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Yucatan minipigs have become increasingly common animal models in neuroscience where recent studies, investigating blast-induced traumatic brain injury, stroke, and glioblastoma, aim to uncover brain injury mechanisms [1-3]. Magnetic Resonance Imaging (MRI) has the potential to validate and optimize unknown parameters in controlled populations. The key to group-level MRI analysis within a species is to align (or register) subject scans to the same volumetric space using a brain template. However, large animal brain templates are lacking, which limits the use of MRI as an effective research tool to study group effects. The objective of this study was to create an MRI-based Yucatan minipig brain template allowing for uniform group-level analysis of this animal model in a standard volumetric space to characterize brain mechanisms. To do this, 5-7 month old, male Yucatan minipigs were scanned using a 3 Tesla whole-body scanner (Siemens AG, Erlangen) in accordance with IACUC. T1-weighted anatomical volumes (resolution = 1×1×1 mm3; TR = 2300 ms; TE= 2.89 ms; TI = 900 ms; FOV = 256 mm2 ; FA = 8 deg) were collected with a three-dimensional magnetization prepared rapid acquisition gradient echo (MPRAGE) pulse sequence [4]. The volumes were preprocessed, co-registered, and averaged using both linear and non-linear registration algorithms in AFNI [5] to create four templates (n=58): linear brain, non-linear brain, linear head, and non-linear head. To validate the templates, tissue probability maps (TPMs) and variance maps were created, and landmark variation was measured. TPMs computed in FSL [6] and AFNI show enhanced tissue probability and contrast in the non-linear template. Additionally, variance maps showed a more uniform spatial variance in the non-linear template compared to the linear. Registration variation within the brain template was within 1.5 mm and displayed improved landmark variation in the non-linear brain template. External evaluation subjects (n=12), not included in the template, were registered to the four templates to assess functionality. The results indicate that the developed templates provide acceptable registration accuracy to enable population comparisons. With these templates, researchers will be able to use MRI as a tool to further neurological discovery and collaborate in a uniform space. / M.S. / Magnetic resonance imaging (MRI) is commonly used in neuroscience as a non-invasive diagnostic tool with the potential to reveal unknown brain injury mechanisms. MRI is particularly useful in large animal models to validate and optimize unknown parameters in controlled populations. The key to group-level MRI analysis within a species is to align (or register) subject scans to the same volumetric space using a brain template. However, large animal brain templates are lacking, which limits the use of MRI as an effective research tool to study group effects. The objective of this study was to create an MRI-based Yucatan minipig brain template allowing for uniform group-level analysis of this animal model in a standard volumetric space to better characterize brain mechanisms. The neuroanatomy of the Yucatan minipig, which is characterized by an increased brain size and gyrencephalic intricacies similar to humans, has made it an increasingly common animal model in neuroscience. Linear and non-linear registration methods were performed in Analysis of Functional NeuroImages (AFNI) software to create both brain and head templates for 5-7 month old, male Yucatan minipigs (n=58). This study was validated looking at template variance, tissue probability maps (TPMs) of segmented grey matter, white matter, and cerebrospinal fluid, and landmark variation. The results indicate that the developed templates provide acceptable registration accuracy to enable population comparisons. With these templates, researchers will be able to use MRI as a tool to further neurological discovery and collaborate in a uniform space.

