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MRI Analysis to Detect Gray Matter Tissue Loss in Multiple Sclerosis

Nakamura, Kunio

Abstract Details

2011, Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering.
Multiple sclerosis (MS) has been traditionally characterized by primary demyelination and inflammation in white matter (WM). However, recent histopathologic studies have shown that gray matter (GM) of MS patients is also abnormal. My aim was to develop methods for quantifying GM damage in terms of GM atrophy and cortical atrophy, to investigate the evolution in various MS disease stages, and to assess relevance to clinical status. First, I developed an automated algorithm that segmented GM and WM in magnetic resonance images (MRI) and measured the normalized GM volume. The algorithm was designed to be applicable to MRI of MS patients, which had focal lesions and significant atrophy. The algorithm was validated and applied in a longitudinal study that included patients with clinically isolated syndrome (CIS), relapsing-remitting (RRMS) and secondary progressive (SPMS) MS as well as healthy normal controls. Other conventional MRI markers of focal damage and clinical measures were available to explore the correlations and predictors of GM atrophy. We found that (1) the rate of GM atrophy increased in a stage-dependent manner, which was similar to that of whole brain atrophy, (2) GM atrophy had moderately strong correlations with the disability measures, and (3) predictors of GM atrophy changed from RRMS to SPMS. Next, I developed a registration and deformable model-based longitudinal method (CLADA, Cortical Longitudinal Atrophy Detection Algorithm) that had high reproducibility and could measure global and regional cortical atrophy in terms of cortical thickness and its change. CLADA was validated and applied to the full longitudinal MRI dataset to explore the evolution of cortical thinning, its clinical correlations, and predictors. The rate of cortical thinning increased with advancing disease, correlated with clinical disability, and distinguished stable and worsening patients with more significance than GM atrophy. In summary, my research showed that GM and cortical atrophy could be measured reliably with the new techniques. Furthermore, application of these methods in MS patients demonstrated that GM and cortical atrophy measurements were (1) relevant both clinically and biologically (2) able to provide insights on MS pathogenesis; and (3) suitable for future clinical trials of potential MS therapies.
Andrew Rollins, PhD (Committee Chair)
Elizabeth Fisher, PhD (Advisor)
Bruce Trapp, PhD (Committee Member)
David Wilson, PhD (Committee Member)
186 p.

Recommended Citations

Citations

  • Nakamura, K. (2011). MRI Analysis to Detect Gray Matter Tissue Loss in Multiple Sclerosis [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1309874290

    APA Style (7th edition)

  • Nakamura, Kunio. MRI Analysis to Detect Gray Matter Tissue Loss in Multiple Sclerosis. 2011. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1309874290.

    MLA Style (8th edition)

  • Nakamura, Kunio. "MRI Analysis to Detect Gray Matter Tissue Loss in Multiple Sclerosis." Doctoral dissertation, Case Western Reserve University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1309874290

    Chicago Manual of Style (17th edition)