Cardiac resynchronization therapy (CRT) has recently emerged as an effective treatment option for heart failure patients with dyssynchrony. Patients have traditionally been chosen for CRT based on a prolonged QRS interval. However, this selection method is far from ideal, as approximately 30% of those receiving CRT do not show any clinical improvement. Tissue Doppler imaging (TDI) suggests that one of the best predictors of response to CRT is the underlying level of mechanical dyssynchrony in the myocardial wall prior to CRT. As a result, there has been growing interest in direct imaging of the myocardial wall. Because myocardial contraction is a complex, three-dimensional movement, providing an accurate picture of myocardial wall motion can be challenging. Echocardiography initially emerged as the modality of choice, but the long list of limitations (limited echocardiographic windows, one direction of motion, poor reproducibility) has fostered interest in exploring the use of MR for myocardial wall imaging. Although MR presents some unique drawbacks (expensive equipment, longer imaging times), it is able to overcome many of the limitations of TDI. In particular, Phase Velocity Mapping (MR PVM) can provide a complete, three-directional description of motion throughout the entire myocardial wall at high spatial and temporal resolution. The overall goal of this project was to develop a patient-selection method for CRT based on myocardial wall velocities acquired with MR PVM. First the image acquisition and post-processing protocols for MR PVM imaging of myocardial tissue were developed. A myocardial motion phantom was used to verify the accuracy of, and optimize the acquisition parameters for, the developed MR PVM sequence. Excellent correlation was demonstrated between longitudinal myocardial velocity curves acquired with the optimized MR PVM sequence and Tissue Doppler velocities. A database describing the normal myocardial contraction pattern was constructed. A small group of dyssynchrony patients was compared to the normal database, and several areas of delayed contraction were identified in the patients. Furthermore, significantly higher levels of dyssynchrony were detected in the patients than the normal volunteers. Finally, a method for computing transmural, endocardial, and epicardial, radial strains and strain rates from MR PVM velocity data was developed

Advanced nuclear magnetic resonance (NMR) imaging methodologies have been developed to determine porous media properties associated with fluid flow processes. This dissertation presents the development of NMR experimental and analysis methodologies, called NMR probes, particularly for determination of porosity, permeability, and pore-size distributions of porous media while the developed methodologies can be used for other properties. The NMR relaxation distribution can provide various information about porous systems having NMR active nuclei. The determination of the distribution from NMR relaxation data is an ill-posed inverse problem that requires special care, but conventionally the problem has been solved by ad-hoc methods. We have developed a new method based on sound statistical theory that suitably implements smoothness and equality/inequality constraints. This method is used for determination of porosity distributions. A Carr-Purcell-Meiboom-Gill (CPMG) NMR experiment is designed to measure spatially resolved NMR relaxation data. The determined relaxation distribution provides the estimate of intrinsic magnetization which, in turn, is scaled to porosity. A pulsed-field-gradient stimulated-echo (PFGSTE) NMR velocity imaging experiment is designed to measure the superficial average velocity at each volume element. This experiment measures velocity number distributions as opposed to the average phase shift, which is conventionally measured, to suitably quantify the velocities within heterogeneous porous media. The permeability distributions are determined by solving the inverse problem formulated in terms of flow models and the velocity data. We present new experimental designs associated with flow conditions to enhance the accuracy of the estimates. Efforts have been put forth to further improve the accuracy by introducing and evaluating global optimization methods. The NMR relaxation distribution can be scaled to a pore-size distribution once the surface relaxivity is known. We have developed a new method, which avoids limitations on the range of time for which data may be used, to determine surface relaxivity by the PFGSTE NMR diffusion experiment.

Background: Although Bevacizumab (BVZ) and Sunitinib (SNT) prolong survival in cancer patients, an unanticipated side-effect is cardiotoxicity. Early indices of left ventricular (LV) systolic dysfunction would be useful to address the cardiac safety of anti-cancer drugs. Objective: Whether cardiac biomarkers, tissue velocity imaging (TVI), and/or strain rate (SR) can detect early cardiac dysfunction. Methods: A total of 95 C57Bl/6 mice received one of the following drug regimens: i) 0.9% saline; ii) BVZ; or iii) SNT and followed for 14 days. Serial blood pressure, high sensitivity troponin I (hsTnI), and echocardiography were performed. Results: BVZ- and SNT-treated mice demonstrated an increase in mean arterial blood pressure, hsTnI, cardiac apoptosis, and loss of cell integrity. TVI and SR values confirmed early LV systolic dysfunction at day 8, compared to conventional LVEF at day 13. Conclusions: Novel imaging techniques can detect early LV systolic dysfunction in a model of drug-mediated cardiomyopathy.

