Noninvasive prediction of axillary lymph node breast cancer metastasis using morphometric analysis of nodal tumor microvessels in a contrast-free ultrasound approach.

PURPOSE: Changes in microcirculation of axillary lymph nodes (ALNs) may indicate metastasis. Reliable noninvasive imaging technique to quantify such variations is lacking. We aim to develop and investigate a contrast-free ultrasound quantitative microvasculature imaging technique for detection of metastatic ALN in vivo. EXPERIMENTAL DESIGN: The proposed ultrasound-based technique, high-definition microvasculature imaging (HDMI) provides superb images of tumor microvasculature at sub-millimeter size scales and enables quantitative analysis of microvessels structures. We evaluated the new HDMI technique on 68 breast cancer patients with ultrasound-identified suspicious ipsilateral axillary lymph nodes recommended for fine needle aspiration biopsy (FNAB). HDMI was conducted before the FNAB and vessel morphological features were extracted, analyzed, and the results were correlated with the histopathology. RESULTS: Out of 15 evaluated quantitative HDMI biomarkers, 11 were significantly different in metastatic and reactive ALNs (10 with P << 0.01 and one with 0.01 < P < 0.05). We further showed that through analysis of these biomarkers, a predictive model trained on HDMI biomarkers combined with clinical information (i.e., age, node size, cortical thickness, and BI-RADS score) could identify metastatic lymph nodes with an area under the curve of 0.9 (95% CI [0.82,0.98]), sensitivity of 90%, and specificity of 88%. CONCLUSIONS: The promising results of our morphometric analysis of HDMI on ALNs offer a new means of detecting lymph node metastasis when used as a complementary imaging tool to conventional ultrasound. The fact that it does not require injection of contrast agents simplifies its use in routine clinical practice.

Mapping Pharmacologically Evoked Neurovascular Activation and Its Suppression in a Rat Model of Tremor Using Functional Ultrasound: A Feasibility Study.

Functional ultrasound (fUS), an emerging hemodynamic-based functional neuroimaging technique, is especially suited to probe brain activity and primarily used in animal models. Increasing use of pharmacological models for essential tremor extends new research to the utilization of fUS imaging in such models. Harmaline-induced tremor is an easily provoked model for the development of new therapies for essential tremor (ET). Furthermore, harmaline-induced tremor can be suppressed by the same classic medications used for essential tremor, which leads to the utilization of this model for preclinical testing. However, changes in local cerebral activities under the effect of tremorgenic doses of harmaline have not been completely investigated. In this study, we explored the feasibility of fUS imaging for visualization of cerebral activation and deactivation associated with harmaline-induced tremor and tremor-suppressing effects of propranolol. The spatial resolution of fUS using a high frame rate imaging enabled us to visualize time-locked and site-specific changes in cerebral blood flow associated with harmaline-evoked tremor. Intraperitoneal administration of harmaline generated significant neural activity changes in the primary motor cortex and ventrolateral thalamus (VL Thal) regions during tremor and then gradually returned to baseline level as tremor subsided with time. To the best of our knowledge, this is the first functional ultrasound study to show the neurovascular activation of harmaline-induced tremor and the therapeutic suppression in a rat model. Thus, fUS can be considered a noninvasive imaging method for studying neuronal activities involved in the ET model and its treatment.

Volumetric imaging and morphometric analysis of breast tumor angiogenesis using a new contrast-free ultrasound technique: a feasibility study.

