Transcranial volumetric imaging using a conformal ultrasound patch.

Accurate and continuous monitoring of cerebral blood flow is valuable for clinical neurocritical care and fundamental neurovascular research. Transcranial Doppler (TCD) ultrasonography is a widely used non-invasive method for evaluating cerebral blood flow1, but the conventional rigid design severely limits the measurement accuracy of the complex three-dimensional (3D) vascular networks and the practicality for prolonged recording2. Here we report a conformal ultrasound patch for hands-free volumetric imaging and continuous monitoring of cerebral blood flow. The 2 MHz ultrasound waves reduce the attenuation and phase aberration caused by the skull, and the copper mesh shielding layer provides conformal contact to the skin while improving the signal-to-noise ratio by 5 dB. Ultrafast ultrasound imaging based on diverging waves can accurately render the circle of Willis in 3D and minimize human errors during examinations. Focused ultrasound waves allow the recording of blood flow spectra at selected locations continuously. The high accuracy of the conformal ultrasound patch was confirmed in comparison with a conventional TCD probe on 36 participants, showing a mean difference and standard deviation of difference as -1.51 ± 4.34 cm s-1, -0.84 ± 3.06 cm s-1 and -0.50 ± 2.55 cm s-1 for peak systolic velocity, mean flow velocity, and end diastolic velocity, respectively. The measurement success rate was 70.6%, compared with 75.3% for a conventional TCD probe. Furthermore, we demonstrate continuous blood flow spectra during different interventions and identify cascades of intracranial B waves during drowsiness within 4 h of recording.

US Backscatter for Liver Fat Quantification: An AIUM-RSNA QIBA Pulse-Echo Quantitative Ultrasound Initiative.

Nonalcoholic fatty liver disease (NAFLD) is believed to affect one-third of American adults. Noninvasive methods that enable detection and monitoring of NAFLD have the potential for great public health benefits. Because of its low cost, portability, and noninvasiveness, US is an attractive alternative to both biopsy and MRI in the assessment of liver steatosis. NAFLD is qualitatively associated with enhanced B-mode US echogenicity, but visual measures of B-mode echogenicity are negatively affected by interobserver variability. Alternatively, quantitative backscatter parameters, including the hepatorenal index and backscatter coefficient, are being investigated with the goal of improving US-based characterization of NAFLD. The American Institute of Ultrasound in Medicine and Radiological Society of North America Quantitative Imaging Biomarkers Alliance are working to standardize US acquisition protocols and data analysis methods to improve the diagnostic performance of the backscatter coefficient in liver fat assessment. This review article explains the science and clinical evidence underlying backscatter for liver fat assessment. Recommendations for data collection are discussed, with the aim of minimizing potential confounding effects associated with technical and biologic variables.

Pulse-Echo Quantitative US Biomarkers for Liver Steatosis: Toward Technical Standardization.

Excessive liver fat (steatosis) is now the most common cause of chronic liver disease worldwide and is an independent risk factor for cirrhosis and associated complications. Accurate and clinically useful diagnosis, risk stratification, prognostication, and therapy monitoring require accurate and reliable biomarker measurement at acceptable cost. This article describes a joint effort by the American Institute of Ultrasound in Medicine (AIUM) and the RSNA Quantitative Imaging Biomarkers Alliance (QIBA) to develop standards for clinical and technical validation of quantitative biomarkers for liver steatosis. The AIUM Liver Fat Quantification Task Force provides clinical guidance, while the RSNA QIBA Pulse-Echo Quantitative Ultrasound Biomarker Committee develops methods to measure biomarkers and reduce biomarker variability. In this article, the authors present the clinical need for quantitative imaging biomarkers of liver steatosis, review the current state of various imaging modalities, and describe the technical state of the art for three key liver steatosis pulse-echo quantitative US biomarkers: attenuation coefficient, backscatter coefficient, and speed of sound. Lastly, a perspective on current challenges and recommendations for clinical translation for each biomarker is offered.

Scattering in Cancellous Bone.

Two theoretical models for ultrasonic scattering from cancellous bone have been extensively validated in human cancellous bone in vitro. Many metrics have been devised to assess scattering in vivo. In the diagnostic frequency range (<1 MHz), multiple scattering is much weaker than single scattering. However, evidence for multiple scattering has been detected. At higher frequencies (>1 MHz), the effects of multiple scattering are more pronounced. Clinical trials indicate that backscatter parameters provide useful diagnostic information regarding bone status in adults and neonates. This chapter will emphasize developments in scattering research in the last decade since the previous volume Bone QUS was published.

