Soft-tissue thickness compensation for ultrasound transit time spectroscopy estimated bone volume fraction - an experimental replication study

Quantitative Ultrasound (QUS) offers a reliable means to predict osteoporotic fracture risk, although to date it has not been generally used within routine clinical management since it does not provide a direct estimate of bone mineral density (BMD), and hence, the associated WHO criteria for osteopenia and osteoporosis. Langton has proposed that ultrasound propagation through cancellous bone may be considered as an array of parallel sonic-rays, the transit-time of each determined by the corresponding proportion of bone and marrow propagated. This concept has led to the development of ultrasound transit time spectroscopy (UTTS) to estimate solid (bone) volume fraction (SVF). However, within the real-world clinical environment, a bone, such as the calcaneus, has overlying soft-tissues that would result in a significantly time-extended transit time spectrum (TTS), and hence, an underestimated SVF. The aims of this experimental replication study were firstly, to investigate the effect of overlying soft-tissues upon UTTS derived SVF (UTTS-SVF) estimation, and secondly, to develop and evaluate a method to compensate for this, thereby providing a more accurate estimation of SVF. Four 3D-cylindrical replica cancellous bone samples, with flat-parallel cortex discs on opposite faces, were studied; with varying thicknesses of water-replicating overlying soft-tissues. Through-transmission ultrasound signals were recorded, from which the apparent TTS was derived via deconvolution. Pulse-echo signals were utilised to measure the thickness of water overlying the replica cortices. The TTS was then corrected for the ultrasound transit-time associated with the overlying water. Ultrasound transit time spectroscopy derived solid volume fraction (UTTS-SVF) was then calculated, and compared with the SVF value measured with microcomputed tomography (μCT-SVF). The results demonstrated that varying water- thicknesses for each sample provided very similar formats of ultrasound transit-time spectra, but with significant extended time shifts. Compensation for overlying water thickness provided an accurate estimate of SVF for all samples; the overall of agreement between UTTS-SVF with μCT-SVF being 92.68%. It is therefore suggested that UTTS has the potential to provide a reliable in-vivo estimate of BMD and hence application of the established WHO T-score for routine clinical assessment of osteoporosis

Data fusion for a multi-scale model of a wheat leaf surface: a unifying approach using a radial basis function partition of unity method

Realistic digital models of plant leaves are crucial to fluid dynamics simulations of droplets for optimising agrochemical spray technologies. The presence and nature of small features (on the order of 100$\mathrm{\mu m}$) such as ridges and hairs on the surface have been shown to significantly affect the droplet evaporation, and thus the leaf's potential uptake of active ingredients. We show that these microstructures can be captured by implicit radial basis function partition of unity (RBFPU) surface reconstructions from micro-CT scan datasets. However, scanning a whole leaf ($20\mathrm{cm^2}$) at micron resolutions is infeasible due to both extremely large data storage requirements and scanner time constraints. Instead, we micro-CT scan only a small segment of a wheat leaf ($4\mathrm{mm^2}$). We fit a RBFPU implicit surface to this segment, and an explicit RBFPU surface to a lower resolution laser scan of the whole leaf. Parameterising the leaf using a locally orthogonal coordinate system, we then replicate the now resolved microstructure many times across a larger, coarser, representation of the leaf surface that captures important macroscale features, such as its size, shape, and orientation. The edge of one segment of the microstructure model is blended into its neighbour naturally by the partition of unity method. The result is one implicit surface reconstruction that captures the wheat leaf's features at both the micro- and macro-scales.Comment: 23 pages, 11 figure

In vivo characterization of 3D-printed polycaprolactone-hydroxyapatite scaffolds with Voronoi design to advance the concept of scaffold-guided bone regeneration

Three-dimensional (3D)-printed medical-grade polycaprolactone (mPCL) composite scaffolds have been the first to enable the concept of scaffold-guided bone regeneration (SGBR) from bench to bedside. However, advances in 3D printing technologies now promise next-generation scaffolds such as those with Voronoi tessellation. We hypothesized that the combination of a Voronoi design, applied for the first time to 3D-printed mPCL and ceramic fillers (here hydroxyapatite, HA), would allow slow degradation and high osteogenicity needed to regenerate bone tissue and enhance regenerative properties when mixed with xenograft material. We tested this hypothesis in vitro and in vivo using 3D-printed composite mPCL-HA scaffolds (wt 96%:4%) with the Voronoi design using an ISO 13485 certified additive manufacturing platform. The resulting scaffold porosity was 73% and minimal in vitro degradation (mass loss <1%) was observed over the period of 6 months. After loading the scaffolds with different types of fresh sheep xenograft and ectopic implantation in rats for 8 weeks, highly vascularized tissue without extensive fibrous encapsulation was found in all mPCL-HA Voronoi scaffolds and endochondral bone formation was observed, with no adverse host-tissue reactions. This study supports the use of mPCL-HA Voronoi scaffolds for further testing in future large preclinical animal studies prior to clinical trials to ultimately successfully advance the SGBR concept

