Contactless Remote Induction of Shear Waves in Soft Tissues Using a Transcranial Magnetic Stimulation Device

This study presents the first observation of shear wave induced remotely within soft tissues. It was performed through the combination of a transcranial magnetic stimulation device and a permanent magnet. A physical model based on Maxwell and Navier equations was developed. Experiments were performed on a cryogel phantom and a chicken breast sample. Using an ultrafast ultrasound scanner, shear waves of respective amplitude of 5 and 0.5 micrometers were observed. Experimental and numerical results were in good agreement. This study constitutes the framework of an alternative shear wave elastography method

Ultrasound metrology and phantom materials for validation of photoacoustic thermometry

High intensity focused ultrasound is an emerging non-invasive cancer therapy during which a focused ultrasound beam is used to destroy cancer cells within a confined volume of tissue. In order to increase its successful implementation in practice, an imaging modality capable of accurately mapping the induced temperature rise in tissue is necessary. Photoacoustic thermometry, a rapidly emerging technique for non-invasive temperature monitoring, exploits the temperature dependence of the Grüneisen parameter of tissues, which leads to changes in the recorded photoacoustic signal amplitude with temperature. However, the implementation of photoacoustic thermometry approaches is hindered by a lack of rigorous validation. This includes both the equipment and methodology used. This work investigates the effect of temperature on ultrasound transducers used in photoacoustic thermometry imaging as well as characterisation of potential phantom materials for its validation. The variation in transducer sensitivity with temperature is investigated using two approaches. The first one utilises a reference transducer whose output power is known as a function of temperature to characterise the sensitivity of the hydrophone. As the knowledge of variability of transducer output with temperature is not readily available, two standard metrology techniques using radiation force balances and laser vibrometry are extended beyond room temperature to characterise the effect of temperature on the output of PZT tranducers. For the second approach to transducer sensitivity calibration, a novel method is developed utilising water as a laser-generated ultrasound source and validated using the self-reciprocity calibration method. The calibrated hydrophone is then used to characterise the relevant temperature-dependent properties of several phantom materials in a custom-built setup. The measurement results are used to determine the most suitable phantom for photoacoustic thermometry. Finally, the phantom is heated and imaged in a proof-of-concept photoacoustic thermometry setup using a linear array. These contributions are of vital importance for allowing the translation of photoacoustic thermometry into clinical practice

Design and development of magnetic resonance imaging (MRI) compatible tissue mimicking phantoms for evaluating focused ultrasound thermal protocols

Animal models are often used to test the efficacy and safety of clinical applications employing focused ultrasound that range in various stages of research, development and commercialization. The animals are usually subjected to conditions that cause pain, distress and euthanasia. Access to cadaveric models is not easy and affordable for all research institutions, whereas conservation and changes of their physical properties over time can be a delimiting factor for translational research. The above set the motivation for this project, which its primary objective is to design and develop appropriate tissue mimicking phantoms using a simplistic and cost effective methodology. These phantoms are expected to contribute in reducing the need for animal testing and allow researchers to get hands experience with tools that will promote and accelerate testing in focused ultrasound thermal protocols. The main requirements for these phantoms are to be geometrically accurate, compatible with magnetic resonance imaging (MRI) and to be composed of materials that approximate the acoustic and thermal properties of the replicated tissues. Throughout the duration of the project three ultrasonic composite phantoms (head, femur bone-muscle and breast-rib) were developed. The acoustic properties of candidate materials were assessed using pulse-echo immersion and through transmission techniques. The thermal properties were estimated by observing the rate of heat diffusion following a sonication in the soft tissue parts with MR thermometry. Acrylonitrile butadiene styrene (ABS) was used to replicate bone tissue, where its acoustic attenuation coefficient was found to be 16.01 ± 6.18 dB/cm at 1 MHz and the speed of sound at 2048 ± 79 m/s. Soft tissue parts consisted out of agar-based gels doped with varying concentrations of additives that controlled the relative contribution of acoustic absorption (evaporated milk) and scatter (silica dioxide) to total attenuation independently. Brain tissue phantom (2 % w/v agar - 1.2 % w/v SiO2 - 25 % v/v evaporated milk) matched an attenuation coefficient of 0.59 ± 0.05 dB/cm-MHz whereas muscle and breast mimicking phantom (2 % w/v agar - 2 % w/v SiO2 - 40 % v/v evaporated milk) were estimated of inducing an attenuation coefficient of the order of 0.99 ±0.08 dB/cm-MHz. The speed of sound for the brain and muscle/breast recipe were estimated at 1485 ± 12 m/s and 1529 ± 13 m/s respectively. The thermal conductivity of the brain phantom was estimated to be 0.52 ± 0.06 W/mº-C and 0.57 ± 0.10 W/mº-C for the muscle/breast phantom. The acoustic and thermal properties of candidate materials were within range of the replicated tissues extracted from literature, except the speed of sound in ABS compared which was lower compared to bone (~3000 m/s). Three dimensional models of bone parts (skull, femur, rib) were reconstructed in Standard Tessellation Language (STL) format by segmenting bony tissue of interest from adult human computed tomography (CT) images. The STL bone models were 3D printed in ABS using a fused deposition modelling (FDM) machine. The final composite phantoms were fabricated by molding the agar based soft tissue phantoms inside/around the ABS bone phantoms. The functionality of all three composite phantoms was assessed with focused ultrasound sonications applied by a 1 MHz single element transducer while temperature was monitored with 1.5 Tesla MRI scanner. A spoiled gradient recalled (SPGR) pulse sequence was used to produce phase images that were analyzed using a custom coded software developed in Matlab that employed proton-resonance frequency shift (PRFS) thermometry

