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High-powered MRI scanners could identify Parkinson’s patients for noradrenaline treatments, say University of Cambridge researchers



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Ultra-powerful MRI scanners capable of showing structures in the brain down to the size of a grain of sand could be used to identify patients with Parkinson’s disease and similar conditions who could benefit from new treatments.

University of Cambridge researchers used the 7T magnetic resonance imaging (MRI) scanners to measure changes in the brains of people with Parkinson’s and the related brain disease progressive supranuclear palsy (PSP).

Locus coeruleus as seen in 7T MRI scan. Image: Rong Ye/University of Cambridge (56717560)
Locus coeruleus as seen in 7T MRI scan. Image: Rong Ye/University of Cambridge (56717560)

They found the enhanced power meant they were able to examine a tiny region of the brain responsible for the production of noradrenaline, a chemical that plays a critical role in brain functions including attention and arousal, thinking and motivation.

Prof James Rowe, from the Department of Clinical Neurosciences at the University of Cambridge, who led the study, said: “Noradrenaline is very important for brain function. All of our brain’s supply comes from a tiny region at the back of the brain called the locus coeruleus – which means ‘the blue spot’. It's a bit like two short sticks of spaghetti half an inch long: it's thin, it's small, and it's tucked away at the very base of the brain in the brain stem.

“The locus coeruleus is a devil to see on a normal scanner. Even good hospital scanners just can't see it very well. And if you can't measure it, you can't work out how two people differ: who's got more, who's got less?”

Parkinson’s and PSP are progressive brain diseases affecting movement, damaging motivation and cognition, which leads to impacts on their general wellbeing and survival, as well as stress for families.

Drugs such as L-DOPA, which compensate for the severe loss of dopamine, are often given to these patients, but it does little to tackle the many non-motor symptoms of these diseases, so scientists are turning their attention towards noradrenaline.

A study last year from Prof Rowe’s team that examined brains donated to the Cambridge Brain Bank found some people with PSP had lost as much as 90 per cent of the noradrenaline-producing locus coeruleus.

For their latest research, the team wanted to learn whether the tiny region could be studied in patients while they were alive.

Normal MRI scanners do not have sufficient resolution - typically only showing structures down to the size of the grain of rice.

Locus coeruleus as seen in 3T MRI scan. Image: Rong Ye/University of Cambridge (56717557)
Locus coeruleus as seen in 3T MRI scan. Image: Rong Ye/University of Cambridge (56717557)

Most have a magnetic field strength labelled 3T or below, but the new 7T MRI scanners at the Wolfson Brain Imaging Centre allowed the team to show the greater damage to the locus coeruleus, the more severe the symptoms of apathy and the worse patients performed at cognitive tests.

Such patients could benefit from new drugs that boost noradrenaline, a number of which have been through clinical trials for other conditions, showing them to be safe and well tolerated.

Prof Rowe and his colleagues are now leading a clinical trial at Cambridge University Hospitals NHS Foundation Trust to ascertain if these drugs alleviate symptoms in PSP.

Dr Rong Ye, from the Department of Clinical Neurosciences at the University of Cambridge, the study’s joint first author, said: “Not every PSP or Parkinson’s patient is going to benefit from noradrenaline-boosting drugs. They’re more likely to benefit those people with damage to their locus coeruleus – and the greater the damage, the more benefit they’re likely to see.

“The ultra-powerful 7T scanner may help us identify those patients who we think will benefit the most. This will be important for the success of the clinical trial, and, if the drugs are effective, will mean we know which patients to give the treatment to.

“In the long term, this will prove more cost-effective than giving noradrenaline boosters to patients who ultimately would see no benefit.”

Damage to the locus coeruleus in PSP patients is believed to be caused by a build-up of the junk protein tau.

The breakdown of noradrenaline appears to trigger changes in the tau protein that lead to its build-up. This damages the same cells that produce noradrenaline, creating a vicious circle. It is thought something similar may occur in Parkinson’s disease.

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