Passive Acoustic Mapping for Convex Arrays With the Helical Wave Spectrum Method.

Passive acoustic mapping (PAM) has emerged as a valuable imaging modality for monitoring the cavitation activity in focused ultrasound therapies. When it comes to imaging in the human abdomen, convex arrays are preferred due to their large acoustic window. However, existing PAM methods for convex arrays rely on the computationally expensive delay-and-sum (DAS) operation limiting the image reconstruction speed when the field-of-view (FOV) is large. In this work, we propose an efficient and frequency-selective PAM method for convex arrays. This method is based on projecting the helical wave spectrum (HWS) between cylindrical surfaces in the imaging field. Both the in silico and in vitro experiments showed that the HWS method has comparable image quality and similar acoustic cavitation source localization accuracy as the DAS-based methods. Compared to the frequency-domain and time-domain DAS methods, the time-complexity of the HWS method is reduced by one order and two orders of magnitude, respectively. A parallel implementation of the HWS method realized millisecond-level image reconstruction speed. We also show that the HWS method is inherently capable of mapping microbubble (MB) cavitation activity of different status, i.e., no cavitation, stable cavitation, or inertial cavitation. After compensating for the lens effects of the convex array, we further combined PAM formed by the HWS method and B-mode imaging as a real-time dual-mode imaging approach to map the anatomical location where MBs cavitate in a liver phantom experiment. This method may find use in applications where convex arrays are required for cavitation activity monitoring in real time.

Fast volumetric ultrasound facilitates high-resolution 3D mapping of tissue compartments.

Volumetric ultrasound imaging has the potential for operator-independent acquisition and enhanced field of view. Panoramic acquisition has many applications across ultrasound; spanning musculoskeletal, liver, breast, and pediatric imaging; and image-guided therapy. Challenges in high-resolution human imaging, such as subtle motion and the presence of bone or gas, have limited such acquisition. These issues can be addressed with a large transducer aperture and fast acquisition and processing. Programmable, ultrafast ultrasound scanners with a high channel count provide an unprecedented opportunity to optimize volumetric acquisition. In this work, we implement nonlinear processing and develop distributed beamformation to achieve fast acquisition over a 47-centimeter aperture. As a result, we achieve a 50-micrometer -6-decibel point spread function at 5 megahertz and resolve in-plane targets. A large volume scan of a human limb is completed in a few seconds, and in a 2-millimeter dorsal vein, the image intensity difference between the vessel center and surrounding tissue was ~50 decibels, facilitating three-dimensional reconstruction of the vasculature.

Deep-Learning-Enabled Microwave-Induced Thermoacoustic Tomography Based on ResAttU-Net for Transcranial Brain Hemorrhage Detection.

OBJECTIVE: Hemorrhagic stroke is a leading threat to human's health. The fast-developing microwave-induced thermoacoustic tomography (MITAT) technique holds potential to do brain imaging. However, transcranial brain imaging based on MITAT is still challenging due to the involved huge heterogeneity in speed of sound and acoustic attenuation of human skull. This work aims to address the adverse effect of the acoustic heterogeneity using a deep-learning-based MITAT (DL-MITAT) approach for transcranial brain hemorrhage detection. METHODS: We establish a new network structure, a residual attention U-Net (ResAttU-Net), for the proposed DL-MITAT technique, which exhibits improved performance as compared to some traditionally used networks. We use simulation method to build training sets and take images obtained by traditional imaging algorithms as the input of the network. RESULTS: We present ex-vivo transcranial brain hemorrhage detection as a proof-of-concept validation. By using an 8.1-mm thick bovine skull and porcine brain tissues to perform ex-vivo experiments, we demonstrate that the trained ResAttU-Net is capable of efficiently eliminating image artifacts and accurately restoring the hemorrhage spot. It is proved that the DL-MITAT method can reliably suppress false positive rate and detect a hemorrhage spot as small as 3 mm. We also study effects of several factors of the DL-MITAT technique to further reveal its robustness and limitations. CONCLUSION: The proposed ResAttU-Net-based DL-MITAT method is promising for mitigating the acoustic inhomogeneity issue and performing transcranial brain hemorrhage detection. SIGNIFICANCE: This work provides a novel ResAttU-Net-based DL-MITAT paradigm and paves a compelling route for transcranial brain hemorrhage detection as well as other transcranial brain imaging applications.

Improving plane wave ultrasound imaging through real-time beamformation across multiple arrays.

