The optimal site at which to pace the right ventricle (RV) is still unclear. This study aimed to answer this question utilising cardiac magnetic resonance imaging, which up until recently was contraindicated in pacemaker patient cohorts. The objective was to determine the effect of apical and outflow tract septal pacing on cardiac function and remodeling as assessed by MRI. In addition, physcial and psychological functional parameters were assessed. A series of sub-studies were performed as part of the research. Study 1 validated the velocity phase encoding used to determine flow measurements. This found measurements were reproducible. Study 2 and 3 focused on the method of CPEX testing in pacing dependent patients and whether a training effect was observed with the CPEX testing. It found that treadmill testing resulted in a greater heart rate response and higher VO2 max results. No significant training effect was observed. Study 4 used phantom models to determine the effect of metal susceptibility artefact on mapping and velocity encoded MR sequences. An inverse relationship between artefact and distance from the pacemaker was observed. At approximinately 10 cm from the device, artefact is negligible. Study 5 determined the best methods of image optimization in the presence of the pacemaker. T1 weighted imaging along with spoiled gradient imaging was less affected by artefact compared to late gadolinium and bSSFP imaging. Study 6 evaluated in-house developed software to measure torsion using data derived from commercial available tagging and feature tracking software. At low heart rates measures were comparable but tagging became less accurate with heart rates over 100 bpm. The main study comprised of the baseline data of 50 patients from the ongoing MAPS trial and some intermediate data after 9 months for a smaller cohort. There was not a significant difference in left ventricular volumes or ejection fraction at baseline but differences were observed in deformational indices including longitudinal strain, strain rate, twist and torsion. At 9 months a difference in ejection fraction was observed between the pacing modes along with differences in deformational parameters. Clinically significant differences were not seen between pacing positions at baseline or 9 months but the outflow tract septal position was superior based on deformational data.

Magnetic resonance imaging (MRI) of patients with cardiac implantable electronic devices (CIED) has been associated with risks such as device/lead movement, device dysfunction, and lead heating. New technological advancements have made it possible for MRI to be safely performed when adhering to an evidence-based protocol; however, this practice has not yet been widely adopted. The purpose of this practice-focused question project was to examine the safety of MRI as a diagnostic modality for the aggregate population of adult patients with MR conditional pacemakers when a nurse-practitioner-led, evidence-based protocol was used. The Iowa model served as the guide for implementation of the program, and the Donabedian framework was used to evaluate the program through process, structure, and outcomes. Evidence was obtained through a documentation template that served as the procedural record in the electronic health record. Demographic information, program fidelity, and manufacturer adherence were analyzed through descriptive statistics. Clinical outcomes related to device function were measured pre- and post- MRI and analyzed with chi square and paired t-test inferential statistics to determine if statistically significant change occurs in the setting of MRI scanning. According to data analysis of 34 studies, there were no statistically significant changes in lead impedance, pacing thresholds, or patient reported symptoms pre- and post- MRI. The pilot program has been recommended for organizational adoption and will increase the scope of advanced practice nurses within the organization and provide the CIED aggregate population with access to an important diagnostic modality.

