Quantitative Ultrasound: An Emerging Technology for Detecting, Diagnosing, Imaging, Evaluating, and Monitoring Disease.

Ultrasound has been a popular clinical imaging modality for decades. It is a well-established means of displaying the macroscopic anatomy of soft-tissue structures. While conventional ultrasound methods, i.e., B-mode and Doppler methods, are well proven and continue to advance technically in many ways, e.g., by extending into higher frequencies and taking advantage of harmonic phenomena in tissues, fundamentally new so-called quantitative ultrasound (QUS) technologies also are emerging and offer exciting promise for making significant improvements in clinical imaging and characterization of disease. These emerging quantitative methods include spectrum analysis, image statistics, elasticity imaging, contrast-agent methods, and flow-detection and -measurement techniques. Each provides independent information. When used alone, each can provide clinically valuable imaging capabilities; when combined with each other, their capabilities may be more powerful in many applications. Furthermore, all can be used fused with other imaging modalities, such as computed tomography (CT), magnetic-resonance (MR), positron-emission-tomography (PET), or single-photon emission computerized tomography (SPECT) imaging, to offer possibly even greater improvements in detecting, diagnosing, imaging, evaluating, and monitoring disease. This chapter focuses on QUS methods that are based on spectrum analysis and image statistics.

Ultrasound Imaging With a Flexible Probe Based on Element Array Geometry Estimation Using Deep Neural Network.

Conventionally, ultrasound (US) diagnosis is performed using hand-held rigid probes. Such devices are difficult to be used for long-term monitoring because they need to be continuously pressed against the body to remove the air between the probe and body. Flexible probes, which can deform and effectively adhere to the body, are a promising technology for long-term monitoring applications. However, owing to the flexible element array geometry, the reconstructed image becomes blurred and distorted. In this study, we propose a flexible probe U.S. imaging method based on element array geometry estimation from radio frequency (RF) data using a deep neural network (DNN). The input and output of the DNN are the RF data and parameters that determine the element array geometry, respectively. The DNN was first trained from scratch with simulation data and then fine-tuned with in vivo data. The DNN performance was evaluated according to the element position mean absolute error (MAE) and the reconstructed image quality. The reconstructed image quality was evaluated with peak-signal-to-noise ratio (PSNR) and mean structural similarity (MSSIM). In the test conducted with simulation data, the average element position MAE was 0.86 mm, and the average reconstructed image PSNR and MSSIM were 20.6 and 0.791, respectively. In the test conducted with in vivo data, the average element position MAE was 1.11 mm, and the average reconstructed image PSNR and MSSIM were 19.4 and 0.798, respectively. The average estimation time was 0.045 s. These results demonstrate the feasibility of the proposed method for long-term real-time monitoring using flexible probes.

A Flexible Ultrasound Array for Local Pulse Wave Velocity Monitoring.

Pulse wave velocity (PWV) measured at a specific artery location is called local PWV, which provides the elastic characteristics of arteries and indicates the degree of arterial stiffness. However, the large and cumbersome ultrasound probes require an appropriate sensor position and pressure maintenance, introducing usability constraints. In this paper, we developed a light (0.5 g) and thin (400 µm) flexible ultrasound array by encapsulating 1-3 composite piezoelectric transducers with a silicone elastomer. It can capture the distension waveforms of four arterial positions with a spacing of 10 mm and calculate the local PWV by multi-point fitting. This is illustrated by in vivo experiments, where the local PWV value of five normal subjects ranged from 3.07 to 4.82 m/s, in agreement with earlier studies. The beat-to-beat coefficient of variation (CV) is 12.0% ± 3.5%, showing high reliability. High reproducibility is shown by the results of two groups of independent measurements of three subjects (the error between the mean values is less than 0.3 m/s). These properties of the developed flexible ultrasound array enable the bandage-like application of local PWV monitoring to skin surfaces.

Quantitative imaging of ultrasound backscattered signals with information entropy for bone microstructure characterization.

