Advanced parallel magnetic resonance imaging methods with applications to MR spectroscopic imaging

Parallel magnetic resonance imaging offers a framework for acceleration of conventional MRI encoding using an array of receiver coils with spatially-varying sensitivities. Novel encoding and reconstruction techniques for parallel MRI are investigated in this dissertation. The main goal is to improve the actual reconstruction methods and to develop new approaches for massively parallel MRI systems that take advantage of the higher information content provided by the large number of small receivers. A generalized forward model and inverse reconstruction with regularization for parallel MRI with arbitrary k-space sub-sampling is developed. Regularization methods using the singular value decomposition of the encoding matrix and pre-conditioning of the forward model are proposed to desensitize the solution from data noise and model errors. Variable density k-space sub-sampling is presented to improve the reconstruction with the common uniform sub-sampling. A novel method for massively parallel MRI systems named Superresolution Sensitivity Encoding (SURE-SENSE) is proposed where acceleration is performed by acquiring the low spatial resolution representation of the object being imaged and the stronger sensitivity variation from small receiver coils is used to perform intra-pixel reconstruction. SURE-SENSE compares favorably the performance of standard SENSE reconstruction for low spatial resolution imaging such as spectroscopic imaging. The methods developed in this dissertation are applied to Proton Echo Planar Spectroscopic Imaging (PEPSI) for metabolic imaging in human brain with high spatial and spectral resolution in clinically feasible acquisition times. The contributions presented in this dissertation are expected to provide methods that substantially enhance the utility of parallel MRI for clinical research and to offer a framework for fast MRSI of human brain with high spatial and spectral resolution

Quantitative Susceptibility Imaging of Tissue Microstructure Using Ultra-High Field MRI

This thesis has used ultra-high field (UHF) magnetic resonance imaging (MRI) to investigate the fundamental relationships between tissue microstructure and such susceptibility-based contrast parameters as the apparent transverse relaxation rate (R2*), the local Larmor frequency shift (LFS) and quantitative volume magnetic susceptibility (QS). The interaction of magnetic fields with biological tissues results in shifts in the LFS which can be used to distinguish underlying cellular architecture. The LFS is also linked to the relaxation properties of tissues in a gradient echo MRI sequence. Equally relevant, histological analysis has identified iron and myelin as two major sources of the LFS. As a result, computation of LFS and the associated volume magnetic susceptibility from MRI phase data may serve as a significant method for in vivo monitoring of changes in iron and myelin associated with normal, healthy aging, as well as neurological disease processes. In this research, the cellular level underpinnings of the R2* and LFS signals were examined in a model rat brain system using 9.4 T MRI. The study was carried out using biophysical modeling and correlation with quantitative histology. For the first time, multiple biophysical modeling schemes were compared in both gray and white matter of excised rat brain tissue. Suprisingly, R2* dependence on tissue orientation has not been fully understood. Accordingly, scaling relations were derived for calculating the reversible, mesoscopic magnetic field component, R2\u27, of the apparent transverse relaxation rate from the orientation dependence in gray and white matter. Our results demonstrate that the orientation dependence of R2* and LFS in both white and cortical gray matter has a sinusoidal dependence on tissue orientation and a linear dependence on the volume fraction of myelin in the tissue. A susceptibility processing pipeline was also developed and applied to the calculation of phase-combined LFS and QS maps. The processing pipeline was subsequently used to monitor myelin and iron changes in multiple sclerosis (MS) patients compared to healthy, age and gender-matched controls. With the use of QS and R2* mapping, evidence of statistically significant increases in iron deposition in sub-cortical gray matter, as well as myelin degeneration along the white matter skeleton, were identified in MS patients. The magnetic susceptibility-based MRI methods were then employed as potential clinical biomarkers for disease severity monitoring of MS. It was demonstrated that the combined use of R2* and QS, obtained from multi-echo gradient echo MRI, could serve as an improved metric for monitoring both gray and white matter changes in early MS

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

Adaptive kernel estimation for enhanced filtering and pattern classification of magnetic resonance imaging: novel techniques for evaluating the biomechanics and pathologic conditions of the lumbar spine

