Zooming in on Alzheimer’s: Ex vivo mapping of the dentate gyrus using 16.4T MRI

By Alexander Albury

Advanced techniques in neuroimaging technology are pushing the boundaries of how neuroscientists study Alzheimer’s disease. While there’s no lack of research related to Alzheimer’s disease, we’re still a long way from understanding exactly what exactly the disease does to the brain. Modern MRI methods have allowed doctors and researchers to study smaller and smaller parts of the brain. But improved techniques and equipment come with their own set of challenges. Researchers at the University of Southern California set out to investigate if these cutting edge MRI methods are a reliable tool to study Alzheimer’s.

MRI scanners use a magnetic field to obtain images of the brain. In the past decade scanners have been getting better and better and the magnets they use to obtain images have become stronger, allowing researchers to examine the brain at greater resolutions than ever before. But there are practical and safety limitations that prevent scanners with the strongest magnets - often called ultra-high-field MRI - from being used on humans. However, being able to look at the brain with even higher resolution would allow neuroscientists to better understand the disease, and potentially develop more effective treatments for it.

Nien-Chuh Shih and colleagues opted to take advantage of ultra-high-field MRI by studying the brains of persons who were already deceased, also known as ex vivo imaging. They compared the brains of persons diagnosed with Alzheimer’s to a group of healthy control patients. In particular, they focused on an area of the brain called the dentate gyrus, a brain region important for the creation of new memories, and one that is particularly susceptible to deterioration in Alzheimer’s.

Using ultra-high-field MRI, the researchers were able to examine sections of the brain as small as 100 micrometers - that’s about the thickness of a piece of paper. By comparison, many of the standard MRI scanners used in medicine only have a resolution of about 3mm. Additionally, using a technique called Diffusion Tensor Imaging (DTI) they were able to examine the white matter tracts in the dentate gyrus - the pathways in the brain that carry information and resources across the brain. Lastly, the researchers also collected tissue cells from the brain areas studied and examined them directly using chemical techniques and microscopes. 

This combination of techniques allowed the researchers to study the effects of Alzheimer’s in extremely high detail. By comparing results from MRI imaging techniques and physical analysis of brain tissue, they were able to evaluate how well the MRI measures represented the brain areas being studied. They found that MRI measurements of tissue were strongly related to the measurements taken of the tissue itself.
These encouraging results support the use of MRI in living patients because they make neuroscientists more confident in the images they receive from MRI scanners. Although we’re not yet at a point where we can use ultra-high-field MRI on living patients, ex vivo studies like Shih’s are invaluable for spurring discoveries that will ultimately improve the lives of patients with Alzheimer’s.

Original Research:

Shih, N.-C., Kurniawan, N. D., Cabeen, R. P., Korobkova, L., Wong, E., Chui, H. C., Clark, K. A., Miller, C. A., Hawes, D., Jones, K. T., & Sepehrband, F. (2023). Microstructural mapping of dentate gyrus pathology in Alzheimer’s disease: A 16.4 Tesla MRI study. NeuroImage. Clinical, 37, 103318. https://doi.org/10.1016/j.nicl.2023.103318

Nien-Chu Shih is the winner of 2023 Neuroimage Clinical Award