Lung Quantitative Ultrasound to Stage and Monitor Interstitial Lung Diseases.

Chronic interstitial lung diseases (ILDs) require frequent point-of-care monitoring. X-ray-based methods lack resolution and are ionizing. Chest computerized tomographic (CT) scans are expensive and provide more radiation. Conventional ultrasound can detect severe lung damage via vertical artifacts (B-lines). However, this information is not quantitative, and the appearance of B-lines is operator- and system-dependent. Here we demonstrate novel ultrasound-based biomarkers to assess severity of ILDs. Lung alveoli scatter ultrasound waves, leading to a complex acoustic signature, which is affected by changes in alveolar density due to ILDs. We exploit ultrasound scattering in the lung and combine Quantitative Ultrasound (QUS) parameters, to develop ultrasound-based biomarkers that significantly correlate to the severity of pulmonary fibrosis and edema in rodent lungs. These innovative QUS biomarkers will be very significant for monitoring severity of chronic ILDs and response to treatment, especially in this new era of miniaturized and highly portable ultrasound devices.

Improved cancer risk stratification of isoechoic thyroid nodules to reduce unnecessary biopsies using quantitative ultrasound.

Objective: Gray-scale ultrasound (US) is the standard-of-care for evaluating thyroid nodules (TNs). However, the performance is better for the identification of hypoechoic malignant TNs (such as classic papillary thyroid cancer) than isoechoic malignant TNs. Quantitative ultrasound (QUS) utilizes information from raw ultrasonic radiofrequency (RF) echo signal to assess properties of tissue microarchitecture. The purpose of this study is to determine if QUS can improve the cancer risk stratification of isoechoic TNs. Methods: Patients scheduled for TN fine needle biopsy (FNB) were recruited from the Thyroid Health Clinic at Boston Medical Center. B-mode US and RF data (to generate QUS parameters) were collected in 274 TNs (163 isoechoic, 111 hypoechoic). A linear combination of QUS parameters (CQP) was trained and tested for isoechoic [CQP(i)] and hypoechoic [CQP(h)] TNs separately and compared with the performance of conventional B-mode US risk stratification systems. Results: CQP(i) produced an ROC AUC value of 0.937+/- 0.043 compared to a value of 0.717 +/- 0.145 (p >0.05) for the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) and 0.589 +/- 0.173 (p >0.05) for the American Thyroid Association (ATA) risk stratification system. In this study, CQP(i) avoids unnecessary FNBs in 73% of TNs compared to 55.8% and 11.8% when using ACR TI-RADS and ATA classification system. Conclusion: This data supports that a unique QUS-based classifier may be superior to conventional US stratification systems to evaluate isoechoic TNs for cancer and should be explored further in larger studies.

Machine Independence of Ultrasound-Based Quantification of Vitreous Echodensities.

Purpose: Quantitative ultrasound (QUS) provides objective indices of Vision Degrading Myodesopsia (VDM) that correlate with contrast sensitivity (CS). To date, QUS methods were only tested on a single ultrasound machine. Here, we evaluate whether QUS measurements are machine independent. Methods: In this cross-sectional study, 47 eyes (24 subjects; age = 53.2 ± 14.4 years) were evaluated with Freiburg acuity contrast testing (%Weber), and ultrasonography using 2 machines: one with a 15-MHz single-element transducer and one with a 5-ring, 20-MHz annular-array. Images were acquired from each system in sequential scans. Artifact-free, log-compressed envelope data were processed to yield three parameters (mean amplitude, M; energy, E; and percentage filled by echodensities, P50) and a composite score (C). A B-mode normalization method was applied to the 20-MHz datasets to match QUS parameters at both frequencies. Statistical analyses were performed to evaluate correlations among CS, E, M, P50, and C for both machines. Results: QUS parameters from each machine correlated with CS (R ≥ 0.57, P < 0.001) and there was correlation between machines (R ≥ 0.84, P < 0.001). Correlations between CS and QUS parameters were statistically similar for both machines (P ≥ 0.14) except when the 20-MHz data were normalized (P = 0.04). Reproducibility of QUS parameters computed from 20-MHz data were satisfactory (52.3%-96.3%) with intraclass correlation values exceeding 0.80 (P < 0.001). Conclusions: The high correlation between QUS parameters from both machines combined with a statistically similar correlation to CS suggests QUS is an effective, machine-independent, quantitative measure of vitreous echodensities. Translational Relevance: QUS may be applied across clinical ophthalmic ultrasound scanners and imaging frequencies to effectively evaluate VDM.

