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.

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.

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.

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.

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 .

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.

Photoacoustic imaging phantoms for assessment of object detectability and boundary buildup artifacts.

Standardized phantoms and test methods are needed to accelerate clinical translation of emerging photoacoustic imaging (PAI) devices. Evaluating object detectability in PAI is challenging due to variations in target morphology and artifacts including boundary buildup. Here we introduce breast fat and parenchyma tissue-mimicking materials based on emulsions of silicone oil and ethylene glycol in polyacrylamide hydrogel. 3D-printed molds were used to fabricate solid target inclusions that produced more filled-in appearance than traditional PAI phantoms. Phantoms were used to assess understudied image quality characteristics (IQCs) of three PAI systems. Object detectability was characterized vs. target diameter, absorption coefficient, and depth. Boundary buildup was quantified by target core/boundary ratio, which was higher in transducers with lower center frequency. Target diameter measurement accuracy was also size-dependent and improved with increasing transducer frequency. These phantoms enable evaluation of multiple key IQCs and may support development of comprehensive standardized test methods for PAI devices.

Tissue-mimicking phantoms for performance evaluation of photoacoustic microscopy systems.

Phantom-based performance test methods are critically needed to support development and clinical translation of emerging photoacoustic microscopy (PAM) devices. While phantoms have been recently developed for macroscopic photoacoustic imaging systems, there is an unmet need for well-characterized tissue-mimicking materials (TMMs) and phantoms suitable for evaluating PAM systems. Our objective was to develop and characterize a suitable dermis-mimicking TMM based on polyacrylamide hydrogels and demonstrate its utility for constructing image quality phantoms. TMM formulations were optically characterized over 400-1100 nm using integrating sphere spectrophotometry and acoustically characterized using a pulse through-transmission method over 8-24 MHz with highly confident extrapolation throughout the usable band of the PAM system. This TMM was used to construct a spatial resolution phantom containing gold nanoparticle point targets and a penetration depth phantom containing slanted tungsten filaments and blood-filled tubes. These phantoms were used to characterize performance of a custom-built PAM system. The TMM was found to be broadly tunable and specific formulations were identified to mimic human dermis at an optical wavelength of 570 nm and acoustic frequencies of 10-50 MHz. Imaging results showed that tungsten filaments yielded 1.1-4.2 times greater apparent maximum imaging depth than blood-filled tubes, which may overestimate real-world performance for vascular imaging applications. Nanoparticles were detectable only to depths of 120-200 µm, which may be due to the relatively weaker absorption of single nanoparticles vs. larger targets containing high concentration of hemoglobin. The developed TMMs and phantoms are useful tools to support PAM device characterization and optimization, streamline regulatory decision-making, and accelerate clinical translation.

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.

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.

AAPM Task Group 241: A medical physicist's guide to MRI-guided focused ultrasound body systems.

Magnetic resonance-guided focused ultrasound (MRgFUS) is a completely non-invasive technology that has been approved by FDA to treat several diseases. This report, prepared by the American Association of Physicist in Medicine (AAPM) Task Group 241, provides background on MRgFUS technology with a focus on clinical body MRgFUS systems. The report addresses the issues of interest to the medical physics community, specific to the body MRgFUS system configuration, and provides recommendations on how to successfully implement and maintain a clinical MRgFUS program. The following sections describe the key features of typical MRgFUS systems and clinical workflow and provide key points and best practices for the medical physicist. Commonly used terms, metrics and physics are defined and sources of uncertainty that affect MRgFUS procedures are described. Finally, safety and quality assurance procedures are explained, the recommended role of the medical physicist in MRgFUS procedures is described, and regulatory requirements for planning clinical trials are detailed. Although this report is limited in scope to clinical body MRgFUS systems that are approved or currently undergoing clinical trials in the United States, much of the material presented is also applicable to systems designed for other applications.

Polyacrylamide hydrogel phantoms for performance evaluation of multispectral photoacoustic imaging systems.

As photoacoustic imaging (PAI) begins to mature and undergo clinical translation, there is a need for well-validated, standardized performance test methods to support device development, quality control, and regulatory evaluation. Despite recent progress, current PAI phantoms may not adequately replicate tissue light and sound transport over the full range of optical wavelengths and acoustic frequencies employed by reported PAI devices. Here we introduce polyacrylamide (PAA) hydrogel as a candidate material for fabricating stable phantoms with well-characterized optical and acoustic properties that are biologically relevant over a broad range of system design parameters. We evaluated suitability of PAA phantoms for conducting image quality assessment of three PAI systems with substantially different operating parameters including two commercial systems and a custom system. Imaging results indicated that appropriately tuned PAA phantoms are useful tools for assessing and comparing PAI system image quality. These phantoms may also facilitate future standardization of performance test methodology.

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.

Hydrophone Spatial Averaging Correction for Acoustic Exposure Measurements From Arrays-Part II: Validation for ARFI and Pulsed Doppler Waveforms.

This article reports the experimental validation of a method for correcting underestimates of peak compressional pressure ( pc) , peak rarefactional pressure ( pr) , and pulse intensity integral (pii) due to hydrophone spatial averaging effects that occur during output measurement of clinical linear and phased arrays. Pressure parameters ( pc , pr , and pii), which are used to compute acoustic exposure safety indexes, such as mechanical index (MI) and thermal index (TI), are often not corrected for spatial averaging because a standardized method for doing so does not exist for linear and phased arrays. In a companion article (Part I), a novel, analytic, inverse-filter method was derived to correct for spatial averaging for linear or nonlinear pressure waves from linear and phased arrays. In the present article (Part II), the inverse filter is validated on measurements of acoustic radiation force impulse (ARFI) and pulsed Doppler waveforms. Empirical formulas are provided to enable researchers to predict and correct hydrophone spatial averaging errors for membrane-hydrophone-based acoustic output measurements. For example, for a 400- [Formula: see text] membrane hydrophone, inverse filtering reduced errors (means ± standard errors for 15 linear array/hydrophone pairs) from about 34% ( pc) , 22% ( pr) , and 45% (pii) down to within 5% for all three parameters. Inverse filtering for spatial averaging effects significantly improves the accuracy of estimates of acoustic pressure parameters for ARFI and pulsed Doppler signals.

