmentations at the center A-line. This weak annotation approach facilitated validation of over 1000 segmentation labels in 2 hours. A lightweight deep neural network that segments entire 2D images was designed and trained on this weakly-labeled dataset. Averaged over six folds of cross-validation, segmentation accuracy was 57% for the thresholding method and 78% for the neural network. In particular, the network was better at finding the distal skin margin, which is the primary challenge for skin segmentation. Both algorithms have been made publicly available to aid future applications in skin characterization and elastography.

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

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

Apparent Diffusion Coefficient Values of the Benign Central Zone of the Prostate: Comparison With Low- and High-Grade Prostate Cancer.

OBJECTIVE: The apparent diffusion coefficient (ADC) values for benign central zone (CZ) of the prostate were compared with ADC values of benign peripheral zone (PZ), benign transition zone (TZ), and prostate cancer, using histopathologic findings from radical prostatectomy as the reference standard. MATERIALS AND METHODS: The study included 27 patients with prostate cancer (mean [± SD] age, 60.0 ± 7.6 years) who had 3-T endorectal coil MRI of the prostate performed before undergoing prostatectomy with whole-mount histopathologic assessment. Mean ADC values were recorded from the ROI within the index tumor and within benign CZ, PZ, and TZ, with the use of histopathologic findings as the reference standard. ADC values of the groups were compared using paired t tests and ROC curve analysis. RESULTS: The ADC of benign CZ in the right (1138 ± 123 × 10(-6) mm(2)/s) and left (1166 ± 141 × 10(-6) mm(2)/s) lobes was not significantly different (p = 0.217). However, the ADC of benign CZ (1154 ± 129 × 10(-6) mm(2)/s) was significantly lower (p < 0.001) than the ADCs of benign PZ (1579 ± 197 × 10(-6) mm(2)/s) and benign TZ (1429 ± 180 × 10(-6) mm(2)/s). Although the ADC of index tumors (1042 ± 134 × 10(-6) mm(2)/s) was significantly lower (p = 0.002) than the ADC of benign CZ there was no significant difference (p = 0.225) between benign CZ and tumors with a Gleason score of 6 (1119 ± 87 × 10(-6) mm(2)/s). In 22.2% of patients (6/27), including five patients who had tumors with a Gleason score greater than 6, the ADC was lower in benign CZ than in the index tumor. The AUC of ADC for the differentiation of benign CZ from index tumors was 72.4% (sensitivity, 70.4%; specificity, 51.9%), and the AUC of ADC for differentiation from tumors with a Gleason score greater than 6 was 76.7% (sensitivity, 75.0%; specificity, 65.0%). CONCLUSION: The ADC of benign CZ is lower than the ADC of other zones of the prostate and overlaps with the ADC of prostate cancer tissue, including high-grade tumors. Awareness of this potential diagnostic pitfall is important to avoid misinterpreting the normal CZ as suspicious for tumor.

Detection of prostate cancer with multiparametric MRI (mpMRI): effect of dedicated reader education on accuracy and confidence of index and anterior cancer diagnosis.

PURPOSE: To evaluate the impact of dedicated reader education on accuracy/confidence of peripheral zone index cancer and anterior prostate cancer (PCa) diagnosis with mpMRI; secondary aim was to assess the ability of readers to differentiate low-grade cancer (Gleason 6 or below) from high-grade cancer (Gleason 7+). MATERIALS AND METHODS: Five blinded radiology fellows evaluated 31 total prostate mpMRIs in this IRB-approved, HIPAA-compliant, retrospective study for index lesion detection, confidence in lesion diagnosis (1-5 scale), and Gleason grade (Gleason 6 or lower vs. Gleason 7+). Following a dedicated education program, readers reinterpreted cases after a memory extinction period, blinded to initial reads. Reference standard was established combining whole mount histopathology with mpMRI findings by a board-certified radiologist with 5 years of prostate mpMRI experience. RESULTS: Index cancer detection: pre-education accuracy 74.2%; post-education accuracy 87.7% (p = 0.003). Confidence in index lesion diagnosis: pre-education 4.22 ± 1.04; post-education 3.75 ± 1.41 (p = 0.0004). Anterior PCa detection: pre-education accuracy 54.3%; post-education accuracy 94.3% (p = 0.001). Confidence in anterior PCa diagnosis: pre-education 3.22 ± 1.54; post-education 4.29 ± 0.83 (p = 0.0003). Gleason score accuracy: pre-education 54.8%; post-education 73.5% (p = 0.0005). CONCLUSIONS: A dedicated reader education program on PCa detection with mpMRI was associated with a statistically significant increase in diagnostic accuracy of index cancer and anterior cancer detection as well as Gleason grade identification as compared to pre-education values. This was also associated with a significant increase in reader diagnostic confidence. This suggests that substantial interobserver variability in mpMRI interpretation can potentially be reduced with a focus on education and that this can occur over a fellowship training year.