Frequency independence of ultrasound transit time spectroscopy

Recent studies have shown that ultrasound transit time spectroscopy (UTTS) is an alternative method to describe ultrasound wave propagation through complex samples as an array of parallel sonic rays. This technique has the potential to characterize bone properties including volume fraction and may be implemented in clinical systems to predict osteoporotic fracture risk. In contrast to broadband ultrasound attenuation, which is highly frequency dependent, we hypothesise that UTTS is frequency independent. This study measured 1 MHz and 5 MHz broadband ultrasound signals through a set of acrylic step-wedge samples. Digital deconvolution of the signals through water and each sample was applied to derive a transit time spectrum. The resulting spectra at both 1 MHz and 5 MHz were compared to the predicted transit time values. Linear regression analysis yields agreement (R2) of 99.23% and 99.74% at 1 MHz and 5 MHz respectively indicating frequency independence of transit time spectra

Ultrasound transit time spectral analysis of complex porous media

This thesis describes a new concept to explain ultrasound wave propagation through complex porous media with the aim of accurately estimating bone volume fraction. Excellent agreement is reported between computer-simulated predictions and experimental measurements in bone replica models and natural tissue samples. Bone volume fraction is the primary indicator of osteoporosis. Transit Time Spectroscopy has the potential to offer for the first time using ultrasound, a diagnostic and monitoring tool for osteoporosis that is cost-effective, non-ionising, portable, and implementable into an integrated healthcare service

Solid volume fraction estimation of bone:marrow replica models using ultrasound transit time spectroscopy

The acceptance of broadband ultrasound attenuation (BUA) for the assessment of osteoporosis suffers from a limited understanding of both ultrasound wave propagation through cancellous bone and its exact dependence upon the material and structural properties. It has recently been proposed that ultrasound wave propagation in cancellous bone may be described by a concept of parallel sonic rays; the transit time of each ray defined by the proportion of bone and marrow propagated. A Transit Time Spectrum (TTS) describes the proportion of sonic rays having a particular transit time, effectively describing the lateral inhomogeneity of transit times over the surface aperture of the receive ultrasound transducer. The aim of this study was to test the hypothesis that the solid volume fraction (SVF) of simplified bone:marrow replica models may be reliably estimated from the corresponding ultrasound transit time spectrum. Transit time spectra were derived via digital deconvolution of the experimentally measured input and output ultrasonic signals, and compared to predicted TTS based on the parallel sonic ray concept, demonstrating agreement in both position and amplitude of spectral peaks. Solid volume fraction was calculated from the TTS; agreement between true (geometric calculation) with predicted (computer simulation) and experimentally-derived values were R2=99.9% and R2=97.3% respectively. It is therefore envisaged that ultrasound transit time spectroscopy (UTTS) offers the potential to reliably estimate bone mineral density and hence the established T-score parameter for clinical osteoporosis assessment

Application of ultrasound transit time spectroscopy to human cancellous bone for derivation of bone volume fraction in-vitro

We have previously demonstrated that ultrasound propagation in complex composite media may be described as an array of parallel sonic rays. The transit time of each sonic ray is determined by the proportion of solid (bone) and fluid (marrow) traversed, the received ultrasound signal being a superposition of all sonic rays. An Ultrasound Transit Time Spectrum (UTTS) for a test sample may be obtained via digital deconvolution of input and output ultrasound signals, describing the proportion of sonic rays having a particular transit time, from which the bone volume fraction (BVF) of the sample may be estimated. In a recent in-vitro study, 21 cancellous bone samples, extracted from 5 human femoral heads following total hip replacement, were measured with microCT to derive the true BVF value. Transmission ultrasound signals of 1 MHz were recorded and UTTS-derived BVF calculated. A coefficient of determination (R2) of 82% was achieved between ultrasound and microCT derived BVF values. Current work is clinically implementing UTTS, noting its potential to estimate bone mineral density, and hence, a means to diagnose osteopenia and osteoporosis using WHO T-score criteria