BACKGROUND: There is a strong correlation between the morphological features of new tumor vessels and malignancy. However, angiogenic heterogeneity necessitates 3D microvascular data of tumor microvessels for more reliable quantification. To provide more accurate information regarding vessel morphological features and improve breast lesion characterization, we introduced a quantitative 3D high-definition microvasculature imaging (q3D-HDMI) as a new easily applicable and robust tool to morphologically characterize microvasculature networks in breast tumors using a contrast-free ultrasound-based imaging approach. METHODS: In this prospective study, from January 2020 through December 2021, a newly developed q3D-HDMI technique was evaluated on participants with ultrasound-identified suspicious breast lesions recommended for core needle biopsy. The morphological features of breast tumor microvessels were extracted from the q3D-HDMI. Leave-one-out cross-validation (LOOCV) was applied to test the combined diagnostic performance of multiple morphological parameters of breast tumor microvessels. Receiver operating characteristic (ROC) curves were used to evaluate the prediction performance of the generated pooled model. RESULTS: Ninety-three participants (mean age 52 ± 17 years, 91 women) with 93 breast lesions were studied. The area under the ROC curve (AUC) generated with q3D-HDMI was 95.8% (95% CI 0.901-1.000), yielding a sensitivity of 91.7% and a specificity of 98.2%, that was significantly higher than the AUC generated with the q2D-HDMI (p = 0.02). When compared to q2D-HDMI, the tumor microvessel morphological parameters obtained from q3D-HDMI provides distinctive information that increases accuracy in differentiating breast tumors. CONCLUSIONS: The proposed quantitative volumetric imaging technique augments conventional breast ultrasound evaluation by increasing specificity in differentiating malignant from benign breast masses.

Hybrid high-definition microvessel imaging/shear wave elastography improves breast lesion characterization.

BACKGROUND: Low specificity in current breast imaging modalities leads to increased unnecessary follow-ups and biopsies. The purpose of this study is to evaluate the efficacy of combining the quantitative parameters of high-definition microvasculature imaging (HDMI) and 2D shear wave elastography (SWE) with clinical factors (lesion depth and age) for improving breast lesion differentiation. METHODS: In this prospective study, from June 2016 through April 2021, patients with breast lesions identified on diagnostic ultrasound and recommended for core needle biopsy were recruited. HDMI and SWE were conducted prior to biopsies. Two new HDMI parameters, Murray's deviation and bifurcation angle, and a new SWE parameter, mass characteristic frequency, were included for quantitative analysis. Lesion malignancy prediction models based on HDMI only, SWE only, the combination of HDMI and SWE, and the combination of HDMI, SWE and clinical factors were trained via elastic net logistic regression with 70% (360/514) randomly selected data and validated with the remaining 30% (154/514) data. Prediction performances in the validation test set were compared across models with respect to area under the ROC curve as well as sensitivity and specificity based on optimized threshold selection. RESULTS: A total of 508 participants (mean age, 54 years ± 15), including 507 female participants and 1 male participant, with 514 suspicious breast lesions (range, 4-72 mm, median size, 13 mm) were included. Of the lesions, 204 were malignant. The SWE-HDMI prediction model, combining quantitative parameters from SWE and HDMI, with AUC of 0.973 (95% CI 0.95-0.99), was significantly higher than the result predicted with the SWE model or HDMI model alone. With an optimal cutoff of 0.25 for the malignancy probability, the sensitivity and specificity were 95.5% and 89.7%, respectively. The specificity was further improved with the addition of clinical factors. The corresponding model defined as the SWE-HDMI-C prediction model had an AUC of 0.981 (95% CI 0.96-1.00). CONCLUSIONS: The SWE-HDMI-C detection model, a combination of SWE estimates, HDMI quantitative biomarkers and clinical factors, greatly improved the accuracy in breast lesion characterization.

Ultrasound high-definition microvasculature imaging with novel quantitative biomarkers improves breast cancer detection accuracy.

