Development of Continuous Assessment of Muscle Quality and Frailty in Older Patients Using Multiparametric Combinations of Ultrasound and Blood Biomarkers: Protocol for the ECOFRAIL Study.

BACKGROUND: Frailty resulting from the loss of muscle quality can potentially be delayed through early detection and physical exercise interventions. There is a demand for cost-effective tools for the objective evaluation of muscle quality, in both cross-sectional and longitudinal assessments. Literature suggests that quantitative analysis of ultrasound data captures morphometric, compositional, and microstructural muscle properties, while biological assays derived from blood samples are associated with functional information. OBJECTIVE: This study aims to assess multiparametric combinations of ultrasound and blood-based biomarkers to offer a cross-sectional evaluation of the patient frailty phenotype and to track changes in muscle quality associated with supervised exercise programs. METHODS: This prospective observational multicenter study will include patients aged 70 years and older who are capable of providing informed consent. We aim to recruit 100 patients from hospital environments and 100 from primary care facilities. Each patient will undergo at least two examinations (baseline and follow-up), totaling a minimum of 400 examinations. In hospital environments, 50 patients will be measured before/after a 16-week individualized and supervised exercise program, while another 50 patients will be followed up after the same period without intervention. Primary care patients will undergo a 1-year follow-up evaluation. The primary objective is to compare cross-sectional evaluations of physical performance, functional capacity, body composition, and derived scales of sarcopenia and frailty with biomarker combinations obtained from muscle ultrasound and blood-based assays. We will analyze ultrasound raw data obtained with a point-of-care device, along with a set of biomarkers previously associated with frailty, using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Additionally, we will examine the sensitivity of these biomarkers to detect short-term muscle quality changes and functional improvement after a supervised exercise intervention compared with usual care. RESULTS: At the time of manuscript submission, the enrollment of volunteers is ongoing. Recruitment started on March 1, 2022, and ends on June 30, 2024. CONCLUSIONS: The outlined study protocol will integrate portable technologies, using quantitative muscle ultrasound and blood biomarkers, to facilitate an objective cross-sectional assessment of muscle quality in both hospital and primary care settings. The primary objective is to generate data that can be used to explore associations between biomarker combinations and the cross-sectional clinical assessment of frailty and sarcopenia. Additionally, the study aims to investigate musculoskeletal changes following multicomponent physical exercise programs. TRIAL REGISTRATION: ClinicalTrials.gov NCT05294757; https://clinicaltrials.gov/ct2/show/NCT05294757. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50325.

Aberration correction in diagnostic ultrasound: A review of the prior field and current directions.

Medical ultrasound images are reconstructed with simplifying assumptions on wave propagation, with one of the most prominent assumptions being that the imaging medium is composed of a constant sound speed. When the assumption of a constant sound speed are violated, which is true in most in vivoor clinical imaging scenarios, distortion of the transmitted and received ultrasound wavefronts appear and degrade the image quality. This distortion is known as aberration, and the techniques used to correct for the distortion are known as aberration correction techniques. Several models have been proposed to understand and correct for aberration. In this review paper, aberration and aberration correction are explored from the early models and correction techniques, including the near-field phase screen model and its associated correction techniques such as nearest-neighbor cross-correlation, to more recent models and correction techniques that incorporate spatially varying aberration and diffractive effects, such as models and techniques that rely on the estimation of the sound speed distribution in the imaging medium. In addition to historical models, future directions of ultrasound aberration correction are proposed.

Comparative Study of Raw Ultrasound Data Representations in Deep Learning to Classify Hepatic Steatosis.

