Robust Magnetic Resonance Imaging of Short T2 Tissues

Tissues with short transverse relaxation times are defined as ‘short T2 tissues’, and short T2 tissues often appear dark on images generated by conventional magnetic resonance imaging techniques. Common short T2 tissues include tendons, meniscus, and cortical bone. Ultrashort Echo Time (UTE) pulse sequences can provide morphologic contrasts and quantitative maps for short T2 tissues by reducing time-of-echo to the system minimum (e.g., less than 100 us). Therefore, UTE sequences have become a powerful imaging tool for visualizing and quantifying short T2 tissues in many applications. In this work, we developed a new Flexible Ultra Short time Echo (FUSE) pulse sequence employing a total of thirteen acquisition features with adjustable parameters, including optimized radiofrequency pulses, trajectories, choice of two or three dimensions, and multiple long-T2 suppression techniques. Together with the FUSE sequence, an improved analytical density correction and an auto-deblurring algorithm were incorporated as part of a novel reconstruction pipeline for reducing imaging artifacts. Firstly, we evaluated the FUSE sequence using a phantom containing short T2 components. The results demonstrated that differing UTE acquisition methods, improving the density correction functions and improving the deblurring algorithm could reduce the various artifacts, improve the overall signal, and enhance short T2 contrast. Secondly, we applied the FUSE sequence in bovine stifle joints (similar to the human knee) for morphologic imaging and quantitative assessment. The results showed that it was feasible to use the FUSE sequence to create morphologic images that isolate signals from the various knee joint tissues and carry out comprehensive quantitative assessments, using the meniscus as a model, including the mappings of longitudinal relaxation (T1) times, quantitative magnetization transfer parameters, and effective transverse relaxation (T2*) times. Lastly, we utilized the FUSE sequence to image the human skull for evaluating its feasibility in synthetic computed tomography (CT) generation and radiation treatment planning. The results demonstrated that the radiation treatment plans created using the FUSE-based synthetic CT and traditional CT data were able to present comparable dose calculations with the dose difference of mean less than a percent. In summary, this thesis clearly demonstrated the need for the FUSE sequence and its potential for robustly imaging short T2 tissues in various applications

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

Magnetisation transfer effects at ultra high field MRI

Increased signal to noise ratio in ultra high field Magnetic Resonance Imaging (MRI) has allowed the development of quantitative imaging techniques and new contrast mechanisms, such as Chemical Exchange Saturation Transfer (CEST) to be probed. The development of CEST contrast imaging has involved overcoming a number of technical challenges associated with ultra high field MRI. The B1 transmit field was, and still is, a major challenge. Presented in this thesis, the B1 transmit field in regions of low B1 are improved with the use of dielectric pads and a simulation study shows that the overall B1 transmit field homogeneity is significantly improved when multi-transmit slice-selective RF spokes pulse sequences are used. Multiple methods have been developed to quantify the chemical exchange from slow exchanging proton pools seen in CEST contrast imaging. However, magnetisation transfer (MT) from the macromolecular bound pool contaminates current quantification methods, and presented in this thesis is a method whereby the CEST and MT are simultaneously saturated using dual frequency saturation pulses, allowing the CEST contrast in z-spectra to be separated from the MT and to enhance visualisation of the CEST effects. Despite the considerable interest in CEST, only one study has probed the CEST effects in blood, and interestingly high levels of CEST signals can be observed from the superior sagittal sinus. To investigate these effects, z-spectra from ex vivo blood samples considering the effects of oxygenation, haematocrit levels and cell structure were quantified. Quantification shows that the main source of the CEST signals was from the cells within the blood

Magnetic Resonance Imaging of Short-T2 Tissues with Applications for Quantifying Cortical Bone Water and Myelin