Ultrasound imaging is a widely used diagnostic tool but has limitations in the imaging of deep lesions or obese patients where the large depth to aperture size ratio (f-number) reduces image quality. Reducing the f-number can improve image quality, and in this work, we combined three commercial arrays to create a large imaging aperture of 100 mm and 384 elements. To maintain the frame rate given the large number of elements, plane wave imaging was implemented with all three arrays transmitting a coherent wavefront. On wire targets at a depth of 100 mm, the lateral resolution is significantly improved; the lateral resolution was 1.27 mm with one array (1/3 of the aperture) and 0.37 mm with the full aperture. After creating virtual receiving elements to fill the inter-array gaps, an autoregressive filter reduced the grating lobes originating from the inter-array gaps by - 5.2 dB. On a calibrated commercial phantom, the extended field-of-view and improved spatial resolution were verified. The large aperture facilitates aberration correction using a singular value decomposition-based beamformer. Finally, after approval of the Stanford Institutional Review Board, the three-array configuration was applied in imaging the liver of a volunteer, validating the potential for enhanced resolution.

Measurement of Cortical Bone Elasticity Tensor with Resonant Ultrasound Spectroscopy.

Resonant Ultrasound Spectroscopy estimates the stiffness coefficients of a material from the free resonant frequencies of a single specimen. It is particularly suitable for complete stiffness characterization of anisotropic materials available only as small samples (typically a few mm), and it does not suffer from some limitations associated to quasi-static mechanical test and ultrasound wave velocity measurements. RUS has been used for decades on geological samples and single crystals, but was until recently not applied to mineralized tissues such as bone. The reason is the significant mechanical damping presents in these materials, which causes the resonant peaks to overlap and prevent a direct measurement of the resonant frequencies. This chapter describes the use of RUS for the elastic characterization of mineralized tissues, cortical bone in particular. All steps are described, from sample preparation and measurement setup to signal processing and data analysis, including the developments and adaptions necessary to overcome the difficulties linked to damping. Viscoelastic characterization, from the width of the resonant peaks, is also presented. Mostly technical aspects are developed in this chapter, while the data obtained from RUS on several collections of mineralized tissues specimens are presented and discussed in Chap. 13.

Documenting the Anisotropic Stiffness of Hard Tissues with Resonant Ultrasound Spectroscopy.

Recent advances in resonant ultrasound spectroscopy (RUS) leverage accurate measurements of the anisotropic stiffness of hard tissues at millimeter scale. RUS is the only available technique to date to assess the entire stiffness tensor of bone from a unique rectangular parallelepiped specimen. Accurately measured stiffness constants are required for bone mechanics models and may provide information on some fundamental aspects of hard tissues biology such as regulation of bone mass, remodeling and healing. In this chapter, we review the anisotropic stiffness data of human hard tissues measured with RUS, mostly during the last decade. Hard tissues covered here include human enamel and dentin, cortical bone from the femur and tibia of human adults, and child cortical bone tissue, accounting for 288 specimens in total. Data was collected in the literature and from previous works of our group. We performed a comparative study to depict the differences in the elastic properties of these hard tissues. Our objectives were to: (1) document the range of anisotropic stiffness constants in human hard tissues (orthotropic or transverse isotropic symmetry); and (2) provide empirical laws between mass density and anisotropic stiffness of cortical bone at different skeletal sites. Finally, we discuss the challenges and perspectives to use RUS for large collections of specimens.

Inverse Problem in Resonant Ultrasound Spectroscopy With Sampling and Optimization: A Comparative Study on Human Cortical Bone.

The Bayesian inference with prior knowledge has been proposed recently to solve the inverse problem in resonant ultrasound spectroscopy. It allows inferring the elastic properties of high damping materials, such as cortical bone with less dependence on the initial guessed values. In this method, the estimation of the stiffness coefficients is expressed as a probabilistic solution to the inverse problem, which can be achieved by sampling or optimization methods. However, the detailed performance comparison of these two strategies applied to high damping materials has not been fully studied. In this work, the full stiffness tensor of 52 transversely isotropic cortical bone specimens was obtained using Markov chain Monte Carlo (MCMC) sampling and particle swarm optimization (PSO), respectively. Results showed that the local probability distributions of stiffness coefficients estimated by the two methods are consistent. Compared with MCMC, the average calculation speed of PSO is ten times faster [614 s ± 59 s (MCMC) versus 53 s ± 22 s (PSO)]. The mean standard error between theoretical and experimental resonant frequencies was slightly smaller for PSO compared with MCMC. In conclusion, PSO, a global optimization strategy, is suitable to solve the inverse problem for high damping materials.