An analytic, Fourier domain description of shear wave propagation in a viscoelastic medium using asymmetric Gaussian sources.

Recent measurements of shear wave propagation in viscoelastic materials have been analyzed by constructing the two-dimensional Fourier transform (2D-FT) of the spatial-temporal shear wave signal and using an analysis procedure derived under the assumption the wave is described as a plane wave, or as the asymptotic form of a wave expanding radially from a cylindrically symmetric source. This study presents an exact, analytic expression for the 2D-FT description of shear wave propagation in viscoelastic materials following asymmetric Gaussian excitations and uses this expression to evaluate the bias in 2D-FT measurements obtained using the plane or cylindrical wave assumptions. A wide range of biases are observed depending on specific values of frequency, aspect ratio R of the source asymmetry, and material properties. These biases can be reduced significantly by weighting the shear wave signal in the spatial domain to correct for the geometric spreading of the shear wavefront using a factor of x(p). The optimal weighting power p is found to be near the theoretical value of 0.5 for the case of a cylindrical source with R = 1, and decreases for asymmetric sources with R > 1.

B-mode and acoustic radiation force impulse (ARFI) imaging of prostate zonal anatomy: comparison with 3T T2-weighted MR imaging.

Prostate cancer (PCa) is the most common non-cutaneous malignancy among men in the United States and the second leading cause of cancer-related death. Multi-parametric magnetic resonance imaging (mpMRI) has gained recent popularity to characterize PCa. Acoustic Radiation Force Impulse (ARFI) imaging has the potential to aid PCa diagnosis and management by using tissue stiffness to evaluate prostate zonal anatomy and lesions. MR and B-mode/ARFI in vivo imaging datasets were compared with one another and with gross pathology measurements made immediately after radical prostatectomy. Images were manually segmented in 3D Slicer to delineate the central gland (CG) and prostate capsule, and 3D models were rendered to evaluate zonal anatomy dimensions and volumes. Both imaging modalities showed good correlation between estimated organ volume and gross pathologic weights. Ultrasound and MR total prostate volumes were well correlated (R(2) = 0.77), but B-mode images yielded prostate volumes that were larger (16.82% ± 22.45%) than MR images, due to overestimation of the lateral dimension (18.4% ± 13.9%), with less significant differences in the other dimensions (7.4% ± 17.6%, anterior-to-posterior, and -10.8% ± 13.9%, apex-to-base). ARFI and MR CG volumes were also well correlated (R(2) = 0.85). CG volume differences were attributed to ARFI underestimation of the apex-to-base axis (-28.8% ± 9.4%) and ARFI overestimation of the lateral dimension (21.5% ± 14.3%). B-mode/ARFI imaging yielded prostate volumes and dimensions that were well correlated with MR T2-weighted image (T2WI) estimates, with biases in the lateral dimension due to poor contrast caused by extraprostatic fat. B-mode combined with ARFI imaging is a promising low-cost, portable, real-time modality that can complement mpMRI for PCa diagnosis, treatment planning, and management.

Automated Spontaneous Echo Contrast Detection Using a Multisequence Attention Convolutional Neural Network.

