yes / Purpose To characterize the intracranial volumetric changes that influence the cerebrospinal fluid (CSF) pulse in the Aqueduct of Sylvius (AoS). Materials and methods Neck MRI data were acquired from 12 healthy adults (8 female and 4 males; mean age = 30.9 years), using a 1.5 T scanner. The intracranial arterial, venous and CSF volumes changes, together with the aqueductal CSF (aCSF) volume, were estimated from flow rate data acquired at C2/C3 level and in the AoS. The correlations and temporal relationships among these volumes were computed. Results The aCSF volumetric changes were strongly correlated (r = 0.967, p < 0.001) with the changes in intracranial venous volume, whose peak occurred 7.0% of cardiac cycle (p = 0.023) before peak aCSF volume, but less correlated with the intracranial arterial and CSF volume changes (r = −0.664 and 0.676 respectively, p < 0.001). The intracranial CSF volume change was correlated with the intracranial venous volume change (r = 0.820, p < 0.001), whose peak occurred slightly before (4.2% of CC, p = 0.059). Conclusion The aCSF pulse is strongly correlated with intracranial venous volume, with expansion of the cortical veins occurring prior to aCSF flow towards the third ventricle. Both caudal-cranial aCSF flow and venous blood retention occur when arterial blood volume is at a minimum.

Patients who are treated in an intensive care unit need continuous monitoring in orderfor clinicians to be prepared to intervene should a secondary event occur. For patientstreated at the neurointensive care unit (NICU) who have suffered a subarachnoid hemorrhage (SAH) this secondary event could be ischemia, resulting in a lack of blood flow.Blood flow can be measured using magnetic resonance imaging (MRI). The process is facilitated with a software called NOVA. Repeated measurements can therefore be performedas a way to monitor the patients, which in this context would be referred to as longitudinalmeasurements. As more data can be collected ways of analyzing and visualizing the datain a comprehensible way is needed. The aim of this thesis was therefore to develop and implement a method for analyzing and visualizing the longitudinal MR measurement data.With this aim in mind two research questions were relevant. The first one was how NOVAflow longitudinal measurements can be visualized to simplify interpretation by cliniciansand the second one was in what ways the longitudinal data can be analyzed. A graphicaluser interface (GUI) was created to present the developed analysis and visualization tool.Development of the tool progressed using feedback from supervisors and neurosurgeons.Visualization and analysis was done through plots of blood velocity and blood flow as themain component as well as a 2D vessel map. The final implementation showed multipleexamples of how the longitudinal data could be both visualized and analyzed. The resultstherefore provided a tool to analyze and visualize NOVA flow longitudinal measurementsin a way which was easily interpreted. Further improvements of the tool is possible andan area of improvement could involve increasing the adaptability of the tool.

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Doppler echocardiography is the conventional method for measurement of myocardial motion. However, the same clinical parameters can be measured with phase contrast magnetic resonance imaging (MRI). Suppression of the blood signal with black-blood methods can reduce flow-related artifacts that may affect quantitative measurements with phase contrast MRI. Conventional blood suppression techniques are not time efficient and a potential approach to achieve the black-blood effect in phase contrast imaging is through application of stimulated echo acquisition mode (STEAM). This thesis describes the development of a pulse sequence where a STEAM-based preparation was combined with conventional phase contrast imaging to achieve a black-blood effect in the produced images.The results of the performed imaging experiments showed that black-blood contrast was achieved with the proposed pulse sequence, and the blood suppression was also maintained during the cardiac cycle. Myocardial tissue velocity measurement with the suggested approach showed good agreement with conventional phase contrast imaging. It was concluded that black-blood phase contrast imaging can be achieved through the application of a STEAM-based preparation. / Dopplerekokardiografi är den konventionella metoden för mätning av myokardiell rörelse. Liknande mätningar kan dock utföras genom faskontrastavbildning som är en metod inom magnetisk resonanstomografi. Signal från blod kan orsaka flödesrelaterade bildartefakter vid faskontrastavbildning som kan påverka hastighetsmätningar i myokardiet. Utsläckning av blodsignalen kan mitigera artefakternas påverkan på kvantitativa mätningar som utförs med faskontrast. Konventionella metoder för utsläckning av blodsignalen är inte tidseffektiva och en potentiell metod för att åstadkomma blodutsläckning vid faskontrastavbildning är applicering av en preparation baserad på stimulated echo acquisition mode (STEAM). I detta arbete utvecklades en pulssekvens där en STEAM-baserad preparation kombinerades med en traditionell faskontrastsekvens. De resulterande bilderna visade att blodutsläckning hade åstadkommits och att denna effekt kunde bibehållas under hjärtcykelns gång. Hastighetsmätningar utfördes även i myokardiet och var jämförbara med traditionell faskontrast. Slutsatsen var att utsläckning av blodsignalen vid faskontrastavbildning är möjligt genom applicering av en STEAM-baserad preparation.

