The PSP Association

Researcher Dr Luke Massey (Clinical Research Fellow)
Supervisors: Professor Tarek Yousry and Professor Andrew Lees
Co-researchers Mario Miranda and Othman Al-Helli

Institution Sara Koe PSP Research Centre and Queen Square Brain Bank for Neurological Disorders, Institute of Neurology, University College London

Duration 2 years
Start February 2007 End January 2009

Grant £132,475

Aim of research
To:
• Define the anatomy of the substantia nigra, subthalamic nucleus and pedunculopontine nucleus using high field MRI
• Characterize the changes seen in diseases including progressive supranuclear palsy, Parkinson's disease and multiple system atrophy
• Compare quantitative MRI measurements in brain regions affected by these diseases with the aim of developing tools to increase the accuracy of diagnosis and monitor disease progression. The latter will be helpful to determine the effectiveness of any forthcoming treatments.

About the research
In PSP and other diseases including Parkinson's disease and multiple system atrophy, the substantia nigra, subthalamic nucleus and pedunculopontine nucleus are some of the key brain structures affected. Using conventional MRI scans (1.5 Tesla) these areas of the brain cannot be clearly defined. The aim of this project is to achieve better definition of these regions using high field MRI scanning (9.4 Tesla) of post mortem tissue. This approach enables us to use high strength magnets (6 times stronger than the standard MRI machines used for patients) and to do long scans (up to 3 days) to produce detailed images which can then be directly compared with histological samples (post mortem material viewed under a microscope).

Findings
So far we have shown that it is possible to obtain detailed MRI images of the brain using high powered (9.4 Tesla) MRI scans. We are now starting to compare the MRI images with the histological images to accurately define the structures observed on the MRI scans and to detail the changes seen in the various diseases. Some preliminary MRI measurements suggest there are detectable differences in the subthalamic nucleus in patients with Progressive Supranuclear Palsy compared to those with other Parkinsonian diseases.

What will the outcome of this research mean for people with PSP?
There is the potential for MRI to become more useful as a tool for early diagnosis than is currently the case. There are however, significant hurdles to overcome including the safety of using very strong magnets on human subjects.

National/international presentations given on this work
Movement disorders society international congress 2007 (Istanbul)
Demonstration of the anatomy of the midbrain using high field MRI

International Society for Magnetic Resonance Imaging in Medicine British Chapter 2007
Post-mortem high field MRI of the midbrain at 9.4T: Normal anatomy and qualitative comparison with Progressive Supranuclear Palsy.

British Neuropathological Society Meeting (London 2008)
Anatomy of the midbrain including the subthalamic nucleus and substantia nigra as seen using high field MRI at 9.4 Tesla: Preliminary work involving correlation of MR and histopathological images

International Society for Magnetic Resonance in Medicine (Toronto 2008)
The normal anatomy of the substantia nigra using high field 9T MRI: Correlation of post-mortem images and histopathology

Queen Square Symposium (London 2008)
Characterisation of the subthalamic nucleus, substantia nigra and midbrain structures using high field 9.4 Tesla MRI of post-mortem tissue

Movement Disorders Society International Congress (Chicago 2008)
Determining the anatomy of the subthalamic nucleus and substantia nigra on MRI using 9.4Tesla

17th Annual NMR Symposium (Sheffield 2008)
Determining the anatomy and MRI characteristics of the subthalamic nucleus at 9.4Tesla.

Awards and prizes received for work conducted under this grant
Junior Award for Excellence in Clinical Research (Movement Disorders Society International Congress Chicago 2008)

Weblink
Molecular Neuroscience - The Institute of Neurology