Carotid atherosclerosis, one of the leading causes of ischemic stroke worldwide, can induce severe narrowing or even occlusion of the vessel, restricting blood flow to the brain and resulting in perfusion deficits. The plaque that has a high probability of undergoing rapid progression or future ruptures is defined as “vulnerable plaque”. Identifying vulnerable plaque is of great importance in clinical carotid atherosclerosis imaging. To date, a multi-contrast magnitude-based MR approach with blood suppression technique has been widely used to detect vulnerable plaque features. However, due to the limitations of magnitude-based methods, developing new MR techniques that have better sensitivity to hemorrhage and calcification is of great interest. Quantitative Susceptibility Mapping (QSM) is a technique that utilizes the MR phase information and has been widely used for quantifying the tissue susceptibility in the brain. The susceptibility contrast is extremely sensitive to hemorrhage and calcium which makes QSM a potential tool for carotid plaque imaging to identify intraplaque hemorrhage (IPH) and calcification. However, existing QSM methods have not been successfully implemented in the neck due to several challenges. The presence of air/tissue interface, plaque that has high susceptibility, and fat surrounding the carotid arteries can cause severe phase aliasing and other problems that will induce errors in the resultant susceptibility maps. To overcome these challenges and thus, develop a robust method for carotid QSM, a protocol that includes both data acquisition strategy and post-processing methods is proposed. For data acquisition, four echoes including two water/fat in-phase echoes and two water/fat out-of-phase echoes were collected. For data post-processing, temporal domain algorithm Catalytic Multiecho Phase Unwrapping Scheme (CAMPUS) was used to unwrap the phase images and local QSM was proposed. This protocol is able to properly unwrap the phase images even with the presence of high susceptibility plaque and eliminate the water/fat chemical shift effect in QSM reconstructions which will generate reliable susceptibility maps. From our results, the proposed QSM protocol has demonstrated the ability to generate reliable susceptibility maps and excellent sensitivity to IPH and calcification. Combining QSM with existing magnitude-based methods will lead to a major improvement in the diagnosis of carotid atherosclerosis. / Thesis / Master of Applied Science (MASc)

