The current work investigated the stimulation induced spatial response of the cerebral microvascular network by reconstruction of the 3D microvascular morphology from in vivo two photon fluorescence microscopy (2PFM) volumes using an automated, model based tracking algorithm. In vivo 2PFM imaging of the vasculature in the forelimb representation of the primary somatosensory cortex of alpha-chloralose anesthetized rats was achieved via implantation of a closed cranial window, and intravascular injection of fluorescent dextran. The dilatory and constrictory responses of the cerebral microvascular network to functional stimulation were heterogeneous and depended on resting vascular radius and response latency. Capillaries experienced large relative dilations and constrictions, but the larger vessel absolute volume changes dominated the overall network cerebral blood volume change.

This thesis investigated the role of CBF assessment in the management of stroke in children with sickle cell disease (SCD). It is divided into two parts. In the first part, a systematic review of CBF assessment using different imaging modalities in SCD children was designed. The prevalence of CBF abnormalities was found to be equal to or higher than those of structural MRI and transcranial Doppler (TCD) in SCD children who have not experienced stroke. Studies reviewed suggested CBF assessment in SCD could aid in addressing brain abnormalities at the tissue level. In the second part, the arterial spin labeling (ASL) technique was used to depict CBF abnormalities in SCD children. ASL demonstrated perfusion abnormalities that seem to remain invisible in TCD measurements; CBF interhemispheric asymmetries were associated with clinically silent infarctions with no corresponding flow velocity interhemispheric asymmetries assessed with TCD.

Purpose: To determine the vascular reactivity (VR) capacity and visual function (VF) response to potent vasoconstrictor and vasodilatory provocations of retinal arterioles in healthy subjects. Methods: One hyperoxic hypocapnic and two graded hypoxic hypercapnic stimuli were administered. VR in response to gas provocation was assessed using the Canon Laser Blood Flowmeter. VF was assessed using high and low contrast ETDRS logMAR charts, Medmont C-100, and H.R.R. Pseudoisochromatic Plates. Results: Flow reduced by 23% (p=0.0001) during hyperoxic hypocapnia and increased by 18% (p=0.0129) during hypoxic hypercapnia. During hyperoxic hypocapnia, high contrast VA improved by -0.026 (p=0.0372). During hypoxic hypercapnia, high and low contrast VA were reduced (+0.033, p=0.0110; +0.025, p=0.0058, respectively). Colour vision was unaffected. Conclusions: The retinal arterioles demonstrated a greater capacity for vasoconstriction than vasodilation in response to the stimuli used in our study. Hyperoxic hypocapnia improved high contrast VA while hypoxic hypercapnia reduced high and low contrast VA.

The current work investigated the stimulation induced spatial response of the cerebral microvascular network by reconstruction of the 3D microvascular morphology from in vivo two photon fluorescence microscopy (2PFM) volumes using an automated, model based tracking algorithm. In vivo 2PFM imaging of the vasculature in the forelimb representation of the primary somatosensory cortex of alpha-chloralose anesthetized rats was achieved via implantation of a closed cranial window, and intravascular injection of fluorescent dextran. The dilatory and constrictory responses of the cerebral microvascular network to functional stimulation were heterogeneous and depended on resting vascular radius and response latency. Capillaries experienced large relative dilations and constrictions, but the larger vessel absolute volume changes dominated the overall network cerebral blood volume change.

This thesis investigated the role of CBF assessment in the management of stroke in children with sickle cell disease (SCD). It is divided into two parts. In the first part, a systematic review of CBF assessment using different imaging modalities in SCD children was designed. The prevalence of CBF abnormalities was found to be equal to or higher than those of structural MRI and transcranial Doppler (TCD) in SCD children who have not experienced stroke. Studies reviewed suggested CBF assessment in SCD could aid in addressing brain abnormalities at the tissue level. In the second part, the arterial spin labeling (ASL) technique was used to depict CBF abnormalities in SCD children. ASL demonstrated perfusion abnormalities that seem to remain invisible in TCD measurements; CBF interhemispheric asymmetries were associated with clinically silent infarctions with no corresponding flow velocity interhemispheric asymmetries assessed with TCD.

Phase-contrast magnetic resonance imaging (PC-MRI) is a powerful tool for measuring blood flow and has a wide range of cardiovascular applications. Simulation of PC-MRI from numerical flow data would be useful for addressing the data quality of PC-MRI measurements and to study and understand different artifacts. It would also make it possible to optimize imaging parameters prior to the PC-MRI measurements and to evaluate different methods for measuring wall shear stress. Based on previous studies a PC-MRI simulation tool was developed. An Eulerian-Lagrangian approach was used to solve the problem. Computational fluid dynamics (CFD) data calculated on a fix structured mesh (Eulerian point of view) were used as input. From the CFD data spin particle trajectories were computed. The magnetization of the spin particle is then evaluated as the particle travels along its trajectory (Lagrangian point of view). The simulated PC-MRI data were evaluated by comparison with PC-MRI measurements on an in vitro phantom. Results indicate that the PC-MRI simulation tool functions well. However, further development is required to include some of the artifacts. Decreasing the computation time will make more accurate and powerful simulations possible. Several suggestions for improvements are presented in this report.

In the human body, turbulent flow is associated with many complications. Turbulence typically occurs downstream from stenoses and heart valve prostheses and at branch points of arteries. A proper way to study turbulence may enhance the understanding of the effects of stenoses and improve the functional assessment of damaged heart valves and heart valve prostheses. The methods of today for studying turbulence in the human body lack in either precision or speed. This thesis exploits a magnetic resonance imaging (MRI) phenomenon referred to as signal loss in order to develop a method for estimating turbulence intensity in blood flow. MRI measurements were carried out on an appropriate flow phantom. The turbulence intensity results obtained by means of the proposed method were compared with previously known turbulence intensity results. The comparison indicates that the proposed method has great potential for estimation of turbulence intensity.

