3D brain reconstructions to measure brain shrinkage in Huntington’s disease. Image credit: Ioakeimidis et al. (CC BY-4.0)
Our ability to move smoothly depends on a group of brain structures called the basal ganglia. In Huntington's disease, an inherited condition caused by a faulty gene, these structures are gradually damaged, leading to worsening problems with movement, thinking and mood.
The brain is made up of two main types of cells. Neurons carry information, while glial cells support and protect them. Each cell has a central body, called the soma, and long, thin branches that connect with other cells. In Huntington's disease, neurons in a part of the basal ganglia called the striatum gradually die. At the same time, glial cells change shape and switch from helping neurons to contributing to damage.
MRI scans allow us to study the living brain without surgery. Conventional structural MRI can show that the striatum shrinks in people with Huntington's disease, but it cannot reveal what is happening to the brain cells themselves. A technique called diffusion MRI provides more detailed information by measuring how water moves through brain tissue.
Ioakeimidis et al. tested a new diffusion MRI model called SANDI (Soma and Neurite Density Imaging), which estimates the apparent density and size of cell bodies. The researchers analysed brain scans from 56 people with Huntington's disease and 57 healthy volunteers. People with Huntington's had lower estimates of cell bodies in the striatum, along with larger estimates of cell body size and more space between cells than healthy volunteers. This pattern closely matches changes previously seen in brain tissue after death, where neurons are lost and glial cells become more active. Together with age, these measurements explained up to 63% of the shrinkage seen in the striatum and were linked to worse movement problems. As expected, a nearby brain region called the thalamus, which is less affected in the early stages of Huntington's disease, showed no similar changes.
In the future, SANDI could help doctors and researchers track how Huntington's disease progresses and determine whether new treatments are protecting brain cells. The technique could also prove useful for studying other brain disorders, including Alzheimer's and Parkinson's disease. However, larger studies following people over time are needed to confirm these findings, and the method must be adapted for the MRI scanners commonly used in hospitals.