This dissertation investigates the contribution the lumbar spine musculature has on etiological and pathogenic characteristics of low back pain and lumbar spondylosis. This endeavor necessarily required a two-step process: 1) design of an accurate post-processing method for extracting relevant information via magnetic resonance images and 2) determine pathological trends by elucidating high-dimensional datasets through multivariate pattern classification. The lumbar musculature was initially evaluated by post-processing and segmentation of magnetic resonance (MR) images of the lumbar spine, which characteristically suffer from nonlinear corruption of the signal intensity. This so called intensity inhomogeneity degrades the efficacy of traditional intensity-based segmentation algorithms. Proposed in this dissertation is a solution for filtering individual MR images by extracting a map of the underlying intensity inhomogeneity to adaptively generate local estimates of the kernel’s optimal bandwidth. The adaptive kernel is implemented and tested within the structure of the non-local means filter, but also generalized and extended to the Gaussian and anisotropic diffusion filters. Testing of the proposed filters showed that the adaptive kernel significantly outperformed their non-adaptive counterparts. A variety of performance metrics were utilized to measure either fine feature preservation or accuracy of post-processed segmentation. Based on these metrics the adaptive filters proposed in this dissertation significantly outperformed the non-adaptive versions. Using the proposed filter, the MR data was semi-automatically segmented to delineate between adipose and lean muscle tissues. Two important findings were reached utilizing this data. First, a clear distinction between the musculature of males and females was established that provided 100% accuracy in being able to predict gender. Second, degenerative lumbar spines were accurately predicted at a rate of up to 92% accuracy. These results solidify prior assumptions made regarding sexual dimorphic anatomy and the pathogenic nature of degenerative spine disease

Beat Pilot Tone: Versatile, Contact-Free Motion Sensing in MRI with Radio Frequency Intermodulation

Motion in Magnetic Resonance Imaging (MRI) scans results in image corruption and remains a barrier to clinical imaging. Motion correction algorithms require accurate sensing, but existing sensors are limited in sensitivity, comfort, or general usability. We propose Beat Pilot Tone (BPT), a radio frequency (RF) motion sensing system that is sensitive, comfortable, versatile, and scalable. BPT operates by a novel mechanism: two or more transmitted RF tones form standing wave patterns that are modulated by motion and sensed by the same receiver coil arrays used for MR imaging. By serendipity, the tones are mixed through nonlinear intermodulation in the receiver chain and digitized simultaneously with the MRI data. We demonstrate BPT's mechanism in simulations and experiments. Furthermore, we show in healthy volunteers that BPT can sense head, bulk, respiratory, and cardiac motion, including small vibrations such as displacement ballistocardiograms. BPT can distinguish between different motion types, achieve greater sensitivity than other methods, and operate as a multiple-input multiple-output (MIMO) system. Thus, BPT can enable motion-robust MRI scans at high spatiotemporal resolution in many applications

Application of Parallel Imaging to Murine Magnetic Resonance Imaging

The use of parallel imaging techniques for image acceleration is now common in clinical magnetic resonance imaging (MRI). There has been limited work, however, in translating the parallel imaging techniques to routine animal imaging. This dissertation describes foundational level work to enable parallel imaging of mice on a 4.7 Tesla/40 cm bore research scanner. Reducing the size of the hardware setup associated with typical parallel imaging was an integral part of achieving the work, as animal scanners are typically small-bore systems. To that end, an array element design is described that inherently decouples from a homogenous transmit field, potentially allowing for elimination of typically necessary active detuning switches. The unbalanced feed of this "dual-plane pair" element also eliminates the need for baluns in this case. The use of the element design in a 10-channel adjustable array coil for mouse imaging is presented, styled as a human cardiac top-bottom half-rack design. The design and construction of the homogenous transmit birdcage coil used is also described, one of the necessary components to eliminating the active detuning networks on the array elements. In addition, the design of a compact, modular multi-channel isolation preamplifier board is described, removing the preamplifiers from the elements and saving space in the bore. Several additions/improvements to existing laboratory infrastructure needed for parallel imaging of live mice are also described, including readying an animal preparation area and developing the ability to maintain isoflurane anesthesia delivery during scanning. In addition, the ability to trigger the MRI scanner to the ECG and respiratory signals from the mouse in order to achieve images free from physiological motion artifacts is described. The imaging results from the compact 10-channel mouse array coils are presented, and the challenges associated with the work are described, including difficulty achieving sample-loss dominance and signal-to-noise ratio (SNR) limitations. In conclusion, in vivo imaging of mice with cardiac and respiratory gating has been demonstrated. Compact array coils tailored for mice have been studied and potential future work and design improvements for our lab in this area are discussed

