Access Type

Open Access Dissertation

Date of Award

January 2021

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Biomedical Engineering

First Advisor

Ewart Mark Haacke

Abstract

Diagnosing early-stage Parkinson’s disease (PD) and its manifestations is still a clinical challenge. Previous imaging studies using iron, neuromelanin (NM) and the Nigrosome-1 (N1) measures in the substantia nigra (SN) by themselves have been unable to provide sufficiently high diagnostic performance for these methods to be adopted clinically. In this dissertation, we start by studying idiopathic PD patients at their intermediate stages of the disease to evaluate the role of global and regional iron in the major deep gray matter nuclei. Then, we only focus on the NM complex in the midbrain and how neuronal loss interact with iron overload as well as their relationship with clinical scores strictly on early PD patients. Finally, by taking one more step back in the disease progression process, we investigate the impact of iron deposition and N1 appearance in idiopathic rapid eye movement sleep behavior disorder (RBD) as the prodromal stage of PD.

The results of this work are summarized as the following: 1) the increase in iron in the SN in some PD patients is higher than the normal range in healthy controls (HC) as found in both regional and global analyses and that regional high iron content may provide a means to separate two populations of PD patients; one with and one without iron increases in the SN; 2) we have introduced a rapid five-minute 3D approach to depict NM degeneration and iron deposition simultaneously which provides a practical MR imaging method to differentiate early stage subjects with PD from HCs with an approximately 98% accuracy; and finally 3) iRBD patients were found to have a higher incidence of N1 loss, reduced volume and elevated iron levels in a few brain structures as well as cognitive and motor impairment scores being correlated with iron deposition of several cerebral nuclei. All these in vivo biomarkers put together can significantly contribute to a better understanding of the underlying pathophysiology in PD onset and progression with the ultimate goal being a more confident clinical diagnosis prior to symptomatic dysfunction.

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