Advanced Topics in Quantitative Acoustic Microscopy.

Quantitative acoustic microscopy (QAM) reconstructs two-dimensional (2D) maps of the acoustic properties of thin tissue sections. Using ultrahigh frequency transducers (≥ 100 MHz), unstained, micron-thick tissue sections affixed to glass are raster scanned to collect radiofrequency (RF) echo data and generate parametric maps with resolution approximately equal to the ultrasound wavelength. 2D maps of speed of sound, mass density, acoustic impedance, bulk modulus, and acoustic attenuation provide unique and quantitative information that is complementary to typical optical microscopy modalities. Consequently, many biomedical researchers have great interest in utilizing QAM instruments to investigate the acoustic and biomechanical properties of tissues at the micron scale. Unfortunately, current state-of-the-art QAM technology is costly, requires operation by a trained user, and is accompanied by substantial experimental challenges, many of which become more onerous as the transducer frequency is increased. In this chapter, typical QAM technology and standard image formation methods are reviewed. Then, novel experimental and signal processing approaches are presented with the specific goal of reducing QAM instrument costs and improving ease of use. These methods rely on modern techniques based on compressed sensing and sparsity-based deconvolution methods. Together, these approaches could serve as the basis of the next generation of QAM instruments that are affordable and provide high-resolution QAM images with turnkey solutions requiring nearly no training to operate.

RECURRENT FLOATERS AFTER LIMITED VITRECTOMY FOR VISION DEGRADING MYODESOPSIA.

PURPOSE: Limited vitrectomy improves vision degrading myodesopsia, but the incidence of recurrent floaters postoperatively is not known. We studied patients with recurrent central floaters using ultrasonography and contrast sensitivity (CS) testing to characterize this subgroup and identify the clinical profile of patients at risk of recurrent floaters. METHODS: A total of 286 eyes (203 patients, 60.6 ± 12.9 years) undergoing limited vitrectomy for vision degrading myodesopsia were studied retrospectively. Sutureless 25G vitrectomy was performed without intentional surgical posterior vitreous detachment (PVD) induction. CS (Freiburg Acuity Contrast test: Weber index, %W) and vitreous echodensity (quantitative ultrasonography) were assessed prospectively. RESULTS: No eyes (0/179) with preoperative PVD experienced new floaters. Recurrent central floaters occurred in 14/99 eyes (14.1%) without complete preoperative PVD (mean follow-up = 39 months vs. 31 months in 85 eyes without recurrent floaters). Ultrasonography identified new-onset PVD in all 14 (100%) recurrent cases. Young (younger than 52 years; 71.4%), myopic (≥-3D; 85.7%), phakic (100%) men (92.9%) predominated. Reoperation was elected by 11 patients, who had partial PVD preoperatively in 5/11 (45.5%). At study entry, CS was degraded (3.55 ± 1.79 %W) but improved postoperatively by 45.6% (1.93 ± 0.86 %W, P = 0.033), while vitreous echodensity reduced by 86.6% ( P = 0.016). New-onset PVD postoperatively degraded CS anew, by 49.4% (3.28 ± 0.96 %W; P = 0.009) in patients electing reoperation. Repeat vitrectomy normalized CS to 2.00 ± 0.74%W ( P = 0.018). CONCLUSION: Recurrent floaters after limited vitrectomy for vision degrading myodesopsia are caused by new-onset PVD, with younger age, male sex, myopia, and phakic status as risk factors. Inducing surgical PVD at the primary operation should be considered in these select patients to mitigate recurrent floaters.

High-frequency ultrasound point-of-care device to quantify myopia-induced microstructural changes in the anterior sclera.