A Signal Domain Object Segmentation Method for Ultrasound and Photoacoustic Computed Tomography.

Image segmentation is important in improving the diagnostic capability of ultrasound computed tomography (USCT) and photoacoustic computed tomography (PACT), as it can be included in the image reconstruction process to improve image quality and quantification abilities. Segmenting the imaged object out of the background using image domain methods is easily complicated by low contrast, noise, and artifacts in the reconstructed image. Here, we introduce a new signal domain object segmentation method for USCT and PACT which does not require image reconstruction beforehand and is automatic, robust, computationally efficient, accurate, and straightforward. We first establish the relationship between the time-of-flight of the received first arrival waves and the object's boundary which is described by ellipse equations. Then, we show that the ellipses are tangent to the boundary. By looking for tangent points on the common tangent of neighboring ellipses, the boundary can be approximated with high fidelity. Imaging experiments of human fingers and mice cross-sections showed that our method provided equivalent or better segmentations than the optimal ones by active contours. In summary, our method greatly reduces the overall complexity of object segmentation and shows great potential in eliminating user dependency without sacrificing segmentation accuracy. The method can be further seamlessly incorporated into algorithms for other processing purposes in USCT and PACT, such as high-quality image reconstruction.

Maximum effect of the heterogeneity of tissue mineralization on the effective cortical bone elastic properties.

The mineralization level is heterogeneous in cortical bone extracellular matrix as a consequence of remodeling. Models of the effective elastic properties at the millimeter scale have been developed based on idealizations of the vascular pore network and matrix properties. Some popular models do not take into account the heterogeneity of the matrix. However, the errors on the predicted elasticity when the difference in elastic properties between osteonal and interstitial tissues is not modeled have not been quantified. This work provides an estimation of the maximum error. We compare the effective elasticity of a representative volume element (RVE) assuming (1) different elastic properties in osteonal and interstitial tissues vs. (2) average matrix properties. In order to account for the variability of bone microstructure, we use a collection of high resolution images of the pore network to build RVEs. In each RVE we assumed a constant osteonal wall thickness and we artificially varied this thickness between 35 and 140 [Formula: see text]m to create RVEs with different amounts of osteonal tissue. The homogenization problem was solved with a fast Fourier transform (FFT)-based numerical scheme. We found that the error depends on pore volume fraction and varies on average from 1 to [Formula: see text] depending on the assumed diameter of the osteons. The results suggest that matrix heterogeneity may be disregarded in cortical bone models in most practical cases.

Estimation of Tissue Attenuation from Ultrasonic B-Mode Images-Spectral-Log-Difference and Method-of-Moments Algorithms Compared.

We report on results from the comparison of two algorithms designed to estimate the attenuation coefficient from ultrasonic B-mode scans obtained from a numerical phantom simulating an ultrasound breast scan. It is well documented that this parameter significantly diverges between normal tissue and malignant lesions. To improve the diagnostic accuracy it is of great importance to devise and test algorithms that facilitate the accurate, low variance and spatially resolved estimation of the tissue's attenuation properties. A numerical phantom is realized using k-Wave, which is an open source Matlab toolbox for the time-domain simulation of acoustic wave fields that facilitates both linear and nonlinear wave propagation in homogeneous and heterogeneous tissue, as compared to strictly linear ultrasound simulation tools like Field II. k-Wave allows to simulate arbitrary distributions, resolved down to single voxel sizes, of parameters including the speed of sound, mass density, scattering strength and to include power law acoustic absorption necessary for simulation tasks in medical diagnostic ultrasound. We analyze the properties and the attainable accuracy of both the spectral-log-difference technique, and a statistical moments based approach and compare the results to known reference values from the sound field simulation.

Cortical bone viscoelastic damping assessed with resonant ultrasound spectroscopy reflects porosity and mineral content.

