Overactive bladder (OAB) is considered to be a disorder of the urinary bladder and is defined by the International Continence Society Terminology Committee as "urgency, with or without urge incontinence, usually with frequency and nocturia". There is some preliminary evidence using functional magnetic resonance imaging (fMRI) that the brain response to bladder filling in OAB patients is abnormal. The purpose of this research is to determine whether there are Central Nervous System (CNS) differences in modulating bladder function that contribute to, or are themselves the cause of the symptoms in OAB patients. We further investigated the pharmacological fMRI changes / Electrical and Computer Engineering

BACKGROUND: There has been renewed interest in the study of brown adipose tissue (BAT) as a potential therapeutic target for obesity, diabetes and non-alcoholic fatty liver disease (NAFLD). There is now much evidence to suggest that BAT is not only important in thermogenesis but also plays an important role in metabolism. In adults, cold-induced BAT activation has led to a significant increase in insulin sensitivity and energy expenditure as well as decreased blood sugar levels. Thus, it is important to identify factors associated with these metabolic disorders such as the presence and activity of BAT to better understand if and how BAT can be targeted to treat these disorders. However, as a potential therapeutic target, it is important to develop accurate, precise, robust and reproducible non-invasive modalities to measure BAT. PROJECT OBJECTIVES: 1) Develop and assess protocols for the use of MRI in measuring BAT characteristics and activity 2) Examine the relationship between BAT MR outcomes and known covariates such as age, sex, body fat percentage and outdoor temperature in adult humans 3) Determine if there is any association between BAT outcomes and liver fat in adult humans, before and after adjusting for potential covariates of liver fat such as age, sex and body fat percentage METHODS: In total, 36 healthy participants (i.e. no conditions or medications that could influence BAT metabolism and/or liver disease) aged 18 to 60 years were recruited to this cross-sectional study. There were two study visits. In visit 1, anthropometrics (i.e. height, weight and waist circumference), blood pressure and body composition (via dual x-ray energy absorptiometry) were measured. Additionally, fasting bloodwork was collected and a 75-g oral glucose tolerance test (OGTT) was administered. During visit 2, participants were exposed to a standardized cold exposure set at 18°C for 3 hours using a water-perfused suit. MRI scans were acquired to evaluate changes in fat-fraction (FF%) and T2* relaxation (T2*) (BAT MR outcomes), liver fat and abdominal fat after a cold exposure. During the cold exposure protocol, mean skin temperature (MST) was monitored using 12 wireless temperature loggers placed at different sites of the body while electromyography (EMG) was used to measure shivering intensity. RESULTS: In the current study, an MRI protocol capable of detecting BAT in the supraclavicular (SCV) region was developed. This protocol included the use of FF and T2* masks to more accurately characterize BAT in the SCV region. Additionally, the MR segmentation protocol was found to be very reliable, as demonstrated by excellent ICC values (i.e. ICCagreement and ICCconsistency ≥ 0.90) for all BAT MR outcomes irrespective of cold exposure. As expected, FF% (mean difference = -2.97; p < 0.0001*) and T2* (mean difference = -0.84; p < 0.0001*) values in the SCV significantly decreased after cold exposure, consistent with BAT activation. Furthermore, the decline in both FF% and T2* after cooling was specific to the SCV region, as these changes did not occur in the posterior neck fat. In examining the relationship between BAT MR outcomes and known covariates of BAT (i.e. age, sex, body fat percentage and outdoor temperature), it is important to note that lower FF% or T2* values are reflective of a browner phenotype while a greater reduction in FF% is indicative of higher BAT activity. BAT characteristics (A: pre-cold FF%; B: pre-cold T2*) and BAT activity (C: FF% reduction) were correlated with age (A: r = 0.54; p = 0.0007*; B: r = 0.42; p = 0.0112*; C: r = -0.39; p = 0.0213*) and body fat percentage (A: r = 0.83; p < 0.0001*; B: r = 0.58; p = 0.0002*; C: r = -0.64; p < 0.0001*). That is, higher age and body fat were associated with a less brown phenotype prior to cold exposure and with less BAT activity (i.e. lower FF% decline) in response to cold exposure. However, no associations were found between BAT MR outcomes and sex or outdoor temperature. Lastly, liver fat was associated with higher values of pre-cold FF% (r = 0.60; p < 0.0001*) and pre-cold T2* (r = 0.47; p = 0.0040*) while FF% reduction was inversely correlated with liver fat (r = -0.38; p = 0.0295*). Additionally, the relationship between BAT MR outcomes and liver fat still existed after adjusting for age and sex while its effects were mediated by adiposity. CONCLUSION: In this study, a highly reliable MR segmentation protocol was developed that is capable of measuring BAT characteristics and activity irrespective of cold exposure. Additionally, the cold exposure protocol used was sufficient to elicit changes in BAT MR outcomes, as demonstrated by significant changes in FF% and T2* after cooling. Consistent with previous studies, BAT outcomes (as measured by MRI) were associated with age and body fat percentage. Lastly, findings in this thesis provide strong supporting data that BAT may regulate liver lipid content, however, the extent and mechanisms remain to be determined. / Thesis / Master of Science (MSc)