Ultrafast Ultrasound Imaging

Among medical imaging modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI), ultrasound imaging stands out due to its temporal resolution. Owing to the nature of medical ultrasound imaging, it has been used for not only observation of the morphology of living organs but also functional imaging, such as blood flow imaging and evaluation of the cardiac function. Ultrafast ultrasound imaging, which has recently become widely available, significantly increases the opportunities for medical functional imaging. Ultrafast ultrasound imaging typically enables imaging frame-rates of up to ten thousand frames per second (fps). Due to the extremely high temporal resolution, this enables visualization of rapid dynamic responses of biological tissues, which cannot be observed and analyzed by conventional ultrasound imaging. This Special Issue includes various studies of improvements to the performance of ultrafast ultrasoun

Optimisation of the acousto optic signal detection for biomedical applications

Near infrared light has been widely used to probe human tissue oxygenation non-invasively. However the highly scattering nature of tissue limits light penetration depths and optical measurement is more sensitive to optical changes in the superficial region (SFR) of tissue. It is proposed that the penetration depth and the localisation of the optical measurement can be improved by the Acousto-Optic (AO) method. The AO method tags diffuse photons in an optically tissue mimicking medium by using focused ultrasound waves. Generally it is believed that the region probed by the AO method is decided by the position of the focused ultrasound region (FUR). Therefore the AO method can potentially improve the penetration depth and reduce the susceptibility in the SFR of the optical measurement by relocating the FUR to deeper region in tissue. The spatial sensitivity of the AO measurement is mapped and compared to the spatial sensitivity of the optical measurement experimentally. The AO method can monitor absorption and scattering changes in deeper regions than the optical measurement. The AO method is less affected by the optical changes in the SFR. The most sensitive region probed by the AO method can be relocated by re-positioning the FUR. But it does not always coincide with the FUR. The AO spatial sensitivity depends on the overlap of the FUR and the photon path distribution. This overlap region affects the AO signal differently for absorption and scattering changes. Thus, concurrent monitoring of absorption and scattering changes require careful positioning of the FUR. Finally, it is also demonstrated that the pulsed-wave ultrasound can be used with the AO method in a cylindrical geometry. An optimal optodes’ positions for the AO signal detection can be predicted experimentally for a given location of the FUR within a cylindrical geometry

Development of a Complex Flow Phantom for Diagnostic Imaging

Literature and market analysis have highlighted the lack of flow phantom technologies able to challenge innovative medical imaging devices, such as Ultrasound and Magnetic Resonance. A novel, cost-effective, compact and robust Complex Flow Phantom prototype was proposed. The design relies on the generation of stable, reproducible, predictable and controllable vortex rings. Vortex rings were chosen because bring together high stability and physiological relevance. The design was tested with multiple and independent measurement methods under challenging working conditions. Overall, it demonstrated to produce reproducible flows with variability always lower than +/- 10 %. This variability was assessed with regards to translational velocity, however, macro-flow reproducibility implies micro-flow stability. Computational Fluid Dynamics (CFD) and optical/video acquisitions were used as first methods to independently validate two early prototypes operating in air and water. CFD overall well approximate theoretical predictions but accuracy was insufficient to provide a reference standard. Overall, the early prototypes demonstrated encouraging stability and a Vortex Ring based Complex Flow Phantom prototype was manufactured. Laser PIV acquisitions were performed to establish flow reference standard values. Optical/video acquisitions were performed and results were compared with Laser PIV to assess the rigour of the methods. Results obtained by the two different measurement methods on two identically manufactured but different systems showed credible consistency. Conventional and advanced (Vector Flow Imaging) Ultrasound acquisitions were also performed on the design. An instrumentation pack was designed and is provided as tool for self-calibrating the phantom and for estimating flow reference values under different generating conditions. An MRI compatible version of the phantom was manufactured and was tested in laboratory. Design and experiments are supported by journal article and conference proceeding publications, poster and oral presentation in international conferences. The phantom is purchasable from Leeds Test Objects Ltd or can be manufactured in laboratory following the specifications provided

