1,721,012 research outputs found
Synchronised dataset from two ULA-OP systems
RF data saved from two probes with synchronised acquisition using the ULA-OP system.
Please cite as:
Christensen-Jeffries, Kirsten; Brown,Jemma Brown; Aljabar, Paul; Tang, Mengxing; Dunsby, Christopher; Eckersley, Robert (2017) Synchronised dataset from two ULA-OP systems. King's College London. http://doi.org/doi:10.18742/RDM01-21
Effect of agent concentration in ultrasound super- resolution imaging at clinically low frequency
Imaging of microvasculature can be valuable for the diagnosis and treatment monitoring of cancer and other diseases. Ultrasound has the potential due to its excellent spatial and temporal resolution. Super-resolution ultrasound imaging using contrast enhanced ultrasound localization microscopy is able to visualize microvasculature beyond the wave diffraction limit. The microbubble based super-resolution depends on controlling the bubble concentration, which needs to be low enough to locate isolated microbubbles. However too low a concentration will prolong the data acquisition. The aim of the thesis was to evaluate the impact of microbubble concentration on super-resolution ultrasound imaging, and to improve the signal processing in super-resolution imaging. First, various concentrations of microbubble contrast agents (6×10^3 to 1.5×10^6particles/ml) were injected into a 200 microns cross-tube flow phantom. The experimental results show that the concentration affects the resolution of the cross-tube images. When the concentration is lower than the 1.5×10^5particles/ml, two tubes in a selected region of interest near the intersection that are 370 microns apart can be separated, which is close to the expected distance (390 microns). Second, the comprehensive effects of data acquisition time and concentration on imaging resolution were studied. The preferred range of concentration was determined between 1.5×10^4 to 6×10^4particles/ml. This result can be used to better inform data acquisition in the further research. Third, a weight adaptive denoising method based on morphology was developed to remove noises which were produced in the step of microbubble detection at the preferred range of concentration. Therefore, the resolution and the accuracy of the velocity map were further improved.Open Acces
Nonlinear propagation artefact correction in contrast enhanced ultrasound imaging
In contrast enhanced ultrasound images (CEUS) that use microbubbles, nonlinear propagation of ultrasound creates artefacts which significantly impact the qualitative and quantitative assessments of tissue perfusion. Such artefact originates from tissue reflecting/scattering nonlinearly propagated ultrasound pulse. Consequently such tissue is misclassified as microbubbles which also generate nonlinear signals. This thesis reports the development and evaluation of an algorithm to reduce the nonlinear propagation artefact in CEUS. The method was evaluated in simulations, and on in vitro and in vivo data at both high and low ultrasound frequencies. Ways to further improve the performance of the method were also investigated.
Firstly, the artefact correction algorithm was developed. The algorithm makes use of two independent datasets that are acquired simultaneously during CEUS; the Bmode image, which is dominated by tissue information, and the contrast specific image, which contains information on blood (signal) due to microbubbles, but confounded with some amount of tissue signals (artefact). The unwanted tissue contribution of the contrast specific image is reconstructed by estimating the two components that make up this contribution, namely, the underlying tissue distribution and the nonlinear point spread function (PSF) of the imaging system. To initially evaluate the algorithm, a simulation platform was developed to study artefact generation at various Mechanical Indices (MI), microbubble concentrations and frequencies. The algorithm was then evaluated using the simulation data. The results show that the algorithm is able to reduce the nonlinear propagation artefact at different MI, concentration and frequency under both ideal and noisy conditions.
Next, artefact correction was applied to carotid artery imaging. The performance of the algorithm was evaluated using flow phantoms with large and small vessels containing microbubbles of various concentrations at different acoustic pressures. The algorithm significantly reduces nonlinear artefacts while maintaining the contrast signal from bubbles to increase the contrast to tissue ratio (CTR) by up to 11 dB. Contrast signal from a small vessel of 600 µm in diameter buried in tissue artefacts prior to correction is recovered after the correction. The algorithm was then evaluated using in vivo CEUS data acquired on patients’ carotid arteries. The algorithm is able to increase the CTR at the far-wall by up to 7.4 dB in vivo.
