Time-resolved velocity information of carotid blood flow can be used to estimate haemodynamic conditions associated with carotid artery disease leading to stroke. MRI provides high-resolution measurement of such information but long scan time limits its clinical application in this area. In order to reduce scan time the MRI signal is often undersampled by skipping part of the signal during data acquisition. The aim of this work is to implement and evaluate different undersampling techniques for carotid velocity measurement on a 1.5 T clinical scanner. Most recent undersampling techniques assume spatial and temporal redundancies of real time-resolved MRI signal. In these techniques different undersampling strategies were proposed. Prior information or different assumptions of the nature of true signal were used in signal reconstruction. A brief review of these techniques and details of a representative technique, known as k-t BLAST, are presented. Another undersampling scheme, termed ktVD, is proposed to use predesigned undersampling patterns with variable sampling densities in both temporal and spatial dimensions. It aims to collect enough signal content at the signal acquisition stage and simplify signal reconstruction. Fidelity of the results from undersampled data is affected by many factors, such as signal dynamic content, degree of signal redundancy, noise level, degree of undersampling, undersampling patterns, and parameters of post-processing algorithms. Simulations and in vivo scans were conducted to investigate the effects of these factors in time-resolved 2D scans and time-resolved 3D scans. The results suggested velocity measurement became less reliable when they were obtained from less than 25% of the full signal. In time-resolved 3D scans the signal can be undersampled in either one or two spatial dimensions in addition to the temporal dimension. This allows more options in the design of undersampling patterns, which were tested in vivo. In order to test undersampling in three dimensions in high resolution 3D scans and measure velocity in three dimensions, a flow phantom was also scanned at high degrees of undersampling to test the proposed method.

The hippocampus is a complex brain structure that has been studied extensively and is subject to abnormal structural change in various neuropsychiatric disorders. The highest definition in vivo method of visualizing the anatomy of this structure is structural Magnetic Resonance Imaging (MRI). Gross structure can be assessed by the naked eye inspection of MRI scans but measurement is required to compare scans from individuals within normal ranges, and to assess change over time in individuals. The gold standard of such measurement is manual tracing of the boundaries of the hippocampus on scans. This is known as a Region Of Interest (ROI) approach. ROI is laborious and there are difficulties with test-retest and inter-rater reliability. These difficulties are primarily due to uncertainty in designation of the hippocampus boundary. An improved, less labour intensive and more reliable method is clearly desirable. This thesis describes a fully automated hybrid methodology that is able to first locate and then extract hippocampal volumes from 3D 1.5T MRI T1 brain scans automatically. The hybrid algorithm uses brain atlas mappings and fuzzy inference to locate hippocampal areas and create initial hippocampal boundaries. This initial location is used to seed a deformable manifold algorithm. Rule based deformations are then applied to refine the estimate of the hippocampus locations. Finally, the hippocampus boundaries are corrected through an inference process that assures adherence to an expected hippocampus volume. The ICC values of this methodology when compared to the manual segmentation of the same hippocampi result in a 0.73 for the left and 0.81 for the right hippocampi. These values both fall within the range of reliability testing according to the manual ‘gold standard’ technique. Thus, this thesis describes the development and validation of a genuinely automated approach to hippocampal volume extraction of potential utility in studies of a range of neuropsychiatric disorders and could eventually find clinical applications.