New experimental and computational methods for ultrasound brain tomography

Fast, portable, and affordable neuroimaging is currently unavailable in clinical practice, hindering prevention and treatment of pathologies such as stroke, a leading cause of death and disability worldwide. Full-waveform inversion (FWI), an ultrasound-based tomographic technique, has been recently proposed as a solution to this problem, but is yet to be successfully applied experimentally. Two fundamental barriers hinder its experimental application: a lack of numerical models that accurately replicate experimental measurements, and of domain-specific software that implements FWI algorithms efficiently. Here, I address both problems, opening the door to universally available neuroimaging. Addressing the first barrier entails finding numerical models that can explain the behaviour of the acquisition system: the transmission and reception response of the transducers, and their spatial location and orientation. As I demonstrate here, existing position-estimation methods fail when the surface of the transducers is bigger than the wavelength, a prerequisite for imaging through the skull, while available response-estimation techniques cannot achieve the precision required by full-wave methods. Therefore, I present spatial response identification, a new algorithm for transducer calibration and modelling, and show how it can be used to explain experimental devices with higher accuracy than existing methods. Additionally, I present experimental reconstructions of a tissue-mimicking phantom, achieving improved imaging quality with respect to standard calibration techniques. The second barrier stems from the fact that FWI is mathematically challenging and orders of magnitude more computationally expensive than conventional ultrasound imaging, while there is an absence of open codes, slowing the pace of research and hindering reproducibility. Therefore, I introduce Stride, an open-source Python library that combines high-level interfaces with automatically generated, high-performance solvers and scalable parallelisation. Here, I demonstrate that Stride can achieve state-of-the-art modelling accuracy and how it can be used to image in 2D and 3D, scaling from a local workstation to a high-performance cluster.Open Acces

Ultrasound and magnetic resonance techniques for the haemodynamic quantification of the peripheral vascular system

The aim of this thesis was to determine whether the blood flow velocities in the peripheral vascular system measured using phase contrast magnetic resonance imaging, PC-MRI, techniques could be used in the same way that blood flow velocities measured using spectral Doppler ultrasound are used to aid in the diagnosis of peripheral vascular disease. Specifically, we aimed to investigate the measurement of maximum velocities and the use of maximum velocity ratios; an area of investigation which has been neglected in studies of PC-MRI blood flow quantification to date. A series of optimisation and comparison studies were carried out using in-house developed test phantoms. Key to the in-vitro work was the establishment of a dual modality flow test system which would allow comparison of identical flow conditions measured using ultrasound and MRI. The work was complemented by in-vivo studies in healthy volunteers. A 4D PC-MRI commercial work-in-progress protocol and software package became available during the study and was evaluated in-vitro and in-vivo using similar methods as for the 2D PC-MRI studies. The main findings of the thesis were that 2D PC-MRI measurement of maximum velocities significantly underestimated those measured using spectral Doppler ultrasound. However, if corrections were applied to account for the overestimation of ultrasound maximum velocity due to spectral broadening, then the two methods were in agreement. In contrast, the use of maximum velocity ratios showed no difference between spectral Doppler ultrasound and 2D PC-MRI measurements. It was noted that one of the potential problems with the use of 2D PC-MRI in the measurement of the maximum velocity at a stenosis is the accurate positioning of the 2D velocity encoded slice in the stenotic jet. 4D PC-MRI, with a time resolved velocity encoded volume dataset, offers a potential solution to this. However, our evaluation of 4D PC-MRI showed that it can significantly underestimate both maximum velocities and maximum velocity ratios in comparison with 2D PC-MRI and spectral Doppler ultrasound and requires further development before it can be used for peripheral vascular applications

Temperature Mapping using Mid-Field Magnetic Resonance Imaging

Magnetic Resonance Imaging (MRI) is a non-invasive imaging modality with excellent soft tissue contrast and sensitivity to tissue temperature. MRI use is growing in Canada with expectation that this is expected to continue in the medium term, with more wide adoption of MRI and in particular a renewed focus on MR systems which deviate from the most commonly used 1.5T field strength system. By implementing systems which do not use as strong magnets and instead operate Generally, as the field strength of an MR system decreases, the signal received when imaging also decreases, which makes it difficult to implement some applications which are standard at higher field. One such application is temperature mapping on a these \u3c1T \u3esystems, which can be used to monitor thermal therapies interventionally. This thesis addresses the potentials for implementing temperature mapping at 0.5T, both in the creation of a tissue mimicking phantom which can be used to compare temperature mapping methods and implementing temperature maps both in vivo and in the custom phantom. As well, motivated by the sensitivity that thermal mapping has to external disturbances, the challenges that these accessible MR systems face when being in non-specialized environments is addressed, as this can potentially limit the efficacy of temperature mapping. This work ultimately demonstrates the acceptable capabilities of a 0.5T system to map temperatures with an adequate temporal resolution, along with presenting practical solutions to operating a system in non-traditional locations