PURPOSE: To develop a point-of-care (POC) device using high-frequency ultrasound (US) for evaluating microstructural changes in the anterior sclera associated with myopia. METHODS: The proposed POC device must satisfy four primary requirements for effective clinical use: the measurement component is handheld; the software must be simple and provide real-time feedback; patient safety and health data security requirements set forth by relevant governing bodies must be satisfied and the measurement data must have sufficient signal-to-noise ratio (SNR) and repeatability. Radiofrequency (RF) echo data acquired by the POC device will be processed using our quantitative US methods to characterise tissue microstructure and biomechanical properties. RESULTS: All stated requirements have been met in the developed POC device. The high-frequency transducer is housed in a custom, 3D-printed, pen-like holder that allows for easy measurements of the anterior sclera. Custom software provides a simple interface for data acquisition, real-time data display and secure data storage. Exposimetry measurements of the US pressure field indicate device compliance with United States Food and Drug Administration limits for ophthalmic US. In vivo measurements on a volunteer suggest the RF data SNR and acquisition consistency are suitable for quantitative analysis. CONCLUSIONS: A fully functioning POC device using high-frequency US has been created for evaluating the microstructure of the anterior sclera. Planned studies using the POC device to scan the eyes of myopia patients will help clarify how the anterior sclera microstructure may be affected by myopia. If effective, this portable, inexpensive and user-friendly system could be an important part of routine eye examinations.

Classification of Metastatic Lymph Nodes In Vivo Using Quantitative Ultrasound at Clinical Frequencies.

Quantitative ultrasound (QUS) methods characterizing the backscattered echo signal have been of use in assessing tissue microstructure. High-frequency (30 MHz) QUS methods have been successful in detecting metastases in surgically excised lymph nodes (LNs), but limited evidence exists regarding the efficacy of QUS for evaluating LNs in vivo at clinical frequencies (2-10 MHz). In this study, a clinical scanner and 10-MHz linear probe were used to collect radiofrequency (RF) echo data of LNs in vivo from 19 cancer patients. QUS methods were applied to estimate parameters derived from the backscatter coefficient (BSC) and statistics of the envelope-detected RF signal. QUS parameters were used to train classifiers based on linear discriminant analysis (LDA) and support vector machines (SVMs). Two BSC-based parameters, scatterer diameter and acoustic concentration, were the most effective for accurately detecting metastatic LNs, with both LDA and SVMs achieving areas under the receiver operating characteristic (AUROC) curve ≥0.94. A strategy of classifying LNs based on the echo frame with the highest cancer probability improved performance to 88% specificity at 100% sensitivity (AUROC = 0.99). These results provide encouraging evidence that QUS applied at clinical frequencies may be effective at accurately identifying metastatic LNs in vivo, helping in diagnosis while reducing unnecessary biopsies and surgical treatments.

Longitudinal in Utero Analysis of Engrailed-1 Knockout Mouse Embryonic Phenotypes Using High-Frequency Ultrasound.

Large-scale international efforts to generate and analyze loss-of-function mutations in each of the approximately 20,000 protein-encoding gene mutations are ongoing using the "knockout" mouse as a model organism. Because one-third of gene knockouts are expected to result in embryonic lethality, it is important to develop non-invasive in utero imaging methods to detect and monitor mutant phenotypes in mouse embryos. We describe the utility of 3-D high-frequency (40-MHz) ultrasound (HFU) for longitudinal in utero imaging of mouse embryos between embryonic days (E) 11.5 and E14.5, which represent critical stages of brain and organ development. Engrailed-1 knockout (En1-ko) mouse embryos and their normal control littermates were imaged with HFU in 3-D, enabling visualization of morphological phenotypes in the developing brains, limbs and heads of the En1-ko embryos. Recently developed deep learning approaches were used to automatically segment the embryonic brain ventricles and bodies from the 3-D HFU images, allowing quantitative volumetric analyses of the En1-ko brain phenotypes. Taken together, these results show great promise for the application of longitudinal 3-D HFU to analyze knockout mouse embryos in utero.

Automated Classification and Detection of Staphyloma with Ultrasound Images in Pathologic Myopia Eyes.

The aim of this study was to develop an eyewall curvature- and axial length (AxL)-based algorithm to automate detection (clinician-free) of staphyloma ridge and apex locations using ultrasound (US). Forty-six individuals (with emmetropia, high myopia or pathologic myopia) were enrolled in this study (AxL range: 22.3-39.3 mm), yielding 130 images in total. An intensity-based segmentation algorithm automatically tracked the posterior eyewall, calculating the posterior eyewall local curvature (K) and distance (L) to the transducer and the location of the staphyloma apex. By use of the area under the receiver operator characteristic (AUROC) curve to evaluate the diagnostic ability of eight local statistics derived from K, L and AxL, the algorithm successfully quantified non-uniformity of eye shape with an AUROC > 0.70 for most K-based parameters. The performance of binary classification (staphyloma absence vs. presence) was assessed with the best classifier (the combination of AxL, standard deviation of K and standard deviation of L) yielding a diagnostic validation performance of 0.897, which was comparable to the diagnostic performance of junior clinicians. The staphyloma apex was localized with an average error of 1.35 ± 1.34 mm. Combined with the real-time data acquisition capabilities of US, this method can be employed as a screening tool for clinician-free in vivo staphyloma detection.