Heart dysfunction is a worldly widespread problem that currently is one of the leading causes of death. Studies indicate that many deaths related to cardiac dysfunction could have been prevented if discovered early. Contemporarily, ultrasound and electrocardiography are indispensable modalities for diagnostic purposes and analysis of cardiac function. The Ventricorder is an Ultra-Wideband radar sensor manufactured by the Norwegian company Novelda. Ventricorder has been shown to be able detect heart movements and breathing but its actual clinical value remains to be investigated. The Cardiac State Diagram (CSD) is a pre-clinical software tool for visualization of the heart's mechanical function. The CSD is confirmed by pilot studies to be able to constitute a basis for diagnosis and cardiac function assessment. Theoretically, the CSD is well suited to be used with the Ventricorder since the Ventricorder detects small changes over time and information about time events is all that is required for the creation of a CSD. Contemporarily, ultrasound tissue velocity imaging (TVI) is usually used for production of CSDs and in this master thesis we examined if the Ventricorder can be used to produce CSDs. This was done by mainly comparing velocity data from the Ventricorder with velocity data from temporally synchronized apical four-chamber images acquired with ultrasound TVI. The results indicate that there is an apparent correlation between these data sets and the Ventricorder should therefore be able to produce data that could constitute the basis for the production of a CSD. What remain now is to confirm these results statistically with a larger test group and to investigate whether all the time instants needed for the production of a CSD can be identified objectively. / Hjärtdysfunktion är ett värdsligt utbrett problem som ligger bakom många dödsfall varje år. Studier har visat att många dödsfall som är relaterade till hjärtdysfunktion hade kunnat förebyggas om de upptäckts i tid. För närvarande är bland annat ultraljud och EKG oumbärliga metoder för diagnostisering och analys av hjärtfunktion. Ventricorder är en typ av radarsensor som utnyttjar ett brett frekvensspektrum, så kallat Ultra Wideband, och är tillverkad av det norska företaget Novelda. Ventricorder har visat sig kunna detektera exempelvis hjärtrörelser och andning men dess kliniska värde har ännu inte undersökts. Cardiac State Diagram (CSD) är ett prekliniskt mjukvaruverktyg för att visualisera hjärtats mekaniska funktion och som har bekräftats genom pilotstudier att kunna användas som underlag för diagnostik och bedömning av hjärtats funktion. Teoretiskt sett är CSD väl lämpat för att användas med Ventricordern eftersom Ventricordern registrerar små rörelser över tid och just ändringar över tid är precis vad som behövs för att skapa ett CSD. I dagsläget används vanligen vävnadsdoppler (TVI) för produktion av CSD och i denna masteruppsats undersöktes huruvida Ventricorder kan användas för att producera CSD. Detta gjordes genom att jämföra mätdata från Ventricorder med temporalt synkroniserade apikala fyrkammar-bilder framställda med vävnadsdoppler. Resultaten indikerar att det finns en påtaglig korrelation mellan dessa data och att mätdatat från en Ventricorder således bör kunna användas för produktion av CSD. Det kvarstår att bekräfta dessa resultat statistiskt med en större testgrupp och att undersöka om samtliga tidsmarkörer som behövs för produktion av ett CSD kan identifieras objektivt.

Cette étude présente la mise au point de mesures de porosité et de vitesse d’écoulement faites par IRM dans des colonnes de billes de verre et de polymère de différentes granulométries saturées en eau. L’avantage des billes en polymère est qu’elles ne contiennent pas d’éléments ferro ou paramagnétiques, contrairement aux billes de verre qui perturbent le champ magnétique créant des artéfacts sur les images IRM. La séquence d’IRM utilisée pour l’étude des écoulements en milieu poreux a été préalablement paramétrée à l’aide d’une étude sur un écoulement de Poiseuille. Deux situations ont été examinées : d’une part, l’observation des écoulements interstitiels entre les billes permet de minimiser les effets de volume partiel et de faciliter la correction du phénomène de repliement de phase. D’autre part, la mesure de vitesses moyennes (Darcy) nécessite d’utiliser simultanément les images de vitesse et les images de porosité. Dans ce cas, il est préférable d’ajuster la puissance des gradients d’encodage de vitesse de façon à éviter tout phénomène de repliement de phase. La géométrie du dispositif utilisé a permis une comparaison rigoureuse des mesures de débit de façon intrinsèque uniquement par IRM (débit en milieu poreux et dans l’espace annulaire) et aussi à partir de la mesure directe du débit (pesée). / This study presents the development of measurement of porosity and velocity of flow made by MRI in packed beds with glass and polymer beads of various size saturated in water. The advantage of polymer beads is that they do not contain elements ferro or paramagnetics, contrary to the glass beads which disrupt the magnetic field creating artifacts on the MRI images. The calibration of the MRI velocity measurements was achieved from Poiseuille flow in a tube at different flow rates. Two situations were examined: first, the observation of interstitial flows between the beads minimizes partial volume effects and facilitates the correction of the phenomenon of phase aliasing. On the other hand, the measurement of average interstitial velocity (Darcy) requires using simultaneous velocity image and porosity image. In this case, it is preferable to adjust the strength of magnetic field gradient in the velocimetry sequence in a way to avoid any phase aliasing. The geometry of the flow cell was chosen to enable comparison by the MRI method between volume flow rates of water in the porous media and in the outer annulus.