OBJECTIVES: To overcome the limitations of power Doppler in imaging angiogenesis, we sought to develop and investigate new quantitative biomarkers of a contrast-free ultrasound microvasculature imaging technique for differentiation of benign from malignant pathologies of breast lesion. METHODS: In this prospective study, a new high-definition microvasculature imaging (HDMI) was tested on 521 patients with 527 ultrasound-identified suspicious breast masses indicated for biopsy. Four new morphological features of tumor microvessels, microvessel fractal dimension (mvFD), Murray's deviation (MD), bifurcation angle (BA), and spatial vascularity pattern (SVP) as well as initial biomarkers were extracted and analyzed, and the results correlated with pathology. Multivariable logistic regression analysis was used to study the performance of different prediction models, initial biomarkers, new biomarkers, and combined new and initial biomarkers in differentiating benign from malignant lesions. RESULTS: The new HDMI biomarkers, mvFD, BA, MD, and SVP, were statistically significantly different in malignant and benign lesions, regardless of tumor size. Sensitivity and specificity of the new biomarkers in lesions > 20 mm were 95.6% and 100%, respectively. Combining the new and initial biomarkers together showed an AUC, sensitivity, and specificity of 97% (95% CI: 95-98%), 93.8%, and 89.2%, respectively, for all lesions regardless of mass size. The classification was further improved by adding the Breast Imaging Reporting and Data System (BI-RADS) score to the prediction model, showing an AUC, sensitivity, and specificity of 97% (95% CI: 95-98%), 93.8%, and 89.2%, respectively. CONCLUSION: The addition of new quantitative HDMI biomarkers significantly improved the accuracy in breast lesion characterization when used as a complementary imaging tool to the conventional ultrasound. KEY POINTS: • Novel quantitative biomarkers extracted from tumor microvessel images increase the sensitivity and specificity in discriminating malignant from benign breast masses. • New HDMI biomarkers Murray's deviation, bifurcation angles, microvessel fractal dimension, and spatial vascularity pattern outperformed the initial biomarkers. • The addition of BI-RADS scores based on US descriptors to the multivariable analysis using all biomarkers remarkably increased the sensitivity, specificity, and AUC in all size groups.

Early assessment of shear wave elastography parameters foresees the response to neoadjuvant chemotherapy in patients with invasive breast cancer.

BACKGROUND: Early prediction of tumor response to neoadjuvant chemotherapy (NACT) is crucial for optimal treatment and improved outcome in breast cancer patients. The purpose of this study is to investigate the role of shear wave elastography (SWE) for early assessment of response to NACT in patients with invasive breast cancer. METHODS: In a prospective study, 62 patients with biopsy-proven invasive breast cancer were enrolled. Three SWE studies were conducted on each patient: before, at mid-course, and after NACT but before surgery. A new parameter, mass characteristic frequency (fmass), along with SWE measurements and mass size was obtained from each SWE study visit. The clinical biomarkers were acquired from the pre-NACT core-needle biopsy. The efficacy of different models, generated with the leave-one-out cross-validation, in predicting response to NACT was shown by the area under the receiver operating characteristic curve and the corresponding sensitivity and specificity. RESULTS: A significant difference was found for SWE parameters measured before, at mid-course, and after NACT between the responders and non-responders. The combination of Emean2 and mass size (s2) gave an AUC of 0.75 (0.95 CI 0.62-0.88). For the ER+ tumors, the combination of Emean_ratio1, s1, and Ki-67 index gave an improved AUC of 0.84 (0.95 CI 0.65-0.96). For responders, fmass was significantly higher during the third visit. CONCLUSIONS: Our study findings highlight the value of SWE estimation in the mid-course of NACT for the early prediction of treatment response. For ER+ tumors, the addition of Ki-67improves the predictive power of SWE. Moreover, fmass is presented as a new marker in predicting the endpoint of NACT in responders.

Shear wave elastography of the median nerve: A mechanical study.

BACKGROUND: Shear wave elastography (SWE) shows promise in peripheral neuropathy evaluation but has potential limitations due to tissue size and heterogeneity. We tested SWE sensitivity to elasticity change and the effect of probe position in a median nerve cadaver model. METHODS: Ten specimens were used to measure median nerve elasticity under increasing loads using SWE and indentation. Measurements were compared using repeated-measures analysis of variance. RESULTS: Indentation and SWE-based longitudinal nerve elasticity increased with tensile loading (P < .01), showing a similar relationship. Acquisition in a transverse plane showed lower values compared with longitudinal measurements, mostly under higher loads (P = .03), as did postdissection elasticity (P = .02). Elasticity did not change when measured proximal to the carpal tunnel. CONCLUSIONS: Longitudinal SWE is sensitive to changes in median nerve elasticity. Measuring elasticity of peripheral nerves noninvasively could elucidate intra-neural pathology related to compression neuropathies, and proof to be of added value as a diagnostic or prognostic tool.