Artefact correction was then improved by taking the spatial variance of the ultrasound field into account and improving the nonlinear PSF estimation. The new version of the algorithm was tested on in vitro and in vivo data and the improvements verified. The new version of the algorithm provides an additional increase in CTR by up to 5.4 dB in the far field, 4.3 dB at focus and 3.2 dB in the near field for the in vitro data over previous results. The additional increase in CTR for the in vivo data is up to 4 dB more in the near field and 5 dB more in the far field over the previous results.
Nonlinear propagation correction was also applied to deep tissue imaging where lower ultrasound frequency than carotid imaging was used. The algorithm could suppress tissue signal more than 6 dB. However, due to the strong presence of the microbubbles in the B-mode image at low frequencies, the algorithm reduces microbubble signal by up to 2 dB. The resulting increase in CTR is up to 4 dB under specific imaging conditions. However, depending on the imaging geometry and acquisition settings used, it could fail to produce an increase in CTR.
A possible future direction is to combine the algorithm with an attenuation correction method to improve perfusion quantification. The clinical efficacy of the combined nonlinear propagation and attenuation correction could be evaluated. Given that the method is purely post-processing, it is easier to implement it on current commercial scanners than some other existing techniques. The implementation of the algorithm using GPUs could be investigated and could possibly instigate translation into clinics.Open Acces
Imaging lymphatic system using high frame rate contrast enhanced and super-resolution ultrasound: In vitro, in vivo and clinical study
The lymphatic system acts as an avenue through which cancer cells can spread from tumour. Lymph nodes (LNs) linking the lymphatic vessels play a critical role in filtering the cancer cells. Thus, the presence of metastases in LN is an important indicator for cancer staging [1]. As angiogenesis is a key feature of cancer, any variations in LN microcirculation can be a biomarker for metastasis. However, a non-invasive technique capable of visualising and quantifying vasculature and blood flow in LNs is lacking and highly desirable. Contrast-enhanced ultrasound (CEUS) utilising microbubbles shows great potential for visualising lymphatic vessels and identifying sentinel LNs. It allows for the diagnosis of metastatic LNs through the visualisation of perfusion pattern. However, current CEUS imaging techniques have several limitations that prevent the accurate identification, visualisation and diagnosisof LNs: (i) Tissue artefacts and bubble disruption can reduce the image contrast. (ii) Limited spatial and temporal resolution diminishes the amount of information that can be captured by CEUS. (iii) The slow flow in both the lymphatic system and the micro-vessels inside LNs makes Doppler-based approaches less effective. (iv) The identification of enhancement pattern is subjective and can vary between different observers. In this thesis, we aim to improve the capability of CEUS in non-invasive identification and evaluation of LNs through the use of high frame rate (HFR) imaging and super-resolution (SR) ultrasound (US) imaging.
Firstly, we evaluate the feasibility of using HFR CEUS for the detection of lymphatic vessels where flow is slow. The study is carried out on a lymphatic vessel phantom. Specifically, the work investigates how CEUS lymphatic imaging is affected by several key factors such as ultrasound pressure, flow velocity probe motion and image contrast. Experiments were also conducted to observe microbubble behaviour under HFR CEUS. Our results show that (i) HFR imaging and singular value decomposition (SVD) filtering can significantly reduce tissue artefacts in the phantom at high clinical frequencies; (ii) the slow flow rate within the lymphatic system makes image contrast and signal persistence more susceptible to changes in ultrasound amplitude or mechanical index (MI), and a suitable MI value can be chosen to reach a compromise between image contrast and bubble disruption under slow flow condition; (iii) probe motion significantly decreases image contrast of the vessel, which can be improved by applying motion correction before SVD filtering; (iv) the optical observation of the impact of ultrasound pressure on HFR CEUS further confirms the importance of optimising ultrasound amplitude.