Adiposity accumulation in the liver is an early-stage indicator of non-alcoholic fatty liver disease. Analysis of ultrasound (US) backscatter echoes from liver parenchyma with deep learning (DL) may offer an affordable alternative for hepatic steatosis staging. The aim of this work was to compare DL classification scores for liver steatosis using different data representations constructed from raw US data. Steatosis in N = 31 patients with confirmed or suspected non-alcoholic fatty liver disease was stratified based on fat-fraction cutoff values using magnetic resonance imaging as a reference standard. US radiofrequency (RF) frames (raw data) and clinical B-mode images were acquired. Intermediate image formation stages were modeled from RF data. Power spectrum representations and phase representations were also calculated. Co-registered patches were used to independently train 1-, 2- and 3-D convolutional neural networks (CNNs), and classifications scores were compared with cross-validation. There were 67,800 patches available for 2-D/3-D classification and 1,830,600 patches for 1-D classification. The results were also compared with radiologist B-mode annotations and quantitative ultrasound (QUS) metrics. Patch classification scores (area under the receiver operating characteristic curve [AUROC]) revealed significant reductions along successive stages of the image formation process (p < 0.001). Patient AUROCs were 0.994 for RF data and 0.938 for clinical B-mode images. For all image formation stages, 2-D CNNs revealed higher patch and patient AUROCs than 1-D CNNs. CNNs trained with power spectrum representations converged faster than those trained with RF data. Phase information, which is usually discarded in the image formation process, provided a patient AUROC of 0.988. DL models trained with RF and power spectrum data (AUROC = 0.998) provided higher scores than conventional QUS metrics and multiparametric combinations thereof (AUROC = 0.986). Radiologist annotations indicated lower hepatic steatosis classification accuracies (Acc = 0.914) with respect to magnetic resonance imaging proton density fat fraction that DL models (Acc = 0.989). Access to raw ultrasound data combined with artificial intelligence techniques may offer superior opportunities for quantitative tissue diagnostics than conventional sonographic images.

Speed of sound and shear wave speed for calf soft tissue composition and nonlinearity assessment.

BACKGROUND: The purpose of this study was threefold: (I) to study the correlation of speed-of-sound (SoS) and shear-wave-speed (SWS) ultrasound (US) in the gastrocnemius muscle, (II) to use reproducible tissue compression to characterize tissue nonlinearity effects, and (III) to compare the potential of SoS and SWS for tissue composition assessment. METHODS: Twenty gastrocnemius muscles of 10 healthy young subjects (age range, 23-34 years, two females and eight males) were prospectively examined with both clinical SWS (GE Logiq E9, in m/s) and a prototype system that measures SoS (in m/s). A reflector was positioned opposite the US probe as a timing reference for SoS, with the muscle in between. Reproducible tissue compression was applied by reducing probe-reflector distance in 5 mm steps. The Ogden hyperelastic model and the acoustoelastic theory were used to characterize SoS and SWS variations with tissue compression and extract novel metrics related to tissue nonlinearity. The body fat percentage (BF%) of the subjects was estimated using bioelectrical impedance analysis. RESULTS: A weak negative correlation was observed between SWS and SoS (r=-0.28, P=0.002). SWS showed an increasing trend with increasing tissue compression (P=0.10) while SoS values decayed nonlinearly (P<0.001). The acoustoelastic modeling showed a weak correlation for SWS (r=-0.36, P<0.001) but a very strong correlation for SoS (r=0.86, P<0.001), which was used to extract the SoS acoustoelastic parameter. SWS showed higher variability between both calves [intraclass correlation coefficient (ICC) =0.62, P=0.08] than SoS (ICC =0.91, P<0.001). Correlations with BF% were strong and positive for SWS (r=0.60, P<0.001), moderate and negative for SoS (r=-0.43, P=0.05), and moderate positive for SoS acoustoelastic parameter (r=0.48, P=0.03). CONCLUSIONS: SWS and SoS provide independent information about tissue elastic properties. SWS correlated stronger with BF% than SoS, but measurements were less reliable. SoS enabled the extraction of novel metrics related to tissue nonlinearity with potential complementary information.

Comparison of ultrasound speed-of-sound of the lower extremity and lumbar muscle assessed with computed tomography for muscle loss assessment.