An essential component of developing successful neural stem cell (NSC)-based therapies involves the establishment of methodologies to noninvasively monitor grafted NSCs within brain tissues in real time. In this context, ex vivo labeling with ultrasmall superparamagnetic iron oxide (USPIO) particles has been shown to enable efficient tracking of transplanted NSCs via magnetic resonance imaging (MRI). However, whether and how USPIO labeling affects the intrinsic biology of NSCs is not thoroughly understood, and remains an active area of investigation. Here, we perform a comprehensive examination of rat NSC survival and regenerative function upon labeling with the USPIO, Molday ION Rhodamine B (MIRB), which allows for dual magnetic resonance and optical imaging. After optimization of labeling efficiency, two specific doses of MIRB (20 and 50 mu g/mL) were chosen and were followed for the rest of the study. We observed that both MIRB doses supported the robust detection of NSCs, over an extended period of time in vitro and in vivo after transplantation into the striata of host rats, using MRI and post hoc fluorescence imaging. Both in culture and after neural transplantation, the higher 50 mu g/mL MIRB dose significantly reduced the survival, proliferation, and differentiation rate of the NSCs. Interestingly, although the lower 20 mu g/mL MIRB labeling did not produce overtly negative effects, it increased the proliferation and glial differentiation of the NSCs. Additionally, application of this dose also changed the morphological characteristics of neurons and glia produced after NSC differentiation. Importantly, the transplantation of NSCs labeled with either of the two MIRB doses upregulated the immune response in recipient animals. In particular, in animals receiving the 50 mu g/mL MIRB-labeled NSCs, this immune response consisted of an increased number of CD68(+)-activated microglia, which appeared to have phagocytosed MIRB particles and cells contributing to an exaggerated MRI signal dropout in the animals. Overall, these results indicate that although USPIO particles, such as MIRB, may have advantageous labeling and magnetic resonance-sensitive features for NSC tracking, a further examination of their effects might be necessary before they can be used in clinical scenarios of cell-based transplantation.

Tumor metabolism is a highly dysregulated process that is identified as a unique target for therapy. Current philosophy proposes that tumor metabolism is a plastic and flexible process which sustains proliferative and survival advantages. Tumors employ an anaerobic glycolytic pathway resulting in the overproduction of lactate. Additional thinking suggests that the conversion of pyruvate to lactate regenerates the NAD+ pool in the cell, maintaining a sustainable oxidative environment. Regardless of the reasons for lactate overproduction, its excretion and build up in the microenvironment results in acidic tumor microenvironments. Tumor acidosis has been measured with several different methods, but consistently averages from pH 6.6 to 7.0. Tumor acidity can thus be measured as a biomarker for tumor metabolism. This work examines the commonly explored energy pathways available to the cancer cell and a non-invasive MRI method to measure the efficacy of the tumor metabolism targeting agent. Appendix A is an introduction to tumor metabolism pathways and the large list of candidate therapies in interfering with energy production. Glucose, fatty acid, and glutamine metabolisms are all discussed along with PI3K/AKT/mTOR and HIF growth signals and ion transport. Magnetic resonance imaging and positron emission tomography are examined as imaging methods for non-invasively interrogating tumor acidosis. Appendix B presents the findings in a study where tumor metabolism was targeted with an mTOR inhibitor, where tumor growth rate was initially decreased and accompanied by an early, acute increase in tumor extracellular pH with acidoCEST MRI. Chapter 2 discusses the combination of a lactate dehydrogenase inhibitor in conjunction with doxorubicin in a breast cancer model. Tumor extracellular pH was shown to increase when measured with acidoCEST MRI, and an increase in cell death was measured. Chapter 4 discusses the studies and experimental designs that can be done in the near future.

Analysis of phase-contrast MR images yields cardiac flow information which can be manipulated to produce accurate segmentations of the aorta. New phase contrast segmentation algorithms are proposed that use mean-based calculations and least mean squared curve fitting techniques. A GPU is used to accelerate these algorithms and it is shown that it is possible to achieve up to a 2760x speedup relative to the CPU computation times. Level sets are applied to a magnitude image, where initial conditions are given by the previous segmentation algorithms. A qualitative comparison of results shows that the algorithm parallelized on the GPU appears to produce the most accurate segmentation. After segmentation, particle trace simulations are run to visualize flow patterns in the aorta. A procedure for the definition of analysis planes is proposed from which virtual particles can be emitted/collected within the vessel, which is useful for future quantification of various flow parameters. / October 2014

Diffusion Tensor Magnetic Resonance Imaging (DTI) is a recently-developed technique that can image in vivo the white matter pathways of the central nervous system. This study used 12-direction diffusion-weighted MRI data from nine stroke patients acquired as part of a three-year stroke rehabilitation study coordinated by the Movement Neuroscience Laboratory at the University of Auckland. DTI was used to investigate corticospinal connectivity. From the FA maps, it is found that in those patients whose motor connectivity has been compromised by the stroke to the extent that no motor evoked potential (MEP) can be elicited from a selected affected muscle group, the asymmetry in mean FA values in the posterior limbs of the internal capsules (PLICs) is correlated with functional recovery as measured by the Fugl-Meyer clinical score. Using probabilistic tractography in the contralesional hemisphere produced CST location and somatotopy results that were consistent with those of previous studies. However, in the ipsilesional hemisphere, connectivity results were highly variable. A measure of change in symmetry of mean connectivity is found to correlate with functional recovery as measured by change in FM score. This supports previous work which has correlated CST integrity and functional improvement and it supports the theory that functional recovery after stroke depends on the extent to which motor CNS symmetry can be regained in the new post-stroke architecture. It also suggests that the movement of the fMRI activations occurs in such a way as to make the most of the preserved white matter connectivity.