Viscoelasticity is an essential property of bone related to fragility, which is altered in aging and bone disease. Bone viscoelastic behavior is attributed to several mechanisms involving collagen and mineral properties, porosities, and bone hierarchical tissue organization. We aimed to assess the relationships between cortical bone viscoelastic damping measured with Resonant Ultrasound Spectroscopy (RUS), microstructural and compositional characteristics. We measured 52 bone specimens from the femur of 26 elderly human donors. RUS provided a shear damping coefficient at a frequency of the order of 150 kHz. The characteristics of the structure of the vascular pore network and tissue mineral density were measured using synchrotron radiation high-resolution computed tomography (SR-µCT). Fourier transformed infrared microspectroscopy (FTIRM) was used to quantify mineral-to-organic phase ratio, mineral maturity, crystallinity, and collagen maturity. Cross-links were quantified from biochemistry. Viscoelastic damping was found to increase with vascular porosity (r=0.68), to decrease with the degree of mineralization of the extravascular matrix (r=-0.68), and was marginally affected by collagen. We built a multilinear model suggesting that when porosity is controlled, the variation of mineral content explains a small additional part of the variability of damping. The work supports the consideration of viscoelasticity measurement as a potential biomarker of fragility and provides a documentation of bone viscoelastic behavior and its determinants in a frequency range rarely investigated.

Bulk Wave Velocities in Cortical Bone Reflect Porosity and Compression Strength.

The goal of this study was to evaluate whether ultrasonic velocities in cortical bone can be considered as a proxy for mechanical quality of cortical bone tissue reflected by porosity and compression strength. Micro-computed tomography, compression mechanical testing and resonant ultrasound spectroscopy were used to assess, respectively, porosity, strength and velocity of bulk waves of both shear and longitudinal polarisations propagating along and perpendicular to osteons, in 92 cortical bone specimens from tibia and femur of elderly human donors. All velocities were significantly associated with strength (r = 0.65-0.83) and porosity (r = -0.64 to -0.77). Roughly, according to linear regression models, a decrease in velocity of 100 m/s corresponded to a loss of 20 MPa in strength (which is approximately 10% of the largest strength value) and to an increase in porosity of 5%. These results provide a rationale for the in vivo measurement of one or several velocities for the diagnosis of bone fragility.

Computed tomography porosity and spherical indentation for determining cortical bone millimetre-scale mechanical properties.

The cortex of the femoral neck is a key structural element of the human body, yet there is not a reliable metric for predicting the mechanical properties of the bone in this critical region. This study explored the use of a range of non-destructive metrics to measure femoral neck cortical bone stiffness at the millimetre length scale. A range of testing methods and imaging techniques were assessed for their ability to measure or predict the mechanical properties of cortical bone samples obtained from the femoral neck of hip replacement patients. Techniques that can potentially be applied in vivo to measure bone stiffness, including computed tomography (CT), bulk wave ultrasound (BWUS) and indentation, were compared against in vitro techniques, including compression testing, density measurements and resonant ultrasound spectroscopy. Porosity, as measured by micro-CT, correlated with femoral neck cortical bone's elastic modulus and ultimate compressive strength at the millimetre length scale. Large-tip spherical indentation also correlated with bone mechanical properties at this length scale but to a lesser extent. As the elastic mechanical properties of cortical bone correlated with porosity, we would recommend further development of technologies that can safely measure cortical porosity in vivo.

Homogenization of cortical bone reveals that the organization and shape of pores marginally affect elasticity.

With ageing and various diseases, the vascular pore volume fraction (porosity) in cortical bone increases, and the morphology of the pore network is altered. Cortical bone elasticity is known to decrease with increasing porosity, but the effect of the microstructure is largely unknown, while it has been thoroughly studied for trabecular bone. Also, popular micromechanical models have disregarded several micro-architectural features, idealizing pores as cylinders aligned with the axis of the diaphysis. The aim of this paper is to quantify the relative effects on cortical bone anisotropic elasticity of porosity and other descriptors of the pore network micro-architecture associated with pore number, size and shape. The five stiffness constants of bone assumed to be a transversely isotropic material were measured with resonant ultrasound spectroscopy in 55 specimens from the femoral diaphysis of 29 donors. The pore network, imaged with synchrotron radiation X-ray micro-computed tomography, was used to derive the pore descriptors and to build a homogenization model using the fast Fourier transform (FFT) method. The model was calibrated using experimental elasticity. A detailed analysis of the computed effective elasticity revealed in particular that porosity explains most of the variations of the five stiffness constants and that the effects of other micro-architectural features are small compared to usual experimental errors. We also have evidence that modelling the pore network as an ensemble of cylinders yields biased elasticity values compared to predictions based on the real micro-architecture. The FFT homogenization method is shown to be particularly efficient to model cortical bone.

Anisotropic elastic properties of human femoral cortical bone and relationships with composition and microstructure in elderly.