OBJECTIVE: Spontaneous echo contrast (SEC) is a vascular ultrasound finding associated with increased thromboembolism risk. However, identification requires expert determination and clinician time to report. We developed a deep learning model that can automatically identify SEC. Our model can be applied retrospectively without deviating from routine clinical practice. The retrospective nature of our model means future works could scan archival data to opportunistically correlate SEC findings with documented clinical outcomes. METHODS: We curated a data set of 801 archival acquisitions along the femoral vein from 201 patients. We used a multisequence convolutional neural network (CNN) with ResNetv2 backbone and visualized keyframe importance using soft attention. We evaluated SEC prediction performance using an 80/20 train/test split. We report receiver operating characteristic area under the curve (ROC-AUC), along with the Youden threshold-associated sensitivity, specificity, F1 score, true negative, false negative, false positive and true positive. RESULTS: Using soft attention, we can identify SEC with an AUC of 0.74, sensitivity of 0.73 and specificity of 0.68. Without soft attention, our model achieves an AUC of 0.69, sensitivity of 0.71 and specificity of 0.60. Additionally, we provide attention visualizations and note that our model assigns higher attention score to ultrasound frames containing more vessel lumen. CONCLUSION: Our multisequence CNN model can identify the presence of SEC from ultrasound keyframes with an AUC of 0.74, which could enable screening applications and enable more SEC data discovery. The model does not require the expert intervention or additional clinician reporting time that are currently significant barriers to SEC adoption. Model and processed data sets are publicly available at https://github.com/Ouwen/automatic-spontaneous-echo-contrast.

Rotational 3D shear wave elasticity imaging: Effect of knee flexion on 3D shear wave propagation in in vivo vastus lateralis.

Skeletal muscle is a complex tissue, exhibiting not only direction-dependent material properties (commonly modeled as a transversely isotropic material), but also changes in observed material properties due to factors such as contraction and passive stretch. In this work, we evaluated the effect of muscle passive stretch on shear wave propagation along and across the muscle fibers using a rotational 3D shear wave elasticity imaging system and automatic analysis methods. We imaged the vastus lateralis of 10 healthy volunteers, modulating passive stretch by imaging at 8 different knee flexion angles (controlled by a BioDex system). In addition to demonstrating the ability of this acquisition and automatic processing system to estimate muscle shear moduli over a range of values, we evaluated potential higher order biomarkers for muscle health that capture the change in muscle stiffness along and across the fibers with changing knee flexion. The median within-subject variability of these biomarkers is found to be <16%, suggesting promise as a repeatable clinical metric. Additionally, we report an unexpected observation: that shear wave signal amplitude along the fibers increases with increasing flexion and muscle stiffness, which is not predicted by transversely isotropic (TI) material simulations. This observation may point to an additional potential biomarker for muscle health or inform other material modeling choices for muscle.

Repeatability of Rotational 3-D Shear Wave Elasticity Imaging Measurements in Skeletal Muscle.

Shear wave elasticity imaging (SWEI) usually assumes an isotropic material; however, skeletal muscle is typically modeled as a transversely isotropic material with independent shear wave speeds in the directions along and across the muscle fibers. To capture these direction-dependent properties, we implemented a rotational 3-D SWEI system that measures the shear wave speed both along and across the fibers in a single 3-D acquisition, with automatic detection of the muscle fiber orientation. We tested and examined the repeatability of this system's measurements in the vastus lateralis of 10 healthy volunteers. The average coefficient of variation of the measurements from this 3-D SWEI system was 5.3% along the fibers and 8.1% across the fibers. When compared with estimated respective 2-D SWEI values of 16.0% and 83.4%, these results suggest using 3-D SWEI has the potential to improve the precision of SWEI measurements in muscle. Additionally, we observed no significant difference in shear wave speed between the dominant and non-dominant legs along (p = 0.26) or across (p = 0.65) the muscle fibers.

Full Characterization of in vivo Muscle as an Elastic, Incompressible, Transversely Isotropic Material Using Ultrasonic Rotational 3D Shear Wave Elasticity Imaging.

Using a 3D rotational shear wave elasticity imaging (SWEI) setup, 3D shear wave data were acquired in the vastus lateralis of a healthy volunteer. The innate tilt between the transducer face and the muscle fibers results in the excitation of multiple shear wave modes, allowing for more complete characterization of muscle as an elastic, incompressible, transversely isotropic (ITI) material. The ability to measure both the shear vertical (SV) and shear horizontal (SH) wave speed allows for measurement of three independent parameters needed for full ITI material characterization: the longitudinal shear modulus µL , the transverse shear modulus µT , and the tensile anisotropy χE . Herein we develop and validate methodology to estimate these parameters and measure them in vivo, with µL = 5.77±1.00 kPa, µT = 1.93±0.41 kPa (giving shear anisotropy χµ = 2.11±0.92 ), and χE = 4.67±1.40 in a relaxed vastus lateralis muscle. We also demonstrate that 3D SWEI can be used to more accurately characterize muscle mechanical properties as compared to 2D SWEI.

