Characterisation and correction of respiratory-motion artefacts in cardiac PET-CT

Respiratory motion during cardiac Positron Emission Tomography (PET) Computed Tomography (CT) imaging results in blurring of the PET data and can induce mismatches between the PET and CT datasets, leading to attenuation-correction artefacts. The aim of this project was to develop a method of motion-correction to overcome both of these problems. The approach implemented was to transform a single CT to match the frames of a gated PET study, to facilitate respiratory-matched attenuation-correction, without the need for a gated CT. This is benecial for lowering the radiation dose to the patient and in reducing PETCT mismatches, which can arise even in gated studies. The heart and diaphragm were identied through phantom studies as the structures responsible for generating attenuation-correction artefacts in the heart and their motions therefore needed to be considered in transforming the CT. Estimating heart motion was straight-forward, due to its high contrast in PET, however the poor diaphragm contrast meant that additional information was required to track its position. Therefore a diaphragm shape model was constructed using segmented diaphragm surfaces, enabling complete diaphragm surfaces to be produced from incomplete and noisy initial estimates. These complete surfaces, in combination with the estimated heart motions were used to transform the CT. The PET frames were then attenuation-corrected with the transformed CT, reconstructed, aligned and summed, to produce motion-free images. It was found that motion-blurring was reduced through alignment, although benets were marginal in the presence of small respiratory motions. Quantitative accuracy was improved from use of the transformed CT for attenuation-correction (compared with no CT transformation), which was attributed to both the heart and the diaphragm transformations. In comparison to a gated CT, a substantial dose saving and a reduced dependence on gating techniques were achieved, indicating the potential value of the technique in routine clinical procedures

Intelligent Imaging of Perfusion Using Arterial Spin Labelling

Arterial spin labelling (ASL) is a powerful magnetic resonance imaging technique, which can be used to noninvasively measure perfusion in the brain and other organs of the body. Promising research results show how ASL might be used in stroke, tumours, dementia and paediatric medicine, in addition to many other areas. However, significant obstacles remain to prevent widespread use: ASL images have an inherently low signal to noise ratio, and are susceptible to corrupting artifacts from motion and other sources. The objective of the work in this thesis is to move towards an "intelligent imaging" paradigm: one in which the image acquisition, reconstruction and processing are mutually coupled, and tailored to the individual patient. This thesis explores how ASL images may be improved at several stages of the imaging pipeline. We review the relevant ASL literature, exploring details of ASL acquisitions, parameter inference and artifact post-processing. We subsequently present original work: we use the framework of Bayesian experimental design to generate optimised ASL acquisitions, we present original methods to improve parameter inference through anatomically-driven modelling of spatial correlation, and we describe a novel deep learning approach for simultaneous denoising and artifact filtering. Using a mixture of theoretical derivation, simulation results and imaging experiments, the work in this thesis presents several new approaches for ASL, and hopefully will shape future research and future ASL usage

Patient radiation dose issues resulting from the use of CT in the UK

In this report, COMARE presents a comprehensive review of the radiation dose issues associated with CT scans in the UK. The implications of the increase in the numbers of CT scans in the UK are considered in the report, with focus on the number of younger patients undergoing CT scans, who have greater sensitivity to x-rays. The report provides an update on the radiation protection aspects of justification (balancing risk and benefit) and optimisation (balancing the risk from the radiation dose with the quality of the image)

