HYPERPOLARIZED CARBON-13 MAGNETIC RESONANCE MEASUREMENTS OF TISSUE PERFUSION AND METABOLISM

Hyperpolarized Magnetic Resonance Imaging (HP MRI) is an emerging modality that enables non-invasive interrogation of cells and tissues with unprecedented biochemical detail. This technology provides rapid imaging measurements of the activity of a small quantity of molecules with a strongly polarized nuclear magnetic moment. This polarization is created in a polarizer separate from the imaging magnet, and decays continuously towards a non-detectable thermal equilibrium once the imaging agent is removed from the polarizer and administered by intravenous injection. Specialized imaging strategies are therefore needed to extract as much information as possible from the HP signal during its limited lifetime. In this work, we present innovative strategies for measurement of tissue perfusion and metabolism with HP MRI. These techniques include the capacity to sensitize the imaging signal to the diffusive motion of HP molecules, providing improved accuracy and reproducibility for assessment of agent uptake in tissue. The proposed methods were evaluated in numerical simulations, implemented on a preclinical MRI system and demonstrated in vivo in rodents through imaging of HP 13C urea. Using the simulation and imaging infrastructure developed in this work, established methods for encoding HP chemical signals were compared quantitatively. Lastly, our method was adapted for imaging of [2-13C]dihydroxyacetone, a novel HP agent that probes enzymatic flux through multiple biochemical pathways in vivo. Our results demonstrate the capacity of HP MRI to measure tissue perfusion and metabolism in ways not possible with the imaging modalities currently available in the clinic. As the use of HP MRI advances in clinical investigations of human disease, these imaging measurements can offer real-time and individualized information on disease states for early detection and therapeutic guidance

Magnetic Resonance Velocimetry for Fast Liquid Flows

Magnetic Resonance Velocimetry for Fast Liquid Flow

Robust Arterial Spin Labeling T2 Measurements

Perfusion and bolus arrival time are often quantified physiological parameters. By additionally quantifying permeability it is hoped to better understand tissue physiology or monitor small permeability changes in cerebrovascular diseases, which are difficult to detect by traditional gadolinium contrast agents. A problem of gadolinium contrast agents is the size of the macro molecules. They cannot pass an intact or slightly damaged blood brain barrier, whereas hydrogen molecules are small enough to pass it. In arterial spin labeling (ASL) the hydrogen spins of the water molecules in inflowing blood are selectively inverted and can be used as a non-invasive endogenous contrast agent. In standard ASL modules, generally only T1 effects are considered. This is sufficient for perfusion and arrival time but not for capillary wall permeability quantification, due to the small difference of blood and tissue T1 times. In contrast to this, T2 times of blood and tissue are considerably different, which makes arterial spin labeling T2 measurements a potential method for permeability estimations if current modules are extended and optimized to include T2. Yet, accurate T2 calculations are often very time consuming, limiting the acquisition for an individual patient and the general implementation in clinical routine. In the present work, acquisition techniques and fitting routines of a multi-TI multi-TE 3D-GRASE (gradient and spin echo) sequence are presented allowing a fast and reliable T2 calculation at every inflow time, which can be used for permeability estimations. An optimized acquisition scheme and T2 calculation algorithm is found with regard to accuracy, measurement time, and signal-to-noise ratio (SNR). The concept of adaptive averaging is presented, which allows the acquisition of longer inflow times more often than shorter ones, improving SNR at long inflow times by 1.5 and more, but by simultaneously keeping the total scan time constant. The impact on T2 calculations from stimulated echoes in combination with different kinds of crusher gradients at several refocusing flip angles is evaluated in phantoms and volunteers. The fitted T2 results are compared to simulations and gold standard single spin echo T2 values. Finally, T2 values at multiple inflow times with different turbo factors (TF) are obtained. The impact of the turbo factor on the T2 calculation is simulated and verified in a volunteer study, resulting in a suggestion for an optimised imaging scheme for TF>1. For TF1 the multi-TE ASL 3D-GRASE sequence is already capable of T2 measurements at multiple inflow times, very close to T2 values obtained with the gold standard single spin echo sequence. The T2 values could be directly incorporated in a two compartment model for perfusion quantification, to further study tissue functions or disease related to permeability changes

