3D Volumetric Reconstruction for Light-Field SPECT

Preclinical research on single-photon emission computed tomography (SPECT) imaging is now well acknowledged for its critical role. It is fundamental for functional imaging and is a well-researched area of nuclear medicine emission tomography. Numerous efforts were made to provide an optimized SPECT collimator and detector design. However, these approaches suffer from limited sensitivity and resolution, demanding an efficient reconstruction algorithm development. Moreover, due to the image deterioration induced by the non-stationary collimator-detector response and the single-photon emitting nature of SPECT, it is difficult to quantify the 3D radiopharmaceutical distribution within the patient quantitatively. This dissertation's primary incentive is to design and develop a complete computational framework for the newly proposed L-SPECT scan procedure from the image acquisition to the image reconstruction. Using this framework, I solve several challenging problems related to implementing a dedicated novel 3D L-SPECT image reconstruction algorithm. In particular, a volumetric reconstruction algorithm for L-SPECT system is developed by considering the system configurations. Also, an in-depth analysis of the SPECT imaging system based on the light field concept using the micro pinhole range collimator is presented in this thesis. Moreover, I evaluate the performance of the developed reconstruction algorithms under various imaging circumstances in terms of image quality, computational complexity, and resolution. A Monte Carlo simulation environment for L-SPECT was developed by modelling the properties of the SPECT imaging setup. By examining the existing limitations in the proposed L-SPECT, an improved collimator-detector geometry for the micro-pinhole arrays was introduced in this thesis as one of the main contributions. The modular L-SPECT with the detector heads in a partial ring geometry achieved higher sensitivity and resolution than the planer L-SPECT. The modular L-SPECT was further improved by shifting the centre of the scanning detectors to eliminate the artifacts in the reconstructed images. A dedicated reconstruction algorithm for the modular L-SPECT was developed as proof of concept. In SPECT reconstruction, identification of uncertainty information would help to enhance and mitigate the limitations of the existing reconstruction algorithms. The critical contribution of this thesis is manifested in the development of an image reconstruction algorithm based on Bayesian probabilistic programming for SPECT and L-SPECT. A NUTS based MCMC algorithm is used for probabilistic programming-based reconstruction. The uncertainty associated with the radiation measurement is identified as a distribution from the posterior samples generated using the MCMC algorithm. The performance of the NUTS algorithm improved by using reverse-mode automatic differentiation and distributed programming. The automatic differentiation variational inference-based SPECT reconstruction algorithm is developed to reduce the computational cost in NUTS based reconstruction and uncertainty analysis. Further in this thesis, the L-SPECT simulations are calibrated by comparing with GATE simulations, which are the gold standard in this field. The projection results of MATLAB based simulations are comparable with GATE simulations. The system performance for the proposed different configurations was investigated and contrasted against the existing SPECT modalities and systems, such as LEHR and Inveon SPECT, respectively. The performance analysis of the L-SPECT revealed the system is able to achieve improved sensitivity and better field of view compared to the existing systems. The essential characteristics of this L-SPECT system based on the reconstructed images were assessed with pinhole radii of 0.1 mm and 0.05 mm. In addition, the system sensitivity, spatial resolution, and image quality are appraised from the 3D reconstructed images. The maximum achieved system’s sensitivity was 1000 Cps/Bbq using arrays with a pinhole radius of 0.1 mm at 1 mm pitch, while the highest resolution was obtained using arrays with 0.05 mm pinhole and 3 mm pitch. The designed L-SPECT with different configurations and the developed 3D reconstruction algorithms yielded superior image quality compared with LEHR reconstructions