ABSTRACT: To compare the speed of propagation of ultrasound (US) waves (SoS) of the lower leg with the clinical reference standard computed tomography (CT) at the level of lumbar vertebra 3 (L3) for muscle loss assessment. Both calf muscles of 50 patients scheduled for an abdominal CT were prospectively examined with ultrasound. A plexiglas-reflector located on the opposite side of the probe with the calf in between was used as a timing reference for SoS (m/s). CT measurements were performed at the level of L3 and included area (cm2) and attenuation (HU) of the psoas muscle, abdominal muscles, subcutaneous fat, visceral fat and abdominal area. Correlations between SoS, body mass index (BMI) and CT were determined using Pearson's correlation coefficient. Based on reported CT sarcopenia threshold values, receiver operating characteristic (ROC) analysis was performed for SoS. Inter-examiner agreement was assessed with the median difference, inter-quartile range (IQR) and intraclass correlation coefficients. SoS of the calf correlated moderately with abdominal muscle attenuation (r = 0.48; P < .001), psoas muscle attenuation (r = 0.40; P < .01), abdominal area (r = -0.44; P < .01) and weakly with subcutaneous fat area (r = -0.37; P < .01). BMI correlated weakly with psoas attenuation (r = -0.28; P < .05) and non-significantly with abdominal muscle attenuation. Normalization with abdominal area resulted in moderate correlations with abdominal muscle area for SoS (r = 0.43; P < .01) and BMI (r = -0.46; P < .001). Based on sarcopenia threshold values for skeletal muscle attenuation (SMRA), area under curve (AUC) for SoS was 0.724. Median difference between both examiners was -3.4 m/s with IQR = 15.1 m/s and intraclass correlation coefficient = 0.794. SoS measurements of the calf are moderately accurate based on CT sarcopenia threshold values, thus showing potential for muscle loss quantification.

Quantification of immobilization-induced changes in human calf muscle using speed-of-sound ultrasound: An observational pilot study.

ABSTRACT: Short-term immobilization leads to fatty muscular degeneration, which is associated with various negative health effects. Based on literature showing very high correlations between MRI Dixon fat fraction and Speed-of-Sound (SoS), we hypothesized that we can detect short-term-immobilization-induced differences in SoS.Both calves of 10 patients with a calf cast on one side for a mean duration of 41 ±â€Š26 days were examined in relaxed position using a standard ultrasound machine. Calf perimeters were measured for both sides. A flat Plexiglas-reflector, placed vertically on the opposite side of the probe with the calf in-between, was used as a timing reference for SoS. SoS was both manually annotated by two readers and assessed by an automatic annotation algorithm. The thickness values of the subcutaneous fat and muscle layers were manually read from the B-mode images. Differences between the cast and non-cast calves were calculated with a paired t test. Correlation analysis of SoS and calf perimeter was performed using Pearson's correlation coefficient.Paired t test showed significant differences between the cast and non-cast side for both SoS (P < .01) and leg perimeter (P < .001). SoS was reduced with the number of days after cast installment (r = -0.553, P = .097). No significant differences were found for muscle layer thickness, subcutaneous fat layer thickness, mean fat echo intensity, or mean muscle echo intensity.Short-term-immobilization led to a significant reduction in SoS in the cast calf compared to the healthy calf, indicating a potential role of SoS as a biomarker in detecting immobilization-induced fatty muscular degeneration not visible on B-mode ultrasound.

In-situ quantification of microscopic contributions of individual cells to macroscopic wood deformation with synchrotron computed tomography.

Wood-based composites hold the promise of sustainable construction. Understanding the influence on wood cellular microstructure in the macroscopic mechanical behavior is key for engineering high-performance composites. In this work, we report a novel Individual Cell Tracking (ICT) approach for in-situ quantification of nanometer-scale deformations of individual wood cells during mechanical loading of macroscopic millimeter-scale wood samples. Softwood samples containing > 104 cells were subjected to controlled radial tensile and longitudinal compressive load in a synchrotron radiation micro-computed tomography (SRµCT) setup. Tracheid and wood ray cells were automatically segmented, and their geometric variations were tracked during load. Finally, interactions between microstructure deformations (lumen geometry, cell wall thickness), cellular arrangement (annual growth rings, anisotropy, wood ray presence) with the macroscopic deformation response were investigated. The results provide cellular insight into macroscopic relations, such as anisotropic Poisson effects, and allow direct observation of previously suspected wood ray reinforcing effects. The method is also appropriate for investigation of non-linear deformation effects, such as buckling and deformation recovery after failure, and gives insight into less studied aspects, such as changes in lumen diameter and cell wall thickness during uniaxial load. ICT provides an experimental tool for direct validation of hierarchical mechanical models on real biological composites.

Ultrasound Imaging of Injections in Masseter Muscle without Contrast Agent Using Strain Elastography and a Novel B-Mode Spatiotemporal Filter.