Biomechanical changes in myopic sclera correlate with underlying changes in microstructure.

Myopia alters the microstructural and biomechanical properties of the posterior sclera, which is characterized as a layered structure with potentially different inter-layer collagen fibril characteristics. Scanning acoustic microscopy (SAM) has been used to investigate how the micron-scale bulk mechanical properties of the posterior sclera are affected by myopia. Other investigators have employed second harmonic generation (SHG) imaging to characterize the collagen microstructure of tissues. In the present study, SAM and SHG imaging were used to investigate the existence of biomechanically-distinct scleral layers and identify relationships between mechanical properties and tissue microstructure in myopic guinea pig (GP) eyes. Diffusers were worn over the right eyes of six, 1-week-old GPs for one week to induce unilateral form-deprivation myopia. GPs were euthanized, enucleated, and eyes were cryosectioned. Twelve-micron-thick adjacent vertical cryosections were scanned with SAM or SHG. SAM maps of bulk modulus, mass density, and acoustic attenuation were estimated. A fiber-extraction algorithm applied to SHG images estimated collagen fiber length, width, straightness, alignment, and number density. Results revealed that the posterior sclera may exhibit biomechanically distinct layers that are affected differently in myopia. Specifically, a layered structure was observed in the mechanical-parameter maps of control eyes that was less apparent in myopic eyes. Collagen fibers in myopic eyes had smaller diameters and were more aligned. Myopia-associated biomechanical changes were most significant in the outermost and innermost scleral layers. SAM-measured mechanical parameters were correlated with collagen fiber microstructure, particularly fiber length, alignment, and number density, which may imply the biomechanical parameters estimated from SAM measurements are related to tissue microstructure. Interestingly, some changes were greatest in more-peripheral regions, suggesting interventions to strengthen the sclera may be effective away from the optic nerve and efficacy may be achieved best when intervention is applied to the outermost layer.

Quantitative Ultrasound Assessment of Early Osteoarthritis in Human Articular Cartilage Using a High-Frequency Linear Array Transducer.

Quantitative ultrasound (QUS) assessment of osteoarthritis (OA) using high-frequency, research-grade single-element ultrasound systems has been reported. The objective of this ex vivo study was to assess the performance of QUS in detecting early OA using a high-frequency linear array transducer. Osteochondral plugs (n = 26) of human articular cartilage were scanned with ExactVu Micro-Ultrasound using an EV29L side-fire transducer. For comparison, the samples were also imaged with SAM200Ex, a custom 40-MHz scanning acoustic microscope with a single-element, focused transducer. Thirteen QUS parameters were derived from the ultrasound data. Magnetic resonance imaging (MRI) data, with T1 and T2 extracted as the quantitative parameters, were also acquired for comparison. Cartilage degeneration was graded from histology and correlated to all quantitative parameters. A maximum Spearman rank correlation coefficient (ρ) of 0.75 was achieved using a combination of ExactVu QUS parameters, while a maximum ρ of 0.62 was achieved using a combination of parameters from SAM200Ex. A maximum ρ of 0.75 was achieved using the T1 and T2 MRI parameters. This study illustrates the potential of a high-frequency linear array transducer to provide a convenient method for early OA screening with results comparable to those of research-grade single-element ultrasound and MRI.

Vitrectomy Improves Contrast Sensitivity in Multifocal Pseudophakia With Vision Degrading Myodesopsia.