Auditory feedback control mechanisms do not contribute to cortical hyperactivity within the voice production network in adductor spasmodic dysphonia

Adductor spasmodic dysphonia (ADSD), the most common form of spasmodic dysphonia, is a debilitating voice disorder characterized by hyperactivity and muscle spasms in the vocal folds during speech. Prior neuroimaging studies have noted excessive brain activity during speech in ADSD participants compared to controls. Speech involves an auditory feedback control mechanism that generates motor commands aimed at eliminating disparities between desired and actual auditory signals. Thus, excessive neural activity in ADSD during speech may reflect, at least in part, increased engagement of the auditory feedback control mechanism as it attempts to correct vocal production errors detected through audition. To test this possibility, functional magnetic resonance imaging was used to identify differences between ADSD participants and age-matched controls in (i) brain activity when producing speech under different auditory feedback conditions, and (ii) resting state functional connectivity within the cortical network responsible for vocalization. The ADSD group had significantly higher activity than the control group during speech (compared to a silent baseline task) in three left-hemisphere cortical regions: ventral Rolandic (sensorimotor) cortex, anterior planum temporale, and posterior superior temporal gyrus/planum temporale. This was true for speech while auditory feedback was masked with noise as well as for speech with normal auditory feedback, indicating that the excess activity was not the result of auditory feedback control mechanisms attempting to correct for perceived voicing errors in ADSD. Furthermore, the ADSD group had significantly higher resting state functional connectivity between sensorimotor and auditory cortical regions within the left hemisphere as well as between the left and right hemispheres, consistent with the view that excessive motor activity frequently co-occurs with increased auditory cortical activity in individuals with ADSD.First author draf

Constrained and Spectral-Spatial RF Pulse Design for Magnetic Resonance Imaging

Magnetic Resonance Imaging (MRI) provides a non-invasive glimpse inside the human body, generates excellent soft tissue contrast, uses non-ionizing radiation, and has become a critical tool in diagnosis of disease in medicine. Radio Frequency (RF) pulses are an integral component of MRI pulse sequences and can be tailored to particular applications. This dissertation explores the MRI physics, convex optimization problems, and experimental methodologies required for the design of tailored RF pulses First, we introduce constrained RF pulse design, a process that incorporates meaningful, physical constraints, such as peak RF amplitude and integrated RF power, and enables efficient RF pulse design. With this process we explore simultaneous multislice (SMS) imaging, a method used to accelerate MRI and combat notoriously long acquisition times. Compared to an SMS pulse designed without constraints, our constrained pulses achieved lower magnitude normalized root mean squared error (NRMSE) for an equivalent RF pulse length, or alternatively, the same NRMSE for a shorter pulse length. Constrained RF pulse design forms a basis for the rest of the dissertation. Second, we show that prewinding pulses, a special class of RF pulses, help reduce signal loss due to intravoxel dephasing generated by magnetic field inhomogeneities. We propose a spectral-spatial prewinding pulse that leverages a larger effective recovery bandwidth than equivalent, purely spectral pulses. In an in vivo experiment imaging the brain of a human volunteer, we designed spectral-spatial pulses with a complex NRMSE of 0.18, which is significantly improved from the complex NRMSE of 0.54 in the purely spectral pulse for the same experiment. Finally, we consider a slab-selective prewinding pulse, that extends spectral and spectral-spatial prewinding pulses to a common 3D imaging method. Here we integrate optimal control optimization to further improve the slab-selective spectral pulse design and see an in vivo improvement of excitation NRMSE from 0.40 to 0.37. In the context of a steady-state sequence small-tip fast recovery (STFR), we also show a major reduction in mean residual transverse magnetization magnitude after the STFR “tip-up” recovery pulse from 0.18 to 0.02 when adding optimal control. This method has the potential to connect prewinding pulse design from the MRI physicist engineering workspace to a clinical application. In summary, we show that constrained RF pulse design provides an efficient way of improving MRI in terms of acquisition speed (via multislice imaging) and image quality (via signal recovery).PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/147647/1/sydneynw_1.pd