Magnetic Resonance Imaging (MRI) is a widely used, non-invasive imaging technique that provides a means to reveal structural and functional information of different body tissues in detail. Susceptibility Weighted Imaging (SWI) is a field in MRI that utilizes the information from the magnetic susceptibility property of different tissues using the gradient echo phase information. Although longer echo times (TEs) have been widely used in applications involving SWI, there are a few problems related with the long TE data, such as the strong blooming effect and phase aliasing even at macroscopic levels. In this thesis, the use of very short TEs is proposed to study susceptibility mapping. The short TEs can be used to study structures with susceptibilities an order of magnitude larger (such as air and bones in and around the brain sinuses, skull and teeth) than those within soft tissue. Using a new iterative susceptibility mapping technique that we recently developed, it becomes possible to map the geometry of such structures, which to date has proven difficult due to the lack of water content (for sinuses) or due to very short T2* (for bones). The method of phase replacement inside the sinuses proposed in this thesis provides more accurate phase information for the inversion than assuming zero or some arbitrary constant inside these structures. The first and second iterations were responsible for most of the changes in mapping out the susceptibility values. The mean susceptibility value in the sphenoid sinus is calculated as +9.3 ± 1.1ppm, close to the expected value of +9.4ppm for air. The reconstruction of the teeth in the in-vivo data provides a mean Δχ(teeth-tissue)=–3.3ppm, thanks to the preserved phase inside the jaw. The mean susceptibility inside a relatively homogeneous region of the skull bone was measured to be Δχ(bone-tissue)=–2.1ppm. Finally, these susceptibilities can be used to help remove the unwanted background fields prior to applying either SHARP or HPF. In addition, the effects of the background field gradient on flow compensation are studied. Due to the presence of these background gradients, an unwanted phase term is induced by the blood flow inside the vessels. Using a 3D numerical model and in vivo data, the background gradients were estimated to be as large as 1.5mT/m close to the air-tissue interfaces and 0.7mT/m inside the brain (leading to a potential signal loss of up to 15%). The quantitative susceptibility mapping (QSM) results were improved in the entire image after removing the confounding arterial phase thanks to the reduced ringing artifacts. Lastly, a novel approach to improve the susceptibility mapping results was introduced and utilized to monitor the changes in venous oxygen saturation levels as well as the changes in oxygen extraction fraction instigated by the vasodynamic agents, caffeine and acetazolamide. The internal streaking artifacts in the susceptibility maps were reduced by giving an initial susceptibility value uniformly to the structure-of-interest, based on the a priori information. For veins, the iterative results, when the initial value of 0.45 ppm was used, were the best in terms of the highest accuracy in the mean susceptibility value (0.453 ppm) and the lowest standard deviation (0.013 ppm). Using this technique, the venous oxygen saturation levels (inside the internal cerebral veins (ICVs)) for normal physiological conditions, post-caffeine and post-Diamox for the first volunteer were calculated as (mean ± standard deviation): Y_Normal = 69.1 ± 3.3 %, Y_Caffeine = 60.5 ± 2.8 % and Y_Diamox = 79.1 ± 4.0%. For the caffeine challenge, the percentage change in oxygen extraction fraction (OEF) for pre and post caffeine results was calculated as +27.0 ± 3.8%; and for the Diamox challenge, the percentage change in OEF was calculated as −32.6 ± 2.1 % for the ICVs. These vascular effects of Diamox and caffeine were large enough to be easily measured with susceptibility mapping and can serve as a sensitive biomarker for measuring reductions in cerebro-vascular reserve through abnormal vascular response, an increase in oxygen consumption during reperfusion hyperoxia or locally varying oxygen saturation levels in regions surrounding damaged tissue. In conclusion, our new approach to QSM offers a means to monitor venous oxygen saturation reasonably accurately and may provide a new means to study neurovascular diseases where there are changes in perfusion that affect the oxygen extraction fraction. / Thesis / Doctor of Philosophy (PhD) / Magnetic Resonance Imaging (MRI) is a widely used, non-invasive imaging technique that provides a means to reveal structural and functional information of different body tissues in detail. Susceptibility Weighted Imaging (SWI) is a field in MRI that utilizes the information from the magnetic susceptibility property of different tissues using the gradient echo phase information. Firstly, we demonstrate that using our phase replacement technique, it becomes possible to map the geometry of structures with almost no MR signal, which to date has proven difficult due to the lack of water content (for sinuses) or due to very short T2* (for bones). Secondly, the effects of the background field gradient on flow compensation were studied. Due to the presence of these background gradients, an unwanted phase term is induced by the blood flow inside the vessels. And, lastly, we present our new approach utilizing SWI data, offering a means to monitor venous oxygen saturation reasonably accurately and, potentially, a new means to study neurovascular diseases where there are changes in perfusion that affect the oxygen extraction fraction.

Each year in the United States, approximately 1.35 million people are a ected by mTBI (aka concussion) and subsequent cognitive impairment. Approximately 33% of mTBI cases results in persistent long-term cognitive de cits despite no abnormalities appearing on conventional neuroimaging scans. Therefore, an accurate and reliable imaging method is needed to determine injury location and extent of healing. The goal of this study was to characterize and quantify mTBI through DTI, an advanced MRI technique that encodes voxel-wise tissue water microstructural di usivity as a tensor, as well as QSM, which measures iron deposition within tissues. We hypothesized that personalizing the analysis of DTI and QSM will provide a better understanding of trauma-induced microstructural damage leading to improved diagnosis and prognosis accuracy. Through regression analysis, a preliminary comparison between DTI data to QSM measurements was performed to determine potential correlations between the two MRI techniques. Further, a large database of healthy pediatric brain DTI data was downloaded and each was warped into a standardized brain template to ultimately use for voxel-wise z-score analysis of individual mTBI patients (n=26). This allowed localization and quantitation of abnormal regions on a per-patient basis. Signi cant abnormalities were commonly observed in a number of regions including the longitudinal fasciculus, fronto-occipital fasciculus, and corticospinal tract, while unique abnormalities were localized in a host of other areas (due to the individuality of each childs injury). Further, through group-based Bonferroni corrected T-test analysis, the mTBI group was signi cantly di erent from controls in approximately 65% of regions analyzed. These results show that DTI is sensitive to the detection of microstructural changes caused by mTBI and has potential to be a useful tool for improving mTBI diagnosis accuracy / Thesis / Master of Applied Science (MASc) / Concussions affect over one million people in the United States each year. In a number of cases, these individuals must cope with persistent long-term cognitive impairment resulting from the injury. A current, significant problem is that concussion cannot be reliably diagnosed using conventional CT and MR imaging methods. Therefore, an accurate and reliable imaging method is needed to determine both injury location and severity, as well as to monitor healing. The goal of this study was to quantify concussion through MR imaging techniques known as Di ffusion Tensor Imaging and Quantitative Susceptibility Mapping, which accurately model the brain's mi- crostructure. Analysis utilizing these MRI methods found signifi cant abnormalities in a number of brain regions of concussed subjects relative to healthy individuals. These results suggest that DTI, in particular, is sensitive to microstructural changes caused by concussions and has the potential to be a useful tool for improving diagnosis accuracy.