PURPOSE: Multifocal intraocular lenses (MFIOL) are associated with degradation in contrast sensitivity function (CSF); yet the contribution of vitreous is not known, nor is the benefit of vitrectomy. DESIGN: Prospective, nonrandomized clinical study. METHODS: A total of 180 eyes of 180 patients (55 MFIOL, 60 monofocal intraocular lenses [MIOL], 65 phakic) with symptomatic vitreous opacities were enrolled. Vitreous structure was assessed with quantitative ultrasonography (QUS). Vision was evaluated with visual acuity and CSF measurements. RESULTS: Vitreous echodensity was the same in all lens cohorts, yet CSF was worse in MFIOL eyes (P < .001). In 86 patients who elected vitrectomy, there was 68% greater vitreous echodensity and 31% worse CSF than in observation controls (P < .0001 for each). Preoperatively, CSF was 25% worse in MFIOL than in MIOL (P = .014). Postoperatively, vitreous echodensity decreased by 55%, 51%, and 52%, whereas CSF improved by 37% 48% in and 43% in MFIOL, MIOL, and phakic eyes, respectively (P < .0001 for each). NEI Visual Function Questionnaire analyses showed improved visual well-being. CONCLUSIONS: Patients with vision degrading myodesopsia who elected vitrectomy had greater vitreous echodensity and worse CSF than controls, but no other differences in age, sex, or myopia. MFIOL eyes had worse CSF than MIOL and phakic eyes, very possibly due to combined effects of the MFIOL and vitreous opacification. Limited vitrectomy reduced vitreous echodensity and improved CSF in all eyes. All patients with CSF-degrading vitreous opacities benefited from limited vitrectomy, including those with MFIOL. As MFIOL eyes had 37% improvement in CSF, patients with MFIOL and vision degrading myodesopsia merit consideration of vitrectomy.

In vivo assessment of pulmonary fibrosis and edema in rodents using the backscatter coefficient and envelope statistics.

Quantitative ultrasound methods based on the backscatter coefficient (BSC) and envelope statistics have been used to quantify disease in a wide variety of tissues, such as prostate, lymph nodes, breast, and thyroid. However, to date, these methods have not been investigated in the lung. In this study, lung properties were quantified by BSC and envelope statistical parameters in normal, fibrotic, and edematous rat lungs in vivo. The average and standard deviation of each parameter were calculated for each lung as well as the evolution of each parameter with acoustic propagation time within the lung. The transport mean free path and backscattered frequency shift, two parameters that have been successfully used to assess pulmonary fibrosis and edema in prior work, were evaluated in combination with the BSC and envelope statistical parameters. Multiple BSC and envelope statistical parameters were found to provide contrast between control and diseased lungs. BSC and envelope statistical parameters were also significantly correlated with fibrosis severity using the modified Ashcroft fibrosis score as the histological gold standard. These results demonstrate the potential for BSC and envelope statistical parameters to improve the diagnosis of pulmonary fibrosis and edema as well as monitor pulmonary fibrosis.

A Preliminary Study of Quantitative Ultrasound for Cancer-Risk Assessment of Thyroid Nodules.

Background: Gray-scale, B-mode ultrasound (US) imaging is part of the standard clinical procedure for evaluating thyroid nodules (TNs). It is limited by its instrument- and operator-dependence and inter-observer variability. In addition, the accepted high-risk B-mode US TN features are more specific for detecting classic papillary thyroid cancer rather than the follicular variant of papillary thyroid cancer or follicular thyroid cancer. Quantitative ultrasound (QUS) is a technique that can non-invasively assess properties of tissue microarchitecture by exploiting information contained in raw ultrasonic radiofrequency (RF) echo signals that is discarded in conventional B-mode imaging. QUS provides quantitative parameter-value estimates that are a function of the properties of US scatterers and microarchitecture of the tissue. The purpose of this preliminary study was to assess the performance of QUS parameters in evaluating benign and malignant thyroid nodules. Methods: Patients from the Thyroid Health Center at the Boston Medical Center were recruited to participate. B-mode and RF data were acquired and analyzed in 225 TNs (24 malignant and 201 benign) from 208 patients. These data were acquired either before (167 nodules) or after (58 nodules) subjects underwent fine-needle biopsy (FNB). The performance of a combination of QUS parameters (CQP) was assessed and compared with the performance of B-mode risk-stratification systems. Results: CQP produced an ROC AUC value of 0.857 ± 0.033 compared to a value of 0.887 ± 0.033 (p=0.327) for the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) and 0.880 ± 0.041 (p=0.367) for the American Thyroid Association (ATA) risk-stratification system. Furthermore, using a CQP threshold of 0.263 would further reduce the number of unnecessary FNBs in 44% of TNs without missing any malignant TNs. When CQP used in combination with ACR TI-RADS, a potential additional reduction of 49 to 66% in unnecessary FNBs was demonstrated. Conclusion: This preliminary study suggests that QUS may provide a method to classify TNs when used by itself or when combined with a conventional gray-scale US risk-stratification system and can potentially reduce the need to biopsy TNs.