Parametric Analysis of SV Mode Shear Waves in Transversely Isotropic Materials Using Ultrasonic Rotational 3-D SWEI.

Ultrasonic rotational 3-D shear wave elasticity imaging (SWEI) has been used to induce and evaluate multiple shear wave modes, including both the shear horizontal (SH) and shear vertical (SV) modes in in vivo muscle. Observations of both the SH and SV modes allow the muscle to be characterized as an elastic, incompressible, transversely isotropic (ITI) material with three parameters: the longitudinal shear modulus µL , the transverse shear modulus µT , and the tensile anisotropy χE . Measurement of the SV wave is necessary to characterize χE , but the factors that influence SV mode generation and characterization with ultrasonic SWEI are complicated. This work uses Green's function (GF) simulations to perform a parametric analysis to determine the optimal interrogation parameters to facilitate visualization and quantification of SV mode shear waves in muscle. We evaluate the impact of five factors: µL , µT , χE , fiber tilt angle [Formula: see text], and F-number of the push geometry on SV mode speed, amplitude, and rotational distribution. These analyses demonstrate that the following hold: 1) as µL increases, SV waves decrease in amplitude so are more difficult to measure in SWEI imaging; 2) as µT increases, the SV wave speeds increase; 3) as χE increases, the SV waves increase in speed and separate from the SH waves; 4) as fiber tilt angle [Formula: see text] increases, the measurable SV waves remain approximately the same speed, but change in strength and in rotational distribution; and 5) as the push beam geometry changes with F-number, the measurable SV waves remain approximately the same speed, but change in strength and rotational distribution. While specific SV mode speeds depend on the combinations of all parameters considered, measurable SV waves can be generated and characterized across the range of parameters considered. To maximize measurable SV waves separate from the SH waves, it is recommended to use an F/1 push geometry and [Formula: see text].

Noninvasive evaluation of hepatic fibrosis using acoustic radiation force-based shear stiffness in patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease in developed countries, may progress to nonalcoholic steatohepatitis (NASH) in a minority of people. Those with NASH are at increased risk for cirrhosis and hepatocellular carcinoma. The potential risk and economic burden of utilizing liver biopsy to stage NAFLD in an overwhelmingly large at-risk population are enormous; thus, the discovery of sensitive, inexpensive, and reliable noninvasive diagnostic modalities is essential for population-based screening. METHODS: Acoustic Radiation Force Impulse (ARFI) shear wave imaging, a noninvasive method of assessing tissue stiffness, was used to evaluate liver fibrosis in 172 patients diagnosed with NAFLD. Liver shear stiffness measures in three different imaging locations were reconstructed and compared to the histologic features of NAFLD and AST-to-platelet ratio indices (APRI). RESULTS: Reconstructed shear stiffnesses were not associated with ballooned hepatocytes (p=0.11), inflammation (p=0.69), nor imaging location (p=0.11). Using a predictive shear stiffness threshold of 4.24kPa, shear stiffness distinguished low (fibrosis stage 0-2) from high (fibrosis stage 3-4) fibrosis stages with a sensitivity of 90% and a specificity of 90% (AUC of 0.90). Shear stiffness had a mild correlation with APRI (R(2)=0.22). BMI>40kg/m(2) was not a limiting factor for ARFI imaging, and no correlation was noted between BMI and shear stiffness (R(2)=0.05). CONCLUSIONS: ARFI imaging is a promising imaging modality for assessing the presence or absence of advanced fibrosis in patients with obesity-related liver disease.

An analysis of the mechanical parameters used for finite element compression of a high-resolution 3D breast phantom.