Botulinum toxin type A (BTX-A) injections in masseter muscle can alleviate muscle tightness and aching pain caused by idiopathic masticatory myalgia, a subform of the myofascial pain syndrome. Yet the injection procedure (number, amount) is currently empirical. In this ex vivo study, we determined the feasibility of using contrast-free ultrasound imaging to visualize the short-term injectate propagation. Ultrasound annotations of BTX-A injectate spread in N = 12 porcine masseter muscles were compared with the histopathology of the excised masseter. BTX-A presence was automatically detected in the ultrasound cine by: compensating tissue motion and deformation during injection with a novel spatiotemporal filtering (SF) algorithm, and by imaging tissue swelling strains with strain elastography (SE). BTX-A injectate introduced 6.5% (standard deviation = 5.0%) echogenicity contrast and 13.9% (standard deviation = 3.7%) tissue swelling strain. Muscle fasciae were a border for BTX-A distribution. The SF algorithm achieved significantly higher noise rejection (contrast-to-noise ratio = 4.63) than SE (2.56, p = 0.01), and state-of-the-art 2-D digital image correlation (1.81, p < 0.001) and direct image subtraction (1.29, p < 0.001) methods. Histopathology agreed well with ultrasound (Dice coefficient = 0.48), with deviations mainly explained by the three-dimensional inhomogeneous distribution of BTX-A. Preliminary in vivo patient results indicated that SF and SE discard artifactual BTX-A detection outside the injection region. The proposed methods contribute to objectivize ultrasound-guided injections, with additional applications, for instance, to monitor injectate spread of local anesthetics.

Speed of sound ultrasound: comparison with proton density fat fraction assessed with Dixon MRI for fat content quantification of the lower extremity.

OBJECTIVES: To compare speed of sound (SoS) ultrasound (US) of the calves with Dixon magnetic resonance imaging (MRI) for fat content quantification. MATERIALS AND METHODS: The study was approved by the local ethics committee. Fifty calf muscles of 35 women (age range 22-81 years) prospectively underwent an US and subsequent MRI (Dixon sequence) examination as well as body weight and impedance fat measurements. SoS (in m/s) was calculated positioning a reflector on the opposite side of a conventional US machine probe with the calf in between. Fiducial nitroglycerin markers were placed on the calf at the reflector and US probe end positions for later registration of the US sonification volumetric section. An automatic segmentation algorithm separated MRI adipose tissue, muscle and bone regions. MRI fat fraction of the entire leg slice (total) and intramuscular and adipose tissue fat fraction were calculated and correlation analysis and correlation coefficient comparison were performed. RESULTS: Median SoS demonstrated a very strong (r = - 0.83 (95% CI - 0.90; - 0.72); p < 0.001) correlation with MRI total fat fraction, a strong (r = - 0.61 (95% CI - 0.76; - 0.40); p < 0.001) correlation with MRI adipose tissue fat fraction and a moderate (r = - 0.54 (95% CI - 0.71; - 0.31); p < 0.001) correlation with MRI intramuscular fat fraction. Impedance body fat percentage correlated strongly with SoS (r = - 0.72 (95% CI - 0.85; - 0.51); p < 0.001) and MRI total fat fraction (r = 0.61 (95% CI 0.34; 0.78); p < 0.001). For electrical impedance, significantly lower correlations (p = 0.033) were found for MRI total fat fraction compared with SoS. CONCLUSIONS: Correlations of SoS with Dixon MRI fat fraction measurements were very strong to moderate. KEY POINTS: • Correlations of speed of sound with Dixon MRI fat fraction measurements of the same body location were very strong to moderate. • Speed of sound measurements showed a high repeatability. • Speed of sound provides a sufficient discrimination range for fat fraction estimates.

Air-Coupled Ultrasound Time Reversal (ACU-TR) For Subwavelength Nondestructive Imaging.