25 years after the first sodium images of the human brain were created, sodium MRI remains on the periphery of MR research, despite intimate sodium involvement in cellular metabolism and implicated abnormal concentrations in numerous disorders. The difficulties of sodium MRI include not only tissue concentration, ~1750x less than proton, but also rapid biexponential signal decay. The purpose of this work was to optimize human brain sodium MRI and facilitate a study of sodium increase following onset of acute human stroke, with potential timing application for those patients who present with unknown time-of-onset, as effective treatment is currently bound by a 4.5 hour time-window. Optimization begins with radial center-out k-space acquisition, which minimizes echo time (TE) and signal loss, and in particular concerns the twisted projection imaging (TPI) technique, which has not found wide use. This thesis first considers a new application of TPI, i.e. k-space filtering by sampling density design to minimize detrimental ringing artifact associated with cerebral spinal fluid. Image noise correlation is addressed next, and a method for measuring volumes of statistical noise independence presented, as this correlation together with signal-to-noise ratio (SNR) defines the confidence of signal-averaging measurements. Radial acquisition is then considered with respect to a new imaging metric, i.e. the minimum object volume that can be precisely (with respect to noise) and accurately (with respect to image intensity modulation with object volume) quantified. It is suggested that TPI is a highly beneficial radial acquisition technique when implemented with long readout duration (countering common thought), reduced SNR (i.e. small voxel volumes), and in particular small TPI parameter p. Sequence optimization for bulk-tissue sodium analysis demonstrates a large SNR/voxel-volume advantage for TPI implementation in a steady-state approach, even though excitation pulse length and TE must be increased to mitigate power deposition. Finally, an inversion-recovery based fluid-nulling method that facilitates sodium environment separation based on rapid relaxation during soft inversion pulses is presented, with possible application for intracellular weighted imaging. On high quality sodium images a clear trend of lesion intensity increase with time-after-onset is demonstrated for the first time in acute stroke patients, as expected from animal models.

There is a clear need for improved methods (e.g. computer modelling, imaging) to characterize the substrate of abnormal rhythms like ventricular tachycardia (VT) developed by patients who have suffered a heart attack. Progress leading to improved disease management and treatment planning (based on predictive models) as well as outcomes assessment will have immediate impact on the quality of life in this large patient population. Prior to integration into clinical applications, the predictive models have to be properly validated using experimental techniques selected to reflect the electrophysiological phenomena at spatio-temporal scales similar to those considered in simulations. This thesis advanced us toward this goal by addressing the challenge of building more accurate models of electrophysiology for individual hearts. A novel construction of a realistic 3D cardiac model from Magnetic Resonance Images (MRI), with a long-term aim to predict propagation of the electrical impulse in normal and pathologic large hearts (translatable to human hearts), and associated inducibility of VT is described. To parameterize the model, an original evaluation method of electrophysiological (EP) characteristics of the heart tissue was used. The method combined state-of-the-art experimental physiology tools like optical fluorescence imaging using voltage-sensitive dyes and a CARTO electro-anatomical system, with a cardiac computer model generated from high resolution MR scans of explanted normal and pathologic porcine hearts. Several input model parameters (e.g., conductivity, anisotropy, restitution) were successfully adjusted using the ex-vivo measurements of action potential to yield close correspondence between model output and experiments. Moreover, a simple, fast, and macroscopic mathematical model was used with computation times less than 1h, attractive for clinical EP applications.

There is a clear need for improved methods (e.g. computer modelling, imaging) to characterize the substrate of abnormal rhythms like ventricular tachycardia (VT) developed by patients who have suffered a heart attack. Progress leading to improved disease management and treatment planning (based on predictive models) as well as outcomes assessment will have immediate impact on the quality of life in this large patient population. Prior to integration into clinical applications, the predictive models have to be properly validated using experimental techniques selected to reflect the electrophysiological phenomena at spatio-temporal scales similar to those considered in simulations. This thesis advanced us toward this goal by addressing the challenge of building more accurate models of electrophysiology for individual hearts. A novel construction of a realistic 3D cardiac model from Magnetic Resonance Images (MRI), with a long-term aim to predict propagation of the electrical impulse in normal and pathologic large hearts (translatable to human hearts), and associated inducibility of VT is described. To parameterize the model, an original evaluation method of electrophysiological (EP) characteristics of the heart tissue was used. The method combined state-of-the-art experimental physiology tools like optical fluorescence imaging using voltage-sensitive dyes and a CARTO electro-anatomical system, with a cardiac computer model generated from high resolution MR scans of explanted normal and pathologic porcine hearts. Several input model parameters (e.g., conductivity, anisotropy, restitution) were successfully adjusted using the ex-vivo measurements of action potential to yield close correspondence between model output and experiments. Moreover, a simple, fast, and macroscopic mathematical model was used with computation times less than 1h, attractive for clinical EP applications.