Robust Arterial Spin Labeling T2 Measurements

Perfusion and bolus arrival time are often quantified physiological parameters. By additionally quantifying permeability it is hoped to better understand tissue physiology or monitor small permeability changes in cerebrovascular diseases, which are difficult to detect by traditional gadolinium contrast agents. A problem of gadolinium contrast agents is the size of the macro molecules. They cannot pass an intact or slightly damaged blood brain barrier, whereas hydrogen molecules are small enough to pass it. In arterial spin labeling (ASL) the hydrogen spins of the water molecules in inflowing blood are selectively inverted and can be used as a non-invasive endogenous contrast agent. In standard ASL modules, generally only T1 effects are considered. This is sufficient for perfusion and arrival time but not for capillary wall permeability quantification, due to the small difference of blood and tissue T1 times. In contrast to this, T2 times of blood and tissue are considerably different, which makes arterial spin labeling T2 measurements a potential method for permeability estimations if current modules are extended and optimized to include T2. Yet, accurate T2 calculations are often very time consuming, limiting the acquisition for an individual patient and the general implementation in clinical routine. In the present work, acquisition techniques and fitting routines of a multi-TI multi-TE 3D-GRASE (gradient and spin echo) sequence are presented allowing a fast and reliable T2 calculation at every inflow time, which can be used for permeability estimations. An optimized acquisition scheme and T2 calculation algorithm is found with regard to accuracy, measurement time, and signal-to-noise ratio (SNR). The concept of adaptive averaging is presented, which allows the acquisition of longer inflow times more often than shorter ones, improving SNR at long inflow times by 1.5 and more, but by simultaneously keeping the total scan time constant. The impact on T2 calculations from stimulated echoes in combination with different kinds of crusher gradients at several refocusing flip angles is evaluated in phantoms and volunteers. The fitted T2 results are compared to simulations and gold standard single spin echo T2 values. Finally, T2 values at multiple inflow times with different turbo factors (TF) are obtained. The impact of the turbo factor on the T2 calculation is simulated and verified in a volunteer study, resulting in a suggestion for an optimised imaging scheme for TF>1. For TF1 the multi-TE ASL 3D-GRASE sequence is already capable of T2 measurements at multiple inflow times, very close to T2 values obtained with the gold standard single spin echo sequence. The T2 values could be directly incorporated in a two compartment model for perfusion quantification, to further study tissue functions or disease related to permeability changes

Doctor of Philosophy

dissertationMagnetic resonance imaging (MRI) techniques are widely applied in various disease diagnoses and scientific research projects as noninvasive methods. However, lower signal-to-noise ratio (SNR), B1 inhomogeneity, motion-related artifact, susceptibility artifact, chemical shift artifact and Gibbs ring still play a negative role in image quality improvement. Various techniques and methods were developed to minimize and remove the degradation of image quality originating from artifacts. In the first part of this dissertation, a motion artifact reduction technique based on a novel real time self-gated pulse sequence is presented. Diffusion weighted and diffusion tensor magnetic resonance imaging techniques are generally performed with signal averaging of multiple measurements to improve the signal-to-noise ratio and the accuracy of diffusion measurement. Any discrepancy in images between different averages causes errors that reduce the accuracy of diffusion MRI measurements. The new scheme is capable of detecting a subject's motion and reacquiring motion-corrupted data in real time and helps to improve the accuracy of diffusion MRI measurements. In the second part of this dissertation, a rapid T1 mapping technique (two dimensional singleshot spin echo stimulated echo planar image--2D ss-SESTEPI), which is an EPI-based singleshot imaging technique that simultaneously acquires a spin-EPI (SEPI) and a stimulated-EPI (STEPI) after a single RF excitation, is discussed. The magnitudes of SEPI and STEPI differ by T1 decay for perfect 90o RF pulses and can be used to rapidly measure the T1 relaxation time. However, the spatial variation of B1 amplitude induces uneven splitting of the transverse magnetization for SEPI and STEPI within the imaging FOV. Therefore, correction for B1 inhomogeneity is critical for 2D ss-SESTEPI to be used for T1 measurement. In general, the EPI-based pulse sequence suffers from geometric distortion around the boundary of air-tissue or bone tissue. In the third part of this dissertation, a novel pulse sequence is discussed, which was developed based on three dimensional singleshot diffusion weighted stimulated echo planar imaging (3D ss-DWSTEPI). A parallel imaging technique was combined with 3D ss-DWSTEPI to reduce the image distortion, and the secondary spin echo formed by three RF pulses (900-1800-900) is used to improve the SNR. Image quality is improved

Design of spectralâ spatial phase prewinding pulses and their use in smallâ tip fast recovery steadyâ state imaging

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141089/1/mrm26794_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141089/2/mrm26794.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141089/3/mrm26794-sup-0001-suppinfo.pd