A Deep Learning Approach for Segmentation, Classification, and Visualization of 3-D High-Frequency Ultrasound Images of Mouse Embryos.

Segmentation and mutant classification of high-frequency ultrasound (HFU) mouse embryo brain ventricle (BV) and body images can provide valuable information for developmental biologists. However, manual segmentation and identification of BV and body requires substantial time and expertise. This article proposes an accurate, efficient and explainable deep learning pipeline for automatic segmentation and classification of the BV and body. For segmentation, a two-stage framework is implemented. The first stage produces a low-resolution segmentation map, which is then used to crop a region of interest (ROI) around the target object and serve as the probability map of the autocontext input for the second-stage fine-resolution refinement network. The segmentation then becomes tractable on high-resolution 3-D images without time-consuming sliding windows. The proposed segmentation method significantly reduces inference time (102.36-0.09 s/volume ≈ 1000× faster) while maintaining high accuracy comparable to previous sliding-window approaches. Based on the BV and body segmentation map, a volumetric convolutional neural network (CNN) is trained to perform a mutant classification task. Through backpropagating the gradients of the predictions to the input BV and body segmentation map, the trained classifier is found to largely focus on the region where the Engrailed-1 (En1) mutation phenotype is known to manifest itself. This suggests that gradient backpropagation of deep learning classifiers may provide a powerful tool for automatically detecting unknown phenotypes associated with a known genetic mutation.

Vitreous Structure and Visual Function in Myopic Vitreopathy Causing Vision-Degrading Myodesopsia.

PURPOSE: Myopic vitreopathy features precocious fibrous vitreous liquefaction and early posterior vitreous detachment (PVD). It is unclear whether visual function is affected by myopic vitreopathy and PVD. This study assessed the relationships among axial length, structural vitreous density, PVD, and visual function. DESIGN: Retrospective case-control study. METHODS: Ultrasonography measurements were made of axial length, logMAR VA, contrast sensitivity function (CSF [Freiburg acuity contrast test]), and quantitative B-scan ultrasonography. RESULTS: Seventy-nine subjects (45 men and 34 women; mean age: 49 ± 14 years) were analyzed. Axial lengths ranged from 22 to 29.2 mm (mean: 24.9 ± 1.8 mm; myopic eyes: 26.35 ± 1.35 mm; and nonmyopic eyes: 23.45 ± 0.75 mm; P < .001). With increasing axial length there was greater vitreous echodensity (R: 0.573; P < .01) and degradation in CSF (R: 0.611; P < .01). Subgroup analyses found that myopic eyes (>- 3 diopters) had 37% more vitreous echodensity than nonmyopic eyes (762 ± 198 arbitrary units [AU] vs. 557 ± 171 AU, respectively; P < .001) and that CSF was 53% worse in myopic eyes (3.30 ± 1.24 Weber index [%W]) than in nonmyopic eyes (2.16 ± .59 %W; P < .001). Myopic eyes with PVD had 33% greater vitreous echodensity (815 ± 217 AU; P < .001) and 62% degradation in CSF (3.63 ± 2.99 %W) compared to nonmyopic eyes with PVD (613 ± 159 AU; 2.24 ± 0.69 %W; P < .001, each). Limited vitrectomy was performed in 11 of 40 cases (27.5%), normalizing vitreous echodensity and CSF in each case. CONCLUSIONS: Axial myopia is associated with increased fibrous vitreous liquefaction and echodensity, as well as profound degradation of CSF. PVD in myopic eyes is associated with even more structural and functional abnormalities, normalized by limited vitrectomy. These findings may explain some common complaints of myopic patients with respect to vision and quality of life.

DEEP MOUSE: AN END-TO-END AUTO-CONTEXT REFINEMENT FRAMEWORK FOR BRAIN VENTRICLE & BODY SEGMENTATION IN EMBRYONIC MICE ULTRASOUND VOLUMES.

