Doctor of Philosophy

dissertationThis dissertation presents original research that improves the ability of magnetic resonance imaging (MRI) to measure temperature in aqueous tissue using the proton resonance frequency (PRF) shift and T1 measurements in fat tissue in order to monitor focused ultrasound (FUS) treatments. The inherent errors involved in measuring the longitudinal relaxation time T1 using the variable flip angle method with a two-dimensional (2D) acquisition are presented. The edges of the slice profile can contribute a significant amount of signal for large flip angles at steady state, which causes significant errors in the T1 estimate. Only a narrow range of flip angle combinations provided accurate T1 estimates. Respiration motion causes phase artifacts, which lead to errors when measuring temperature changes using the PRF method. A respiration correction method for 3D imaging temperature of the breast is presented. Free induction decay (FID) navigators were used to measure and correct phase offsets induced by respiration. The precision of PRF temperature measurements within the breast was improved by an average factor of 2.1 with final temperature precision of approximately 1 °C. Locating the position of the ultrasound focus in MR coordinates of an ultrasound transducer with multiple degrees of freedom can be difficult. A rapid method for predicting the position using 3 tracker coils with a special MRI pulse iv sequence is presented. The Euclidean transformation of the coil's current positions to their calibration positions was used to predict the current focus position. The focus position was predicted to within approximately 2.1 mm in less than 1 s. MRI typically has tradeoffs between imaging field of view and spatial and temporal resolution. A method for acquiring a large field of view with high spatial and temporal resolution is presented. This method used a multiecho pseudo-golden angle stack of stars imaging sequence to acquire the large field of view with high spatial resolution and k-space weighted image contrast (KWIC) to increase the temporal resolution. The pseudo-golden angle allowed for removal of artifacts introduced by the KWIC reconstruction algorithm. The multiple echoes allowed for high readout bandwidth to reduce blurring due to off resonance and chemical shift as well as provide separate water/fat images, estimates of the initial signal magnitude M(0), T2 * time constant, and combination of echo phases. The combined echo phases provided significant improvement to the PRF temperature precision, and ranged from ~0.3-1.0 °C within human breast. M(0) and T2 * values can possibly be used as a measure of temperature in fat

A new class of smart gadolinium contrast agent for tissue pH probing using magnetic resonance imaging

Detecting tissue pH in vivo is extremely vital for medical diagnosis and formulation of treatment decisions. To this end, many investigations have been carried out to develop an accurate and efficient method of in vivo pH measurement. Most of the techniques developed so far suffer from inadequate accuracy, due to poor sensitivity at low concentration of the target or nonspecific interactions within the tissue matrix. To overcome these issues, we describe herein the development of a simple, yet reliable, way to estimate pH with high precision using a Gd(III)-DOTA-silyl-based acid-labile group as a pH-sensitive contrast agent with Magnetic Resonance Imaging (MRI). With this method, a change in T1 weighted image intensity of the newly developed pH-sensitive contrast is directly linked to the proton concentration in the media. As a result, we were able estimate the pH of the target with 95% reliability

Towards in vivo g-ratio mapping using MRI: unifying myelin and diffusion imaging

The g-ratio, quantifying the comparative thickness of the myelin sheath encasing an axon, is a geometrical invariant that has high functional relevance because of its importance in determining neuronal conduction velocity. Advances in MRI data acquisition and signal modelling have put in vivo mapping of the g-ratio, across the entire white matter, within our reach. This capacity would greatly increase our knowledge of the nervous system: how it functions, and how it is impacted by disease. This is the second review on the topic of g-ratio mapping using MRI. As such, it summarizes the most recent developments in the field, while also providing methodological background pertinent to aggregate g-ratio weighted mapping, and discussing pitfalls associated with these approaches. Using simulations based on recently published data, this review demonstrates the relevance of the calibration step for three myelin-markers (macromolecular tissue volume, myelin water fraction, and bound pool fraction). It highlights the need to estimate both the slope and offset of the relationship between these MRI-based markers and the true myelin volume fraction if we are really to achieve the goal of precise, high sensitivity g-ratio mapping in vivo. Other challenges discussed in this review further evidence the need for gold standard measurements of human brain tissue from ex vivo histology. We conclude that the quest to find the most appropriate MRI biomarkers to enable in vivo g-ratio mapping is ongoing, with the potential of many novel techniques yet to be investigated.Comment: Will be published as a review article in Journal of Neuroscience Methods as parf of the Special Issue with Hu Cheng and Vince Calhoun as Guest Editor