The human body contains a variety of tissue species with short T2 ranging from a few microseconds to hundreds of microseconds. Detection and quantification of these short-T2 species is of considerable clinical and scientific interest. Cortical bone water and myelin are two of the most important tissue constituents. Quantification of cortical bone water concentration allows for indirect estimation of bone pore volume and noninvasive assessment of bone quality. Myelin is essential for the proper functioning of the central nervous system (CNS). Direct assessment of myelin would reveal CNS abnormalities and enhance our understanding of neurological diseases. However, conventional MRI with echo times of several milliseconds or longer is unable to detect these short-lived MR signals. Recent advances in MRI technology and hardware have enabled development of a number of short-T2 imaging techniques, key among which are ultra-short echo time (UTE) imaging, zero echo time (ZTE) imaging, and sweep imaging with Fourier transform (SWIFT). While these pulse sequences are able to detect short-T2 species, they still suffer from signal interference between different T2 tissue constituents, image artifacts and excessive scan time. These are primary technical hurdles for application to whole-body clinical scanners. In this thesis research, new MRI techniques for improving short-T2 tissue imaging have been developed to address these challenges with a focus on direct detection and quantification of cortical bone water and myelin on a clinical MRI scanner. The first focus of this research was to optimize long-T2 suppression in UTE imaging. Saturation and adiabatic RF pulses were designed to achieve maximum long-T2 suppression while maximizing the signal from short-T2 species. The imaging protocols were optimized by Bloch equation simulations and were validated using phantom and in vivo experiments. The results show excellent short-T2 contrast with these optimized pulse sequences. The problem of blurring artifacts resulting from the inhomogeneous excitation profile of the rectangular pulses in ZTE imaging was addressed. The proposed approach involves quadratic phase-modulated RF excitation and iterative solution of an inverse problem formulated from the signal model of ZTE imaging and is shown to effectively remove the image artifacts. Subsequently image acquisition efficiency was improved in order to attain clinically-feasible scan times. To accelerate the acquisition speed in UTE and ZTE imaging, compressed sensing was applied with a hybrid 3D UTE sequence. Further, the pulse sequence and reconstruction procedure were modified to enable anisotropic field-of-view shape conforming to the geometry of the elongated imaged object. These enhanced acquisition techniques were applied to the detection and quantification of cortical bone water. A new biomarker, the suppression ratio (a ratio image derived from two UTE images, one without and the other with long-T2 suppression), was conceived as a surrogate measure of cortical bone porosity. Experimental data suggest the suppression ratio may be a more direct measure of porosity than previously measured total bone water concentration. Lastly, the feasibility of directly detecting and quantifying spatially-resolved myelin concentration with a clinical imager was explored, both theoretically and experimentally. Bloch equation simulations were conducted to investigate the intrinsic image resolution and the fraction of detectable myelin signal under current scanner hardware constraints. The feasibility of quantitative ZTE imaging of myelin extract and lamb spinal cord at 3T was demonstrated. The technological advances achieved in this dissertation research may facilitate translation of short-T2 MRI methods from the laboratory to the clinic

Magnetisation transfer effects at ultra high field MRI

Increased signal to noise ratio in ultra high field Magnetic Resonance Imaging (MRI) has allowed the development of quantitative imaging techniques and new contrast mechanisms, such as Chemical Exchange Saturation Transfer (CEST) to be probed. The development of CEST contrast imaging has involved overcoming a number of technical challenges associated with ultra high field MRI. The B1 transmit field was, and still is, a major challenge. Presented in this thesis, the B1 transmit field in regions of low B1 are improved with the use of dielectric pads and a simulation study shows that the overall B1 transmit field homogeneity is significantly improved when multi-transmit slice-selective RF spokes pulse sequences are used. Multiple methods have been developed to quantify the chemical exchange from slow exchanging proton pools seen in CEST contrast imaging. However, magnetisation transfer (MT) from the macromolecular bound pool contaminates current quantification methods, and presented in this thesis is a method whereby the CEST and MT are simultaneously saturated using dual frequency saturation pulses, allowing the CEST contrast in z-spectra to be separated from the MT and to enhance visualisation of the CEST effects. Despite the considerable interest in CEST, only one study has probed the CEST effects in blood, and interestingly high levels of CEST signals can be observed from the superior sagittal sinus. To investigate these effects, z-spectra from ex vivo blood samples considering the effects of oxygenation, haematocrit levels and cell structure were quantified. Quantification shows that the main source of the CEST signals was from the cells within the blood