Level of physical fitness may be an important factor influencing the effects of brain aging and age-related cognitive decline. Multiple measures of aerobic fitness were used in a cohort of healthy older adults 50-89 years of age to identify how individual differences in fitness relate to brain aging and age-associated cognitive decline. Healthy adults (n=123; 65 F and 58 M; mean ± sd age = 67.9 ± 10.0; Mini-Mental State Exam = 29.1 ± 1.2) were screened to exclude neurological, psychiatric, and medical illnesses that could affect cognitive function, including hypertension. The Scaled Subprofile Model (SSM) with voxel-based morphometry and Statistical Parametric Mapping version 8 (VBM; SPM8 Dartel) were performed on T1-weighted 3T volumetric magnetic resonance imaging (MRI) scans to identify a gray matter pattern associated with brain aging. Performance on aerobic fitness measures, assessed during a graded exercise treadmill test (GXT), was evaluated in relation to the age-associated MRI gray matter network pattern and indices of neuropsychological function. Multivariate SSM VBM network analysis identified a linear combination of patterns that predicted age (R² = 0.48, p = 8.71e-19). This combined pattern was characterized by reductions in bilateral lateral and medial frontal, parietal, lateral temporal, and cerebellar regions with relative preservations in thalamic, occipital, and medial temporal regions including the hippocampus. Higher expression of the age-related network pattern was associated with poorer performance on multiple fitness indices. The best combination of fitness measures in predicting brain aging included overall treadmill exercise time, ventilatory efficiency, and the difference between basal and maximal respiratory rate (p = 6.67e-7). A higher combined fitness index score related to brain aging was associated with better performance on measures of memory, executive function, and processing speed in this cohort (6.08e-9≤ p≤ 0.05). Those individuals with higher levels of aerobic fitness had lower expression of the gray matter brain aging pattern and better performance on measures of memory, executive function, and processing speed. Identifying those fitness indices that are the best predictors of brain aging and cognitive performance may aid efforts in developing and evaluating exercise based interventions for age-related cognitive decline.

MRI-guided percutaneous needle-based surgery has become part of routine clinical practice. There are millions of these procedures performed in Canada. The conventional MRI-guided needle intervention is usually performed with the primary goal of navigating a needle to a target while sparing healthy and/or critical structures. Potential limitations of conventional unassisted free-hand needle placement include the physician's ability to align and maintain the correct trajectory and angle toward a target, especially in case of deep targets. In contemporary practice, images are displayed on the operator's 2D console only outside the treatment room, where the physician plans the intervention. Then the physician enters the room, mentally registers the images with the anatomy of the actual patient, and uses hand-eye coordination to execute the planned intervention. Previous concept has been shown and preliminary results discussed from demonstrated MRI-guided needle intervention using an augmented reality 2D image overlay system in a closed configuration 1.5T MRI scanner. However, the limited availability of interventional MR imaging systems and the length of time of MR-guided interventions have been limiting factors in the past. This dissertation addresses topics related to evaluating and developing the 2D augmented reality system, the assistance device for MRI-guided needle interventions. This research effort has primarily focused on developing a new adjustable 2D MR image overlay system and validating the previous 2D image overlay system in the clinical environment. The adjustable system requirement is to overcome the oblique insertions, difficulties inherent to MR-guided procedures, and to promise safe and reliable needle placement inside closed high-field MRI scanners. This thesis describes development of the image overlay system including requirements, mechanism design and evaluation of MR compatibility. Additionally, a standalone realization of an MR image overlay system, named “The Perk Station” was developed, implemented and evaluated. The system was deployed in the laboratory as a training/teaching tool with non-bio-hazardous specimens. This laboratory version of the system allows for evaluation of trial interventions. The system also supports recording of the complete intervention trajectory for operator performance, technical efficacy, and accuracy studies of insertion techniques. / Thesis (Ph.D, Mechanical and Materials Engineering) -- Queen's University, 2013-09-30 22:21:51.469