INTRODUCTION: Despite the use of modern minimally invasive surgical techniques, post-operative complications following lung cancer resection remain common and challenging to predict. Pulmonary ventilation imaging modalities offer detailed regional assessment of airflow obstruction and are highly sensitive to subclinical airway and/or parenchymal disease. Nevertheless, ventilation imaging is seldom integrated into pre-operative lung function assessment and risk stratification procedures. Therefore, the objective of this thesis was to quantify the burden of ventilation defects observed by Technegas SPECT and 129Xe MRI before lung cancer resection and establish their association with the occurrence and clinical impact of post-operative complications. METHODS: Patients undergoing lung cancer resection at St. Joseph’s Healthcare Hamilton were recruited into a prospective, proof-of-concept, six-week observational study. Participants were evaluated prior to resection surgery to document baseline demographics and clinical characteristics, performed standard pulmonary function tests and sputum induction, and underwent Technegas SPECT and 129Xe MRI to assess ventilation. Abnormal ventilation was quantified as the ventilation defect percent (VDP) and was considered abnormal if VDP was ≥mean+2 standard deviations of a healthy population. Following surgery, participants were followed for 4 weeks to document the incidence of post-operative complications, as specified by the Ottawa TM&M categorization system, and the length of hospital stay. RESULTS: One hundred and twenty-three participants were enrolled, of whom 103 were evaluated pre-operatively and followed for post-operative outcomes. Of the 103 participants (69±8 years, 58% female), 89% (92/103) underwent minimally invasive surgery, and 74% (76/103) underwent lobectomy. Abnormal ventilation was observed pre-operatively by Technegas SPECT and 129Xe MRI for 59% (58/99) and 84% (82/98) of participants, respectively. In a subset of 69 participants in whom sputum was collected, 51% (35/69) had intraluminal inflammation. A total of 64 post-operative complications occurred; 16 (25%) were pulmonary, and 48 (75%) were pleural complications. A post-operative complication occurred in 42% (41/103) of participants. Pre-operative Technegas SPECT and 129Xe MRI VDP were higher for participants with post-operative complications compared to those without (Technegas SPECT: 26±17% vs 19±7%, p=0.02; 129Xe MRI: 13±12% vs 7±6% p=0.003) and were positively correlated with post-operative length of hospital stay (Technegas SPECT: r=0.43, p<0.0001; 129Xe MRI: r=0.49, p<0.0001). Multivariable regression models revealed that preoperative Technegas SPECT and 129Xe MRI VDP were predictors of post-operative complications (Technegas SPECT: Odds ratio=1.08, p=0.005; 129Xe MRI: Odds ratio=1.16, p=0.002) and post-operative length of hospital stay (Technegas SPECT: unstandardized β=0.13, p<0.001; 129Xe MRI: unstandardized β=0.24, p<0.001). CONCLUSIONS: Abnormal ventilation, quantified by Technegas SPECT and 129Xe MRI VDP, is prevalent prior to lung cancer resection and a predictor of post-operative complications and length of hospital stay. / Thesis / Master of Science (MSc) / Post-operative complications are frequent adverse events following lung cancer resection, resulting in substantial patient morbidity and mortality that have a significant clinical and economic impact. Despite this, post-operative complications remain inadequately predicted, and limited research has been dedicated to reducing the risk of pulmonary complications after lung cancer resection. Standard clinical screening tools, such as pulmonary function tests, are used for patient selection in lung cancer resection surgery; however, they provide a global estimate of a complex multicompartment organ and may lack the sensitivity to detect subclinical lung pathology that influences post-operative outcomes. Thus, using high-resolution medical imaging modalities such as single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI), we investigated the prevalence and clinical relevance of abnormal ventilation, a functional consequence of airway and/or parenchymal disease. One hundred and three participants were enrolled in a six-week prospective, proof-of-concept observational study. Participants performed pre-operative imaging and were followed for four weeks post-operatively to document post-operative complications and relevant clinical outcomes. Pre-operative SPECT and MRI revealed a high prevalence of abnormal ventilation. The pre-operative ventilation defect burden was greater in participants who developed one or more complications during the four-week post-operative period and was an independent predictor of both the incidence of post-operative complications and the length of hospital stay. These observations provide proof-of-concept evidence that abnormal ventilation, assessed by two ventilation imaging modalities, is prevalent and clinically relevant prior to lung cancer resection. Taken together, this thesis establishes that ventilation imaging may have implications for risk stratification and risk modification in patients scheduled to undergo lung cancer resection.

Yes / To assess whether magnetic resonance imaging (MRI)-based measurements of T2, fat fraction, diffusion tensor imaging, and muscle volume can detect differences between the muscles of myositis patients and healthy controls, and to identify how they compare with semi-quantitative MRI diagnosis. Sixteen myositis patients and 16 age- and gender-matched healthy controls underwent MRI of their thigh. Quantitative MRI measurements and radiologists' semi-quantitative scores were assessed. Strength was assessed using an isokinetic dynamometer. Fat fraction and T2 values were higher in myositis patients whereas muscle volume was lower compared to healthy controls. There was no difference in diffusion. Muscle strength was lower in myositis patients compared to healthy controls. In a subgroup of eight patients, scored as unaffected by radiologists, T2 values were still significantly higher in myositis patients. Quantitative MRI measurements can detect differences between myositis patients and healthy controls. Changes in the muscles of myositis patients, undetected by visual, semi-quantitative scoring, can be detected using quantitative T2 measurements. This suggests that MRI T2 values may be useful for the management of myositis patients. / National Institute for Health Research (NIHR) Leeds (BRC) and Health Education England

