New MRI Technique Can Visualize Brain Molecular Composition, Study Shows

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A new magnetic resonance imaging (MRI) technique allows for the visualization of molecular changes in the brain, a study reports.

This technique will allow researchers to further understand how the brain works and how it changes with ageing or during the onset of neurodegenerative diseases like Parkinson’s.

Moreover, in the future, clinicians may use the brain’s “molecular signature” for early diagnoses — allowing patients to get access to treatment at early stages of disease and increasing their likelihood for better outcomes.

The study, “Disentangling molecular alterations from water-content changes in the aging human brain using quantitative MRI,” was published in the journal Nature Communications.

An MRI scan is obtained using magnetic fields and powerful detectors that track water compositions in tissues. However, brain function depends vastly on molecular interactions within the brain that current MRI scans fail to detect.

“When we take a blood test, it shows us the exact number of white blood cells [key cells of the immune system] in our body and whether that number is higher than normal due to illness,” Shir Filo, a PhD student and the study’s first author, said in a press release.

“MRI scans provide images of the brain but don’t show changes in the composition of the human brain, changes that could potentially differentiate normal aging from the beginnings of Alzheimer’s or Parkinson’s,” Filo added.

Now, researchers found a way to “see” the brain composition at the molecular level. The technique, called quantitative MRI, is able to detect changes in the molecular composition of lipid (fat) molecules within the brain.

The research was led by Aviv Mezer and his team at the Hebrew University of Jerusalem (HUJI)’s Edmond and Lily Safra Center for Brain Sciences.

“Instead of images, our quantitative MRI model provides molecular information about the brain tissue we’re studying. This could allow doctors to compare brain scans taken over time from the same patient, and to differentiate between healthy and diseased brain tissue, without resorting to invasive or dangerous procedures, such as brain tissue biopsies,” Mezer said.

Researchers started by testing their new MRI technique in synthetic, or lab-made complex fat mixtures to validate whether the MRI scans were sensitive enough to detect changes at the molecular level.

The results revealed their technique was able to distinguish between different lipids with high sensitivity. Because the brain is rich in lipids — such as phosphatidylcholine, sphingomyelin or phosphatidylcholine-cholesterol — the team used a measurement called macromolecular tissue volume (MTV) that provides quantitative information about these molecules in a sample.

Quantitative MRI scans of human brains revealed that MTV measures changed depending on the brain region analyzed, demonstrating that this technique works like a detailed map of the living brain.

Importantly, using post-mortem (after death) brain samples, the team found that the variability of certain MTV parameters between human brain regions also correlated with specific gene-expression profiles. Gene expression is the process by which information in a gene is synthesized to create a working product, like a protein.

Next, the researchers investigated whether the molecular composition of the brain varied according to age, specifically young versus old. They scanned 23 young adults (mean age 27 years) and 18 older adults (mean age 67 years).

Researchers focused their analysis on the brain’s white and gray matter. White matter is made up of nerve cell projections, known as axons or fibers, that connect distinct parts of gray matter. The length and condition of the fibers influence the way the brain processes information. Gray matter includes neuronal cell bodies as well as synapses, or the junctions between nerve cells that allow them to communicate with each other.

The results showed not only evident changes in the brain’s size, but also tiny and region-specific molecular changes in various brain regions related to aging. Even in the absence of age-related reductions in brain size, molecular changes were detected using the new MRI technique.

Overall, this supports the potential of this new type of MRI method to better understand how our brains age.

“[W]hen we scanned young and old patients’ brains, we saw that different brain areas ages differently. For example, in some white-matter areas, there is a decrease in brain tissue volume, whereas in the gray-matter, tissue volume remains constant. However, we saw major changes in the molecular makeup of the gray matter in younger versus older subjects,” Mezer said.

Researchers hope that, in the future, they can apply this new MRI technique to provide an early diagnosis of diseases like Parkinson’s. That could allow access to treatment that may delay or even halt disease progression.