Advanced MRI scan reveals Huntington’s disease damage in the living brain

An advanced type of MRI scan could be a valuable tool for tracking Huntington’s disease and testing whether new treatments are working, according to new research.

Published in the journal eLife, the Soma and Neurite Density Imaging (SANDI) technique was found to detect Huntington's disease-related abnormalities at a cellular level in living people.

The technique uses the way water moves through brain tissue to produce indirect estimates of the size and density of cell bodies, properties that in the past could only be assessed by examining brain tissue after death.

Dr Claudia Metzler-Baddeley, based at Cardiff University’s Brain Research Imaging Centre (CUBRIC) at the School of Psychology, said: “Huntington’s Disease is an inherited condition, that causes a gradual decline in mood, thinking and movement. It happens because brain cells are lost in the basal ganglia, a set of deep brain structures that help control these abilities.

“The condition usually starts between 30 and 50 years of age and has no cure yet although new cell and gene therapies are being tested and have shown early promise in slowing it down.

“As we search for better treatments, it is vital that we also improve our ability to track how the condition is progressing and to judge whether a treatment is actually working in patients.”

For the new study, the team combined diffusion MRI with the SANDI technique. Traditional MRI scans provide detailed images of the brain’s shape and anatomy, but they offer limited insight into changes occurring at cellular level. Diffusion MRI tracks the movement of water molecules through brain tissue and SANDI analyses these patterns to estimate the apparent size and density of cell bodies, known as soma.

The researchers from CUBRIC, working with colleagues from Copenhagen University and King’s College London, analysed the diffusion MRI brain data of 56 people with Huntington's disease and 57 healthy people of a similar age, who were all scanned on a strong-gradient scanner in CUBRIC.

Some participants also completed finger-tapping tasks, a standard way of measuring motor control.

Compared with healthy volunteers, people with Huntington's disease showed lower estimates of soma density, larger estimates of soma size, and more space between cells in the basal ganglia. This pattern matches what pathologists have previously observed in donated brain tissue after death - nerve cells are lost, while the brain's support cells multiply and swell in response, disrupting the surrounding tissue. These abnormalities were associated with a person’s disease severity and with poorer performance on the finger-tapping tests.

Dr Metzler-Baddeley said: “The measurements SANDI produced accounted for a large share of the brain shrinkage we saw. Taken together with a person's age, the estimated number and size of cell bodies explained up to 63% of the shrinkage in some basal ganglia regions.

“That suggests SANDI may be capturing biological processes that drive tissue loss. However, this was a snapshot study comparing two groups at a single point in time, so it cannot tell us how these features develop as the disease unfolds.

“Our findings appear to line up with what we know from post-mortem studies. The difference is that SANDI can detect these abnormalities in the living brain, rather than only after death.”

The researchers believe SANDI could be used in clinical trials of new Huntington's therapies, to show whether a treatment is genuinely protecting brain cells.

Dr Metzler-Baddeley added: “This is early evidence, but it is promising. If SANDI can reliably detect these abnormalities in Huntington's disease, the same approach may prove useful in other conditions where brain cells are lost, such as Parkinson's and Alzheimer's disease.

“Larger studies following people over time are now needed to confirm these results, and the method must be adapted for clinical scanners commonly used in hospitals.”

The research, In vivo mapping of striatal neurodegeneration in Huntington’s disease with Soma and Neurite Density Imaging, was published in eLife.