The locus coeruleus (LC) is a nucleus within the brainstem associated with physiological arousal and attention performance, with altered structure and function previously identified in neurodegenerative disorders. Pathologies related to difficulties with attention have previously been understood within a cortical triple network model, abnormalities in which may be relate to dysfunction in either LC structure or function. To examine the possibility of LC alteration being associated with inattentive symptom report, a set of analyses have been performed. In the first analysis, LC neuromelanin contrast was regressed onto ADHD symptom report for 141 individuals across the lifespan, finding a significant negative relationship between neuromelanin in the right hemisphere of the LC and inattentive symptom report. A second analysis tested for possible mediation of the neuromelanin contrasts with structural volumes of regions associated with the salience network, which has also been previously associated with attention deficits and ADHD symptoms. These findings support the relationship between LC and attention-related behavior through both neuromelanin-sensitive and structural imaging, and observes multiple significant structural associations for cortical regions previously associated to inattention functionally. / Master of Science / Within the brainstem is a collection of neurons called the Locus Coeruleus (LC), associated with the production of neurotransmitters associated with attention. In Magnetic Resonance Imaging (MRI) networks of brain regions associated with attention have been previously observed, with both differences in region connections and abnormalities in region composition being observed. Given the small size of the LC general volume measurement is considered difficult, but use of multi-atlas techniques and neuromelanin contrasts allow for methods of LC structure and integrity to be compared. The present study attempts to integrate the LC into this larger concept of attention processing, called the triple network model, by testing associations between structural measures of the LC, regions associated with the three triple network model networks, and attention report in 140 participants. LC contrasts were found to be significantly associated with inattention, as were structural values for the regions connected to the previously identified networks. Mediation of neuromelanin by these regions failed to produce significant results, but neuromelanin was mediated by the volume of the LC itself. The findings here support continued use of these structural techniques with regard to the LC and other applicable neural structures, as well as further work to define the relationship between the LC and the triple network model.

Este trabalho consistiu na implementação de um método de homogeneização de campo, denominado shimming passivo. Esse método é caracterizado pela inserção de pequenas peças ferromagnéticas no interior do magneto; a interação destas peças com o campo magnético principal produz campos locais capazes de corrigir inomogeneidades indesejadas, quando várias peças são estrategicamente combinadas. Embora esse método já tenha sido bem discutido, implementado e publicado por D.I.Hoult na década de 80, ele ainda não havia sido desenvolvido para um magneto resistivo com núcleo de ferro e peças polares, como é o caso do Artro-ToRM. Nosso objetivo era, através do Artro-ToRM, encontrar uma metodologia de modelagem e correção de campo que fosse útil para magnetos com a mesma geometria. Foram utilizados métodos computacionais de ajuste numérico que, a partir de mapas originais de campo, foram capazes de encontrar configurações de peças magnéticas que pudessem reduzir as inomogeneidades presentes. Um dos maiores desafios do trabalho, foi encontrarmos elementos passivos com comportamento previsível quando submetidos ao campo magnético principal, já que os programas de otimização presupunham que trabalhávamos com dipolos magnéticos, para efeitos de simplificação. Finalmente, considerando uma região cilíndrica com raio de 5 cm e comprimento de 10 cm, mostramos uma melhora de 390 ppm para 250 ppm na homogeneidade, após a correção passiva. / This work presents the implementation of a method for field correction, called passive shimming. The method is characterized by the insertion of small iron pieces in magnet bore; the interaction of these pieces with the main magnetic field produces local fields capable of correcting undesired inhomogenity, when some parts are strategically combined. Although this method has been already proposed by D.I.Hoult in the eighties, it still has not been developed for resistive magnets with polar pieces, such as the Artro-ToRM. Our objective were to find a method for field modeling and correction that could be useful for magnets with similar geometry. Computational methods of numerical adjustment were used from the original field maps, it was possible to find the optimal the configurations of magnetic parts for reducing the field inhomogenity. One of the biggest challenges of the work, was to find passive elements with previsible behavior when submitted to magnetic field main, since the optimization programs preassumed that we worked with magnetic dipoles, for the purpose of simplification. Finally, considering a cilindrical region, we show an improvement of 390 ppm to 250 ppm in the homogenity, after the passive correction.

