Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Neuroscience

Supervisor

MacDonald, Penny A.

2nd Supervisor

Khan, Ali R.

Co-Supervisor

3rd Supervisor

Owen, Adrian M.

Co-Supervisor

Abstract

Excessive midbrain iron accumulation in Parkinson’s Disease (PD) contributes to degeneration of the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). Despite this understanding, there are no validated PD biomarkers. Magnetic resonance imaging (MRI) can localize and quantify brain iron for diagnosis of PD. Seventeen early-stage PD patients and twenty-one controls were scanned at 3T and 7T MRI. Using quantitative susceptibility mapping (QSM) and R2* relaxometry, we analyzed the average iron content in the SNc, substantia nigra pars reticulata (SNr), and VTA. QSM detected significantly higher SNc iron content in PD patients compared to controls at both field strengths. R2* only detected differences at 7T and showed lower sensitivity and diagnostic accuracy in diagnostic biomarker analyses. As predicted, the SNr and VTA were spared from iron accumulation. SNc iron overload in early-stage PD, best detected using QSM, could be the first diagnostic biomarker of PD following validation.

Summary for Lay Audience

Parkinson’s disease (PD) is a neurodegenerative disorder that impacts movement and thinking. Loss of cells in a brain area called the substantia nigra contributes to PD. When neurologists diagnose PD based on clinical symptoms, up to 80% of these cells have already degenerated. Therapy becomes less effective with progressing degeneration, which means early diagnosis is vital for more effective treatment and improved patient outcome.

Excessive iron buildup in the substantia nigra cells in PD could potentially identify the degeneration based on previous research findings. This highlights an importance to precisely locate and measure brain iron for potential uses in early diagnosis. Magnetic resonance imaging (MRI) can image brain iron and look for excessive iron buildup. This study aimed to use iron imaging based on MRI methods to determine if this technique can improve diagnosis of PD.

Our study used two different iron imaging techniques in two MRI scanners to measure brain iron in early-stage PD patients and healthy elderly adults. Excessive iron buildup was detected only in a subregion called the substantia nigra pars compacta (SNc), which is the first area affected by PD. The other two areas had no changes in brain iron because they are affected in later stages of PD. Consequently, iron imaging is most effective when using SNc iron levels for early diagnosis of PD. The newer iron imaging technique had better diagnostic accuracy when using SNc iron to sort PD patients from healthy adults. Our research suggests newer iron imaging techniques could diagnose PD though more work is needed to determine its accuracy and reliability in clinical settings. This research could have a major impact on our understanding of PD, the way it is diagnosed, and ultimately the improvement of patients’ lives.

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