New MRI technique captures changes in FA brains
Diffusion MRI may be used to identify therapeutic targets in Friedreich's ataxia
Noninvasive diffusion MRI (dMRI) captured changes in the structure of the brain and brainstem of people with Friedreich’s ataxia (FA), a study reports.
dMRI, a new method that relies on the flow of water in tissue to assess neurodegeneration, has the potential to identify therapeutic targets in FA patients, and support existing measures of disease severity, the researchers said.
The study, “Free-Water Imaging in Friedreich Ataxia Using Multi-Compartment Models,” was published in the journal Movement Disorders.
FA is characterized by the degeneration of nerve cells and inflammation in the brainstem and cerebellum, the region at the back of the brain involved in regulating movement and balance. As a result, people with the condition experience a lack of coordination or muscle control during voluntary movements. This is referred to as ataxia.
A new tool to measure neurodegeneration and inflammation involves so-called brain free-water. Because the degeneration of nerve cells reduces the overall density of cells packed together, fluids can move more freely, which is reflected as an increase in free-water.
Free-water can be noninvasively measured using dMRI and has been applied in other neurological diseases as a sensitive marker of neurodegeneration and disease progression. dMRI can be even more sensitive than traditional MRI in measuring changes in the tiny structures in the brain (microstructures).
Still, according to a team of researchers in Australia, free-water modeling has yet to be used to examine changes in the brainstem and cerebellum of FA patients.
So, the team tested dMRI on 14 people diagnosed with FA (six women), with a mean age of 28 years, and 14 age-matched unaffected individuals (nine women) who served as controls.
Data showed that free-water changes were evident in people with FA compared to controls. Increased free-water levels were observed in all regions of interest, including the brainstem, the cerebellar peduncles that connect the cerebellum to the brainstem, as well as the cerebellum’s outer layer (cerebellar cortex) and inner core (dentate nuclei).
To examine tissue microstructures, the team used the dMRI images to calculate the fractional anisotropy, which measures the degree of water flow in tissues by direction. Lower values reflect more freely flowing fluid in all directions due to microstructural damage.
Compared to controls, fractional anisotropy in FA was significantly reduced in all brainstem regions, the cerebellum’s top layer (anterior lobe), and the upper and lower regions within the cerebellar peduncles.
Across all measures, free-water showed the largest mean effect compared with other markers, especially in the upper region of the cerebellar peduncles that connect the cerebellum to the midbrain.
Whole-brain analysis found similar changes in the brainstem and cerebellum, as well as in the motor cortex, an area of the outer brain that controls movement, and the thalamus, which plays a role in relaying sensory and motor signals to the brain.
dMRI values then were compared to clinical assessments, including scores from the modified Friedreich ataxia rating scale (mFARS), a measure of disease progression focusing on limb coordination, speech and swallowing, and upright stability. Disease burden scores, which combined disease duration and the severity of a patient’s genetic defect, also were compared.
Correlations between dMRI values and across all regions of interest versus mFARS scores did not reach statistical significance. However, moderate free-water correlations with mFARS scores were seen with the outer lobes of the cerebellum, the dentate nucleus, the midbrain, and the upper region of the cerebellar peduncles.
Researchers note ‘compelling evidence’ using diffusion MRI
Statistical significance was reached between a greater disease burden, reflecting more advanced disease severity, with more microstructural changes (lower fractional anisotropy) in the bottom layer of the cerebellum (posterior lobe).
“The current study presents compelling evidence for the sensitivity of free-water to neuropathology in [FA], and its overall advantage over traditional microscopic measures,” the researchers wrote. “These metrics have the potential to be used to identify therapeutic targets in individuals with [FA] and supplement existing measures of disease severity.”