Secondly, the feasibility of in vivo three-dimensional SR US imaging for the visualisation and quantification of LN microvascular and blood flow was studied in a rabbit model. In vivo studies were carried out to image popliteal LNs of two healthy male New Zealand white rabbits aged 6–8 weeks. Three-dimensional, high-frame-rate, contrast enhanced US was achieved by mechanically scanning a linear imaging probe. Individual microbubbles were identified, localised, and tracked to form three-dimensional SR images and super-resolved velocity maps. Acoustic sub-aperture processing was used to improve image contrast and to generate enhanced power Doppler and colour Doppler images. Vessel size and blood flow velocity distributions were evaluated and assessed by using paired Student’s t-test. SR images is able to reveal microvessels in the rabbit LN with branches clearly resolved up to 30 μm. This is less than half the acoustic wavelength and not resolvable by power or colour Doppler. The apparent size distribution of most vessels in the SR images was below 80 μm which agrees with micro-CT data. In contrast, most vessels detected with Doppler techniques were larger than 80 μm. The blood flow velocity distribution indicated that most of the blood flow in rabbit popliteal LN was at velocities lower than 5 mm/sec. We demonstrate that three-dimensional super-resolution US imaging using microbubbles allows non-invasive, non-ionising visualisation and quantification of LN microvascular structures and blood flow dynamics with resolution below the wave diffraction limit. This technology has great potential for further study of the physiological functions of the lymphatic system and the clinical detection of LN metastasis.
Finally, we explore the potential of using SR US for distinguishing metastatic LNs from reactive LNs in human. In this study, SR US images and super resolved velocity maps of LNs are generated from patient data acquired with a clinical ultrasound system. We discuss the challenges of acquiring suitable datasets in the clinical settings and suggest solutions to overcome these challenges. For example, destruction pulses are utilised to achieve suitable microbubble concentration for super-resolution ultrasound imaging. In addition, motion correction is applied before the detection of microbubble to compensate for the significant movement in real clinical settings. After obtaining the super resolution ultrasound images, multiple morphological and functional measures are derived from the super resolution images and super resolved velocity maps. These measures were compared for the reactive and metastatic LNs and assessed using a two sample student’s t-test. Our initial results indicate that metastatic LNs have significantly higher variance in blood flow direction compared to that of reactive LNs. Different factors affecting the quantifications of super-resolution ultrasound imaging are also studied and potential solutions are provided to take these factors into account. This study demonstrates the possibility of using quantifications obtained from super resolution ultrasound images to discriminate between metastatic and reactive LNs.Open Acces
Ultrasound modulated optical tomography in optical diffuse medium using acoustic radiation force
Ultrasound modulated optical tomography (UOT) is a hybrid technique which combines optical contrast with ultrasound (US) resolution to achieve deeper tissue imaging. However, the technique is currently limited due to the weak modulation signal strength and consequently a low Signal-to-Noise Ratio (SNR). One potential way to increase the SNR of UOT is to increase the ultrasound induced particle displacement, by either increasing the ultrasound amplitude or using the acoustic radiation force (ARF). In this thesis, I theoretically studied the relationship between the scatterers‘ displacements and the modulation signal strength and experimentally investigated the ARF in addition to investigating the detrimental effects of shear wave propagation on ultrasound modulated optical (UO) signals. A Monte Carlo simulation tool was developed to investigate how the UOT signal changes with increasing amplitude of ultrasound induced particle displacement in the simulation object. By combining a realistic ultrasound field with UOT simulation, the nonlinear effect of ultrasound on UOT signal was studied for the first time. An UOT experiment system, using a CCD camera and a single element transducer driven by an amplitude-modulated (AM) ultrasound signal to generate an oscillatory ARF, was tested on a tissue mimic phantom. The effect of AM ultrasound on UO signals was investigated for the first time. It was found that with longer CCD exposure times, larger ARF induced particle movements can be captured and the UO signal was increased.