Expertise and training in fine motor skills has been associated with changes in brain structure, function, and connectivity. Fewer studies have explored the neural effects of athletic activities that do not seem to rely on precise fine motor control (e.g., distance running). Here, we compared resting-state functional connectivity in a sample of adult male collegiate distance runners (n = 11; age = 21.3 +/- 2.5) and a group of healthy age matched non-athlete male controls (n = 11; age = 20.6 +/- 1.1), to test the hypothesis that expertise in sustained aerobic motor behaviors affects resting state functional connectivity in young adults. Although generally considered an automated repetitive task, locomotion, especially at an elite level, likely engages multiple cognitive actions including planning, inhibition, monitoring, attentional switching and multi-tasking, and motor control. Here, we examined connectivity in three resting-state networks that link such executive functions with motor control: the default mode network (DMN), the frontoparietal network (FPN), and the motor network (MN). We found two key patterns of significant between-group differences in connectivity that are consistent with the hypothesized cognitive demands of elite endurance running. First, enhanced connectivity between the FPN and brain regions often associated with aspects of working memory and other executive functions (frontal cortex), suggest endurance running may stress executive cognitive functions in ways that increase connectivity in associated networks. Second, we found significant anti-correlations between the DMN and regions associated with motor control (paracentral area), somatosensory functions (post-central region), and visual association abilities (occipital cortex). DMN deactivation with task-positive regions has been shown to be generally beneficial for cognitive performance, suggesting anti-correlated regions observed here are engaged during running. For all between-group differences, there were significant associations between connectivity, self-reported physical activity, and estimates of maximum aerobic capacity, suggesting a dose-response relationship between engagement in endurance running and connectivity strength. Together these results suggest that differences in experience with endurance running are associated with differences in functional brain connectivity. High intensity aerobic activity that requires sustained, repetitive locomotor and navigational skills may stress cognitive domains in ways that lead to altered brain connectivity, which in turn has implications for understanding the beneficial role of exercise for brain and cognitive function over the lifespan.

ABSTRACT   Aim: The aim of this retrospective study was to identify which indications prompted an MRI examination using the protocol ”Brain screening/Stroke” and whether the screening revealed recent infarcts and their localisation.   Method: The data, which was subtracted from RIS (Röntgeninformationssystem), covered all consultation responses from stroke-rounds performed during 2015 at Akademiska Hospital in Uppsala (UAS).  A total of 235 patients underwent an MRI-examination using the protocol ”Brain screening/Stroke”. Of this total population, 9 patients with a suspected or confirmed tumour were excluded. The information was collected at UAS during the period 11-22 April, 2016.   Results: No indications were reported from the material collected. Hence, the method was insufficient to give an answer to the question at hand. In the final selection of 226 patients, no stroke could be detected in 42 % of the cases, 23 % had recent infarcts, 21 % had both recent and old infarcts and 14 % had only old infarcts. By gender the results were as follows: Of the total population, 85 patients were female. In 48% of these cases no stroke was detected, 21 % had recent infarcts, 20 % had old infarcts and 11 % had both recent and old infarcts. The remaining 142 patients were male. In 38% of these no stroke was detected, in 27% of the cases both an old an a recent stroke were detected , in 24% of the cases a recent stroke was detected and 11% had only old infarcts. Looking again at the total population, the consultation responses mentioned only recent infarcts and where these were located. The majority of the recent infarcts detected, 23 % were located in the Lobes of the brain, followed by 16% in the Cortex of the brain, 16% in the Brainstem,  13% in the Cerebellum, 10 % were locaded in ”Other parts of the brain”, 8 % were in the Talamus, 7 % were in White matter and the final 6 % in the Basala ganglia. The total number of recent infarcts detected was 189. Conclusion: The main question for this study was to see if it was possible to discover acute infarcts, using diffusion weighted MRI, and the localisation of those discovered. The method chosen worked well, but to get a better overview, more studies should be done, examining infarcts in greater detail. This knowledge may, in turn, be used as a basis for stroke diagnosis. It might also be of interest to complete this study, with a more in-depth analysis of the connection between different kinds of infarcts and the patient’s gender and age.