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

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

Broadband characterization of plastic and high intensity therapeutic ultrasound phantoms using time delay spectrometry-With validation using Kramers-Kronig relations.

Time delay spectrometry (TDS) is extended for broadband characterization of plastics (low-density polyethylene, LDPE) and tissue-mimicking material (TMM). The results suggest that TDS and the conventional broadband pulse method give comparable measurements for frequency-dependent attenuation coefficient and phase velocity near the center frequency, where signal-to-noise ratio is high. However, TDS measurements show enhanced bandwidth for attenuation coefficient of 30%-40% (LDPE) and 89%-100% (TMM) and for phase velocity of 43% (LDPE) and 36% (TMM) for a single transmitter/receiver pair. In addition, TDS provides measurements of dispersion that are consistent with predictions based on the Kramers-Kronig relations to within 5 m/s over the band from 2 to 12 MHz in LDPE and to within 1 m/s in TMM over the band from 0.5 to 29 MHz.

Conditionally Increased Acoustic Pressures in Nonfetal Diagnostic Ultrasound Examinations Without Contrast Agents: A Preliminary Assessment.

The mechanical index (MI) has been used by the US Food and Drug Administration (FDA) since 1992 for regulatory decisions regarding the acoustic output of diagnostic ultrasound equipment. Its formula is based on predictions of acoustic cavitation under specific conditions. Since its implementation over 2 decades ago, new imaging modes have been developed that employ unique beam sequences exploiting higher-order acoustic phenomena, and, concurrently, studies of the bioeffects of ultrasound under a range of imaging scenarios have been conducted. In 2012, the American Institute of Ultrasound in Medicine Technical Standards Committee convened a working group of its Output Standards Subcommittee to examine and report on the potential risks and benefits of the use of conditionally increased acoustic pressures (CIP) under specific diagnostic imaging scenarios. The term "conditionally" is included to indicate that CIP would be considered on a per-patient basis for the duration required to obtain the necessary diagnostic information. This document is a result of that effort. In summary, a fundamental assumption in the MI calculation is the presence of a preexisting gas body. For tissues not known to contain preexisting gas bodies, based on theoretical predications and experimentally reported cavitation thresholds, we find this assumption to be invalid. We thus conclude that exceeding the recommended maximum MI level given in the FDA guidance could be warranted without concern for increased risk of cavitation in these tissues. However, there is limited literature assessing the potential clinical benefit of exceeding the MI guidelines in these tissues. The report proposes a 3-tiered approach for CIP that follows the model for employing elevated output in magnetic resonance imaging and concludes with summary recommendations to facilitate Institutional Review Board (IRB)-monitored clinical studies investigating CIP in specific tissues.

Nonlinear attenuation and dispersion in human calcaneus in vitro: statistical validation and relationships to microarchitecture.

Through-transmission measurements were performed on 30 human calcaneus samples in vitro. Nonlinear attenuation and dispersion measurements were investigated by estimating 95% confidence intervals of coefficients of polynomial expansions of log magnitude and phase of transmission coefficients. Bone mineral density (BMD) was measured with dual x-ray absorptiometry. Microarchitecture was measured with microcomputed tomography. Statistically significant nonlinear attenuation and nonzero dispersion were confirmed for a clinical bandwidth of 300-750 kHz in 40%-43% of bone samples. The mean linear coefficient for attenuation was 10.3 dB/cm MHz [95% confidence interval (CI): 9.0-11.6 dB/cm MHz]. The mean quadratic coefficient for attenuation was 1.6 dB/cm MHz(2) (95% CI: 0.4-2.8 dB/cm MHz(2)). Nonlinear attenuation provided little information regarding BMD or microarchitecture. The quadratic coefficient for phase (which is related to dispersion) showed moderate correlations with BMD (r = -0.65; 95% CI: -0.82 to -0.36), bone surface-to-volume ratio (r = 0.47; 95% CI: 0.12-0.72) and trabecular thickness (r = -0.40; 95% CI: -0.67 to -0.03). Dispersion was proportional to bone volume fraction raised to an exponent of 2.1 ± 0.2, which is similar to the value for parallel nylon-wire phantoms (2.4 ± 0.2) and supports a multiple-scattering model for dispersion.

Conventional, Bayesian, and Modified Prony's methods for characterizing fast and slow waves in equine cancellous bone.