Radiopharmaceutical dosimetry in targeted radionuclide therapy

La médecine nucléaire est une spécialité médicale dont l'une des applications est l'étude de la physiologie des organes et du métabolisme de divers types de tumeurs. Les produits pharmaceutiques liés à un isotope radioactif (médicament radio-pharmaceutique, MRP) sont étudiés en préclinique avant d'être utilisés chez l'homme. Les rongeurs sont généralement utilisés pour étudier la bio-cinétique du traceur dans un groupe d'organes prédéfinis. L'extrapolation des résultats de ces études de l'animal à l'homme permet d'avoir une estimation du comportement des MRP et de l'irradiation délivrée en clinique. Trois nouveaux MRP ont été mis au point, l'un en France (CHU-Hôpital Purpan) et deux en Uruguay (CUDIM). Deux visent à étudier le cerveau et un vise à diagnostiquer le cancer de la prostate. Dans ce travail, l'extrapolation des résultats précliniques est présentée, les doses absorbées et efficaces sont estimées en utilisant les logiciels OLINDA/EXM V1.0, V2.0 et IDAC2.1. Les différences entre les résultats de chaque programme sont discutées. Au niveau clinique, les protocoles dosimétriques incluent la détermination du facteur d'étalonnage, la segmentation, le recalage, l'ajustement des courbes et le calcul de la dose absorbée. Dans ce travail, l'étalonnage développé pour un SPECT/CT est présenté en utilisant différentes sources d'étalonnage et différentes géométries. L'influence de la méthode de reconstruction sur la détermination du facteur d'étalonnage et les courbes du facteur de récupération sont présentées. Par ailleurs, quatre logiciels commerciaux sont comparés sur la base des informations cliniques de deux patients atteints de tumeurs gastro-entéro- pancréatiques d'origine neuroendocrine et traitées au 177Lu-DOTATATE. Deux cycles de traitement pour chaque patient ont été utilisés afin d'estimer les temps de résidence des reins, du foie, de la rate, de la moelle osseuse et du corps entier. Le calcul des doses absorbées a été initialement réalisé à l'aide de OLINDA/EXM V1.0 & V2.0, en ajustant la masse de chaque organe/tissu. Dans le cas de la moelle osseuse, une nouvelle méthodologie est présentée pour estimer la dose absorbée sans qu'il soit nécessaire de procéder à des mesures de corps entier. Il est possible de constater que le recalage des images a un impact sur la détermination de la dose absorbée. Les résultats sont donc calculés en employant d'un outil permettant de recaler indépendamment chaque organe et non pas toute l'image du champ de vue. Différents algorithmes de calcul ont été utilisés pour déterminer la dose absorbée délivrée aux patients, par exemple le modèle de sphère d'OLINDA/EXM V2.0, les méthodes de convolution et le dépôt d'énergie local de PLANET®Onco Dose de Dosisoft. Les résultats trouvés avec les différents outils sont comparés et discutés.Nuclear medicine is a medical specialty in which one of whose applications is the study of the physiology of organs and the metabolism of various types of tumours. Pharmaceuticals labelled with radionuclides (radiopharmaceuticals) are studied at pre-clinical level before being used in humans. Rodents are generally used to study the biokinetics of tracer in a group of predefined organs. The extrapolation of the results of these studies from animals to humans provides an estimate of the behaviour of the radiopharmaceuticals and the irradiation delivered clinically. Three new radiopharmaceuticals were developed, one in France (CHU-Hôpital Purpan) and two in Uruguay (CUDIM). Two aim to study the brain and one aims to diagnose prostate cancer. In this work, extrapolation of pharmacokinetics preclinical results to the human is presented; absorbed and effective doses are estimated using OLINDA/EXM V1.0, V2.0 and IDAC2.1 software. The differences between the results of each program are discussed. At a clinical level, dosimetric protocols include calibration factor determination, segmentation, registration, curve fitting, and calculation of absorbed dose. In this work, the calibration developed for a SPECT/CT is presented using different calibration sources and different geometries. The influence of the reconstruction method in the determination of the calibration factor and the recovery coefficient curves are shown. In addition, four commercial software are compared based-on clinical information of two patients with gastro-entero-pancreatic tumours of neuroendocrine origin treated with 177Lu-DOTATATE. Two cycles of treatment for each patient were used to estimate residence times for the kidneys, liver, spleen, bone marrow and whole body. Calculation of absorbed dose was initially developed using OLINDA/EXM V1.0 & V2.0, adjusting the mass of each organ/tissue. In the case of the bone marrow, a novel methodology is presented to estimate the absorbed dose without the need for whole-body measurements. It can be seen that the registration of the images has an impact on the determination of the absorbed dose. The results are thus calculated by employing a tool allowing to register independently each organ and not all the image of the field of view. Different calculation algorithms were used to determine the absorbed dose delivered to patients, for example the OLINDA/EXM V2.0 sphere model, convolution and local energy deposition methods of PLANET®Onco Dose from Dosisoft. The results found with the different tools are compared and discussed

Human brain networks: consensus, reproducibility, inter-modal comparison and epilepsy pathology