The strong dependence between cortical bone elasticity at the millimetre-scale (mesoscale) and cortical porosity has been evidenced by previous studies. However, bone is an anisotropic composite material made by mineral, proteins and water assembled in a hierarchical structure. Whether the variations of structural and compositional properties of bone affect the different elastic coefficients at the mesoscale is not clear. Aiming to understand the relationships between bone elastic properties and compositions and microstructure, we applied state-of-the-art experimental modalities to assess these aspects of bone characteristics. All elastic coefficients (stiffness tensor of the transverse isotropic bone material), structure of the vascular pore network, collagen and mineral properties were measured in 52 specimens from the femoral diaphysis of 26 elderly donors. Statistical analyses and micromechanical modeling showed that vascular pore volume fraction and the degree of mineralization of bone are the most important determinants of cortical bone anisotropic mesoscopic elasticity. Though significant correlations were observed between collagen properties and elasticity, their effects in bone mesoscopic elasticity were minor in our data. This work also provides a unique set of data exhibiting a range of variations of compositional and microstructural cortical bone properties in the elderly and gives strong experimental evidence and basis for further development of biomechanical models for human cortical bone. STATEMENT OF SIGNIFICANCE: This study reports the relationships between microstructure, composition and the mesoscale anisotropic elastic properties of human femoral cortical bone in elderly. For the first time, we provide data covering the complete anisotropic elastic tensor, the microstructure of cortical vascular porosity, mineral and collagen characteristics obtained from the same or adjacent samples in each donor. The results revealed that cortical vascular porosity and degree of mineralization of bone are the most important determinants of bone anisotropic stiffness at the mesoscale. The presented data gives strong experimental evidence and basis for further development of biomechanical models for human cortical bone.

Quantification of stiffness measurement errors in resonant ultrasound spectroscopy of human cortical bone.

Resonant ultrasound spectroscopy (RUS) is the state-of-the-art method used to investigate the elastic properties of anisotropic solids. Recently, RUS was applied to measure human cortical bone, an anisotropic material with low Q-factor (20), which is challenging due to the difficulty in retrieving resonant frequencies. Determining the precision of the estimated stiffness constants is not straightforward because RUS is an indirect method involving minimizing the distance between measured and calculated resonant frequencies using a model. This work was motivated by the need to quantify the errors on stiffness constants due to different error sources in RUS, including uncertainties on the resonant frequencies and specimen dimensions and imperfect rectangular parallelepiped (RP) specimen geometry. The errors were first investigated using Monte Carlo simulations with typical uncertainty values of experimentally measured resonant frequencies and dimensions assuming a perfect RP geometry. Second, the exact specimen geometry of a set of bone specimens were recorded by synchrotron radiation micro-computed tomography. Then, a "virtual" RUS experiment is proposed to quantify the errors induced by imperfect geometry. Results show that for a bone specimen of ∼1° perpendicularity and parallelism errors, an accuracy of a few percent ( <6.2%) for all the stiffness constants and engineering moduli is achievable.

Observation of sGAG content of human hip joint cartilage in different old age groups based on EPIC micro-CT.

OBJECTIVES: To observe the age-related changes of sulfated glycosaminoglycan (sGAG) content of hip joint cartilage of elderly people based on Equilibrium Partitioning of an Ionic Contrast Agent (EPIC) micro-CT. METHODS: Seventy human hip cartilage-bone samples were collected from hip-fracture patients (ages 51-96) and divided into five groups (10 years in an age group). They were first immersed in 20% concentration of the contrast agent Meglumine Diatrizoate (MD) for 6 h at 37 °C, and then scanned by micro-CT. Following scanning, samples were stained for sGAG with toluidine blue. The X-ray attenuation and sGAG optical density were calculated by image processing. The correlation between X-ray attenuation and sGAG optical density was then analyzed. RESULTS: The X-ray mean attenuation of the cartilage increased by 18.81% from the 50-80 age groups (p < 0.01), but decreased by 7.15% in the 90 age group compared to the 80 age group. The X-ray mean attenuation of the superficial layer and middle layer increased by 31.60 % and 44.68% from the 50-80 age groups, respectively (p < 0.01), but reduced by 4.67% and 6.05% separately in the 90 age group. However, the deep layer showed no significant change with aging. The sGAG optical density showed a linear correlation (r = -0.91, p < 0.01) with the X-ray attenuation. CONCLUSION: The sGAG content of hip joint cartilage varied with aging in elderly people. The changes in superficial layer and middle layer were more evident than deep layer.