Conventional, Bayesian, and the modified least-squares Prony's plus curve-fitting (MLSP + CF) methods were applied to data acquired using 1 MHz center frequency, broadband transducers on a single equine cancellous bone specimen that was systematically shortened from 11.8 mm down to 0.5 mm for a total of 24 sample thicknesses. Due to overlapping fast and slow waves, conventional analysis methods were restricted to data from sample thicknesses ranging from 11.8 mm to 6.0 mm. In contrast, Bayesian and MLSP + CF methods successfully separated fast and slow waves and provided reliable estimates of the ultrasonic properties of fast and slow waves for sample thicknesses ranging from 11.8 mm down to 3.5 mm. Comparisons of the three methods were carried out for phase velocity at the center frequency and the slope of the attenuation coefficient for the fast and slow waves. Good agreement among the three methods was also observed for average signal loss at the center frequency. The Bayesian and MLSP + CF approaches were able to separate the fast and slow waves and provide good estimates of the fast and slow wave properties even when the two wave modes overlapped in both time and frequency domains making conventional analysis methods unreliable.

Time-domain separation of interfering waves in cancellous bone using bandlimited deconvolution: simulation and phantom study.

In through-transmission interrogation of cancellous bone, two longitudinal pulses ("fast" and "slow" waves) may be generated. Fast and slow wave properties convey information about material and micro-architectural characteristics of bone. However, these properties can be difficult to assess when fast and slow wave pulses overlap in time and frequency domains. In this paper, two methods are applied to decompose signals into fast and slow waves: bandlimited deconvolution and modified least-squares Prony's method with curve-fitting (MLSP + CF). The methods were tested in plastic and Zerdine(®) samples that provided fast and slow wave velocities commensurate with velocities for cancellous bone. Phase velocity estimates were accurate to within 6 m/s (0.4%) (slow wave with both methods and fast wave with MLSP + CF) and 26 m/s (1.2%) (fast wave with bandlimited deconvolution). Midband signal loss estimates were accurate to within 0.2 dB (1.7%) (fast wave with both methods), and 1.0 dB (3.7%) (slow wave with both methods). Similar accuracies were found for simulations based on fast and slow wave parameter values published for cancellous bone. These methods provide sufficient accuracy and precision for many applications in cancellous bone such that experimental error is likely to be a greater limiting factor than estimation error.

Fast and slow wave detection in bovine cancellous bone in vitro using bandlimited deconvolution and Prony's method.

Fast and slow waves were detected in a bovine cancellous bone sample for thicknesses ranging from 7 to 12 mm using bandlimited deconvolution and the modified least-squares Prony's method with curve fitting (MLSP + CF). Bandlimited deconvolution consistently isolated two waves with linear-with-frequency attenuation coefficients as evidenced by high correlation coefficients between attenuation coefficient and frequency: 0.997 ± 0.002 (fast wave) and 0.986 ± 0.013 (slow wave) (mean ± standard deviation). Average root-mean-squared (RMS) differences between the two algorithms for phase velocities were 5 m/s (fast wave, 350 kHz) and 13 m/s (slow wave, 750 kHz). Average RMS differences for signal loss were 1.6 dB (fast wave, 350 kHz) and 0.4 dB (slow wave, 750 kHz). Phase velocities for thickness = 10 mm were 1726 m/s (fast wave, 350 kHz) and 1455 m/s (slow wave, 750 kHz). Results show support for the model of two waves with linear-with frequency attenuation, successful isolation of fast and slow waves, good agreement between bandlimited deconvolution and MLSP + CF as well as with a Bayesian algorithm, and potential variations of fast and/or slow wave properties with bone sample thickness.

Estimation of fast and slow wave properties in cancellous bone using Prony's method and curve fitting.

The presence of two longitudinal waves in poroelastic media is predicted by Biot's theory and has been confirmed experimentally in through-transmission measurements in cancellous bone. Estimation of attenuation coefficients and velocities of the two waves is challenging when the two waves overlap in time. The modified least squares Prony's (MLSP) method in conjuction with curve-fitting (MLSP + CF) is tested using simulations based on published values for fast and slow wave attenuation coefficients and velocities in cancellous bone from several studies in bovine femur, human femur, and human calcaneus. The search algorithm is accelerated by exploiting correlations among search parameters. The performance of the algorithm is evaluated as a function of signal-to-noise ratio (SNR). For a typical experimental SNR (40 dB), the root-mean-square errors (RMSEs) for one example (human femur) with fast and slow waves separated by approximately half of a pulse duration were 1 m/s (slow wave velocity), 4 m/s (fast wave velocity), 0.4 dB/cm MHz (slow wave attenuation slope), and 1.7 dB/cm MHz (fast wave attenuation slope). The MLSP + CF method is fast (requiring less than 2 s at SNR = 40 dB on a consumer-grade notebook computer) and is flexible with respect to the functional form of the parametric model for the transmission coefficient. The MLSP + CF method provides sufficient accuracy and precision for many applications such that experimental error is a greater limiting factor than estimation error.