Classical and contemporary research in neuroscience postulates that connectivity is a fundamental component of human brain function. Recently, advances in computational neuroimaging have enabled reconstruction of macroscopic human brain structural connectivity in vivo using diffusion MRI. Studies show that the structural network topology may discriminate between neurological phenotypes or relate to individual brain function. To investigate disease effectively, it is necessary to determine the network methodological and biological variability. Reproducibility was calculated for two state-of-the-art reconstruction pipelines in healthy subjects. High reproducibility of connection weights was observed, which increased with connection strength. A high agreement between pipelines was found across network density thresholds. In addition, a robust core network was identified coinciding with a peak in similarity across thresholds, and replicated with alternative atlases. This study demonstrates the utility of applying multiple structural network pipelines to diffusion data in order to identify the most important connections. Focal epilepsy is characterised by seizures that can spread to contiguous and non-contiguous sites. Diffusion MRI and cortico-cortical evoked potentials were acquired in focal epilepsy patients to reconstruct and correlate their structural and effective brain networks and examine connectivity of the ictal-onset zone and propagative regions. Automated methods are described to reconstruct comparable largescale structural and effective networks. A high overlap and low correlation was observed between network modalities. Low correlation may be due to imperfections in methodology, such as difficulty tracing U-fibers using tractography. Effective connectivity amplitude, baseline fluctuation, and outward connectivity tended to be higher at ictal-onset regions, while higher structural connectivity between ictal-onset regions was observed. Furthermore, a high prevalence of structural and effective connections to sites of non-contiguous seizure spread was found. These results support the concept of highly excitable cortex underlying ictal-onset regions which promotes non-contiguous seizure spread via high outward connectivity

The Use of Intracoronary Optical Coherence Tomography in Interventional Cardiology: Safety, Feasibility and Clinical Applications

Interventional cardiology has witnessed tremendous change since 1977 when Andreas Gruentzig successfully performed the first balloon angioplasty. Whereas initial concerns revolved around maintaining vessel patency with issues of recoil and restenosis, the introduction of stents changed the landscape forever. Inherent with their use, stents, and, more specifically, drugeluting stents (DES), have become central to improved patient outcomes but, at some cost. Catastrophic, yet fortunately still rare complications such as stent thrombosis have re-ignited an intense need for greater scrutiny when developing and, subsequently implanting DES into our patients. The demand for detailed information regarding coronary artery disease has seen intravascular imaging become pivotal at delineating atherosclerosis and tissue responses following stent implantation. In fact, the strategy that relied on angiography alone is evolving to include better confirmation of disease severity and stenting technique. With this, optical coherence tomography (OCT) has grown exponentially with a broad diffusion amongst catheterisation laboratories worldwide. Optical coherence tomography is a procedurally demanding technique. Individual experience is often frustrated initially with disappointing images as a result of inadequate blood clearance. With perseverance and adequate proctorship however, one cannot help but be impressed by the clarity and resolution afforded by this imaging modality. It is these images that have attracted considerable attention at cardiology conferences internationally and have helped instil OCT as the most sensitive intravascular imaging technique available today. The aim of this thesis was to evaluate the role of OCT in contemporary coronary intervention. Part 1 embraces the principles of the technique and the physical properties of OCT (chapter 2) and gives an insight into where OCT is placed compared to other intravascular imaging modalities (chapter 3). Despite the adoption of OCT in more and more catheterisation laboratories, little has been documented as to its safety, so, in chapter 4, we review the procedural safety of intracoronary OCT in a large group of patients across six leading European centres

The occurrence and origin of salinity in non-coastal groundwater in the Waikato region