Osteoporosis is a critical problem during aging. Ultrasound signals backscattered from bone contain information associated with microstructures. This study proposed using entropy imaging to collect the information in bone microstructures as a possible solution for ultrasound bone tissue characterization. Bone phantoms with different pounds per cubic foot (PCF) were used for ultrasound scanning by using single-element transducers of 1 (nonfocused) and 3.5 MHz (nonfocused and focused). Clinical measurements were also performed on lumbar vertebrae (L3 spinal segment) in participants with different ages (n = 34) and postmenopausal women with low or moderate-to-high risk of osteoporosis (n = 50; identified using the Osteoporosis Self-Assessment Tool for Taiwan). The signals backscattered from the bone phantoms and subjects were acquired for ultrasound entropy imaging by using sliding window processing. The independent t-test, one-way analysis of variance, Spearman correlation coefficient rs, and the receiver operating characteristic (ROC) curve were used for statistical analysis. The results indicated that ultrasound entropy imaging revealed changes in bone microstructures. Using the 3.5-MHz focused ultrasound, small-window entropy imaging (side length: one pulse length of the transducer) was found to have high performance and sensitivity in detecting variation among the PCFs (rs = - 0.83; p < 0.05). Small-window entropy imaging also performed well in discriminating young and old participants (p < 0.05) and postmenopausal women with low versus moderate-to-high osteoporosis risk (the area under the ROC curve = 0.80; cut-off value = 2.65; accuracy = 86.00%; sensitivity = 71.43%; specificity = 88.37%). Ultrasound small-window entropy imaging has great potential in bone tissue characterization and osteoporosis assessment.

The Utility of Handheld Cardiac and Lung Ultrasound in Predicting Outcomes of Hospitalised Patients With COVID-19.

BACKGROUND: Strict isolation precautions limit formal echocardiography use in the setting of COVID-19 infection. Information on the importance of handheld focused ultrasound for cardiac evaluation in these patients is scarce. This study investigated the utility of a handheld echocardiography device in hospitalised patients with COVID-19 in diagnosing cardiac pathologies and predicting the composite end point of in-hospital death, mechanical ventilation, shock, and acute decompensated heart failure. METHODS: From April 28 through July 27, 2020, consecutive patients diagnosed with COVID-19 underwent evaluation with the use of handheld ultrasound (Vscan Extend with Dual Probe; GE Healthcare) within 48 hours of admission. The patients were divided into 2 groups: "normal" and "abnormal" echocardiogram, as defined by biventricular systolic dysfunction/enlargement or moderate/severe valvular regurgitation/stenosis. RESULTS: Among 102 patients, 26 (25.5%) had abnormal echocardiograms. They were older with more comorbidities and more severe presenting symptoms compared with the group with normal echocardiograms. The prevalences of the composite outcome among low- and high-risk patients (oxygen saturation < 94%) were 3.1% and 27.1%, respectively. Multivariate logistic regression analysis revealed that an abnormal echocardiogram at presentation was independently associated with the composite end point (odds ratio 6.19, 95% confidence interval 1.50-25.57; P = 0.012). CONCLUSIONS: An abnormal echocardiogram in COVID-19 infection settings is associated with a higher burden of medical comorbidities and independently predicts major adverse end points. Handheld focused echocardiography can be used as an important "rule-out" tool among high-risk patients with COVID-19 and should be integrated into their routine admission evaluation. However, its routine use among low-risk patients is not recommended.

Speed of sound in the IEC tissue-mimicking material and its maintenance solution as a function of temperature.

Tissue-Mimicking Material (TMM) is defined on IEC International Standards and applied in assessing ultrasonic diagnostic and therapeutic equipment's basic safety and essential performance. One of the TMM that fits IEC standards specification has its recipe described at IEC 60601-2-37, and it is fabricated using glycerol (11.21 %), deionized water (82.95%), benzalkonium chloride (0.47 %), silicon carbide (0.53 %), aluminum oxide 0.3 µm (0.88%), aluminum oxide 3.0 µm (0.94 %), and agar (3.08 %). Glycerol is the component responsible for adjusting the TMM's speed of sound. Moreover, it is recommended to store TMM in a closed container immersed in a mixture of water (88.1 %)/glycerol (11.9 %) to prevent it from drying out and avoiding air contact. The literature points out TMM measurements underwater can alter the speed of sound property as TMM tends to lose glycerol. Herein, the authors proposed to assess the viability of measuring the TMM speed of sound in the water/glycerol maintenance solution. First, the authors characterized the maintenance solution's speed of sound for a temperature range of 20 °C to 45 °C. Then, the group velocity of a set of TMM was measured underwater and in the maintenance solution for the same temperature range. The respective group velocity expanded uncertainty was calculated. The results indicate it is feasible to measure TMM in the maintenance solution, achieving group velocity values with no statistical difference from the ones measured underwater in the temperature range of 20 °C to 40 °C.

