Toward fast and robust in vivo MR quantification of microvasculature

Department of Biomedical EngineeringMagnetic resonance imaging (MRI) assessments of microvascular anatomy and function in diseases, such as cancer and neurodegenerations are important for detecting abnormal vascular behavior and monitoring therapeutic progress in a noninvasive manner. In MRI, quantitative microvascular biomarkers such as vessel permeability, orientation, blood volume, vessel size index are actively being developed for in vivo applications. Firstly, quantitative vessel permeability information is typically measured by dynamic contrast enhanced (DCE) - MRI, which uses extravasating contrast agent (Gd-DOTA). Following pharmacokinetic modelling is usually applied to dynamical signal change curve after the administration of contrast agent to extract vessel-permeability related parameters. On the other hand, it is generally accepted that there are certain limitations in conventional DCE - MRI acquisitions in terms of its accuracy, and the acquisition speed due to the demanding spatio-temporal tradeoffs for dynamic studies. For example, gradient echo based sequence is typically used for DCE - MRI for high temporal resolution requirements, but induces T2* decay that we often neglect, but becomes significant for high contrast agent concentration regions such as artery or kidney. Tradeoff between spatial and temporal resolution also limits the desired spatial coverage or temporal accuracy of time intensity curves. Secondly, vessel orientation, blood volume, and vessel size index are usually measured by detecting transverse relaxation difference before and after the administration of intravascular T2 contrast agent, such as superparamagnetic iron oxide nanoparticles (SPION). However, transverse relaxation is well known to be affected by unwanted environmental conditions such as air-tissue interface and vessel orientation, which frequently causes severe error in the measurement of blood volume and vessel size index. The subjects and goals of this thesis can be categorized by two sub-sections. In the first section, fast and accurate DCE - MRI was achieved by applying compressed sensing (CS) algorithms, which mitigates the spatio-temporal resolution competition of dynamic acquisitions. Firstly, the optimization for the implementation of compressed sensing to conventional fast low-angle shot (FLASH) sequence which is generally used for DCE - MRI acquisition was performed. After optimization step, temporal or spatial resolution improvements were demonstrated by in vivo experiment, especially in the tumor model. Secondly, compressed sensing was implemented to turbo spin echo (TSE) sequence to minimize transverse artifact by replacing T2* to T2 without reducing temporal resolution and slice coverage. This minimized transverse artifact realized calibration-free T1 estimation from T1-weighted signal intensity. Finally, ultrafast 3D spin echo acquisition was developed by applying compressed sensing to multiple-modulation-multiple-echo (MMME) sequence. Improved enhancement in developed sequence was observed, compared to conventional FLASH sequence with 3D coverage. In the second section, alternative methods to improve accuracy in detecting vessel orientation, blood volume, and vessel size index were developed. Firstly, alternative way to measure blood volume, and vessel size index was suggested and demonstrated by using ultra-short echo time (UTE) sequence. UTE sequence realized the measurement of blood volume with the change of longitudinal relaxation before and after administration of contrast agent, not from that of transverse relaxation. Consequently, accurate blood volume measurement was achieved by longitudinal relaxation which is not sensitive to environmental conditions such as air-tissue interface and vessel orientation. Moreover, alternative vessel size index including longitudinal relaxation showed the potential to reduce the error from environmental conditions. Finally, the new concept of obtaining MR tractography with magnetic field anisotropy was introduced. Compared to the conventional way using susceptibility-induced anisotropic magnetic field inhomogeneity studies, this method doesn???t need re-orientation of the subject utilizing the interference pattern between internal and external field gradients. Developed several methodologies in this thesis for the fast and robust in vivo quantification of microvasculature such as vessel permeability, orientation, blood volume, and vessel size index demonstrated the potentials to improve not only the speed of acquisition but also the accuracy of the in vivo microvascular measurements via efficient sensing and reconstruction MR techniques.ope

Measuring and modelling lung microstructure with hyperpolarised gas MRI

This thesis is concerned with the development of new techniques for measuring and modelling lung microstructure with hyperpolarised gas magnetic resonance imaging (MRI). This aim was pursued in the following five chapters: Development of a framework for lobar comparison of lung microstructure measurements derived from computed tomography (CT) and 3He diffusion-weighted MRI evaluated in an asthmatic cohort. Statistically significant linear correlations were obtained between 3He diffusion-weighted MRI and CT lung microstructure metrics in all lobar regions. Implementation of compressed sensing (CS) to facilitate the acquisition of 3D multiple b-value 3He diffusion-weighted MRI in a single breath-hold for whole lung morphometry mapping. Good agreement between CS-derived and fully-sampled whole lung morphometry maps demonstrates that CS undersampled 3He diffusion-weighted MRI is suitable for clinical lung imaging studies. Acquisition of whole lung morphometry maps with 129Xe diffusion-weighted MRI and CS. An empirically-optimised 129Xe diffusion time (8.5 ms) was derived and 129Xe lung morphometry values demonstrated strong agreement with 3He equivalent measurements. This indicates that 129Xe diffusion-weighted MRI is a viable alternative to 3He for whole lung morphometry mapping. Implementation of an in vivo comparison of the stretched exponential and cylinder theoretical gas diffusion models with both 3He and 129Xe diffusion-weighted MRI. Stretched exponential model diffusive length scale was related to cylinder model mean chord length in a non-linear power relationship; while the cylinder model mean alveolar diameter demonstrated excellent agreement with diffusive length scale. Investigation of clinical and physiological changes in lung microstructure with 3He and 129Xe diffusion-weighted MRI. Longitudinal studies with 3He and 129Xe diffusion-weighted MRI were used investigate changes in lung microstructure in cystic fibrosis and idiopathic pulmonary fibrosis. Lung inflation mechanisms at the acinar level were also investigated with 3He and 129Xe diffusion-weighted MRI acquired at two different lung volumes