Note to Physicians and Sonographers on Potential Underestimation of Acoustic Safety Indexes for Diagnostic Array Transducers.

Two scientists from the U.S. Food and Drug Administration comment on limitations of acoustic safety indexes that can arise from spatial averaging effects of hydrophones that are used to measure acoustic output.

Hydrophone Spatial Averaging Correction for Acoustic Exposure Measurements From Arrays-Part I: Theory and Impact on Diagnostic Safety Indexes.

This article reports underestimation of mechanical index (MI) and nonscanned thermal index for bone near focus (TIB) due to hydrophone spatial averaging effects that occur during acoustic output measurements for clinical linear and phased arrays. TIB is the appropriate version of thermal index (TI) for fetal imaging after ten weeks from the last menstrual period according to the American Institute of Ultrasound in Medicine (AIUM). Spatial averaging is particularly troublesome for highly focused beams and nonlinear, nonscanned modes such as acoustic radiation force impulse (ARFI) and pulsed Doppler. MI and variants of TI (e.g., TIB), which are displayed in real-time during imaging, are often not corrected for hydrophone spatial averaging because a standardized method for doing so does not exist for linear and phased arrays. A novel analytic inverse-filter method to correct for spatial averaging for pressure waves from linear and phased arrays is derived in this article (Part I) and experimentally validated in a companion article (Part II). A simulation was developed to estimate potential spatial-averaging errors for typical clinical ultrasound imaging systems based on the theoretical inverse filter and specifications for 124 scanner/transducer combinations from the U.S. Food and Drug Administration (FDA) 510(k) database from 2015 to 2019. Specifications included center frequency, aperture size, acoustic output parameters, hydrophone geometrical sensitive element diameter, etc. Correction for hydrophone spatial averaging using the inverse filter suggests that maximally achievable values for MI, TIB, thermal dose ( t 43 ), and spatial-peak-temporal-average intensity ( [Formula: see text]) for typical clinical systems are potentially higher than uncorrected values by (means ± standard deviations) 9% ± 4% (ARFI MI), 19% ± 15% (ARFI TIB), 50% ± 41% (ARFI t 43 ), 43% ± 39% (ARFI [Formula: see text]), 7% ± 5% (pulsed Doppler MI), 15% ± 11% (pulsed Doppler TIB), 42% ± 31% (pulsed Doppler t 43 ), and 33% ± 27% (pulsed Doppler [Formula: see text]). These values correspond to frequencies of 3.2 ± 1.3 (ARFI) and 4.1 ± 1.4 MHz (pulsed Doppler), and the model predicts that they would increase with frequency. Inverse filtering for hydrophone spatial averaging significantly improves the accuracy of estimates of MI, TIB, t 43 , and [Formula: see text] for ARFI and pulsed Doppler signals.

Correction for Hydrophone Spatial Averaging Artifacts for Circular Sources.

This article reports an investigation of an inverse-filter method to correct for experimental underestimation of pressure due to spatial averaging across a hydrophone sensitive element. The spatial averaging filter (SAF) depends on hydrophone type (membrane, needle, or fiber-optic), hydrophone geometrical sensitive element diameter, transducer driving frequency, and transducer F number (ratio of focal length to diameter). The absolute difference between theoretical and experimental SAFs for 25 transducer/hydrophone pairs was 7% ± 3% (mean ± standard deviation). Empirical formulas based on SAFs are provided to enable researchers to easily correct for hydrophone spatial averaging errors in peak compressional pressure ( pc ), peak rarefactional pressure ( pr ), and pulse intensity integral. The empirical formulas show, for example, that if a 3-MHz, F /2 transducer is driven to moderate nonlinear distortion and measured at the focal point with a 500- [Formula: see text] membrane hydrophone, then spatial averaging errors are approximately 16% ( pc ), 12% ( pr ), and 24% (pulse intensity integral). The formulas are based on circular transducers but also provide plausible upper bounds for spatial averaging errors for transducers with rectangular-transmit apertures, such as linear and phased arrays.

Evaluation of Fluence Correction Algorithms in Multispectral Photoacoustic Imaging.

Multispectral photoacoustic imaging (MPAI) is a promising emerging diagnostic technology, but fluence artifacts can degrade device performance. Our goal was to develop well-validated phantom-based test methods for evaluating and comparing MPAI fluence correction algorithms, including a heuristic diffusion approximation, Monte Carlo simulations, and an algorithm we developed based on novel application of the diffusion dipole model (DDM). Phantoms simulated a range of breast-mimicking optical properties and contained channels filled with chromophore solutions (ink, hemoglobin, or copper sulfate) or connected to a previously developed blood flow circuit providing tunable oxygen saturation (SO2). The DDM algorithm achieved similar spectral recovery and SO2 measurement accuracy to Monte Carlo-based corrections with lower computational cost, potentially providing an accurate, real-time correction approach. Algorithms were sensitive to optical property uncertainty, but error was minimized by matching phantom albedo. The developed test methods may provide a foundation for standardized assessment of MPAI fluence correction algorithm performance.