Improved ultrasound image quality with pixel-based beamforming using a Wiener-filter and a SNR-dependent coherence factor.

Pixel-based beamforming generates focused data by assuming that the waveforms received on a linear transducer array are composed of spherical pulses. It does not take into account the spatiotemporal spread in the data from the length of the excitation pulse or from the transfer functions of the transducer elements. As a result, these beamformers primarily have impacts on lateral, rather than axial, resolution. This paper proposes an efficient method to improve the axial resolution for pixel-based beamforming. We extend our field pattern analysis and show that the received waveforms should be passed through a Wiener filter before being used in the coherent pixel-based beamformer. This filter is designed based on signals echoed from a single scatterer at the transmit focus. The beamformer output is then combined with a coherence factor, that is adaptive to the signal-to-noise ratio, to improve the image contrast and suppress artifacts that have arisen during the filtering process. We validate the proposed method and compare it with other beamforming strategies using a series of experiments, including simulation, phantom and in vivo studies. It is shown to offer significant improvements in axial resolution and contrast over coherent pixel-based beamforming, as well as other spatial filters derived from synthetic aperture imaging. The method also demonstrates robustness to modeling errors in the experimental data. Overall, the imaging results show that the proposed approach has the potential to be of value in clinical applications.

Feasibility and Clinical Impact of Point-of-Care Carotid Artery Examinations by Experts using Hand-Held Ultrasound Devices in Patients with Ischemic Stroke or Transitory Ischemic Attack.

BACKGROUND AND PURPOSE: To evaluate the feasibility and clinical influence of carotid artery examinations in patients admitted with stroke or TIA with hand-held ultrasound by experts, to identify individuals not in need of further carotid artery diagnostics. MATERIALS AND METHODS: Cardiologists experienced in carotid ultrasound examined 80 patients admitted to a stroke unit with suspected stroke or TIA with hand-held ultrasound devices (HUD). Grey scale and color Doppler images were stored using a GE Vscan with dual probe (phased array and linear transducer). High-end triplex ultrasound performed by a cardiologist, blinded to the details of the HUD study, was performed in all patients and used as reference. Computer tomography angiography was performed when clinically indicated. RESULTS: Stroke or TIA was diagnosed in 62 (78%) patients. Age was median (range) 72 (23-93) years. A significant stenosis (> 50% diameter reduction) was ruled out in 61 (76%) of patients by the HUD examinations. Sensitivity and specificity for diagnosing a significant stenosis was 92% and 93%, respectively. One of 12 significant stenoses was missed by HUD. All four patients in need of surgery were identified by the HUD examination. Sensitivity and specificity to identify a significant stenosis by HUD was 87% and 83%, respectively, compared to CT angiography. CONCLUSION: HUD examinations of the carotid arteries by experts, using hand-held ultrasound devices, were feasible and may reduce the need for high-end diagnostic imaging of the carotid vessels in patients with stroke and TIA. Thus, HUD may improve diagnostic workflow in stroke units in the future.

Point-of-care ultrasound in a multiplace hyperbaric chamber.

Historically, electronic devices have been generally prohibited during hyperbaric oxygen (HBO2) therapy due to risk of fire in a pressurized, oxygen-rich environment. Point-of-care ultrasound (POCUS) however has emerged as a useful imaging modality in diverse clinical settings. Hyperbaric chambers treating critically ill patients would benefit from the application of POCUS at pressure to make real-time patient assessments. Thus far, POCUS during HBO2 therapy has been limited due to required equipment modifications to meet safety standards. Here we demonstrate proof of concept, safety, and successful performance of an off-the-shelf handheld POCUS system (SonoSite iViz) in a clinical hyperbaric environment without need for modification.

Impact of an epic-integrated point-of-care ultrasound workflow on ultrasound performance, compliance, and potential revenue.