L'Imagerie par Résonance Magnétique de la cinématique de la contraction cardiaque est une technique d'imagerie relativement lente. En comparaison, les mouvements du patient, en particulier cardiaque et respiratoire, sont rapides et peuvent provoquer des artéfacts sur les images. La vitesse de contraction cardiaque apporte justement des informations cliniquement utiles. Premièrement, nous avons montré qu'il était possible d'effectuer cette mesure en IRM Cine à contraste de phase, et d'obtenir des valeurs similaires à celles obtenues de façon clinique en échographie cardiaque. La condition est d'obtenir une haute résolution temporelle, or, pour ce faire, la durée d'acquisition doit être plus longue qu'une apnée. La gestion du mouvement respiratoire en respiration libre a été réalisée de deux façons : avec moyennage puis avec correction de mouvement à l'aide de Cine-GRICS. Deuxièmement, pour atteindre une bonne reconstruction de la résolution temporelle en Cine, nous avons proposé une gestion temps réel de la variation du rythme cardiaque pendant l'acquisition IRM Cine, avec la construction d'un modèle cardiaque adapté au patient à l'aide de l'IRM à contraste de phase temps réel. Enfin, la gestion du mouvement cardio-respiratoire en IRM Cine est appliquée chez le petit animal à l'aide d'écho navigateurs IntraGate / Cine MRI of cardiac contraction is a relatively slow imaging technique. Comparatively, patient motion, especially cardiac beating and breathing, are fast and can lead to imaging artefacts. Cardiac contraction velocity provides clinically useful information. Firstly, we have shown that making this measurement was possible using phase contrast Cine MRI, and that getting similar values as those obtained in clinical routine using cardiac echography. The condition is to reach high temporal resolution, but to do so, the acquisition duration must be longer than a breathhold. Free-breathing motion management was done by two approaches: by averaging then by motion compensation using Cine-GRICS. Secondly, in order to achieve high temporal resolution Cine reconstruction, we proposed a way to deal with changing heart rate during Cine MRI acquisition, by the construction of a patient adapted cardiac model using realtime phase contrast MRI. Finally, cardio-respiratory motion management was adapted to small animal Cine MRI thanks to IntraGate echo navigators

In patients with aortic stenosis, accurate assessment of severity with echocardiography is central to surgical decision making. But, when image quality is poor or equivocal results obtained, another robust non-invasive technique would be invaluable. Cardiac magnetic resonance (CMR) may be a useful alternative. Phase contrast CMR can measure ow and velocity, therefore it is theoretically possible to estimate the main determinant of severity aortic valve area, using the continuity approach. However, it was found that the phase contrast estimate of stroke volume, sampled in the stenotic jet, systematically underestimated left ventricular stroke volume. This underestimation was greater with increasing aortic stenosis severity. Critical clinical treatment decisions depend on the ability to reliably differentiate between patients with moderate and severe aortic stenosis. To achieve accurate estimation of aortic valve areas the velocity and ow data obtained in these turbulent, high velocity jets must be accurate. In this thesis, non-stenotic and stenotic phantoms were designed and constructed to experimentally interrogate the error. It was determined that signal loss, due to intravoxel dephasing, decreased the reliability of the measured forward ow jet velocities. Extreme signal loss in the jet eventuated in salt and pepper noise, which, with a mean velocity of zero, resulted in the underestimation. Intravoxel dephasing signal loss due to higher order motions, turbulence and spin mixing could all be mitigated by reducing the duration of the velocity sensitivity gradients and shortening the overall echo time (TE). However, improvements in an optimised PC sequence (TE 1:5ms) were not satisfactory. Flow estimates remained variable and were underestimated beyond the aortic valve. To reduce the TE further, a new phase contrast pulse sequence based on an ultrashort TE readout trajectory and velocity dependent slice excitation with gradient inversion was designed and implemented. The new sequence's TE is approximately 25% (0:65ms) of what is currently clinically available (TE 2:8ms). Good agreement in the phantom was maintained up to very high ow rates with improved signal characteristics shown in-vivo. This new phase contrast pulse sequence is worthy of further investigation as an accurate evaluation of patients with aortic stenosis. / This work in this thesis was conducted at The Auckland Bioengineering Institute, The Centre for Advanced MRI and The Oxford Centre for Clinical Magnetic Resonance in collaboration with Siemens Health care.