Is attention all you need in medical image analysis? A review

Medical imaging is a key component in clinical diagnosis, treatment planning and clinical trial design, accounting for almost 90% of all healthcare data. CNNs achieved performance gains in medical image analysis (MIA) over the last years. CNNs can efficiently model local pixel interactions and be trained on small-scale MI data. The main disadvantage of typical CNN models is that they ignore global pixel relationships within images, which limits their generalisation ability to understand out-of-distribution data with different 'global' information. The recent progress of Artificial Intelligence gave rise to Transformers, which can learn global relationships from data. However, full Transformer models need to be trained on large-scale data and involve tremendous computational complexity. Attention and Transformer compartments (Transf/Attention) which can well maintain properties for modelling global relationships, have been proposed as lighter alternatives of full Transformers. Recently, there is an increasing trend to co-pollinate complementary local-global properties from CNN and Transf/Attention architectures, which led to a new era of hybrid models. The past years have witnessed substantial growth in hybrid CNN-Transf/Attention models across diverse MIA problems. In this systematic review, we survey existing hybrid CNN-Transf/Attention models, review and unravel key architectural designs, analyse breakthroughs, and evaluate current and future opportunities as well as challenges. We also introduced a comprehensive analysis framework on generalisation opportunities of scientific and clinical impact, based on which new data-driven domain generalisation and adaptation methods can be stimulated

Improving Quantification in Lung PET/CT for the Evaluation of Disease Progression and Treatment Effectiveness

Positron Emission Tomography (PET) allows imaging of functional processes in vivo by measuring the distribution of an administered radiotracer. Whilst one of its main uses is directed towards lung cancer, there is an increased interest in diffuse lung diseases, for which the incidences rise every year, mainly due to environmental reasons and population ageing. However, PET acquisitions in the lung are particularly challenging due to several effects, including the inevitable cardiac and respiratory motion and the loss of spatial resolution due to low density, causing increased positron range. This thesis will focus on Idiopathic Pulmonary Fibrosis (IPF), a disease whose aetiology is poorly understood while patient survival is limited to a few years only. Contrary to lung tumours, this diffuse lung disease modifies the lung architecture more globally. The changes result in small structures with varying densities. Previous work has developed data analysis techniques addressing some of the challenges of imaging patients with IPF. However, robust reconstruction techniques are still necessary to obtain quantitative measures for such data, where it should be beneficial to exploit recent advances in PET scanner hardware such as Time of Flight (TOF) and respiratory motion monitoring. Firstly, positron range in the lung will be discussed, evaluating its effect in density-varying media, such as fibrotic lung. Secondly, the general effect of using incorrect attenuation data in lung PET reconstructions will be assessed. The study will compare TOF and non-TOF reconstructions and quantify the local and global artefacts created by data inconsistencies and respiratory motion. Then, motion compensation will be addressed by proposing a method which takes into account the changes of density and activity in the lungs during the respiration, via the estimation of the volume changes using the deformation fields. The method is evaluated on late time frame PET acquisitions using ¹⁸F-FDG where the radiotracer distribution has stabilised. It is then used as the basis for a method for motion compensation of the early time frames (starting with the administration of the radiotracer), leading to a technique that could be used for motion compensation of kinetic measures. Preliminary results are provided for kinetic parameters extracted from short dynamic data using ¹⁸F-FDG

Variational Multi-Task Models for Image Analysis: Applications to Magnetic Resonance Imaging

This thesis deals with the study and development of several variational multi-task models for solving inverse problems in imaging, with a particular focus on Magnetic Resonance Imaging (MRI). In most image processing problems, one usually deals with the reconstruction task, i.e., the task of reconstructing an image from indirect measurements, and then performs various operations, one after the other (i.e. sequentially), to improve the quality of the reconstruction and to extract useful information. However, recent developments in a variational context, have shown that performing those tasks jointly (i.e. in a multi-task framework) offers great benefits, and this is the perspective that we follow in this thesis. We go beyond traditional sequential approaches and set a new basis for variational multi-task methods for MRI analysis. We demonstrate that by sharing representation between tasks and carefully interconnecting them, one can create synergies across challenging problems and reduce error propagation. More precisely, firstly we propose a multi-task variational model to tackle the problems of image reconstruction and image segmentation using non-convex Bregman iteration. We describe theoretical and numerical details of the problem and its optimisation scheme. Moreover, we show that our multi-task model achieves better results in several examples and MRI applications than existing approaches in the same context. Secondly, we show that our approach can be extended to a multi-task reconstruction and segmentation model for the nonlinear inverse problem of velocity-encoded MRI. In this context, the aim is to estimate not only the magnitude from MRI data, but also the phase and its flow information, whilst simultaneously identify regions of interest through the segmentation task. Finally, we go beyond two-task frameworks and introduce for the first time a variational multi-task model to handle three imaging tasks. To this end, we design a variational multi-task framework addressing reconstruction, super-resolution and registration for improving the quality of MRI reconstruction. We demonstrate that our model is theoretically well-motivated and it outperforms sequential models whilst requiring less computational cost. Furthermore, we show through experimental results the potential of this approach for clinical applications