Fully Automated Segmentation of Bladder Sac and Measurement of Detrusor Wall Thickness from Transabdominal Ultrasound Images.

Ultrasound measurements of detrusor muscle thickness have been proposed as a diagnostic biomarker in patients with bladder overactivity and voiding dysfunction. In this study, we present an approach based on deep learning (DL) and dynamic programming (DP) to segment the bladder sac and measure the detrusor muscle thickness from transabdominal 2D B-mode ultrasound images. To assess the performance of our method, we compared the results of automated methods to the manually obtained reference bladder segmentations and wall thickness measurements of 80 images obtained from 11 volunteers. It takes less than a second to segment the bladder from a 2D B-mode image for the DL method. The average Dice index for the bladder segmentation is 0.93 ± 0.04 mm, and the average root-mean-square-error and standard deviation for wall thickness measurement are 0.7 ± 0.2 mm, which is comparable to the manual ground truth. The proposed fully automated and fast method could be a useful tool for segmentation and wall thickness measurement of the bladder from transabdominal B-mode images. The computation speed and accuracy of the proposed method will enable adaptive adjustment of the ultrasound focus point, and continuous assessment of the bladder wall during the filling and voiding process of the bladder.

In vivo assessment of the mechanical properties of crystalline lenses in a rabbit model using ultrasound elastography: Effects of ultrasound frequency and age.

PURPOSE: The occurrence of presbyopia and cataract is closely related to changes in the mechanical properties of the crystalline lens. There are no established methods so far for in vivo assessment. By introducing ultrasound elastography, we proposed group velocity (Vg) of an induced shear wave as a new biomarker to characterize the mechanical properties of the lens in our previous study. Here, we investigated the effect of the ultrasound frequency on measurement accuracy and validated the results with a conventional ex vivo compression testing. We also demonstrated a change trend in Vg and its correlation with age in a rabbit model. METHODS: Eight New Zealand white rabbits were fed normally from the fourth to seventh month. An ultrasound elastography system was developed to measure Vgin vivo on every eye once per month. The performances when using a high-frequency (L22-11v) and low-frequency (L11-4v) probe were compared. Rabbits were sacrificed after in vivo measurements by the end of the seventh month and this was followed by ex vivo ultrasound measurements and conventional compression tests on the extracted lenses. RESULTS: The results demonstrated that there were no significance differences in Vg between measurements with high-frequency (USE-HF) and low-frequency (USE-LF) probes in the same month-age group. The mean Vg and the standard deviation of four rabbits that were 7 months old were 2.37 ±â€¯0.24  m/s, 2.36 ±â€¯0.25 m/s, 2.43 ±â€¯0.26 m/s and 2.44 ±â€¯0.38 m/s, with USE-HF for ex vivo and in vivo measurements and USE-LF for ex vivo and in vivo measurements, respectively. There were no significant differences (p > 0.05) and they were all in agreement with the results of compression tests, which was 16.16 ±â€¯1.84 kPa in Young's modulus. The results also showed that Vg increased with age. In combination with the results of our previous study, Vg showed a relatively sharp increase from 2 to 5 months, while it had a slight increase from 5 to 7 months. CONCLUSIONS: The USE-HF and USE-LF has comparable accuracy in Vg measurements while USE-HF had an advantage regarding better spatial resolution. The change trend of Vg was in accord with the growth phase of New Zealand white rabbits, which usually results in sexual maturity at 5 months old. This implies that Vg can be used as a biomarker parameter for evaluating the mechanical properties of the lens undergoing physiological changes.

Gap-filling method for suppressing grating lobes in ultrasound imaging: Theory and simulation results.