<p>Magnetic resonance imaging is a research and clinical tool that has been applied in a wide variety of sciences. One area of magnetic resonance imaging that has exhibited terrific promise and growth in the past decade is magnetic susceptibility imaging. Imaging tissue susceptibility provides insight into the microstructural organization and chemical properties of biological tissues, but this image contrast is not well understood. The purpose of this work is to develop effective approaches to image, assess, and model the mechanisms that generate both isotropic and anisotropic magnetic susceptibility contrast in biological tissues, including myocardium and central nervous system white matter. </p><p>This document contains the first report of MRI-measured susceptibility anisotropy in myocardium. Intact mouse heart specimens were scanned using MRI at 9.4 T to ascertain both the magnetic susceptibility and myofiber orientation of the tissue. The susceptibility anisotropy of myocardium was observed and measured by relating the apparent tissue susceptibility as a function of the myofiber angle with respect to the applied magnetic field. A multi-filament model of myocardial tissue revealed that the diamagnetically anisotropy α-helix peptide bonds in myofilament proteins are capable of producing bulk susceptibility anisotropy on a scale measurable by MRI, and are potentially the chief sources of the experimentally observed anisotropy.</p><p>The growing use of paramagnetic contrast agents in magnetic susceptibility imaging motivated a series of investigations regarding the effect of these exogenous agents on susceptibility imaging in the brain, heart, and kidney. In each of these organs, gadolinium increases susceptibility contrast and anisotropy, though the enhancements depend on the tissue type, compartmentalization of contrast agent, and complex multi-pool relaxation. In the brain, the introduction of paramagnetic contrast agents actually makes white matter tissue regions appear more diamagnetic relative to the reference susceptibility. Gadolinium-enhanced MRI yields tensor-valued susceptibility images with eigenvectors that more accurately reflect the underlying tissue orientation.</p><p>Despite the boost gadolinium provides, tensor-valued susceptibility image reconstruction is prone to image artifacts. A novel algorithm was developed to mitigate these artifacts by incorporating orientation-dependent tissue relaxation information into susceptibility tensor estimation. The technique was verified using a numerical phantom simulation, and improves susceptibility-based tractography in the brain, kidney, and heart. This work represents the first successful application of susceptibility-based tractography to a whole, intact heart.</p><p>The knowledge and tools developed throughout the course of this research were then applied to studying mouse models of Alzheimer’s disease in vivo, and studying hypertrophic human myocardium specimens ex vivo. Though a preliminary study using contrast-enhanced quantitative susceptibility mapping has revealed diamagnetic amyloid plaques associated with Alzheimer’s disease in the mouse brain ex vivo, non-contrast susceptibility imaging was unable to precisely identify these plaques in vivo. Susceptibility tensor imaging of human myocardium specimens at 9.4 T shows that susceptibility anisotropy is larger and mean susceptibility is more diamagnetic in hypertrophic tissue than in normal tissue. These findings support the hypothesis that myofilament proteins are a source of susceptibility contrast and anisotropy in myocardium. This collection of preclinical studies provides new tools and context for analyzing tissue structure, chemistry, and health in a variety of organs throughout the body.</p> / Dissertation

<p>Quantitative susceptibility mapping (QSM) is a promising technique to study tissue properties and function <em>in vivo</em>. The presence of a susceptibility source will lead to a non-local field variation which manifests as a non-local behavior in magnetic resonance phase images. QSM is an ill-posed inverse problem that maps the phase back to the susceptibility source. In practice, the phase images are usually contaminated by background field inhomogeneities. In this thesis, several technical advances in QSM have been made which accelerate the data processing and improve the accuracy of this ill-posed problem. For background field removal, the local spherical mean value filtering (LSMV) is proposed, in which the global phase unwrapping is bypassed. This algorithm improves the time-efficiency and robustness of background field removal. For solving the inverse problem, an improved version of the k-space/image domain iterative algorithm is demonstrated using multi-level thresholding to account for the variation in the susceptibilities of different structures in the brain. The susceptibility maps could be used to generate orientation independent weighting masks, to form a new type of susceptibility weighted image (SWI), referred to here as true-SWI (tSWI). The tSWI data show improved contrast-to-noise ratio (CNR) of the veins and reduced blooming artefacts of the microbleeds. Finally, it is shown that the effective magnetic moment, being the product of the apparent volume and the measured susceptibility of the small object, is constant. This can be used to improve the susceptibility quantification, if <em>a priori</em> information of the volume is available.</p> / Doctor of Philosophy (PhD)

