Disentangling molecular alterations from water-content changes in the aging human brain using quantitative MRI

Area of Science:

• Neuroscience
• Biophysics
• Molecular Biology

Background:

• Aging-related brain changes may stem from common or distinct molecular mechanisms.
• Quantitative magnetic resonance imaging (qMRI) non-invasively maps the aging human brain using biophysical parameters.
• Standard qMRI signals are influenced by both molecular composition and water content, complicating interpretation.

Purpose of the Study:

• To develop a novel approach to disentangle molecular composition and water content from qMRI signals.
• To decode molecular information within the MRI signal for brain aging research.
• To establish a non-invasive method for characterizing biological sources of brain aging.

Main Methods:

• A tissue relaxivity approach was developed to separate molecular composition and water content.
• The method decodes molecular information directly from the MRI signal.
• Lipidomics measurements and gene-expression profiles were used for validation.

Main Results:

• The approach successfully revealed molecular composition of lipid samples and predicted brain lipidomics.
• Unique molecular signatures were generated across the brain, correlating with gene-expression profiles.
• Region-specific molecular changes associated with brain aging were identified, independent of other MRI aging markers.

Conclusions:

• The developed tissue relaxivity approach enables quantitative characterization of molecular changes in the aging brain.
• This method provides novel insights into the biological drivers of brain aging non-invasively.
• It opens new avenues for understanding aging mechanisms at a molecular level in vivo.