An age-related decline in cerebral blood flow (CBF) is widely acknowledged. However, uncertainty exists as to whether this reduction is the result of a reduced metabolic demand (cerebral atrophy) or an impaired delivery system (cerebrovascular disease). The purpose of these experiments was to examine the relationship of CBF and dynamic cerebrovascular regulation with changes in common carotid intima-media thickness (cIMT), brachial-ankle pulse wave velocity (baPWV) and common carotid distensibility. Additionally, we took an exploratory view into the effect of vascular aging and CBF reduction on brain function, as expressed through the performance of motor and cognitive tasks. An important finding in elderly participants was that seated anterior CBF declined as a function of arterial stiffness, independently of age. Linear regression analysis developed a model that predicts CBF drops 22 ml/min (95% confidence interval (CI): 6, 38) for each 100 cm/s increase in baPWV and 8 ml/min (95% CI: 1, 15) for each additional year in age. The effect of baPWV appears to be mediated through an increase in cerebrovascular resistance (r2 = 0.84, p < 0.0001). Additionally, CBF showed postural dependency and the volume of the drop in CBF between supine and seated positions was greatest in elderly participants (YOUNG: 65 ± 81 ml/min; ELDERLY: 155 ± 119 ml/min; p = 0.001). Despite this negative impact of vascular aging on steady state flow, dynamic regulation does not appear to be affected. Cerebrovascular responses to an acute drop in blood pressure or to activation of the motor cortex were not attenuated in the elderly participants. Finally, seated CBF had modest directionally relevant relationships with perceptuo-motor and complex sequencing processes; while cIMT appeared to influence performance on initiation and inhibition tasks.

Introduction and Purpose: Vascular pathologies play an important role in the etiology and progression of number of ocular diseases. Many instruments are developed to monitor retinal hemodynamics, including the Canon Laser Blood Flowmeter (CLBF), in an attempt to better understand the pathophysiology of the disease (Chapter 2). The purpose of this thesis is to determine the impact of light scatter on retinal arteriolar hemodynamic measurement assessed by the CLBF as intraocular light scatter is an inevitable consequence of ageing and particularly cataract. Methodology: Chapter 4 – Artificial light scatter model: One eye from each of 10 healthy young subjects between the ages of 18 and 30 (23.6 ± 3.4) was randomly selected. To simulate light scatter, cells comprising a plastic collar and two plano lenses were filled with solutions of differing concentrations of polystyrene microspheres (Polysciences Inc., USA). 0.002%, 0.004%, 0.006%, 0.008% were prepared, as well as distilled water only. After a preliminary screening to confirm subject eligibility, seven arteriolar hemodynamic measurements were taken by randomly placing the cells between the CLBF objective lens and the subjects’ cornea. Chapter 5 – Ten patients scheduled for extracapsular cataract extraction using phacoemulsification and intraocular lens implantation between the ages of 61 and 84 (mean age 73 years, SD ± 8) were prospectively recruited. Two visits were required to complete the study; One prior to the surgery and one at least six weeks after the surgery to allow for full post-operative recovery. The severity of cataract was documented using the Lens Opacity Classification System (LOCS, III) at the first visit. Each subject underwent visual function assessment at both visits using logMAR Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts and the Brightness Acuity Tester (BAT). Retinal arteriolar hemodynamics were measured at both visits using the high intensity setting of the Canon Laser Blood Flowmeter. Results: Chapter 4: Our light scatter model resulted in an artifactual increase of retinal arteriolar diameter (p<0.0001) and thereby increased retinal blood flow (p<0.0001). The 0.006% and 0.008% microsphere concentrations produced significantly higher diameter and flow values than baseline. Centerline blood velocity, however, was not affected by light scatter. Retinal arteriolar diameter values were significantly less with the high intensity laser than with the low intensity laser (p=0.0007). Chapter 5: Group mean retinal arteriolar diameter and blood flow were reduced following extracapsular cataract extraction (Wilcoxon signed-rank test, p=0.022 and p=0.028 respectively); however, centerline blood velocity was unchanged (Wilcoxon signed-rank test, p=0.074). Conclusions: Using an artificial light scatter model (Chapter 3), we demonstrated that the densitometry assessment of vessel diameter is increasingly impacted as the magnitude of artificial light scatter increases; this effect can be partially negated by increasing laser intensity. We showed similar results in the presence of cataract (Chapter 4) by measuring the retinal arteriolar hemodynamics before and after removal of cataract. Care needs to be exercised in the interpretation of studies of retinal vessel diameter that use similar densitometry techniques as cataract is an inevitable consequence of aging.

MRI is a well known and widely spread technique to characterize cardiac pathologies due to its high spatial resolution, its accessibility and its adjustable contrast among soft tissues. In attempt to close the gap between blood flow, myocardial movement and the cardiac fucntion, researching in the MRI field addresses the quantification of some of the most relevant blood and myocardial parameters. During this proyect a new tool that allows reading, postprocessing, quantifying and visualizing 2D motion sense MR data has been developed. In order to analyze intracardiac blood flow and wall motion, the new tool quantifies velocity, turbulent kinetic energy, pressure and strain. In the results section the final tool is presented, describing the visualization modes, which represent the quantified parameters both individually and combined; and detailing auxiliary tool features as masking, thresholding, zooming, and cursors. Finally, thecnical aspects as the convenience of two dimensional examinations to create compact tools, and the challenges of masking as part of the relative pressure calculation, among others, are discussed; ending up with the proposal of some future developments.