<p>The kidney's major role in filtration depends on its high blood flow, concentrating mechanisms, and biochemical activation. The kidney's greatest strengths also lead to vulnerability for drug-induced nephrotoxicity and other renal injuries. The current standard to diagnose renal injuries is with a percutaneous renal biopsy, which can be biased and insufficient. In one particular case, biopsy of a kidney with renal cell carcinoma can actually initiate metastasis. Tools that are sensitive and specific to detect renal disease early are essential, especially noninvasive diagnostic imaging. While other imaging modalities (ultrasound and x-ray/CT) have their unique advantages and disadvantages, MRI has superb soft tissue contrast without ionizing radiation. More importantly, there is a richness of contrast mechanisms in MRI that has yet to be explored and applied to study renal disease.</p><p>The focus of this work is to advance preclinical imaging tools to study the structure and function of the renal system. Studies were conducted in normal and disease models to understand general renal physiology as well as pathophysiology. This dissertation is separated into two parts--the first is the identification of renal architecture with ex vivo MRI; the second is the characterization of renal dynamics and function with in vivo MRI. High resolution ex vivo imaging provided several opportunities including: 1) identification of fine renal structures, 2) implementation of different contrast mechanisms with several pulse sequences and reconstruction methods, 3) development of image-processing tools to extract regions and structures, and 4) understanding of the nephron structures that create MR contrast and that are important for renal physiology. The ex vivo studies allowed for understanding and translation to in vivo studies. While the structure of this dissertation is organized by individual projects, the goal is singular: to develop magnetic resonance imaging biomarkers for renal system. </p><p>The work presented here includes three ex vivo studies and two in vivo studies:</p><p> </p><p>1) Magnetic resonance histology of age-related nephropathy in sprague dawley.</p><p>2) Quantitative susceptibility mapping of kidney inflammation and fibrosis in type 1 angiotensin receptor-deficient mice. </p><p>3) Susceptibility tensor imaging of the kidney and its microstructural underpinnings. </p><p>4) 4D MRI of renal function in the developing mouse. </p><p>5) 4D MRI of polycystic kidneys in rapamycin treated Glis3-deficient mice.</p> / Dissertation

No description available.

<p dir="ltr">Manganese (Mn) is an essential trace element for humans that functions primarily as a coenzyme in several biological processes such as nerve and brain development, energy metabolism, bone growth and development, as well as cognitive functioning. However, overexposure to environmental Mn via occupational settings or contaminated drinking water can lead to toxic effects on the central nervous systems and cause a Parkinsonian disorder that features symptoms such as fine motor control deficits, dystonia rigidity, speech and mood disturbances, and cognitive deficits summarized under the term “manganism”. Over time, Mn exposure has shifted from acute, high-level instances leading to manganism, to low-level chronic exposure. Considering that Mn exposure is significantly lower than in the past, it is unlikely to expect manganism from chronic Mn exposure under current working conditions. Therefore, there is a need to develop sensitive methods to aid in updating the clinical diagnostic standards for manganism and Mn neurotoxicity as chronic exposure to Mn leads to more subtle symptoms.</p><p><br></p><p dir="ltr">Historically, magnetic resonance imaging (MRI) has been used as a non-invasive tool for detecting excess brain Mn accumulation. Specifically, T1-weighted images show bilateral hyperintensities of the globus pallidus (GP) due to the paramagnetic properties of Mn which increases the MR relaxation rate R1. Although the GP is considered the hallmark of excess brain Mn, this brain area is not necessarily associated with symptoms, exposure, or neuropsychological outcomes. Thus, the focus should not be on the GP only but on the entire brain. With recent advances in quantitative MRI (qMRI), whole brain mapping techniques allow for the direct measurement of relaxation rate changes due to Mn accumulation. The work in this dissertation uses such quantitative techniques and network science to establish novel computational in vivo imaging methods to a) visualize and quantify excess Mn deposition at the group and individual level, and b) characterize the toxicokinetics of excess brain Mn accumulation and the role of different brain regions in the development of neurotoxicity effects.</p><p><br></p><p dir="ltr">First, we developed a novel method for depicting excess Mn accumulation at the group level using high-resolution R1 relaxation maps to identify regional differences using voxel-based quantification (VBQ) and statistical parametric mapping. Second, we departed from a group analysis and developed subject-specific maps of excess brain Mn to gain a better understanding of the relationship between the spatial distribution of Mn and exposure settings. Third, we developed a novel method that combines network science with MRI relaxometry to characterize the storage and propagation of Mn and Fe in the human brain and the role of different brain regions in the development of neurotoxic effects. Lastly, we explore the application of ultra-short echo (UTE) imaging to map Fe content in the brain and compare it against R2* and quantitative susceptibility mapping (QSM).</p><p><br></p><p dir="ltr">Overall, this dissertation is a successful step towards establishing sensitive neuroimaging screening methods to study the effects of occupational Mn exposure. The individual Mn maps offer great potential for evaluating personal risk assessment for Mn neurotoxicity and allow monitoring of temporal changes in an individual, offering valuable information about the toxicokinetics of Mn. The integration of network science provides a holistic analysis to identify subtle changes in the brain’s mediation mechanisms of excess metal depositions and their associations with health outcomes.</p>