Air-coupled ultrasound (ACU) is increasingly used for nondestructive testing (NDT). With ACU, no contact or coupling agent (e.g., water and ultrasound gel) is needed between transducers and test sample, which provides high measurement reproducibility. However, for testing in production, a minimum separation is often necessary between the sample and the transducers to avoid contamination or transducer damage. Due to wave diffraction, the collimation of the ultrasound beam decreases for larger propagation distances, and ACU images become blurred and show lower defect lateral resolution with increasing sample-transducer separation. This is especially critical to thick composites, where large-size planar sources are used to bridge the large ACU transmission loss with good collimation. In this work, ACU reradiation in unbounded media is extended to NDT of multilayered composites. The extended method is named ACU time reversal (ACU-TR) and significantly improves the defect resolution of ACU imaging. With ACU-TR, the complete pressure distribution radiated by large ACU source is measured with point receivers (RXs) in one plane arbitrarily separated from the sample. By applying acoustic holography physics, it is then possible to quantitatively reconstruct the pressure field directly at arbitrary sample defect planes, which compensates for undesired diffraction phenomena and improves minimum detectable defect size, thereby achieving subwavelength lateral resolution. We tested the method on complex wood-based composite samples based on the ACU far-field measurements at a separation of 160 mm between the sample and the RX transducer. With the proposed method, it is possible to detect surface defects as well as inner defects within composite boards. In the future, by using point RX arrays instead of a scanned microphone, both data acquisition and evaluation can be potentially implemented in real time.

Spectral Quantification of Nonlinear Elasticity Using Acoustoelasticity and Shear-Wave Dispersion.

Tissue biomechanical properties are known to be sensitive to pathological changes. Accordingly, various techniques have been developed to estimate tissue mechanical properties. Shear-wave elastography (SWE) measures shear-wave speed (SWS) in tissues, which can be related to shear modulus. Although viscosity or stress-strain nonlinearity may act as confounder of SWE, their explicit characterization may also provide additional information about tissue composition as a contrast modality. Viscosity can be related to frequency dispersion of SWS, which can be characterized using multi-frequency measurements, herein called spectral SWE (SSWE). Additionally, nonlinear shear modulus can be quantified and parameterized based on SWS changes with respect to applied stress, a phenomenon called acoustoelasticity (AE). In this work, we characterize the nonlinear parameters of tissue as a function of excitation frequency by utilizing both AE and SSWE together. For this, we apply incremental amounts of quasi-static stress on a medium, while imaging and quantifying SWS dispersion via SSWE. Results from phantom and ex vivo porcine liver experiments demonstrate the feasibility of measuring frequency-dependent nonlinear parameters using the proposed method. SWS propagation in porcine liver tissue was observed to change from 1.8 m/s at 100 Hz to 3.3 m/s at 700 Hz, while increasing by approximately 25% from a strain of 0% to 12% across these frequencies.

Which Confounders Have the Largest Impact in Shear Wave Elastography of Muscle and How Can They be Minimized? An Elasticity Phantom, Ex Vivo Porcine Muscle and Volunteer Study Using a Commercially Available System.

The goal of the study was to investigate the quantitative impact of region of interest (ROI), software choice, muscle fiber orientation and preload tension on shear wave velocity (SWV). First, SWV was assessed in an isotropic elasticity phantom and ex vivo porcine muscle using a commercially available clinical ultrasound system. Secondly, SWV was acquired in relaxed and stretched calf muscles of healthy volunteers (dorsal extension of the talocrural joint), for both parallel and transverse probe direction to the fibers, as well as for different ROIs and software versions. The effect of intermediate probe-fiber alignments was also analyzed. Finally, the impact of confounding factors on SWV reproducibility was minimized with a second force-controlled volunteer study, in which the calf was isometrically loaded, and fiber orientation and ROI were well-defined. 2046 in vivoSWE images were acquired to analyze SWV reproducibility with different confounder settings. In healthy volunteers, the main variance-contributing factors were in order of importance muscle tension, fiber orientation, horizontal ROI size and insertion depth. Regression analysis showed significantly reduced SWV with increasing insertion depth for each study material. Parallel probe-fiber orientation, muscle stretch and increasing horizontal ROI size led to significantly higher SWV. Based on the results of the study, we provide recommendations to minimize the impact of confounders in musculoskeletal elastography and discuss the main confounding mechanisms and trade-offs between confounding variables. Coefficients of variation can be significantly reduced with a controlled protocol, if the confounders are clinically taken into account.

Breast Density Assessment in Young Women with Ultrasound based on Speed of Sound: Influence of the Menstrual Cycle.