Improving Accuracy of Information Extraction from Quantitative Magnetic Resonance Imaging

Quantitative MRI offers the possibility to produce objective measurements of tissue physiology at different scales. Such measurements are highly valuable in applications such as drug development, treatment monitoring or early diagnosis of cancer. From microstructural information in diffusion weighted imaging (DWI) or local perfusion and permeability in dynamic contrast (DCE-) MRI to more macroscopic observations of the local intestinal contraction, a number of aspects of quantitative MRI are considered in this thesis. The main objective of the presented work is to provide pre-processing techniques and model modification in order to improve the reliability of image analysis in quantitative MRI. Firstly, the challenge of clinical DWI signal modelling is investigated to overcome the biasing effect due to noise in the data. Several methods with increasing level of complexity are applied to simulations and a series of clinical datasets. Secondly, a novel Robust Data Decomposition Registration technique is introduced to tackle the problem of image registration in DCE-MRI. The technique allows the separation of tissue enhancement from motion effects so that the latter can be corrected independently. It is successfully applied to DCE-MRI datasets of different organs. This application is extended to the correction of respiratory motion in small bowel motility quantification in dynamic MRI data acquired during free breathing. Finally, a new local model for the arterial input function (AIF) is proposed. The estimation of the arterial blood contrast agent concentration in DCE-MRI is augmented using prior knowledge on local tissue structure from DWI. This work explores several types of imaging using MRI. It contributes to clinical quantitative MRI analysis providing practical solutions aimed at improving the accuracy and consistency of the parameters derived from image data

Multimodality Imaging of Tumour Pathophysiology and Response to Pharmacological Intervention

This thesis describes the need for imaging the tumour pathophysiological microenvironment in order to understand response to treatment. Specifically looking at tumour vascularisation in in vivo murine xenograft models of disease, response to treatment with vascular disruption is assessed via photoacoustic tomography (PAT) and magnetic resonance imaging (MRI). Photoacoustic imaging is a novel imaging modality based on the detection of ultrasound waves created by the absorption of nano-second pulsed laser energy within tissue chromophores. It has the spectral specificity of optical techniques whilst also achieving the high resolution of ultrasound. Haemoglobin is the main chromophore found in biological tissue and this modality is therefore ideally suited to imaging tumour vascularisation. Using a Fabry-Perot interferometer this thesis demonstrates for the first time the feasibility of using PAT for re-clinical research and the characterisation of typical tumour vascular features in a non-invasive non-ionising manner. Response to different concentrations of a vascular disrupting drug is then demonstrated, with novel insights in to how tumours recover from vascular damage observed. MRI of response to vascular disruption is also presented. As MRI is widely used in the clinic it can serve as a translational tool of novel imaging biomarkers, and serves to further understand the differences in response of pathologically vascularised of tumours. This thesis looks at markers associated with disruption of haemodynamics, using apparent diffusion (ADC) to elucidate onset of necrosis, increase in haemoglobin concentration (R2*) as indication of impaired flow, and arterial spin labelling (ASL) as a marker of tumour blood perfusion. This is shown in both subcutaneous and clinically relevant liver metastasis models. Taken as whole, the results from this thesis indicate that whilst understanding the response of the tumour vasculature to pharmacological intervention is complex, novel imaging techniques can provide invaluable translational information on the pathophysiology of tumours