Sparse array (SA) is an approach to reduce the number of system channels. However, SA suffers from grating lobe (GL) artefacts due to the sparsity of array aperture resulting in degradation of the ultrasound image quality. Based on a given or known data sets of radio frequency (RF) echo acquired from active elements of an array, RF echo data in unknown and/or inactive elements of array can be created virtually and used to suppress the GL artefact in SA. This letter presents gap-filling (GF) approaches to generate channel data, which are not physically acquired. It is demonstrated that the proposed GF technique can reduce the artefacts of SA by filling the gaps in the array aperture. Simulation results show that the GF technique can suppress the GL level of SA by up to 16 dB. Also, the GF technique can improve the image quality of fully sampled arrays with small number of active elements.

Non-Local Based Denoising Framework for In Vivo Contrast-Free Ultrasound Microvessel Imaging.

Vascular networks can provide invaluable information about tumor angiogenesis. Ultrafast Doppler imaging enables ultrasound to image microvessels by applying tissue clutter filtering methods on the spatio-temporal data obtained from plane-wave imaging. However, the resultant vessel images suffer from background noise that degrades image quality and restricts vessel visibilities. In this paper, we addressed microvessel visualization and the associated noise problem in the power Doppler images with the goal of achieving enhanced vessel-background separation. We proposed a combination of patch-based non-local mean filtering and top-hat morphological filtering to improve vessel outline and background noise suppression. We tested the proposed method on a flow phantom, as well as in vivo breast lesions, thyroid nodules, and pathologic liver from human subjects. The proposed non-local-based framework provided a remarkable gain of more than 15 dB, on average, in terms of contrast-to-noise and signal-to-noise ratios. In addition to improving visualization of microvessels, the proposed method provided high quality images suitable for microvessel morphology quantification that may be used for diagnostic applications.

Ultrasound Radiation Force for the Assessment of Bone Fracture Healing in Children: An In Vivo Pilot Study.

Vibrational characteristics of bone are directly dependent on its physical properties. In this study, a vibrational method for bone evaluation is introduced. We propose a new type of quantitative vibro-acoustic method based on the acoustic radiation force of ultrasound for bone characterization in persons with fracture. Using this method, we excited the clavicle or ulna by an ultrasound radiation force pulse which induces vibrations in the bone, resulting in an acoustic wave that is measured by a hydrophone placed on the skin. The acoustic signals were used for wave velocity estimation based on a cross-correlation technique. To further separate different vibration characteristics, we adopted a variational mode decomposition technique to decompose the received signal into an ensemble of band-limited intrinsic mode functions, allowing analysis of the acoustic signals by their constitutive components. This prospective study included 15 patients: 12 with clavicle fractures and three with ulna fractures. Contralateral intact bones were used as controls. Statistical analysis demonstrated that fractured bones can be differentiated from intact ones with a detection probability of 80%. Additionally, we introduce a "healing factor" to quantify the bone healing progress which successfully tracked the progress of healing in 80% of the clavicle fractures in the study.

Three-Dimensional Shear Wave Elastography for Differentiating Benign From Malignant Thyroid Nodules.

OBJECTIVES: To prospectively evaluate the diagnostic performance of 3-dimensional (3D) shear wave elastography (SWE) for assessing thyroid nodules. METHODS: A total of 176 surgically or cytologically confirmed thyroid nodules (63 malignant and 113 benign) in 176 patients who had undergone conventional ultrasound (US), 2-dimensional (2D) SWE, and 3D SWE examinations were included in this study. Quantitative elasticity values (mean elasticity, maximum elasticity, and standard deviation of elasticity of a large region of interest and mean elasticity of a 2-mm region of interest) were measured on 2D and 3D SWE. Diagnostic performances of conventional US, 2D SWE, and 3D SWE were assessed. The role of 2D and 3D SWE in reducing unnecessary fine-needle aspiration (FNA) for nodules with low suspicion was also evaluated. RESULTS: The diagnostic performances in terms of the area under the receiver operating characteristic curve were 0.612 for conventional US, 0.836 for 2D SWE (P < .001 in comparison with conventional US), and 0.839 for 3D SWE (P < .001 in comparison with conventional US). The mean elasticity achieved the highest diagnostic performance in 2D SWE, whereas the standard deviation of elasticity achieved the highest performance in 3D SWE, although no significant difference was found between them (P > .05). Three-dimensional SWE increased the specificity in comparison with 2D SWE (88.5% versus 82.3%; P = .039). For the 37 nodules with low suspicion on conventional US imaging, 2D SWE was able to avoid unnecessary FNA in 77.1% (27 of 35) of benign nodules, and 3D SWE further increased the number to 88.6% (31 of 35). CONCLUSIONS: Three-dimensional SWE is a useful tool for predicting thyroid nodule malignancy and reducing unnecessary FNA procedures in thyroid nodules with low suspicion of malignancy.