Incorporating Relaxivities to More Accurately Reconstruct MR Images

Purpose To develop a mathematical model that incorporates the magnetic resonance relaxivities into the image reconstruction process in a single step. Materials and methods In magnetic resonance imaging, the complex-valued measurements of the acquired signal at each point in frequency space are expressed as a Fourier transformation of the proton spin density weighted by Fourier encoding anomalies: T2⁎, T1, and a phase determined by magnetic field inhomogeneity (∆B) according to the MR signal equation. Such anomalies alter the expected symmetry and the signal strength of the k-space observations, resulting in images distorted by image warping, blurring, and loss in image intensity. Although T1 on tissue relaxation time provides valuable quantitative information on tissue characteristics, the T1 recovery term is typically neglected by assuming a long repetition time. In this study, the linear framework presented in the work of Rowe et al., 2007, and of Nencka et al., 2009 is extended to develop a Fourier reconstruction operation in terms of a real-valued isomorphism that incorporates the effects of T2⁎, ∆B, and T1. This framework provides a way to precisely quantify the statistical properties of the corrected image-space data by offering a linear relationship between the observed frequency space measurements and reconstructed corrected image-space measurements. The model is illustrated both on theoretical data generated by considering T2⁎, T1, and/or ∆B effects, and on experimentally acquired fMRI data by focusing on the incorporation of T1. A comparison is also made between the activation statistics computed from the reconstructed data with and without the incorporation of T1 effects. Result Accounting for T1 effects in image reconstruction is shown to recover image contrast that exists prior to T1 equilibrium. The incorporation of T1 is also shown to induce negligible correlation in reconstructed images and preserve functional activations. Conclusion With the use of the proposed method, the effects of T2⁎ and ∆B can be corrected, and T1 can be incorporated into the time series image-space data during image reconstruction in a single step. Incorporation of T1 provides improved tissue segmentation over the course of time series and therefore can improve the precision of motion correction and image registration

IMAGING POTENTIAL IN SATURATION RECOVERY METHODS FOR SARCOIDOSIS PATIENTS WITH MEDICAL DEVICES

Cardiovascular magnetic resonance (CMR) imaging is a preferred imaging methodology due to its lack of ionizing radiation and ability to detect myocardial inflammation and fibrosis using quantitative T1 mapping techniques. Cardiac sarcoidosis (CS) is characterized as the formation of granulomas in the myocardium. Current methods for detection include measuring non-cardiac specific C-reactive protein (CRP) levels, or PET imaging, which uses ionizing radiation, therefore CMR would make an ideal imaging option. However, many CS patients have implanted cardiac devices which can cause degradation in image. The modified Look-Locker inversion recovery (MOLLI) method is widely used in quantitative T1 mapping with high precision but low accuracy and susceptibility to artifact. Newer methods like saturation recovery single-shot acquisition (SASHA) may be less susceptible to field inhomogeneities but have yet to be compared directly to MOLLI in CS patients with implanted devices. T1-values can further be affected by how the signal data is compiled, or their readout. Common readouts include balanced steady-state free precession (TRUFI) and fast low angle shot (FLASH). First, SASHA sequences provided more consistent images that can be used for diagnostic purposes while MOLLI varied between extreme image quality categories. Finally, SASHA techniques in general show lower variability while GRE readouts suggest higher reproducibility between multiple scans. Through this sub-analysis study, SASHA TRUFI, MOLLI TRUFI, SASHA FLASH, and MOLLI FLASH sequences were optimized to move forward with primary studies of CS patients in the MRI field