Author's School

Graduate School of Arts & Sciences

Author's Department/Program

Chemistry

Language

English (en)

Date of Award

7-26-2012

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Joseph J.H. Ackerman

Abstract

Multiple Sclerosis is a common disease, affecting 2.5 million people world-wide. The clinical course is heterogeneous, ranging from benign disease in which patients live an almost normal life to severe and devastating disease that may shorten life. Despite much research, a fully effective treatment for MS is still unavailable and diagnostic techniques for monitoring MS disease evolution are much needed.

As a non-invasive tool, Magnetic resonance imaging: MRI) plays a key role in MS diagnosis. Numerous MRI techniques have been proposed over the years. Among most widely used are conventional T1-weighted: T1W), T2-weighted: T2W) and FLuid Attenuated Inversion Recovery: FLAIR) imaging techniques. However their results do not correlate well with neurological findings. Several advanced MRI techniques are also used as research tools to study MS. Among them are magnetization transfer contrast imaging: MT), MR spectroscopy: MRS), and Diffusion Tensor Imaging: DTI) but they have not penetrated to clinical arena yet.

Gradient Echo Plural Contrast Imaging: GEPCI) developed in our laboratory is a post processing technique based on multi-echo gradient echo sequence. It offers basic contrasts such as T1W images and T2* maps obtained from magnitude of GEPCI signal, and frequency maps obtained from GEPCI signal phase.

Phase information of Gradient Echo MR signal has recently attracted much attention of the MR community since it manifests superior gray matter/ white matter contrast and sub-cortical contrast, especially at high field: 7 T) MRI. However the nature of this contrast is under intense debates. Our group proposed a theoretical framework - Generalized Lorentzian Approach - which emphasizes that, contrary to a common-sense intuition, phase contrast in brain tissue is not directly proportional to the tissue bulk magnetic susceptibility but is rather determined by the geometrical arrangement of brain tissue components: lipids, proteins, iron, etc.) at the cellular and sub-cellular levels - brain tissue "magnetic architecture". In this thesis we have provide first direct prove of this hypothesis by measurement of phase contrast in isolated optic nerve. We have also provided first quantitative measurements of the contribution to phase contrast from the water-macromolecule exchange effect. Based on our measurement in protein solutions, we demonstrated that the magnitude of exchange effect is 1/2 of susceptibility effect and to the opposite sign.

GEPCI technique also offers a scoring method for monitoring Multiple Sclerosis based on the quantitative T2* maps generated from magnitude information of gradient echo signal. Herein we demonstrated a strong agreement between GEPCI quantitative scores and traditional lesion load assessment. We also established a correlation between GEPCI scores and clinical tests for MS patients. We showed that this correlation is stronger than that found between traditional lesion load and clinical tests. Such studies will be carried out for longer period and on MS subjects with broader range of disease severity in the future.

We have also demonstrated that the magnitude and phase information available from GEPCI experiment can be combined in multiple ways to generate novel contrasts that can help with visualization of neurological brain abnormalities beyond Multiple Sclerosis.

In summary, in this study, we 1) propose novel contrasts for GEPCI from its basic images; 2) investigate the biophysical mechanisms behind phase contrast; 3) evaluate the benefits of quantitative T2* map offered by GEPCI in monitoring disease of Multiple Sclerosis by comparing GEPCI results to clinical standard techniques; 4) apply our theoretical framework - Generalized Lorentzian Approach - to better understand phase contrast in MS lesions.

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Permanent URL: http://dx.doi.org/10.7936/K76971MB

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