Optimization and Application of Chemical Exchange Saturation Transfer Imaging

• Author / Creator

  Dai, Zhuozhi

• Magnetic resonance imaging (MRI) is a non-invasive method that can provide detailed anatomic images and has been widespread in clinical application. Novel MRI techniques are emerging from the development of MR theory and hardware. Among them, chemical exchange saturation transfer (CEST) provides a means to noninvasively measure a range of in-vivo metabolic and chemical biomarkers. By measuring the water signal and looking at indirect saturation by exchangeable protons, this new technique may provide valuable diagnostic information and early indicators of treatment effectiveness. Because CEST imaging is sensitive to dilute CEST agents, local pH, and temperature, it can be applied in many different ways. Indeed, CEST MRI has been shown capable of detecting a host of biomolecules including glutamate, glycogen, glucose, and gene expression as well as pH and temperature, complementing conventional MRI, which is mainly structural. Compared with magnetic resonance spectroscopy, CEST has higher spatial resolution and superior sensitivity. The applications to disease are still being exploration. Moreover, current CEST techniques are varied and sometimes hardware incompatible. In this thesis, we addressed some of these problems, and applied our methods to animal models at Shantou University using 7.0T MRI and human brain at the University of Alberta using 4.7T and 3.0T MRI. The overall hypothesis is that CEST sequences can be optimized under standard criteria and improved CEST methods may provide noninvasive measures of pH, glutamate and intracellular protein in animal models and in human brain.The thesis contains three major projects, including sequence development and optimization at 7T (Chapter 2), animal studies at 7T (Chapter 3), and human application at 3T (Chapter 4). A brief introduction of CEST will be presented in Chapter 1. A smaller project on pH imaging in CEST, including pH weighted imaging in a diabetic stroke model, and quantitative pH imaging, was compressed into another independent chapter (Chapter 5). In project 1 (sequence development and optimization at 7T), we proposed a magnetization transfer (MT) prepared gradient echo (GRE) MRI sequence for CEST imaging. Routine CEST MRI includes a long RF saturation pulse followed by fast image readout, which is associated with high specific absorption rate and limited spatial resolution. In addition, echo planar imaging (EPI)-based fast image readout is prone to image distortion, particularly severe at high field. To address these limitations, we evaluated MT prepared GRE MRI for CEST imaging. We proved the feasibility using numerical simulations and experiments in vitro and in vivo. We then optimized the sequence and further demonstrated endogenous amide proton CEST imaging in rat brains that underwent permanent middle cerebral artery occlusion. In project 2, we applied glutamate imaging in schizophrenia models at 7T, which may provide a powerful indicator of the diagnosis of schizophrenia prodrome. In this project, we examined glutamate variation in different brain regions in an early schizophrenia model using glutamate CEST imaging. Our results proved that the signal intensity of glutamate image was strictly related to glutamate concentration, and that other neuro metabolites contribute negligible glutamate CEST effects except GABA. Compared to healthy controls, glutamate signals of schizophrenic models increased in the whole brain, especially in cerebral cortex, hippocampus, and thalamus. In addition, glutamate CEST image has excellent correlation with glutamate measured by spectroscopy. In project 3, we detected changes of Amide Proton Transfer (APT) in the motor cortex and corticospinal tract of amyotrophic lateral sclerosis (ALS) patients, which has the potential to be an objective imaging biomarker for ALS diagnosis. There is a lack of objective imaging indicators for ALS diagnosis. This study aimed to explore the value of APT in ALS patients and the correlation between APT and diffusion tensor imaging (DTI). Compared with healthy controls, the APT signal intensities in ALS were significantly reduced in motor cortex and corticospinal tract, which was undetectable under routine imaging methods. In addition, APT was negatively correlated with FA and positively correlated with ADC. The combination of APT and DTI can simultaneously detect changes of metabolism and microstructure in ALS patients.In summary, developments in CEST imaging have been made including sequence development, post processing, animal studies, and clinical translation to human subjects using a wide range of MRI strengths from 3T to 7T. The results make valuable contributions to the growing field of CEST imaging.

• Subjects / Keywords

  • Optimization, Application, Chemical Exchange Saturation Transfer

• Graduation date

  Spring 2019

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-rqzv-7a15

• License

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