Osteoarthritis (OA) currently affects 41 million Americans, and knee OA (KOA) alone causes the highest risk of mobility disability of any medical condition in people 65 years and older. There are no current treatments to reverse the degenerative changes of KOA, and research is aimed at finding biomarkers of KOA progression to aid in the development of effective therapies. Osteophytes are a hallmark feature of KOA and may act as a biomarker of joint space loss and pain progression. MR imaging, which is an accurate and non-invasive method to monitor KOA disease status, may aid in clarifying the role of osteophytes in KOA, especially using semi-automated quantitative software methods to accurately and efficiently calculate osteophyte volume in longitudinal studies. This study investigated the association of osteophyte volume change with joint space narrowing and pain progression in a randomized sample of 505 subjects from the FNIH OA Biomarker Consortium Project, a case-control study based on a larger longitudinal study of patients with KOA. We also aimed to further validate a software method that measured osteophyte volume in MRI. We found a moderate and significant association with osteophyte volume and joint space narrowing, but no significant association with pain progression. The software was further validated as responsive and efficient method to measure KOA osteophyte volume change.

The percutaneous revascularization of chronic total occlusions represents a major challenge to interventional cardiologists. Procedural success is currently limited by the inadequate soft-tissue contrast of x-ray fluoroscopy and the inability to visualize the position and orientation of a revascularization device with respect to the lesion and the vessel wall. In this thesis methods are developed that enable the percutaneous revascularization of occlusive lesions to be guided using magnetic resonance (MR) imaging. Unlike x-rays, MR has excellent soft-tissue contrast and this can be exploited to provide valuable information regarding the composition and geometry of the lesion. The first method is a robust and redundant technique for determining the position and orientation of a catheter inside an MR scanner. The technique uses phase information introduced into the MR signal by a small receive coil located at the distal tip of the catheter. The technique is developed theoretically and is demonstrated with a feasibility experiment. A forward-looking intravascular imaging catheter is then presented that is capable of acquiring of high-resolution MR images of occlusive lesions and the vessel wall in front of the catheter. The imaging catheter consists of two orthogonal receive coils located at the distal tip of the catheter. The use of the imaging catheter is demonstrated in phantoms and in vivo. A third method enables active visualization of MR compatible guidewires. The method utilizes a catheter-based pick-up coil that is magnetically coupled to the guidewire. The proposed technique enables one to concentrate all active components on a catheter thereby facilitating the use of safety features. Complete characterization is presented theoretically and validated experimentally. In addition, the use of a practical catheter device is demonstrated in an in situ environment. Finally, future work required for the development of an integrated catheter-based device for the MR-guided revascularization of chronic total occlusions is discussed.

The percutaneous revascularization of chronic total occlusions represents a major challenge to interventional cardiologists. Procedural success is currently limited by the inadequate soft-tissue contrast of x-ray fluoroscopy and the inability to visualize the position and orientation of a revascularization device with respect to the lesion and the vessel wall. In this thesis methods are developed that enable the percutaneous revascularization of occlusive lesions to be guided using magnetic resonance (MR) imaging. Unlike x-rays, MR has excellent soft-tissue contrast and this can be exploited to provide valuable information regarding the composition and geometry of the lesion. The first method is a robust and redundant technique for determining the position and orientation of a catheter inside an MR scanner. The technique uses phase information introduced into the MR signal by a small receive coil located at the distal tip of the catheter. The technique is developed theoretically and is demonstrated with a feasibility experiment. A forward-looking intravascular imaging catheter is then presented that is capable of acquiring of high-resolution MR images of occlusive lesions and the vessel wall in front of the catheter. The imaging catheter consists of two orthogonal receive coils located at the distal tip of the catheter. The use of the imaging catheter is demonstrated in phantoms and in vivo. A third method enables active visualization of MR compatible guidewires. The method utilizes a catheter-based pick-up coil that is magnetically coupled to the guidewire. The proposed technique enables one to concentrate all active components on a catheter thereby facilitating the use of safety features. Complete characterization is presented theoretically and validated experimentally. In addition, the use of a practical catheter device is demonstrated in an in situ environment. Finally, future work required for the development of an integrated catheter-based device for the MR-guided revascularization of chronic total occlusions is discussed.