Marie-Luise Wille

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

The measurement of broadband ultrasound attenuation 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 attenuation mechanism is 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 may be considered as an array of parallel ‘sonic rays’. 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, from which a transit time spectrum, may be defined describing the proportion of sonic rays having a particular transit time. The aim of this study was to test the hypothesis that there is a dependence of phase interference upon the lateral inhomogeneity of transit time by comparing experimental measurements and computer simulation predictions of ultrasound propagation through a range of relatively simplistic solid:liquid models. From qualitative and quantitative comparison of the experimental and computer simulation results, there is an extremely high degree of agreement of 94.2%–99.0% between the two approaches. 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 receive ultrasound transducer is implemented as in most commercial ultrasound bone analysis devices.

A deconvolution method for deriving the transit time spectrum for ultrasound propagation through cancellous bone replica models

The acceptance of broadband ultrasound attenuation for the assessment of osteoporosis suffers from a limited understanding of ultrasound wave propagation through cancellous bone. It has recently been proposed that the ultrasound wave propagation can be described by a concept of parallel sonic rays. This concept approximates the detected transmission signal to be the superposition of all sonic rays that travel directly from transmitting to receiving transducer. The transit time of each ray is defined by the proportion of bone and marrow propagated. An ultrasound transit time spectrum describes the proportion of sonic rays having a particular transit time, effectively describing lateral inhomogeneity of transit times over the surface of the receiving ultrasound transducer. The aim of this study was to provide a proof of concept that a transit time spectrum may be derived from digital deconvolution of input and output ultrasound signals. We have applied the active-set method deconvolution algorithm to determine the ultrasound transit time spectra in the three orthogonal directions of four cancellous bone replica samples and have compared experimental data with the prediction from the computer simulation. The agreement between experimental and predicted ultrasound transit time spectrum analyses derived from Bland–Altman analysis ranged from 92% to 99%, thereby supporting the concept of parallel sonic rays for ultrasound propagation in cancellous bone. In addition to further validation of the parallel sonic ray concept, this technique offers the opportunity to consider quantitative characterisation of the material and structural properties of cancellous bone, not previously available utilising ultrasound.

3D printed lattices as an activation and expansion platform for T cell therapy

One of the most significant hurdles to the affordable, accessible delivery of cell therapy is the cost and difficulty of expanding cells to clinically relevant numbers. Immunotherapy to prevent autoimmune disease, tolerate organ transplants or target cancer critically relies on the expansion of specialized T cell populations. We have designed 3D-printed cell culture lattices with highly organized micron-scale architectures, functionalized via plasma polymerization to bind monoclonal antibodies that trigger cell proliferation. This 3D technology platform facilitate the expansion of therapeutic human T cell subsets, including regulatory, effector, and cytotoxic T cells while maintaining the correct phenotype. Lentiviral gene delivery to T cells is enhanced in the presence of the lattices. Incorporation of the lattice format into existing cell culture vessels such as the G-Rex system is feasible. This cell expansion platform is user-friendly and expedites cell recovery and scale-up, making it ideal for translating T cell therapies from bench to bedside.

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 R(2)=99.9% and R(2)=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.

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 10 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 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 were within ±1 standard deviation 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. Furthermore, 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 include improvement of ultrasound image fidelity by improving spatial resolution and reducing phase interference artefacts.

Comparison of active-set method deconvolution and matched-filtering for derivation of an ultrasound transit time spectrum.

The quality of ultrasound computed tomography imaging is primarily determined by the accuracy of ultrasound transit time measurement. A major problem in analysis is the overlap of signals making it difficult to detect the correct transit time. The current standard is to apply a matched-filtering approach to the input and output signals. This study compares the matched-filtering technique with active set deconvolution to derive a transit time spectrum from a coded excitation chirp signal and the measured output signal. The ultrasound wave travels in a direct and a reflected path to the receiver, resulting in an overlap in the recorded output signal. The matched-filtering and deconvolution techniques were applied to determine the transit times associated with the two signal paths. Both techniques were able to detect the two different transit times; while matched-filtering has a better accuracy (0.13 μs versus 0.18 μs standard deviations), deconvolution has a 3.5 times improved side-lobe to main-lobe ratio. A higher side-lobe suppression is important to further improve image fidelity. These results suggest that a future combination of both techniques would provide improved signal detection and hence improved image fidelity.