To investigate changes in breast density (BD) during the menstrual cycle in young women in comparison to inter-breast and -segment changes as well as reproducibility of a novel Speed-of-Sound (SoS) Ultrasound (US) method.SoS-US uses a conventional US system with a reflector and a software add-on to quantify SoS in the retro-mammillary, inner and outer segments of both breasts. Twenty healthy women (18-40 years) with regular menstrual cycles were scanned twice with two weeks in-between. Three of these were additionally measured twice per week for 25 days. Average SoS (m/s) and ΔSoS (segment-variation SoS; m/s) were measured. Variations between follicular and luteal phases and changes over the four-week period were assessed. Inter-examiner and inter-reader agreements were also evaluated. Variances between cycle phases, examiners and readers were compared.No significant SoS difference was observed between follicular and luteal phases for the twenty women (P = .126), and between all different days for the three more frequently measured women (P = .892). Inter-reader (ICC = 0.999) and inter-examiner (ICC = 0.990) agreements were high. The SoS variance due to menstrual variations was not significantly larger than the inter-examiner uncertainty (P = .461). Inter-reader variations were significantly smaller than menstrual and examiner variations (P < .001).SoS-US showed high inter-examiner and inter-reader reproducibility. The alterations during the menstrual cycles were not significantly larger than the confidence interval of measurements.

Breast Cancer Assessment With Pulse-Echo Speed of Sound Ultrasound From Intrinsic Tissue Reflections: Proof-of-Concept.

PURPOSE: The aim of this study was to differentiate malignant and benign solid breast lesions with a novel ultrasound (US) technique, which measures speed of sound (SoS) using standard US transducers and intrinsic tissue reflections and scattering (speckles) as internal reference. MATERIALS AND METHODS: This prospective, institutional review board-approved, Health Insurance Portability and Accountability Act-compliant prospective comparison study was performed with prior written informed consent from 20 women. Ten women with histological proven breast cancer and 10 with fibroadenoma were measured. A conventional US system with a linear probe was used for SoS-US (SonixTouch; Ultrasonix, Richmond, British Columbia, Canada). Tissue speckle reflections served as a timing reference for the US signals transmitted through the breasts. Relative phase inconsistencies were detected using plane wave measurements from different angular directions, and SoS images with 0.5-mm resolution were generated using a spatial domain reconstruction algorithm. The SoS of tumors were compared with the breast density of a larger cohort of 106 healthy women. RESULTS: Breast lesions show focal increments ΔSoS (meters per second) with respect to the tissue background. Peak ΔSoS values were evaluated. Breast carcinoma showed significantly higher ΔSoS than fibroadenomas ([INCREMENT]SoS > 41.64 m/s: sensitivity, 90%; specificity, 80%; area under curve, 0.910) and healthy breast tissue of different densities (area under curve, 0.938; sensitivity, 90%; specificity, 96.5%). The lesion localization in SoS-US images was consistent with B-mode imaging and repeated SoS-US measurements were reproducible. CONCLUSIONS: Using SoS-US, based on conventional US and tissue speckles as timing reference, breast carcinoma showed significantly higher SoS values than fibroadenoma and healthy breast tissue of different densities. The SoS presents a promising technique for differentiating solid breast lesions.

Acoustic Field Characterization of Medical Array Transducers Based on Unfocused Transmits and Single-Plane Hydrophone Measurements.

Medical ultrasonic arrays are typically characterized in controlled water baths using measurements by a hydrophone, which can be translated with a positioning stage. Characterization of 3D acoustic fields conventionally requires measurements at each spatial location, which is tedious and time-consuming, and may be prohibitive given limitations of experimental setup (e.g., the bath and stage) and measurement equipment (i.e., the hydrophone). Moreover, with the development of new ultrasound sequences and modalities, multiple measurements are often required to characterize each imaging mode to ensure performance and clinical safety. Acoustic holography allows efficient characterization of source transducer fields based on single plane measurements. In this work, we explore the applicability of a re-radiation method based on the Rayleigh⁻Sommerfeld integral to medical imaging array characterization. We show that source fields can be reconstructed at single crystal level at wavelength resolution, based on far-field measurements. This is herein presented for three practical application scenarios: for identifying faulty transducer elements; for characterizing acoustic safety parameters in focused ultrasound sequences from 2D planar measurements; and for estimating arbitrary focused fields based on calibration from an unfocused sound field and software beamforming. The results experimentally show that the acquired pressure fields closely match those estimated using our technique.

Speed of sound ultrasound: a pilot study on a novel technique to identify sarcopenia in seniors.