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are a group of invariably fatal neurodegenerative diseases of both humans and animals, thought to be caused by the abnormally folded prion protein PrPSc. Prion disease research continues to be faced by a number of difficult challenges. First, the unequivocal diagnosis of most prion diseases currently requires the post-mortem collection of central nervous system tissue, either for histological examination or Western blot analysis; second, a viable treatment for clinical stage disease has not yet been identified; third, the exact details of disease pathogenesis have not been elucidated; and fourth, the normal function of PrPC is not definitively known. The primary objective of the studies presented here was to diagnose prion disease in live animals, using Magnetic Resonance Imaging (MRI). Increases in T2 relaxation time and apparent diffusion coefficient (ADC) were observed very early following the infection of Syrian golden hamsters with the 263K strain of scrapie. These changes were evident well before the appearance of either clinical symptoms or the typical histological changes characteristic of prion disease, suggesting that they are the result of the progressive accumulation of fluid, and that this may constitute a novel early marker of prion disease pathogenesis. Following the establishment of this model system, a secondary objective was composed: to test the viability of a potential treatment (pentosan polysulphate) using a number of different treatment regimens. It was determined that pentosan polysulphate (PPS) was ineffective as a treatment unless it was administered intra-cerebrally very early in infection, although it was shown to slow the appearance of the histological hallmarks of prion disease. In response to the results of these studies, a potential model was proposed, relating PrP, aquaporin-4 (AQP4) regulation, and oedema. Although speculative, this model may have implications for both normal PrPC function and disease pathogenesis. / February 2009

Acetabular labral tears are associated with hip osteoarthritis. A current surgical treatment strategy for a torn labrum, labral resection, has recently shown poor patient outcomes with radiographic signs of osteoarthritis two-years post-operation. Since mechanical factors play a role in the etiology of osteoarthritis, identifying the mechanical role of the labrum may enhance current surgical treatment strategies. In this pilot study, we assessed the relationship between mean cartilage strain, maximum cartilage strain and the three-dimensional cartilage strain distribution in six human cadaver hips with various pathologic conditions of the labrum. We developed a novel technique of mapping cartilage strain using quantitative magnetic resonance imaging (qMRl). qMRl provides a non-invasive means of quantifying the cartilage strain distribution in the hip in three dimensions. Each specimen was assessed first with an intact labrum, then after surgically simulating a longitudinal peripheral labral tear, then after arthroscopically repairing the tear, and after labral resection. We validated the precision of the technique through use of an additional specimen which served as a control. To minimize motion artifact in the high-resolution MR images, we determined that 225 minutes was required for cartilage to reach a steady-state thickness under load. We also determined 16.5 hours was required for cartilage to recover to a steady-state unloaded thickness. The difference in mean and maximum cartilage strain when the labrum was repaired and resected was assessed using a paired t-test. We found that the resected group had an increased mean and maximum cartilage strain of 4% and 6%, respectively and the 3D cartilage strain distribution was elevated throughout the region of interest. When the condition of the intact labrum was compared to the torn labrum, we found no change in mean and maximum cartilage strain, and little obvious change in the 3D pattern of cartilage strain distribution. Based on our findings of increased cartilage strain after labral resection when compared to labral repair, we hypothesize that the labrum’s contribution of additional surface area assists in load distribution, which spares cartilage from excessive loads. We therefore recommend that the longitudinal peripheral torn labrum should not be resected if it is possible to be repaired, because in vivo, labral resection may create an environment with increased articular cartilage strain, which is thought to be associated with cartilage degeneration.