Melt Electrospinning Writing of Highly Ordered Large Volume Scaffold Architectures

The additive manufacturing of highly ordered, micrometer-scale scaffolds is at the forefront of tissue engineering and regenerative medicine research. The fabrication of scaffolds for the regeneration of larger tissue volumes, in particular, remains a major challenge. A technology at the convergence of additive manufacturing and electrospinning-melt electrospinning writing (MEW)-is also limited in thickness/volume due to the accumulation of excess charge from the deposited material repelling and hence, distorting scaffold architectures. The underlying physical principles are studied that constrain MEW of thick, large volume scaffolds. Through computational modeling, numerical values variable working distances are established respectively, which maintain the electrostatic force at a constant level during the printing process. Based on the computational simulations, three voltage profiles are applied to determine the maximum height (exceeding 7 mm) of a highly ordered large volume scaffold. These thick MEW scaffolds have fully interconnected pores and allow cells to migrate and proliferate. To the best of the authors knowledge, this is the first study to report that z-axis adjustment and increasing the voltage during the MEW process allows for the fabrication of high-volume scaffolds with uniform morphologies and fiber diameters.

Performance and characterization of a non-sintered zeolite porous filter for the simultaneous removal of nitrogen and phosphorus in a biological aerated filter (BAF)

A novel non-sintered zeolite porous filter (ZPF) and commercially available ceramsite (CAC) are used to investigate the simultaneous removal of nitrogen and phosphorus from city wastewater treated by biological aerated filter (BAF) reactors. The chemical and physical characteristics of ZPF and CAC are measured. ZPF has a higher porosity and larger total surface area than CAC. In addition, the interconnected porous structure obtained for ZPF is suitable for microbial biofilm growth. In the present study, the influence of the hydraulic retention time on the removal of phosphorus (PO43−), total nitrogen (TN), ammonia nitrogen (NH3–N), and total organic carbon (TOC) are studied. The results show that the ZPF BAF performs much better than the CAC BAF. Microbial biofilm morphology also shows that more microorganisms are loaded in the ZPF BAF. The polymerase chain reaction and denaturing gradient gel electrophoresis and sequence analysis of 16S RNA gene fragments show that Comamonas testosteroni, uncultured Comamonas sp., and uncultured Nitrospira sp. are primarily detected in the ZPF BAF and this attached growth benefits the simultaneous nitrification and denitrification performance of the ZPF BAF. Thus, ZPF has potential use as novel material for the simultaneous removal of nitrogen and phosphorus of BAF in wastewater treatment.

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...

Transducer impulse response correction for a deconvolution derived ultrasound transit time spectrum

Propagation of ultrasound through a complex composite sample may exhibit phase interference between two or more sonic-rays if differences in transit time are less than the pulse length. The transit time spectrum of a test sample, equivalent to its impulse response, was derived through active-set deconvolution of ultrasound signals with, and without, the test sample. The aim of this study was to test the hypothesis that in cases where only the transmit ultrasound transducers digitally-coded excitation signal is available, hence not the input ultrasound signal without the test sample, incorporation of the transducer impulse response may increase both accuracy and precision of ultrasound transit time spectroscopy. A digital 1 MHz sinusoid signal was used to create an ultrasound pulse that was propagated through a 5 step-wedge acrylic sample immersed in water. Transit time spectra were obtained through deconvolution utilising an ultrasound input signal, along with a digital input signal, with and without incorporation of the transducer impulse response. Incorporation of the transducer impulse response reduced a quantitative measure of noise-to-signal ratio by a factor of 12. The paper has demonstrated the potential for increased accuracy and precision of transit time spectroscopy when the transducer impulse response is incorporated within active-set deconvolution analysis.