Le manuscrit suivant porte sur le développement d’une méthodologie de cartographie de la susceptibilité magnétique. Cette méthodologie a été appliquée au niveau des seins à des fins de détection de microcalcifications. Afin de valider ces algorithmes, un fantôme numérique ainsi qu’un fantôme réel ont été créés. À l’aide de ces images, les paramètres modifiables de notre méthodologie ont été ajustés. Par la suite, les problèmes reliés à l’imagerie du sein ont été explorés, tel la présence de gras ainsi que la proximité des poumons. Finalement, des images in vivo, acquises à 1.5 et 7.0 Tesla ont été analysées par notre méthodologie. Sur ces images 1.5T, nous avons réussi à observer la présence de microcalcifications. D’un autre côté, les images 7.0T nous ont permis de présenter un meilleur contraste que les images standards de magnitude. / The following manuscript is about the development of a methodology called quantitative susceptibility mapping. This methodology was applied to the breast with the purpose of detecting microcalcifications. To validate these algorithms, a digital phantom and a water phantom were created. Using these images, adjustable parameters were adjusted on our methodology. Thereafter, problems related to breast imaging, like the presence of fat and the proximity of the lungs, were explored. Finally, in vivo images, acquired at 1.5 and 7.0 Tesla were analyzed by our methodology. On these 1.5T images, we successfully observed the presence of microcalcifications. On the other hand, the 7.0T images allowed us to provide a better contrast than the standard magnitude images.

Le manuscrit suivant porte sur le développement d’une méthodologie de cartographie de la susceptibilité magnétique. Cette méthodologie a été appliquée au niveau des seins à des fins de détection de microcalcifications. Afin de valider ces algorithmes, un fantôme numérique ainsi qu’un fantôme réel ont été créés. À l’aide de ces images, les paramètres modifiables de notre méthodologie ont été ajustés. Par la suite, les problèmes reliés à l’imagerie du sein ont été explorés, tel la présence de gras ainsi que la proximité des poumons. Finalement, des images in vivo, acquises à 1.5 et 7.0 Tesla ont été analysées par notre méthodologie. Sur ces images 1.5T, nous avons réussi à observer la présence de microcalcifications. D’un autre côté, les images 7.0T nous ont permis de présenter un meilleur contraste que les images standards de magnitude. / The following manuscript is about the development of a methodology called quantitative susceptibility mapping. This methodology was applied to the breast with the purpose of detecting microcalcifications. To validate these algorithms, a digital phantom and a water phantom were created. Using these images, adjustable parameters were adjusted on our methodology. Thereafter, problems related to breast imaging, like the presence of fat and the proximity of the lungs, were explored. Finally, in vivo images, acquired at 1.5 and 7.0 Tesla were analyzed by our methodology. On these 1.5T images, we successfully observed the presence of microcalcifications. On the other hand, the 7.0T images allowed us to provide a better contrast than the standard magnitude images.