OBJECTIVES: The purpose of this study was to describe the design and impact of a point-of-care ultrasound (PoCUS) workflow integrated into the electronic medical record (EMR) on PoCUS utilization, documentation compliance, and resultant revenue potential. METHODS: This was a single-center retrospective study at an academic center. The study period spanned from December 1, 2018 to June 30, 2019 (pre-implementation) to August 1, 2019 to February 29, 2020 (post-implementation). The implementation date was July 11, 2019 at which time a PoCUS workflow was integrated into the EMR in the emergency department without the purchase of middleware. Prior to this new workflow, a non-automated workflow was in place. PoCUS scan data were extracted from the EMR and archived examinations. The mean number of PoCUS examinations performed per month per 100 ED visits before and after implementation of the new workflow were compared using an unpaired t-test, stratified by all health care professionals, and attending physicians alone. The rate of documentation compliance before and after implementation of the new workflow were compared using a chi square contingency test. Potential revenue was calculated for each period by multiplying the number of eligible examinations by the respective 2020 Medicare conversion factor Relative Value Units. RESULTS: Utilization of PoCUS from pre-implementation to post-implementation increased 28.7% from 5.01 to 6.45 mean examinations per month per 100 ED visits by all health care professionals (p = 0.063), and 75.1% from 2.01 to 3.52 by attending physicians (p = 0.0001). Examinations in compliance with workflow requirements increased from 153 (14.7%) to 1307 (94.0%). The rate of workflow compliance improved from 14.7% to 94.0% of examinations (p < 0.0001). Potential revenue increased from $546.01 to $22,014.47. CONCLUSIONS: The implementation of a middleware-free PoCUS workflow at our institution was associated with increased PoCUS utilization, documentation compliance, and potential revenue.

Ultra high-frequency ultrasound with seventy-MHz transducer in hair disorders: Development of a novel noninvasive diagnostic methodology.

BACKGROUND: Ultra high-frequency ultrasound (uHFUS) is a recently developed diagnostic technology. Despite its potential usefulness, no study has assessed its advantage in diagnosis and evaluation of hair disorders in comparison with other diagnostic methods. OBJECTIVES: To assess the practicability of uHFUS in diagnosing hair disorders and propose a diagnostic methodology. METHODS: Ultrasonographic images of scalp and forehead from patients with hair disorders (n = 103) and healthy controls (n = 40) were obtained by uHFUS and analyzed by both descriptive and numerical parameters. Furthermore, the data were compared with trichoscopic and histopathological findings. RESULTS: The pattern of inflammation and fibrosis, hair cycle abnormality, and the findings in subcutis were detected by uHFUS. Significant differences were noted in the numerical parameters associated with the number of hair shafts and follicles, hair diameters and their diversity, and dermal echogenicity in both cicatricial and non-cicatricial hair disorders. Findings in uHFUS were associated with those observed in trichoscopy and scalp biopsy but uHFUS was able to detect pathological findings associated with hair cycle, inflammation, fibrosis, and subcutaneous abnormalities, which are hardly assessable by trichoscopy. CONCLUSION: The findings of this study highlighted usefulness of uHFUS in diagnosing hair disorders, while overcoming the weaknesses and limitations of other diagnostic tools.

Autonomous pick-and-place using the dVRK.

PURPOSE: Robotic-assisted partial nephrectomy (RAPN) is a tissue-preserving approach to treating renal cancer, where ultrasound (US) imaging is used for intra-operative identification of tumour margins and localisation of blood vessels. With the da Vinci Surgical System (Sunnyvale, CA), the US probe is inserted through an auxiliary access port, grasped by the robotic tool and moved over the surface of the kidney. Images from US probe are displayed separately to the surgical site video within the surgical console leaving the surgeon to interpret and co-registers information which is challenging and complicates the procedural workflow. METHODS: We introduce a novel software architecture to support a hardware soft robotic rail designed to automate intra-operative US acquisition. As a preliminary step towards complete task automation, we automatically grasp the rail and position it on the tissue surface so that the surgeon is then able to manipulate manually the US probe along it. RESULTS: A preliminary clinical study, involving five surgeons, was carried out to evaluate the potential performance of the system. Results indicate that the proposed semi-autonomous approach reduced the time needed to complete a US scan compared to manual tele-operation. CONCLUSION: Procedural automation can be an important workflow enhancement functionality in future robotic surgery systems. We have shown a preliminary study on semi-autonomous US imaging, and this could support more efficient data acquisition.

Device profile of exAblate Neuro 4000, the leading system for brain magnetic resonance guided focused ultrasound technology: an overview of its safety and efficacy in the treatment of medically refractory essential tremor.