Breast vibro-acoustography: initial experience in benign lesions.

BACKGROUND: Vibro-acoustography (VA) is a newly developed imaging technology that is based on low-frequency vibrations induced in the object by the radiation force of ultrasound. VA is sensitive to the dynamic characteristics of tissue. Here, we evaluate the performance of VA in identifying benign lesions and compare the results to those of mammography. METHODS: An integrated mammography-VA system designed for in vivo breast imaging was tested on a group of female volunteers, age ≥ 18 years, with suspected breast lesions based on clinical examination. A set of VA scans was acquired after each corresponding mammography. Most lesions were classified as benign based on their histological results. However, in 4 cases, initial diagnosis based on clinical imaging determined that the lesions were cysts. These cysts were aspirated with needle aspiration and disappeared completely under direct ultrasound visualization. Therefore, no biopsies were performed on these cases and lesions were classified as benign based on clinical findings per clinical standards. To define the VA characteristics of benign breast masses, we adopted the features that are normally attributed to such masses in mammography. In a blinded assessment, three radiologists evaluated the VA images independently. The diagnostic accuracy of VA for detection of benign lesions was assessed by comparing the reviewers' evaluations with clinical data. RESULTS: Out of a total 29 benign lesions in the group, the reviewers were able to locate all lesions on VA images and mammography, 100% with (95% confidence interval (CI): 88% to 100%). Two reviewers were also able to correctly classify 83% (95% CI: 65% to 92%), and the third reviewer 86% (95% CI: 65% to 95%) of lesions, as benign on VA images and 86% (95% CI: 69% to 95%) on mammography. CONCLUSIONS: The results suggest that the mammographic characteristics of benign lesion may also be used to identify such lesions in VA. Furthermore, the results show the ability of VA to detect benign breast abnormalities with a performance comparable to mammography. Therefore, the VA technology has the potential to be utilized as a complementary tool for breast imaging applications. Additional studies are needed to compare the capabilities of VA and traditional ultrasound imaging.

In Vivo Ultrasound Shear Wave Elastography Assessment of Acute Compartment Syndrome in a Turkey Model.

OBJECTIVE: The aim of the work described here was to evaluate the objectivity and reproducibility of non-invasive intra-compartment pressure (ICP) measurement using ultrasound shear wave elastography (SWE) in a turkey model in vivo and to determine the biological and histologic changes in acute compartment syndrome (ACS). METHODS: Twenty-four turkeys were randomly divided into four groups based on the duration and fasciotomy of ACS created by infusion of up to 50 mm Hg in the tibialis muscle: group 1, ACS 2 h; group 2, ACS 4 h; group 3, ACS 2 h + fasciotomy 2 h; group 4, ACS 4 h + fasciotomy 2 h. For each turkey, the contralateral limb was considered the control. Time-synchronized measures of SWE and ICP from each leg were collected. Then turkeys were euthanized for histology and quantitative reverse transcription polymerase chain reaction (qRT-PCR) examination. RESULTS: All models created reproducible increases in ICP and SWE, which had a strong linear relationship (r = 0.802, p < 0.0001) during phase 1. SWE remained stable (50.86 ± 9.64 kPa) when ICP remained at 50.28 ± 2.17 mm Hg in phase 2. After fasciotomy, SWE declined stepwise and then normalized (r = 0.737, p < 0.0001). Histologically, the myofiber diameter of group 2 (82.31 ± 22.92 µm) and group 4 (90.90 ± 20.48 µm) decreased significantly (p < 0.01) compared with that of the control group (103.1 ± 20.39 µm); the interstitial space of all groups increased significantly (p < 0.01). Multifocal muscle damage revealed neutrophilic infiltration, degeneration, hemorrhage and necrosis, especially in group 4. Quantitative RT-PCR verified that interleukin-6 and heparin-binding EGF-like growth factor were significantly increased in group 4. CONCLUSION: SWE provided sensitive measurements correlating to ICP in a clinically relevant ACS animal model. Once ACS time was exceeded, progression to irreversible necrosis continued spontaneously, even after fasciotomy. SWE may help surgeons in the early detection, monitoring, prognosis and decision making on fasciotomy for ACS.