Nominal Versus Actual Spatial Resolution: Comparison of Directivity and Frequency-Dependent Effective Sensitive Element Size for Membrane, Needle, Capsule, and Fiber-Optic Hydrophones.

Frequency-dependent effective sensitive element radius [Formula: see text] is a key parameter for elucidating physical mechanisms of hydrophone operation. In addition, it is essential to know [Formula: see text] to correct for hydrophone output voltage reduction due to spatial averaging across the hydrophone sensitive element surface. At low frequencies, [Formula: see text] is greater than geometrical sensitive element radius ag . Consequently, at low frequencies, investigators can overrate their hydrophone spatial resolution. Empirical models for [Formula: see text] for membrane, needle, and fiber-optic hydrophones have been obtained previously. In this article, an empirical model for [Formula: see text] for capsule hydrophones is presented, so that models are now available for the four most common hydrophone types used in biomedical ultrasound. The [Formula: see text] value was estimated from directivity measurements (over the range from 1 to 20 MHz) for five capsule hydrophones (three with [Formula: see text] and two with [Formula: see text]). The results suggest that capsule hydrophones behave according to a "rigid piston" model for k a g ≥ 0.7 ( k = 2π /wavelength). Comparing the four hydrophone types, the low-frequency discrepancy between [Formula: see text] and ag was found to be greatest for membrane hydrophones, followed by capsule hydrophones, and smallest for needle and fiber-optic hydrophones. Empirical models for [Formula: see text] are helpful for choosing an appropriate hydrophone for an experiment and for correcting for spatial averaging (over the sensitive element surface) in pressure and beamwidth measurements. When reporting hydrophone-based pressure measurements, investigators should specify [Formula: see text] at the center frequency (which may be estimated from the models presented here) in addition to ag .

Phantoms for evaluating the impact of skin pigmentation on photoacoustic imaging and oximetry performance.

Recent reports have raised concerns of potential racial disparities in performance of optical oximetry technologies. To investigate how variable epidermal melanin content affects performance of photoacoustic imaging (PAI) devices, we developed plastisol phantoms combining swappable skin-mimicking layers with a breast phantom containing either India ink or blood adjusted to 50-100% SO2 using sodium dithionite. Increasing skin pigmentation decreased maximum imaging depth by up to 25%, enhanced image clutter, and increased root-mean-square error in SO2 from 8.0 to 17.6% due to signal attenuation and spectral coloring effects. This phantom tool can aid in evaluating PAI device robustness to ensure high performance in all patients.

Biomechanical structure-function relations for human trabecular bone - comparison of calcaneus, femoral neck, greater trochanter, proximal tibia, and vertebra.

MicroCT-based finite element models were used to compute power law relations for uniaxial compressive yield stress versus bone volume fraction for 78 cores of human trabecular bone from five anatomic sites. The leading coefficient of the power law for calcaneus differed from those for most of the other sites (p < 0.05). However, after normalizing by site-specific mean values, neither the leading coefficient (p > 0.5) nor exponent (p > 0.5) differed among sites, suggesting that a given percentage deviation from mean bone volume fraction has the same mechanical consequence for all sites investigated. These findings help explain the success of calcaneal x-ray and ultrasound measurements for predicting hip fracture risk.

Clinical, Safety and Engineering Perspectives on Wearable Ultrasound Technology: A Review.

Wearable ultrasound has the potential to become a disruptive technology enabling new applications not only in traditional clinical settings, but also in settings where ultrasound is not currently used. Understanding the basic engineering principles and limitations of wearable ultrasound is critical for clinicians, scientists, and engineers to advance potential applications and translate the technology from bench to bedside. Wearable ultrasound devices, especially monitoring devices, have the potential to apply acoustic energy to the body for far longer durations than conventional diagnostic ultrasound systems. Thus, bioeffects associated with prolonged acoustic exposure as well as skin health need to be carefully considered for wearable ultrasound devices. This paper reviews emerging clinical applications, safety considerations, and future engineering and clinical research directions for wearable ultrasound technology.

Hydrophone Measurements for Biomedical Ultrasound Applications: A Review.