OBJECTIVES: To measure speed of sound (SoS) with a novel hand-held ultrasound technique as a quantitative indicator for muscle loss and fatty muscular degeneration. METHODS: Both calf muscles of 11 healthy, young females (mean age 29 years), and 10 elderly females (mean age 82 years) were prospectively examined with a standard ultrasound machine. A flat Plexiglas® reflector, on the opposite side of the probe with the calf in between, was used as timing reference for SoS (m/s) and ΔSoS (variation of SoS, m/s). Handgrip strength (kPA), Tegner activity scores, and 5-point comfort score (1 = comfortable to 5 = never again) were also assessed. Ultrasound parameters (muscle/adipose thickness, echo intensity) were measured for comparison. RESULTS: Both calves were assessed in less than two minutes. All measurements were successful. The elderly females showed significantly lower SoS (1516 m/s, SD17) compared to the young adults (1545 m/s, SD10; p < 0.01). The ΔSoS of elderly females was significantly higher (12.2 m/s, SD3.6) than for young females (6.4 m/s, SD1.5; p < 0.01). Significant correlations of SoS with hand grip strength (r = 0.644) and Tegner activity score (rs = 0.709) were found, of similar magnitude as the correlation of hand grip strength with Tegner activity score (rs = 0.794). The average comfort score of the elderly was 1.1 and for the young adults 1.4. SoS senior/young classification (AUC = 0.936) was superior to conventional US parameters. CONCLUSIONS: There were significant differences of SoS and ΔSoS between young and elderly females. Measurements were fast and well tolerated. The novel technique shows potential for sarcopenia quantification using a standard ultrasound machine. KEY POINTS: • Speed of sound ultrasound: a novel technique to identify sarcopenia in seniors. • Measurements were fast and well tolerated using a standard ultrasound machine. • The novel technique shows potential for sarcopenia quantification.

Speed-of-Sound Imaging Based on Reflector Delineation.

OBJECTIVE: Speed-of-sound (SoS) has large potential for tissue and pathology differentiation. We aim to develop a novel Ultrasound Computed Tomography (USCT) technique that can reconstruct local SoS in tissue on conventional ultrasound machines with hand-held linear arrays. METHODS: A passive reflector is placed opposite the tissue sample as an echogenic reference to measure the time-of-flight (ToF) of ultrasound wave- fronts. A Dynamic Programming algorithm provides a robust ToF measurements based on global optimization of all transmit- receive echo data. An Anisotropically-Weighted Total Variation (AWTV) algorithm allows sharp delineation of focal lesions based on limited-angle USCT data. RESULTS: Inclusions, which are not visible in conventional ultrasound, could be delineated in SoS images. AWTV allows to reconstruct focal lesions with a contrast-ratio of 93.7% of their nominal value, compared to that of 31.5% with conventional least-squares based algebraic tomographic reconstruction. In full-wave simulations of realistic heterogeneous breast models, a high CR of 84.3% is observed, with the reconstruction filtering out background heterogeneity. In experiments, our proposed method quantifies SoS in a homogeneous background with an accuracy of 0.93ms, allowing to differentiate several tissue types. CONCLUSION: We validate our method using numerical simulations with ray-tracing and full- wave models, and phantom and ex-vivo data. Preliminary in- vivo results show the potential of this new technique to detect and differentiate malignant and benign lesions in the breast. SIGNIFICANCE: Breast cancer is the most common cancer in women. Ultrasound B-mode only provides qualitative information about breast lesions, whereas USCT can provide quantitative tissue imaging biomarkers, such as SoS. The proposed method can potentially be implemented as a complementary modality to ultrasound for tissue and disease differentiation.

Spatial domain reconstruction for imaging speed-of-sound with pulse-echo ultrasound: simulation and in vivo study.