Quantitative Biomarkers Derived from a Novel, Contrast-Free Ultrasound, High-Definition Microvessel Imaging for Differentiating Choroidal Tumors.

Angiogenesis has an essential role in the de novo evolution of choroidal melanoma as well as choroidal nevus transformation into melanoma. Differentiating early-stage melanoma from nevus is of high clinical importance; thus, imaging techniques that provide objective information regarding tumor microvasculature structures could aid accurate early detection. Herein, we investigated the feasibility of quantitative high-definition microvessel imaging (qHDMI) for differentiation of choroidal tumors in humans. This new ultrasound-based technique encompasses a series of morphological filtering and vessel enhancement techniques, enabling the visualization of tumor microvessels as small as 150 microns and extracting vessel morphological features as new tumor biomarkers. Distributional differences between the malignant melanomas and benign nevi were tested on 37 patients with choroidal tumors using a non-parametric Wilcoxon rank-sum test, and statistical significance was declared for biomarkers with p-values < 0.05. The ocular oncology diagnosis was choroidal melanoma (malignant) in 21 and choroidal nevus (benign) in 15 patients. The mean thickness of benign and malignant masses was 1.70 ± 0.40 mm and 3.81 ± 2.63 mm, respectively. Six HDMI biomarkers, including number of vessel segments (p = 0.003), number of branch points (p = 0.003), vessel density (p = 0.03), maximum tortuosity (p = 0.001), microvessel fractal dimension (p = 0.002), and maximum diameter (p = 0.003) exhibited significant distributional differences between the two groups. Contrast-free HDMI provided noninvasive imaging and quantification of microvessels of choroidal tumors. The results of this pilot study indicate the potential use of qHDMI as a complementary tool for characterization of small ocular tumors and early detection of choroidal melanoma.

A Force-Matched Approach to Large-Strain Nonlinearity in Elasticity Imaging for Breast Lesion Characterization.

OBJECTIVE: Ultrasound elasticity imaging is a class of ultrasound techniques with applications that include the detection of malignancy in breast lesions. Although elasticity imaging traditionally assumes linear elasticity, the large strain elastic response of soft tissue is known to be nonlinear. This study evaluates the nonlinear response of breast lesions for the characterization of malignancy using force measurement and force-controlled compression during ultrasound imaging. METHODS: 54 patients were recruited for this study. A custom force-instrumented compression device was used to apply a controlled force during ultrasound imaging. Motion tracking derived strain was averaged over lesion or background ROIs and matched with compression force. The resulting force-matched strain was used for subsequent analysis and curve fitting. RESULTS: Greater median differences between malignant and benign lesions were observed at higher compressional forces (p-value < 0.05 for compressional forces of 2-6N). Of three candidate functions, a power law function produced the best fit to the force-matched strain. A statistically significant difference in the scaling parameter of the power function between malignant and benign lesions was observed (p-value = 0.025). CONCLUSIONS: We observed a greater separation in average lesion strain between malignant and benign lesions at large compression forces and demonstrated the characterization of this nonlinear effect using a power law model. Using this model, we were able to differentiate between malignant and benign breast lesions. SIGNIFICANCE: With further development, the proposed method to utilize the nonlinear elastic response of breast tissue has the potential for improving non-invasive lesion characterization for potential malignancy.

In vivo thyroid vibro-acoustography: a pilot study.