This article presents basic principles of hydrophone measurements, including mechanisms of action for various hydrophone designs, sensitivity and directivity calibration procedures, practical considerations for performing measurements, signal processing methods to correct for both frequency-dependent sensitivity and spatial averaging across the hydrophone sensitive element, uncertainty in hydrophone measurements, special considerations for high-intensity therapeutic ultrasound, and advice for choosing an appropriate hydrophone for a particular measurement task. Recommendations are made for information to be included in hydrophone measurement reporting.

Relationships of quantitative ultrasound parameters with cancellous bone microstructure in human calcaneus in vitro.

Ultrasound parameters (attenuation, phase velocity, and backscatter), bone mineral density (BMD), and microarchitectural features were measured on 29 human cancellous calcaneus samples in vitro. Regression analysis was performed to predict ultrasound parameters from BMD and microarchitectural features. The best univariate predictors of the ultrasound parameters were the indexes of bone quantity: BMD and bone volume fraction (BV/TV). The most predictive univariate models for attenuation, phase velocity, and backscatter coefficient yielded adjusted squared correlation coefficients of 0.69-0.73. Multiple regression models yielded adjusted correlation coefficients of 0.74-0.83. Therefore attenuation, phase velocity, and backscatter are primarily determined by bone quantity, but multiple regression models based on bone quantity plus microarchitectural features achieve slightly better predictive performance than models based on bone quantity alone.

Spatiotemporal Deconvolution of Hydrophone Response for Linear and Nonlinear Beams-Part I: Theory, Spatial-Averaging Correction Formulas, and Criteria for Sensitive Element Size.

This article reports spatiotemporal deconvolution methods and simple empirical formulas to correct pressure and beamwidth measurements for spatial averaging across a hydrophone sensitive element. Readers who are uninterested in hydrophone theory may proceed directly to Appendix A for an easy method to estimate spatial-averaging correction factors. Hydrophones were modeled as angular spectrum filters. Simulations modeled nine circular transducers (1-10 MHz; F/1.4-F/3.2) driven at six power levels and measured with eight hydrophones (432 beam/hydrophone combinations). For example, the model predicts that if a 200- [Formula: see text] membrane hydrophone measures a moderately nonlinear 5-MHz beam from an F/1 transducer, spatial-averaging correction factors are 33% (peak compressional pressure or pc ), 18% (peak rarefactional pressure or p ), and 18% (full width half maximum or FWHM). Theoretical and experimental estimates of spatial-averaging correction factors to were in good agreement (within 5%) for linear and moderately nonlinear signals. Criteria for maximum appropriate hydrophone sensitive element size as functions of experimental parameters were derived. Unlike the oft-cited International Electrotechnical Commission (IEC) criterion, the new criteria were derived for focusing rather than planar transducers and can accommodate nonlinear signals in addition to linear signals. Responsible reporting of hydrophone-based pressure and beamwidth measurements should always acknowledge spatial-averaging considerations.

Spatiotemporal Deconvolution of Hydrophone Response for Linear and Nonlinear Beams-Part II: Experimental Validation.

This article reports experimental validation for spatiotemporal deconvolution methods and simple empirical formulas to correct pressure and beamwidth measurements for spatial averaging across a hydrophone sensitive element. The method was validated using linear and nonlinear beams transmitted by seven single-element spherically focusing transducers (2-10 MHz; F /#: 1-3) and measured with five hydrophones (sensitive element diameters dg : 85-1000 [Formula: see text]), resulting in 35 transducer/hydrophone combinations. Exponential functions, exp( -αx ), where x = dg /( λ1F /#) and λ1 is the fundamental wavelength, were used to model focal pressure ratios p'/p (where p' is the measured value subjected to spatial averaging and p is the true axial value that would be obtained with a hypothetical point hydrophone). Spatiotemporal deconvolution reduced α (followed by root mean squared difference between data and fit) from 0.29-0.30 (7%) to 0.01 (8%) (linear signals) and from 0.29-0.40 (8%) to 0.04 (14%) (nonlinear signals), indicating successful spatial averaging correction. Linear functions, Cx + 1, were used to model FWHM'/FWHM, where FWHM is full-width half-maximum. Spatiotemporal deconvolution reduced C from 9% (4%) to -0.6% (1%) (linear signals) and from 30% (10%) to 6% (5%) (nonlinear signals), indicating successful spatial averaging correction. Spatiotemporal deconvolution resulted in significant improvement in accuracy even when the hydrophone geometrical sensitive element diameter exceeded the beam FWHM. Responsible reporting of hydrophone-based pressure measurements should always acknowledge spatial averaging considerations.