Introduction: Magnetic Resonance guided Focused UltraSound (MRgFUS) is an emerging technique that utilizes multiple high-energy low-frequency ultrasound beams generated from a multi-element transducer focused onto a single site to cause thermal ablation of the target tissue. The ExAblate Neuro 4000 system is the leading MRgFUS brain system, performing targeted thermal ablation on specific nuclei in the brain. Its precision targeting opens up new and exciting possibilities for future treatments of a wide range of neurological diseases.  Areas covered: This article aims to introduce the non-expert reader (clinician and non-clinicians) to the role of the ExAblate Neuro 4000 System in brain MRgFUS. The current clinical uses of the ExAblate system in the brain are explored with a particular focus on Essential Tremor, where internationally there is most experience, this includes reference to current literature. The safety and efficacy of MRgFUS treatments are explored and the challenges the ExAblate system must overcome to balance these juxtaposed outcomes.Expert opinion: We describe the hopes for future clinical uses of the ExAblate Neuro 4000 system to treat neurological disease and consider further advancements in MRgFUS transducer technology that may open up new exciting frontiers within the brain.

Transparent capacitive micromachined ultrasound transducer linear arrays for combined realtime optical and ultrasonic imaging.

Transparent ultrasound transducers could enable many novel applications involving both ultrasonics and optics. Recently, we reported transparent capacitive micromachined ultrasound transducers (CMUTs) and demonstrated through-illumination photoacoustic imaging. This work presents the feasibility of transparent CMUTs for combined ultrasound imaging and through-array white-light imaging with a miniature camera placed behind the array. Transparent CMUT devices are fabricated with an adhesive wafer bonding technique and provide high transparency up to 90% in visible wavelengths. Fabricated linear arrays have a central operating frequency of 9 MHz with 128 active elements. Realtime plane-wave imaging is performed for ultrasound imaging, and lateral and axial resolutions of, respectively, 234 and 338 µm are achieved. Transparent CMUT has demonstrated a high transmit sensitivity of 1.4 kPa/V per channel with a 100 VDC bias voltage. The signal-to-noise ratio for a beamformed image of wire targets is determined to be 28.4 dB. To the best of our knowledge, this is the first report of combined realtime optical and ultrasonic imaging with transparent arrays. This technology may enable one to visually see what is being scanned and scan what one sees without co-registration errors. Future applications could include multi-modality probes for interventional and surgical procedures.

Ultrasound Core Laboratory for the Household Air Pollution Intervention Network Trial: Standardized Training and Image Management for Field Studies Using Portable Ultrasound in Fetal, Lung, and Vascular Evaluations.

Ultrasound Core Laboratories (UCL) are used in multicenter trials to assess imaging biomarkers to define robust phenotypes, to reduce imaging variability and to allow blinded independent review with the purpose of optimizing endpoint measurement precision. The Household Air Pollution Intervention Network, a multicountry randomized controlled trial (Guatemala, Peru, India and Rwanda), evaluates the effects of reducing household air pollution on health outcomes. Field studies using portable ultrasound evaluate fetal, lung and vascular imaging endpoints. The objective of this report is to describe administrative methods and training of a centralized clinical research UCL. A comprehensive administrative protocol and training curriculum included standard operating procedures, didactics, practical scanning and written/practical assessments of general ultrasound principles and specific imaging protocols. After initial online training, 18 sonographers (three or four per country and five from the UCL) participated in a 2 wk on-site training program. Written and practical testing evaluated ultrasound topic knowledge and scanning skills, and surveys evaluated the overall course. The UCL developed comprehensive standard operating procedures for image acquisition with a portable ultrasound system, digital image upload to cloud-based storage, off-line analysis and quality control. Pre- and post-training tests showed significant improvements (fetal ultrasound: 71% ± 13% vs. 93% ± 7%, p < 0.0001; vascular lung ultrasound: 60% ± 8% vs. 84% ± 10%, p < 0.0001). Qualitative and quantitative feedback showed high satisfaction with training (mean, 4.9 ± 0.1; scale: 1 = worst, 5 = best). The UCL oversees all stages: training, standardization, performance monitoring, image quality control and consistency of measurements. Sonographers who failed to meet minimum allowable performance were identified for retraining. In conclusion, a UCL was established to ensure accurate and reproducible ultrasound measurements in clinical research. Standardized operating procedures and training are aimed at reducing variability and enhancing measurement precision from study sites, representing a model for use of portable digital ultrasound for multicenter field studies.