Aims The aims of this project are to describe the occurrence, and determine the origin of non-coastal saline groundwater in the Waikato region. High salinity limits the use of the water for supply and agricultural use. Understanding the origin and distribution of non-coastal salinity will assist with development and management of groundwater resources in the Waikato. Method The occurrence of non-coastal groundwater salinity was investigated by examining driller’s records and regional council groundwater quality information. Selected wells were sampled for water quality analyses and temperatures were profiled where possible. Water quality analyses include halogens such as chloride, fluoride, iodide and bromide. Ratios of these ions are useful to differentiate between geothermal and seawater origins of salinity (Hem, 1992). Other ionic ratio approaches for differentiating sources and influences on salinity such as those developed by Alcala and Emilio (2008) and Sanchez-Martos et al., (2002), may also be applied. Potential sources of salinity include seawater, connate water, geothermal and anthropogenic influences. The hydrogeologic settings of saline occurrence were also investigated, to explore the potential to predict further occurrence. Results Numerous occurrences of non-coastal saline groundwater have been observed in the Waikato region. Where possible, wells with relatively high total dissolved solids (TDS) were selected for further investigation. Several groundwater samples are moderately saline and exceed the TDS drinking water aesthetic guideline of 1,000 g m-3 (Ministry of Health, 2008). Selected ion ratios (predominantly halogens) were used to assist in differentiating between influences on salinity such as seawater and geothermal. Bromide to iodide ratios, in particular, infer a greater geothermal influence on salinity, although other ratios are not definitive. The anomalously elevated salinity observed appears natural but nevertheless has constrained localised groundwater resource development for dairy factory, industrial and prison water supply use. Further work may show some relationship with geology or tectonics, which could assist prediction of inland saline groundwater occurrence

Using a water treatment residual and compost co-amendment as a sustainable soil improvement technology to enhance flood holding capacity

The recycling of clean wastes, such as those from the treatment of drinking water, has gained importance on the environmental agenda due to rising costs of landfill disposal and movement towards a ‘zero’ waste economy. More than one third of the globe’s soils are degraded and as such policies towards determining soil health parameters and reversing destruction of the globe’s most valuable non-renewable source are at the forefront of environmental debate. This thesis questions the opportunity for water treatment residual (WTR) to be used as a beneficial material for the co-amendment of soil with compost to improve the soil’s flood holding capacity (Kerr et al., 2016), which includes functions such as the water holding capacity, hydraulic conductivity, soil structure and shear strength. Currently, water treatment residual is typically sent to landfill for disposal, but this research shows that the reuse of WTR as a co-amendment is able to improve the flood holding capacity of soils. This research crosses the boundary between geotechnical and geoenvironmental and provides a holistic approach to quantifying a soil from both perspectives. Iron based water treatment residual from Northumbrian Water Ltd was used in both laboratory and field trials to establish the effect of single WTR and a compost and WTR co-amendment on the water holding capacity (the gravimetric water content, volumetric water content, volume change of samples i.e. swelling and shrinkage), and the effect of amendment on the erosional resistance, hydraulic conductivity and shear strength compared to a control soil. A series of four trials were conducted to develop and establish a novel method to determine the water holding capacity, supplemented by standard geotechnical methods to determine the flood holding capacity. The use of x-ray computed tomography has provided accompanying information on the morphology of dried WTR and changes in the internal characteristics of amended soil between a dry and wet state. The amendment application rate ranges from 10 – 50%. Experiments have shown that the single amendment of WTR, compared to a control soil, yields significant increases in the hydraulic conductivity (by up to a factor of 28), increases the shear strength of soils at low testing pressure (25 kPa) by 129%, increases the maximum gravimetric water content by up to 13.7%, and improves swelling by up to 12% (but only at the highest amendment rate, 30%), increases the maximum void ratio when saturated by 11%, and reduces shrinkage by maintaining porosity by 14%. However the application of WTR as a single amendment has implications for the chemical health of the soil as it is highly effective at immobilising phosphorous as and such cannot not effectively be used as a soil amendment. The single application of compost yielded significant improvement in the water holding capacity (improving gravimetric water content by up to 34.7%, increasing the sample volume by up to 83.3%, and increased the void ratio by 8.2%), however this application reduces the hydraulic conductivity by up to 84.5% and the shear strength by 3% compared to the control soil. Co-amendment using compost and WTR (in two forms, air dried 80% solids and wet at 20% solids, as produced from water treatment works) improved the flood holding capacity of soils by retaining the structural improvements of amendment using WTR and the water holding capacity improvements of compost. Compared to the control soil, for co-amended soils the gravimetric water content was improved by up to 25%, the volume increased by up to 51.7%, experienced 13% less shrinkage and an 11.5% increase in maximum void ratio. The hydraulic conductivity was also improved by up to 475%, and shear strength was increased at both low and high testing pressures by to 53.8%. Taking into account these effects of co-amendment on essential soil functions that determines a soil’s flood holding capacity (maximum gravimetric water content, volume change, resistance against shrinkage, void ratio (porosity), hydraulic conductivity and shear strength), the economical and environmental sustainability issues, the co-amendment of soil using compost and WTR may provide a solution to both recycling clean waste product and improving the quality of soil