BACKGROUND: The purpose of this study was to evaluate the utility of a noninvasive ultrasound-based method, vibro-acoustography (VA), for thyroid imaging and determine the feasibility and challenges of VA in detecting nodules in thyroid. METHODS: Our study included two parts. First, in an in vitro study, experiments were conducted on a number of excised thyroid specimens randomly taken from autopsy. Three types of images were acquired from most of the specimens: X-ray, B-mode ultrasound, and vibro-acoustography. The second and main part of the study includes results from performing VA and B-mode ultrasound imaging on 24 human subjects with thyroid nodules. The results were evaluated and compared qualitatively. RESULTS: In vitro vibro-acoustography images displayed soft tissue structures, microcalcifications, cysts and nodules with high contrast and no speckle. In this group, all of US proven nodules and all of X-ray proven calcifications of thyroid tissues were detected by VA. In vivo results showed 100% of US proven calcifications and 91% of the US detected nodules were identified by VA, however, some artifacts were present in some cases. CONCLUSIONS: In vitro and in vivo VA images show promising results for delineating the detailed structure of the thyroid, finding nodules and in particular calcifications with greater clarity compare to US. Our findings suggest that, with further development, VA may be a suitable imaging modality for clinical thyroid imaging.

Custom-made flow phantoms for quantitative ultrasound microvessel imaging.

Morphologically realistic flow phantoms are essential experimental tools for quantitative ultrasound-based microvessel imaging. As new quantitative flow imaging tools are developed, the need for more complex vessel-mimicking phantoms is indisputable. In this article, we propose a method for fabricating phantoms with sub-millimeter channels consisting of branches and curvatures in various shapes and sizes suitable for quantifying vessel morphological features. We used different tissue-mimicking materials (TMMs) compatible with ultrasound imaging as the base and metal wires of different diameters (0.15-1.25 mm) to create wall-less channels. The TMMs used are silicone rubber, plastisol, conventional gelatin, and medical gelatin. Mother channels in these phantoms were made in diameters of 1.25 mm or 0.3 mm and the daughter channels in diameters 0.3 mm or 0.15 mm. Bifurcations were created by soldering wires together at branch points. Quantitative parameters were assessed, and accuracy of measurements from the ground truth were determined. Channel diameters were seen to have increased (76-270%) compared to the initial state in the power Doppler images, partly due to blood mimicking fluid pressure. Amongst the microflow phantoms made from the different TMMs, the medical gelatin phantom was selected as the best option for microflow imaging, fulfilling the objective of being easy to fabricate with high transmittance while having a speed of sound and acoustic attenuation close to human tissue. A flow velocity of 0.85 ± 0.01 mm/s, comparable to physiological flow velocity was observed in the smallest diameter phantom (medical gelatin branch) presented here. We successfully constructed more complex geometries, including tortuous and multibranch channels using the medical gelatin as the TMM. We anticipate this will create new avenues for validating quantitative ultrasound microvessel imaging techniques.

Deep Learning in Different Ultrasound Methods for Breast Cancer, from Diagnosis to Prognosis: Current Trends, Challenges, and an Analysis.

Breast cancer is the second-leading cause of mortality among women around the world. Ultrasound (US) is one of the noninvasive imaging modalities used to diagnose breast lesions and monitor the prognosis of cancer patients. It has the highest sensitivity for diagnosing breast masses, but it shows increased false negativity due to its high operator dependency. Underserved areas do not have sufficient US expertise to diagnose breast lesions, resulting in delayed management of breast lesions. Deep learning neural networks may have the potential to facilitate early decision-making by physicians by rapidly yet accurately diagnosing and monitoring their prognosis. This article reviews the recent research trends on neural networks for breast mass ultrasound, including and beyond diagnosis. We discussed original research recently conducted to analyze which modes of ultrasound and which models have been used for which purposes, and where they show the best performance. Our analysis reveals that lesion classification showed the highest performance compared to those used for other purposes. We also found that fewer studies were performed for prognosis than diagnosis. We also discussed the limitations and future directions of ongoing research on neural networks for breast ultrasound.