Next the effects of an ARF induced shear wave on UO signals are studied. The ARF induced shear waves can propagate transversely out of the focal region and may reduce spatial resolution. This is the first examination of the time evolution of the shear wave effect generated by a short ultrasound burst on the UO signal. The spatial resolution of the system was studied by scanning the phantoms. It was found that by adjusting the timing and length of CCD exposure, shear wave effects can be minimised and both the optical and mechanical properties of the phantom can be detected and distinguished
Non Linear Ultrasound Doppler and the Detection of Targeted Contrast Agents
One of the main challenges in molecular imaging with targeted contrast agents is the detection and
discrimination of attached agents from the rest of the signals originating from freely flowing agents
and tissue. The aim of this thesis was to develop methods for the detection of targeted
microbubbles.
One approach consisted of investigating the use of nonlinear Doppler for this purpose. Nonlinear
Doppler enables the differentiation of moving from non-moving and linear from nonlinear
scattering. Targeted microbubbles are static and nonlinear scatterers and they should be detected
using this technique.
A novel nonlinear Doppler technique: Pulse subtraction Doppler, was developed and compared to
pulse inversion Doppler. It is shown that both techniques lead to similar Doppler spectra and
depending on the medical applications and the equipment limitations, both techniques have
benefits.
This served as a starting point for the derivation of a generalised nonlinear Doppler technique,
based on combined linear pulse pair sequences and tested in a simulation study. The response
from a single microbubble was simulated for different pulse combinations and the pulse sequences
were compared with regards to criteria specific to imaging requirements. It was shown that
depending on initially set criteria, such as transmitted energy, mechanical index or scanner
characteristics, certain pulse combinations offer alternatives to the current imaging modalities and
allow to take into account specific constrains due to the targeted application/equipment.
Furthermore, the proposed approach is directly applicable in a strict non linear imaging approach,
without Doppler processing.
An in vitro phantom was designed in order to assess pulse subtraction Doppler for the detection
and discrimination of static nonlinear microbubbles in the presence of free flowing ones. It was
shown that pulse subtraction Doppler enables such discrimination and the practicability for in vivo
situations is discussed.
The pulse subtraction Doppler sequences were also tested on a phantom containing magnetic
bubbles. It was shown that the magnetic bubbles can be immobilised through a magnetic field to a
specific region of interest under flow conditions. The bubbles also showed to be acoustically
detectable and to scatter linearly at diagnostic driving pressures.
Preliminary work regarding experimental biotinylated microbubbles and their attachment to
streptavidin coated surfaces is also presented.
Due to their proximity to a wall, researchers have found that targeted microbubbles exhibit different
acoustic signatures compared to free ones and this knowledge can improve their detection
techniques. The behaviour of microbubbles against a membrane of varying stiffness was also
studied through high speed camera observations. It was found both experimentally and by
comparison to theoretical modelling that within the stiffness range of human blood vessels the
change in acoustical behaviour of microbubbles is negligible.
