MRI case studies

Neurological diseases are the leading cause of disability. Parkinson's Disease (PD) is the second most common neurodegenerative disease demonstrating the fastest growth amongst neurological diseases without a cure. 

The clinical features of PD involve tremor, stiffness, and slowing of movements with increasing recognition of disabling non-motor symptoms such as cognitive decline, depression, fatigue and pain. Key clinical challenges include the late diagnosis and lack to foresee the clinical course, making personalised counselling impossible.

A hallmark of Parkinson’s is the loss of neurons in the brainstem area that produce dopamine, a key signalling molecule linked to motor and non-motor functions. These neurons contain the pigment neuromelanin, resulting in dark appearances of the area (‘substantia nigra’) in healthy brains and brighter appearance in PD; a recognised pathological hallmark of the disease.

Over the past decade, researchers at the University of Nottingham have made great strides in harnessing the power of MRI to develop techniques that can detect PD-specific changes in the substantia nigra1-4 describing a very accurate diagnostic sign of PD (‘the swallow tail’2) and more recently, using neuromelanin MRI to highlight a diagnostic window of five years before clinical symptoms appear4.

We have recently begun a new trial – The InsIghtPD Study – which aims to recruit over 100 patients at an early stage of PD, and then perform a specialist neuromelanin-MRI scan every six months for two years. We hope that by the end of the study we will have established a strong evidence base for using this new type of scan to predict how a newly diagnosed patient will progress over the following years. However, the substantia nigra is very small and at the limit of our ability to image using conventional MRI. Therefore, we have developed optimised MRI sequences and advanced analysis methodology to accurately monitor neuromelanin loss.

Neuromelanin-MRI has the potential to be an important progression biomarker that can be measured in a relatively inexpensive manner, which is non-invasive and without the use of radiation. It will also have the ability to play an important role in future trials of new therapies which can improve the outcomes for patients with PD.

References:

1 Schwarz ST, Rittman T, Gontu V, Morgan PS, Auer DP. T1-Weighted MRI shows stage-dependent substantia nigra signal loss in Parkinson's disease. Movement Disorders 2011, Vol26, Issue9, 1633-1638. https://doi.org/10.1002/mds.23722
2 Blazejewska AI, Schwarz ST, Pitiot A, Stephenson MC, Lowe J, Bajaj N, Bowtell RW, Auer DP, Gowland PA. Visualization of nigrosome 1 and its loss in PD Pathoanatomical correlation and in vivo 7 T MRI. Neurology 2013; 81 (6): 534–540. https://doi.org/10.1212/WNL.0b013e31829e6fd2
3 Schwarz ST, Afzal M, Morgan PS, Bajaj N, Gowland PA, Auer DP. The ‘Swallow Tail’ Appearance of the Healthy Nigrosome – A New Accurate Test of Parkinson's Disease: A Case-Control and Retrospective Cross-Sectional MRI Study at 3T. PLOS One 2014, https://doi.org/10.1371/journal.pone.0093814
4 Xing Yue, Sapuan HS, Martin-Batista A, et al. Neuromelanin-MRI to Quantify and Track Nigral Depigmentation in Parkinson's Disease: A Multicenter Longitudinal Study Using Template-Based Standardized Analysis
Movement Disorders. 2022, https://doi.org/10.1002/mds.28934