Despite many uses of ultrasound, some pathologies such as breast cancer still cannot reliably be diagnosed in either conventional B-mode ultrasound imaging nor with more recent ultrasound elastography methods. Speed-of-sound (SoS) is a quantitative imaging biomarker, which is sensitive to structural changes due to pathology, and hence could facilitate diagnosis. Full-angle ultrasound computed tomography (USCT) was proposed to obtain spatially-resolved SoS images, however, its water-bath setup involves practical limitations. To increase clinical utility and for widespread use, recently, a limited-angle Fourier-domain SoS reconstruction was proposed, however, it suffers from significant image reconstruction artifacts. In this work, we present a SoS reconstruction strategy, where the forward problem is formulated using differential time-of-flight measurements based on apparent displacements along different ultrasound wave propagation paths, and the inverse problem is solved in spatial-domain using a proposed total-variation scheme with spatially-varying anisotropic weighting to compensate for geometric bias from limited angle imaging setup. This is shown to be robust to missing displacement data and easily allow for incorporating any prior geometric information. In numerical simulations, SoS values in inclusions are accurately reconstructed with 90% accuracy up to a noise level of 50%. With respect to Fourier-domain reconstruction, our proposed method improved contrast ratio from 0.37 to 0.67 for even high noise levels such as 50%. Numerical full-wave simulation and our preliminary in vivo results illustrate the clinical applicability of our method in a breast cancer imaging setting. Our proposed method requires single-sided access to the tissue and can be implemented as an add-on to conventional ultrasound equipment, applicable to a range of transducers and applications.

Robust Reconstruction of Elasticity Using Ultrasound Imaging and Multi-Frequency Excitations.

Biomedical parameters of tissue can be important indicators for clinical diagnosis. One such parameter that reflects tissue stiffness is elasticity, the imaging of which is called elastography. In this paper, we use displacements from harmonic excitations to solve the inverse problem of elasticity based on a finite-element method (FEM) formulation. This leads to iterative solution of nonlinear and nonconvex problems. In this paper, we show the importance and selection of viable initializations in numerical simulation studies and propose techniques for the fusion of multiple initializations for ideal reconstructions of unknown tissue as well as combining information from excitations at multiple frequencies. Results show that our method leads up to 76% decrease in root-mean-squared error (RMSE) and 9.9 dB increase in contrast-to-noise ratio (CNR) in simulations with noise, when compared to conventional iterative FEM without multiple initializations and frequencies. As the wave patterns in individually selected frequencies may introduce artifacts, a joint inverse-problem solution of multi-frequency excitations is introduced as a robust solution, where CNR improvements of up to 11.9 dB are observed. We also present the methods on a tissue-mimicking gelatin phantom study using mechanical excitation and ultrafast plane-wave ultrasound imaging, where the RMSE was improved by up to 51%. An experiment of ablation via heating an ex-vivo bovine liver shows that reconstruction artifacts are reduced with our proposed method.

Breast-density assessment with hand-held ultrasound: A novel biomarker to assess breast cancer risk and to tailor screening?

OBJECTIVES: To assess feasibility and diagnostic accuracy of a novel hand-held ultrasound (US) method for breast density assessment that measures the speed of sound (SoS), in comparison to the ACR mammographic (MG) categories. METHODS: ACR-MG density (a=fatty to d=extremely dense) and SoS-US were assessed in the retromamillary, inner and outer segments of 106 women by two radiographers. A conventional US system was used for SoS-US. A reflector served as timing reference for US signals transmitted through the breasts. Four blinded readers assessed average SoS (m/s), ΔSoS (segment-variation SoS; m/s) and the ACR-MG density. The highest SoS and ΔSoS values of the three segments were used for MG-ACR whole breast comparison. RESULTS: SoS-US breasts were examined in <2 min. Mean SoS values of densities a-d were 1,421 m/s (SD 14), 1,432 m/s (SD 17), 1,448 m/s (SD 20) and 1,500 m/s (SD 31), with significant differences between all groups (p<0.001). The SoS-US comfort scores and inter-reader agreement were significantly better than those for MG (1.05 vs. 2.05 and 0.982 vs. 0.774; respectively). A strong segment correlation between SoS and ACR-MG breast density was evident (rs=0.622, p=<0.001) and increased for full breast classification (rs=0.746, p=<0.001). SoS-US allowed diagnosis of dense breasts (ACR c and d) with sensitivity 86.2 %, specificity 85.2 % and AUC 0.887. CONCLUSIONS: Using hand-held SoS-US, radiographers measured breast density without discomfort, readers evaluated measurements with high inter-reader agreement, and SoS-US correlated significantly with ACR-MG breast-density categories. KEY POINTS: • The novel speed-of-sound ultrasound correlated significantly with mammographic ACR breast density categories. • Radiographers measured breast density without women discomfort or radiation. • SoS-US can be implemented on a standard US machine. • SoS-US shows potential for a quantifiable, cost-effective assessment of breast density.