The segmentation of the brain ventricle (BV) and body in embryonic mice high-frequency ultrasound (HFU) volumes can provide useful information for biological researchers. However, manual segmentation of the BV and body requires substantial time and expertise. This work proposes a novel deep learning based end-to-end auto-context refinement framework, consisting of two stages. The first stage produces a low resolution segmentation of the BV and body simultaneously. The resulting probability map for each object (BV or body) is then used to crop a region of interest (ROI) around the target object in both the original image and the probability map to provide context to the refinement segmentation network. Joint training of the two stages provides significant improvement in Dice Similarity Coefficient (DSC) over using only the first stage (0.818 to 0.906 for the BV, and 0.919 to 0.934 for the body). The proposed method significantly reduces the inference time (102.36 to 0.09 s/volume ≈1000x faster) while slightly improves the segmentation accuracy over the previous methods using slide-window approaches.

Quantifying scattering from dense media using two-dimensional impedance maps.

A better understanding of ultrasound scattering in a three-dimensional (3D) medium can provide more accurate methods for ultrasound tissue characterization. The possibility of using two-dimensional impedance maps (2DZMs) based on correlation coefficients has shown promise in the case of isotropic and sparse medium [Luchies and Oelze, J. Acoust. Soc. Am. 139, 1557-1564 (2016)]. The present study investigates the use of 2DZMs in order to quantify 3D scatterer properties of dense media from two-dimensional (2D) histological slices. Two 2DZM approaches were studied: one based on the correlation coefficient and the other based on the 2D Fourier transform of 2DZMs. Both 2DZM approaches consist in estimating the backscatter coefficient (BSC) from several 2DZMs, and then the resulting BSC was fit to the theoretical polydisperse structure factor model to yield 3D scatterer properties. Simulation studies were performed to evaluate the ability of both 2DZM approaches to quantify scattering of a 3D medium containing randomly distributed polydisperse spheres or monodisperse ellipsoids. Experimental studies were also performed using the histology photomicrographs obtained from HT29 cell pellet phantoms. Results demonstrate that the 2DZM Fourier transform-based approach was more suitable than the correlation coefficient-based approach for estimating scatterer properties when using a small number of 2DZMs.

Multiparametric Ultrasound for Targeting Prostate Cancer: Combining ARFI, SWEI, QUS and B-Mode.

Diagnosing prostate cancer through standard transrectal ultrasound (TRUS)-guided biopsy is challenging because of the sensitivity and specificity limitations of B-mode imaging. We used a linear support vector machine (SVM) to combine standard TRUS imaging data with acoustic radiation force impulse (ARFI) imaging data, shear wave elasticity imaging (SWEI) data and quantitative ultrasound (QUS) midband fit data to enhance lesion contrast into a synthesized multiparametric ultrasound volume. This SVM was trained and validated using a subset of 20 patients and tested on a second subset of 10 patients. Multiparametric US led to a statistically significant improvements in contrast, contrast-to-noise ratio (CNR) and generalized CNR (gCNR) when compared with standard TRUS B-mode and SWEI; in contrast and CNR when compared with MF; and in CNR when compared with ARFI. ARFI, MF and SWEI also outperformed TRUS B-mode in contrast, with MF outperforming B-mode in CNR and gCNR as well. ARFI, although only yielding statistically significant differences in contrast compared with TRUS B-mode, captured critical qualitative features for lesion identification. Multiparametric US enhanced lesion visibility metrics and is a promising technique for targeted TRUS-guided prostate biopsy in the future.

Quantitative assessment of media concentration using the Homodyned K distribution.

The Homodyned K distribution has been used successfully as a tool in the ultrasound characterization of sparse media, where the scatterer clustering parameter α accurately discriminates between media with different numbers of scatterers per resolution cell. However, as the number of scatterers increases and the corresponding amplitude statistics become Rician, the reliability of the α estimates decreases rapidly. In the present study, we assess the usefulness of α for the characterization of both sparse and concentrated media, using simulated independent and identically distributed (i.i.d.) samples from Homodyned K distributions, ultrasound images of media with up to 68 scatterers per resolution cell and ultrasound signals acquired from particle phantoms with up to 101 scatterers per resolution cell. All parameter estimates are obtained using the XU estimator (Destrempes et al., 2013). Results suggest that the parameter α can be used to distinguish between media with up to 40 scatterers per resolution cell at 22 MHz, provided that parameter estimation can be performed on very large sample sizes (i.e., >10,000 i.i.d. samples).