PURPOSE: The authors previously introduced a methodology to generate a realistic three-dimensional (3D), high-resolution, computer-simulated breast phantom based on empirical data. One of the key components of such a phantom is that it provides a means to produce a realistic simulation of clinical breast compression. In the current study, they have evaluated a finite element (FE) model of compression and have demonstrated the effect of a variety of mechanical properties on the model using a dense mesh generated from empirical breast data. While several groups have demonstrated an effective compression simulation with lower density finite element meshes, the presented study offers a mesh density that is able to model the morphology of the inner breast structures more realistically than lower density meshes. This approach may prove beneficial for multimodality breast imaging research, since it provides a high level of anatomical detail throughout the simulation study. METHODS: In this paper, the authors describe methods to improve the high-resolution performance of a FE compression model. In order to create the compressible breast phantom, dedicated breast CT data was segmented and a mesh was generated with 4-noded tetrahedral elements. Using an explicit FE solver to simulate breast compression, several properties were analyzed to evaluate their effect on the compression model including: mesh density, element type, density, and stiffness of various tissue types, friction between the skin and the compression plates, and breast density. Following compression, a simulated projection was generated to demonstrate the ability of the compressible breast phantom to produce realistic simulated mammographic images. RESULTS: Small alterations in the properties of the breast model can change the final distribution of the tissue under compression by more than 1 cm; which ultimately results in different representations of the breast model in the simulated images. The model properties that impact displacement the most are mesh density, friction between the skin and the plates, and the relative stiffness of the different tissue types. CONCLUSIONS: The authors have developed a 3D, FE breast model that can yield high spatial resolution breast deformations under uniaxial compression for imaging research purposes and demonstrated that small changes in the mechanical properties can affect images generated using the phantom.

Shear wave dispersion as a potential biomarker for cervical remodeling during pregnancy: evidence from a non-human primate model.

Shear wave dispersion (variation of phase velocity with frequency) occurs in tissues with layered and anisotropic microstructure and viscous components, such as the uterine cervix. This phenomenon, mostly overlooked in previous applications of cervical Shear Wave Elasticity Imaging (SWEI) for preterm birth risk assessment, is expected to change drastically during pregnancy due to cervical remodeling. Here we demonstrate the potential of SWEI-based descriptors of dispersion as potential biomarkers for cervical remodeling during pregnancy. First, we performed a simulation-based pre-selection of two SWEI-based dispersion descriptors: the ratio R of group velocities computed with particle-velocity and particle-displacement, and the slope S of the phase velocity vs. frequency. The pre-selection consisted of comparing the contrast-to-noise ratio (CNR) of dispersion descriptors in materials with different degrees of dispersion with respect to a low-dispersive medium. Shear waves induced in these media by SWEI were simulated with a finite-element model of Zener viscoelastic solids. The pre-selection also considered two denoising strategies to improve CNR: a low-pass filter with automatic frequency cutoff determination, and singular value decomposition of shear wave displacements. After pre-selection, the descriptor-denoising combination that produced the largest CNR was applied to SWEI cervix data from 18 pregnant Rhesus macaques acquired at weeks 10 (mid-pregnancy stage) and 23 (late pregnancy stage) of the 24.5-week full pregnancy. A maximum likelihood linear mixed-effects model (LME) was used to evaluate the dependence of the dispersion descriptor on pregnancy stage, maternal age, parity and other experimental factors. The pre-selection study showed that descriptor S combined with singular value decomposition produced a CNR 11.6 times larger than the other descriptor and denoising strategy combinations. In the Non-Human Primates (NHP) study, the LME model showed that descriptor S significantly decreased from mid to late pregnancy (-0.37 ± 0.07 m/s-kHz per week, p <0.00001) with respect to the base value of 15.5 ± 1.9 m/s-kHz. This change was more significant than changes in other SWEI features such as the group velocity previously reported. Also, S varied significantly between the anterior and posterior portions of the cervix (p =0.02) and with maternal age (p =0.008). Given the potential of shear wave dispersion to track cervical remodeling, we will extend its application to ongoing longitudinal human studies.

Deep Convolutional Neural Networks for Displacement Estimation in ARFI Imaging.