<p> An accurate estimation of Body Segment Parameters (BSPs) is needed to understand human movement. These include segment mass, centre of mass, and moment of inertia about the centre of mass. Bone density scanners, such as DPX, can measure BSPs, but are limited to only two dimensions. MRI produces images in three dimensions, but cannot directly measure mass. For this study, MRI was used in conjunction with a DPX scan of the human body. The result was the development of a method to estimate mass, and subsequently, centre of mass, and moment of inertia from MRI images. Next, ellipses were created from the dimensions of transverse plane slices (produced from MRI). Three different density profiles were applied to the ellipses, and mass, centre of mass and moment of inertia about the centre of mass of each slice was calculated. It was found that constant density transverse plane ellipses could be used to estimate BSPs for most regions of the body. Photogrammetry can also be used to generate the dimensions of ellipses that represent transverse plane slices. Therefore, the suitability of photogrammetry to estimate slice BSPs was tested. It was found that depending on the density profile used, photogrammetry is an effective method for estimating BSPs. An exception to this estimation was in the chest, where ellipses may not be representative of the body. </p> / Thesis / Master of Science (MSc)

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<p dir="ltr">Cerebrospinal fluid (CSF) plays a diverse role within the skull including cushioning the brain, regulating intracranial pressure, and clearing metabolic waste via the glymphatic system. Disruptions in CSF flow have long been investigated for hydrocephalus-related diseases such as idiopathic normal pressure hydrocephalus (iNPH). Recently, changes in CSF flow have been implicated in neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease. It remains difficult to obtain <i>in vivo </i>measurements of CSF flow which contribute to disease initiation, progression, and treatment. Three-directional phase-contrast MR imaging (4D flow MRI) has been used to measure CSF velocities within the cerebral ventricles. However, there remain challenges in balancing acquisition time, spatiotemporal resolution, and velocity-to-noise ratio. This is complicated by the low velocities and long relaxation times associated with CSF flow. Additionally, flow-derived metrics associated with cellular adaptations and transport rely on near-wall velocities which are poorly resolved and noisy. To address these challenges, we have applied physics-guided neural networks (PGNN) to super-resolve and denoise synthetic 4D flow MRI of CSF flow within the 3rd and 4th ventricles using novel physics-based loss functions. These loss functions are specifically designed to ensure that high-resolution estimations of flow fields are physically consistent and temporarily coherent. We apply these PGNN to various test cases including synthetically generated 4D flow MRI in the cerebral ventricles and vasculature, <i>in vitro</i> 4D flow MRI acquired at two resolutions in 3D printed phantoms of the 3rd and 4th ventricles, and in vivo 4D flow MRI in a healthy subject. Lastly, we apply these physics-guided networks to investigate blood flow through cerebral aneurysms. These techniques can empower larger studies investigating the coupling between arterial blood flow and CSF flow in conditions such as iNPH and AD.</p>