Experimental and computer simulation validation of ultrasound phase interference created by lateral inhomogeneity of transit time in replica bone marrow composite models

Purpose: \ud The measurement of broadband ultrasonic attenuation (BUA) in cancellous bone for the assessment of osteoporosis follows a parabolic-type dependence with bone volume fraction; having minima values corresponding to both entire bone and entire marrow. Langton has recently proposed that the primary BUA mechanism may be significant phase interference due to variations in propagation transit time through the test sample as detected over the phase-sensitive surface of the receive ultrasound transducer. This fundamentally simple concept assumes that the propagation of ultrasound through a complex solid : liquid composite sample such as cancellous bone may be considered by an array of parallel ‘sonic rays’. \ud \ud The transit time of each ray is defined by the proportion of bone and marrow propagated, being a minimum (tmin) solely through bone and a maximum (tmax) solely through marrow. A Transit Time Spectrum (TTS), ranging from tmin to tmax, may be defined describing the proportion of sonic rays having a particular transit time, effectively describing lateral inhomogeneity of transit time over the surface of the receive ultrasound transducer. Phase interference may result from interaction of ‘sonic rays’ of differing transit times. The aim of this study was to test the hypothesis that there is a dependence of phase interference upon the lateral inhomogenity of transit time by comparing experimental measurements and computer simulation predictions of ultrasound propagation through a range of relatively simplistic solid:liquid models exhibiting a range of lateral inhomogeneities.\ud \ud Methods: \ud A range of test models was manufactured using acrylic and water as surrogates for bone and marrow respectively. The models varied in thickness in one dimension normal to the direction of propagation, hence exhibiting a range of transit time lateral inhomogeneities, ranging from minimal (single transit time) to maximal (wedge; ultimately the limiting case where each sonic ray has a unique transit time). \ud \ud For the experimental component of the study, two unfocused 1 MHz ¾” broadband diameter transducers were utilized in transmission mode; ultrasound signals were recorded for each of the models. The computer simulation was performed with Matlab, where the transit time and relative amplitude of each sonic ray was calculated. The transit time for each sonic ray was defined as the sum of transit times through acrylic and water components. The relative amplitude considered the reception area for each sonic ray along with absorption in the acrylic. To replicate phase-sensitive detection, all sonic rays were summed and the output signal plotted in comparison with the experimentally derived output signal. \ud \ud Results: \ud From qualtitative and quantitative comparison of the experimental and computer simulation results, there is an extremely high degree of agreement of 94.2% to 99.0% between the two approaches, supporting the concept that propagation of an ultrasound wave, for the models considered, may be approximated by a parallel sonic ray model where the transit time of each ray is defined by the proportion of ‘bone’ and ‘marrow’. \ud \ud Conclusions: \ud This combined experimental and computer simulation study has successfully demonstrated that lateral inhomogeneity of transit time has significant potential for phase interference to occur if a phase-sensitive ultrasound receive transducer is implemented as in most commercial ultrasound bone analysis devices

Pulse-echo ultrasound transit time spectroscopy: A comparison of experimental measurement and simulation prediction

Considering ultrasound propagation through complex composite media as an array of parallel sonic rays, a comparison of computer simulated prediction with experimental data has previously been reported for transmission mode (where one transducer serves as transmitter, the other as receiver) in a series of ten acrylic step-wedge samples, immersed in water, exhibiting varying degrees of transit time inhomogeneity. In this study, the same samples were used but in pulse-echo mode, where the same ultrasound transducer served as both transmitter and receiver, detecting both ‘primary’ (internal sample interface) and ‘secondary’ (external sample interface) echoes. A transit time spectrum (TTS) was derived, describing the proportion of sonic rays with a particular transit time. A computer simulation was performed to predict the transit time and amplitude of various echoes created, and compared with experimental data. Applying an amplitude-tolerance analysis, 91.7±3.7% of the simulated data was within ±1 standard deviation (STD) of the experimentally measured amplitude-time data. Correlation of predicted and experimental transit time spectra provided coefficients of determination (R2) ranging from 100.0% to 96.8% for the various samples tested. The results acquired from this study provide good evidence for the concept of parallel sonic rays. Further, deconvolution of experimental input and output signals has been shown to provide an effective method to identify echoes otherwise lost due to phase cancellation. Potential applications of pulse-echo ultrasound transit time spectroscopy (PE-UTTS) include improvement of ultrasound image fidelity by improving spatial resolution and reducing phase interference artefacts