Emerging technologies in parallel magnetic resonance imaging (MRI) with massive receiver arrays have paved the way for ultra-fast imaging at increasingly high frame rates. With the increase in the number of receiver channels used to implement parallel imaging techniques, there is a corresponding increase in the amount of data that needs to be processed, slowing down the process of image reconstruction. To develop a complete reconstruction system which is easy to assemble in a single computer for a real-time rendition of images is a relevant challenge demanding dedicated resources for high speed digital data transfer and computation. We have enhanced a 64 channel parallel receiver system designed for single echo acquisition (SEA) MRI into a real-time imaging system by interfacing it with two commercially available digital signal processor (DSP) boards which are capable of transferring large amounts of digital data via a dedicated bus from two high performance digitizer boards. The resulting system has been used to demodulate raw image data in real-time data and store them at rates of 200 frames per second (fps) and subsequently display the processed data at rates of 26 fps. A further interest in realtime reconstruction techniques is to reduce the data handling issues. Novel ways to minimize the digitized data are presented using reduced sampling rate techniques. The proposed techniques reduce the amount of data generated by a factor of 5 without compromising the SNR and with no additional hardware. Finally, the usability of this tool is demonstrated by investigating fast imaging applications. Of particular interest among them are MR elastography applications. An exploratory study of SEA MRE was done to study the temperature dependency of shear stiffness in an agarose gel and the results correlate well with existing literature. With the ability to make MRE images in a single echo, the SEA MRE technique has an advantage over the conventional MRE techniques.

Magnetic Resonance Spectroscopy is known as a valuable diagnostic tool for physicians as well as a research tool for biochemists. In addition to hydrogen (which is the most abundant atom with nuclear magnetic resonance capability), other species (such as 31P or 13C) are used as well, to obtain certain information such as metabolite concentrations in neural or muscular tissues. However, this requires nuclear magnetic resonance (NMR) transmitter/receivers (coils) capable of operating at multiple frequencies, while maintaining a good performance at each frequency. The objective of this work is to discuss various design approaches used for second-nuclei RF (radio frequency) coils, and to analyze the performance of a particular design, which includes using inductor-capacitor (LC) trap circuits on a 31P coil. The method can be easily applied to other nuclei. The main advantage of this trapping method is the enabling design of second-nuclei coils that are insertable into standard proton coils, maintaining a near-optimum performance for both nuclei. This capability is particularly applicable as MRI field strengths increase and the use of specialized proton coils becomes more prevalent. A thorough performance analysis shows the benefit of this method over other designs, which usually impose a significant signal-to-noise (SNR) sacrifice on one of the nuclei. A methodology based on a modular coil configuration was implemented, which allowed for optimization of LC trap decoupling as well as performance analysis. The 31P coil was used in conjunction with various standard 1H coil configurations (surface/volume/array), using the trap design to overcome the coupling problem (degraded SNR performance) mentioned above. An analytical model was developed and guidelines on trap design were provided to help optimize sensitivity. The performance was analyzed with respect to the untrapped case, using RF bench measurements as well as data obtained from the NMR scanner. Insertability of this coil design was then verified by using it with general-purpose proton coils available. Phantoms were built to mimic the phosphorus content normally found in biologic tissues in order to verify applicability of this coil for in vivo studies. The contribution of this work lies in the quantification of general design parameters to enable “insertable” second-nuclei coils, in terms of the effects on SNR and resonance frequency of a given proton coil.

A target field method approach to the design of RF phase gradient fields, intended for TRASE MRI, produced a superposition of axial currents C_m*sin(m*phi) for m=1,2,3..., and a solenoidal current C_0*z (m=0), where C_m are constants. Omission of terms m>2 produced a phase gradient field with a linear phase and uniform magnitude within a target ROI of 2.5 cm diameter. A set of three RF coils (uniform birdcage, gradient mode birdcage, and 4-loop Maxwell) was found to be sufficient to generate both positive and negative x and y phase gradients. In addition, the phase gradient amplitude can be controlled by simply adjusting the power split to the three RF component coils. Bench measurements of an experimentally constructed 1.8 deg/mm transverse phase gradient showed excellent agreement with predicted results. A linear phase and magnitude within ± 4% of the median value was achieved within the ROI. / October 2015