In cardiovascular medicine, the assessment of blood flow is fundamental to the understanding and detection of disease. Many pharmaceutical, interventional, and surgical treatments impact the flow. The primary purpose of the cardiovascular system is to drive, control and maintain blood flow to all parts of the body. In the normal cardiovascular system, fluid transport is maintained at high efficiency and the blood flow is essentially laminar. Disturbed and turbulent blood flow, on the other hand, appears to be present in many cardiovascular diseases and may contribute to their initiation and progression. Despite strong indications of an important interrelationship between flow and cardiovascular disease, medical imaging has lacked a non-invasive tool for the in vivo assessment of disturbed and turbulent flow. As a result, the extent and role of turbulence in the blood flow of humans have not yet been fully investigated. Magnetic resonance imaging (MRI) is a versatile tool for the non-invasive assessment of flow and has several important clinical and research applications, but might not yet have reached its full potential. Conventional MRI techniques for the assessment of flow are based on measurements of the mean velocity within an image voxel. The mean velocity corresponds to the first raw moment of the distribution of velocities within a voxel. An MRI framework for the quantification of any moment (mean, standard deviation, skew, etc.) of arbitrary velocity distributions is presented in this thesis. Disturbed and turbulent flows are characterized by velocity fluctuations that are superimposed on the mean velocity. The intensity of these velocity fluctuations can be quantified by their standard deviation, which is a commonly used measure of turbulence intensity. This thesis focuses on the development of a novel MRI method for the quantification of turbulence intensity. This method is mathematically derived and experimentally validated. Limitations and sources of error are investigated and guidelines for adequate application of MRI measurements of turbulence intensity are outlined. Furthermore, the method is adapted to the quantification of turbulence intensity in the pulsatile blood flow of humans and applied to a wide range of cardiovascular diseases. In these applications, elevated turbulence intensity was consistently detected in regions where highly disturbed flow was anticipated, and the effects of potential sources of errors were small. Diseased heart valves are often replaced with prosthetic heart valves, which, in spite of improved benefits and durability, continue to fall short of matching native flow patterns. In an in vitro setting, MRI was used to visualize and quantify turbulence intensity in the flow downstream from four common designs of prosthetic heart valves. Marked differences in the extent and degree of turbulence intensity were detected between the different valves. Mitral valve regurgitation is a common valve lesion associated with progressive left atrial and left ventricular remodelling, which may often require surgical correction to avoid irreversible ventricular dysfunction. The spatiotemporal dynamics of flow disturbances in mitral regurgitation were assessed based on measurements of flow patterns and turbulence intensity in a group of patients with significant regurgitation arising from similar valve lesions. Peak turbulence intensity occurred at the same time in all patients and the total turbulence intensity in the left atrium appeared closely related to the severity of regurgitation. MRI quantification of turbulence intensity has the potential to become a valuable tool in investigating the extent, timing and role of disturbed blood flow in the human cardiovascular system, as well as in the assessment of the effects of different therapeutic options in patients with vascular or valvular disorders.

Single ventricle congenital heart defects afflict 2 per every 1000 births. They are characterized by cyanotic mixing between the de-oxygenated blood coming back from the systemic circulation and the oxygenated blood from the pulmonary circulation. Prior to introduction of the Fontan procedure in 1971, surgical options for single ventricle patients were limited. The Fontan operation involves a series of three palliative procedures aimed at the separation of systemic and pulmonary circulations and reducing the long term effects of chronic hypoxia and ventricular volume overload. The total cavopulmonary connection (TCPC) is completed in the final stage of the surgery with the anastomosis of the inferior vena cava (IVC) and superior vena cava to the pulmonary arteries. Improved quantification and visualization of flow structures within the TCPC has the potential to aid in the planning and design of the Fontan operation. Despite significant development of phase contrast magnetic resonance imaging (PC MRI) for in vivo flow measurements, it is not routinely applied in children with single ventricle congenital heart disease. Limited technologies available for post-processing of PC MRI data has prevented clinicians and scientists from conducting the detailed hemodynamic analyses necessary to better understand the physiology of the single ventricle circulation. This thesis attempts to bridge the gap between PC MRI and fluid dynamics, by developing the necessary post-processing technologies for PC MRI, and then applying these techniques for characterizing single ventricle hemodynamics.

Modern techniques like automated microscopy and spectroscopy now make it possible to study quantitatively, across multiple phenotypic and molecular parameters, how cell populations are affected by different treatments and/or environmental disturbances. As the technology development at the instrument level often is ahead of the data analytical tools and the scientific questions, there is a large and growing need for computational algorithms enabling desired data analysis. These algorithms must have capacity to extract and process quantitative dynamic information about how the cell population is affected by different stimuli with the final goal to transform this information into development of new powerful therapeutic strategies. In particular, there is a great need for automated systems that can facilitate the analysis of massive data streams for label-free methods such as phase contrast microscopy (PCM) imaging and spectroscopy (NMR). Therefore, in this thesis, algorithms for quantitative high-throughput phenotypic and systemic profiling of in vitro growing cell populations via label-free microscopy and spectroscopy are developed and evaluated. First a two-dimensional filter approach for high-throughput screening for drugs inducing autophagy and apoptosis from phase contrast time-lapse microscopy images is studied. Then new methods and applications are presented for label-free extraction and comparison of time-evolving morphological features in phase-contrast time-lapse microscopy images recorded from in vitro growing cell populations. Finally, the use of dynamic morphology and NMR/MS spectra for implementation of a reference database of drug induced changes, analogous to the outstanding mRNA gene expression based Connectivity Map database, is explored. In conclusion, relatively simple computational methods are useful for extraction of very valuable biological and pharmacological information from time-lapse microscopy images and NMR spectroscopy data offering great potential for biomedical applications in general and cancer pharmacology in particular.