This thesis has taken two complementary research approaches which have shown to constitute
advancements for the detection and discrimination of targeted microbubbles
Development of optical polarisation resolved endoscopy
Optical polarization is sensitive to morphological, structural and compositional changes of tissue and has attracted much interest as a tool in tissue sensing and characterisation. The fusion of polarisation imaging techniques and medical endoscopy resulting in polarisation resolved endoscopy is one of the most significant steps to translate the technique from an optical laboratory to clinic so as to benefit the whole spectrum of endoscopic investigations and intra-operative guidance in situ during minimally invasive surgery. The work in this thesis focuses on the proof-of-concept studies concerning the development of polarisation resolved endoscopy. In particular, polarised light scattering spectral imaging, 3×3 and 4×4 Mueller polarimetric imaging are successfully integrated to a rigid endoscope with accompanying validation experiments performed. The results have shown that polarisation resolved endoscopy based on light scattering spectroscopy and Mueller polarimetry is feasible to implement and has great potential to become a powerful tool for tissue imaging and characterisation.Open Acces
Ultrasound imaging augmented 3D flow reconstruction and computational fluid dynamics simulation
Cardiovascular Diseases (CVD), including stroke, coronary/peripheral artery diseases, are currently the leading cause of mortality globally. CVD are usually correlated to abnormal blood flow and vessel wall shear stress, and fast/accurate patient-specific 3D blood flow quantification can provide clinicians/researchers the insights/knowledge for better understanding, prediction, detection and treatment of CVD. Experimental methods including mainly ultrasound (US) Vector Flow Imaging (VFI), and Computational Fluid Dynamics (CFD) are usually employed for blood flow quantification. However current US methods are mainly 1D or 2D, noisy, can only obtain velocities at sparse positions in 3D, and thus have difficulties providing information required for research and clinical diagnosis. On the other hand while CFD is the current standard for 3D blood flow quantification it is usually computationally expensive and suffers from compromised accuracy due to uncertainties in the CFD input, e.g., blood flow boundary/initial condition and vessel geometry.
To bridge the current gap between the clinical needs of 3D blood flow quantification and measurement technologies, this thesis aims at: 1) developing a fast and accurate 3D full field flow reconstruction algorithm, using existing sparse 1D/2D US velocity measurements; 2) developing GPU based and US augmented Lattice Boltzmann Method (LBM) solver for faster and more accurate blood CFD computation. The thesis has made the following contributions:
(1) Chapter 2 proposed a new algorithm for 3D flow reconstruction using Divergence Free Interpolation (DFI) of sparse 2D in-plane velocity vectors obtained from US particle imaging velocimetry (UIV), with interpolation spatial basis functions which satisfy mass conservation. It is validated via two numerical reconstruction cases, and the reconstruction has similar accuracy with CFD and is ~4 times faster than CFD simulation for a range of problems. The proposed algorithm is also demonstrated and evaluated using experimental 2D UIV measurements.
(2) Chapter 3 has conducted optimizations to improve the DFI based 3D flow reconstruction approach in terms of accuracy and the time-to-solution, through optimizing the interpolation spatial basis function parameters and using a highly optimized iterative solver Generalized Minimal Residual method (GMRES) which is faster than the SVD solver used in the Chapter 2. The optimized algorithm is validated by successfully reconstructing 3D flows of in silico and in vitro UIV measurement cases, and the results show improved accuracy of ~3% and up to 728-fold speedup compared with previous method in Chapter 2. In Appendix A1 3D flow reconstruction using 1D vector US Doppler imaging has also been studied, and the feasibility of the method is demonstrated numerically by reconstructing 3D flow of a widely used benchmark (i.e., lid driven cavity flow). The method has a typical reconstruction time of <1s and error of ~5%, and can be ~800 times faster than CFD with slightly reduced but still acceptable accuracy.
(3) Patient-specific CFD suffers from high computational overheads and compromised accuracy due to input uncertainties. A measurement augmented GPU based Lattice Boltzmann Method (LBM) CFD solver is developed in order to speed up LBM simulation and reduce LBM error caused by such uncertainties, as shown in Chapter 4. We assume CFD inlet/outlet velocities and internal flow measurements are from the same US measurements and thus have similar level of fidelity. US VFI internal measurements are integrated into LBM CFD solver to constrain the simulation and augment it in terms of convergence speed and accuracy. The algorithm is validated with both in silico and in vitro cases, and the results show significant improvements of convergence speed (>30%) and accuracy compared with similar CFD without measurement augmentation. Comparing to the divergence free interpolation method, such estimation combines the advantages of the full physics in CFD and the sparse US measurements. In Appendix A2 the solver is then extended to consider the non-Newtonian rheological effects and validated in silico with a low error of ~1% using well-known commercial CFD software as a reference.
The proposed algorithms can be potentially employed to clinical applications/research, for faster and more accurate 3D blood flow quantifications.Open Acces
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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