Ultrasound elasticity imaging in soft tissue with acoustic radiation force requires the estimation of displacements, typically on the order of several microns, from serially acquired raw data A-lines. In this work, we implement a fully convolutional neural network (CNN) for ultrasound displacement estimation. We present a novel method for generating ultrasound training data, in which synthetic 3-D displacement volumes with a combination of randomly seeded ellipsoids are created and used to displace scatterers, from which simulated ultrasonic imaging is performed using Field II. Network performance was tested on these virtual displacement volumes, as well as an experimental ARFI phantom data set and a human in vivo prostate ARFI data set. In the simulated data, the proposed neural network performed comparably to Loupas's algorithm, a conventional phase-based displacement estimation algorithm; the rms error was [Formula: see text] for the CNN and 0.73 [Formula: see text] for Loupas. Similarly, in the phantom data, the contrast-to-noise ratio (CNR) of a stiff inclusion was 2.27 for the CNN-estimated image and 2.21 for the Loupas-estimated image. Applying the trained network to in vivo data enabled the visualization of prostate cancer and prostate anatomy. The proposed training method provided 26 000 training cases, which allowed robust network training. The CNN had a computation time that was comparable to Loupas's algorithm; further refinements to the network architecture may provide an improvement in the computation time. We conclude that deep neural network-based displacement estimation from ultrasonic data is feasible, providing comparable performance with respect to both accuracy and speed compared to current standard time-delay estimation approaches.

Prostate Cancer Detection Using 3-D Shear Wave Elasticity Imaging.

Transrectal ultrasound (TRUS) B-mode imaging provides insufficient sensitivity and specificity for prostate cancer (PCa) targeting when used for biopsy guidance. Shear wave elasticity imaging (SWEI) is an elasticity imaging technique that has been commercially implemented and is sensitive and specific for PCa. We have developed a SWEI system capable of 3-D data acquisition using a dense acoustic radiation force (ARF) push approach that leads to enhanced shear wave signal-to-noise ratio compared with that of the commercially available SWEI systems and facilitates screening of the entire gland before biopsy. Additionally, we imaged and assessed 36 patients undergoing radical prostatectomy using 3-D SWEI and determined a shear wave speed threshold separating PCa from healthy prostate tissue with sensitivities and specificities akin to those for multiparametric magnetic resonance imaging fusion biopsy. The approach measured the mean shear wave speed in each prostate region to be 4.8 m/s (Young's modulus E = 69.1 kPa) in the peripheral zone, 5.3 m/s (E = 84.3 kPa) in the central gland and 6.0 m/s (E = 108.0 kPa) for PCa with statistically significant (p < 0.0001) differences among all regions. Three-dimensional SWEI receiver operating characteristic analyses identified a threshold of 5.6 m/s (E = 94.1 kPa) to separate PCa from healthy tissue with a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) of 81%, 82%, 69%, 89% and 0.84, respectively. Additionally, a shear wave speed ratio was assessed to normalize for tissue compression and patient variability, which yielded a threshold of 1.11 to separate PCa from healthy prostate tissue and was accompanied by a substantial increase in specificity, PPV and AUC, where the sensitivity, specificity, PPV, NPV and AUC were 75%, 90%, 79%, 88% and 0.90, respectively. This work illustrates the feasibility of using 3-D SWEI data to detect and localize PCa and demonstrates the benefits of normalizing for applied compression during data acquisition for use in biopsy targeting studies.

Tractable calculation of the Green's tensor for shear wave propagation in an incompressible, transversely isotropic material.

Assessing material properties from observations of shear wave propagation following an acoustic radiation force impulse (ARFI) excitation is difficult in anisotropic materials because of the complex relations among the propagation direction, shear wave polarizations, and material symmetries. In this paper, we describe a method to calculate shear wave signals using Green's tensor methods in an incompressible, transversely isotropic (TI) material characterized by three material parameters. The Green's tensor is written as the sum of an analytic expression for the SH propagation mode, and an integral expression for the SV propagation mode that can be evaluated by interpolation within precomputed integral functions with an efficiency comparable to the evaluation of a closed-form expression. By using parametrized integral functions, the number of required numerical integrations is reduced by a factor of 102-109 depending on the specific problem under consideration. Results are presented for the case of a point source positioned at the origin and a tall Gaussian source similar to an ARFI excitation. For an experimental configuration with a tilted material symmetry axis, results show that shear wave signals exhibit structures that are sufficiently complex to allow measurement of all three material parameters that characterize an incompressible, TI material.