MRI-based assessment of function and dysfunction in myelinated axons

Area of Science:

• Neuroscience
• Biophysics
• Medical Imaging

Background:

• Repetitive electrical activity induces microstructural alterations in myelinated axons.
• These changes offer potential for noninvasive monitoring of peripheral nervous system (PNS) and central nervous system (CNS) pathways.
• Assessing these alterations requires advanced imaging techniques.

Purpose of the Study:

• To investigate the potential of diffusion functional MRI (fMRI) and dynamic T2 spectroscopy for noninvasively monitoring myelinated axon function.
• To demonstrate the capability of diffusion fMRI in localizing axonal conduction block.
• To correlate electrophysiological findings with MRI parameters.

Main Methods:

• Ex vivo perfused bullfrog sciatic nerves were used as a model system.
• Diffusion fMRI, based on diffusion tensor imaging (DTI), was employed to assess microstructural changes.
• Dynamic T2 spectroscopy and diffusion basis spectrum imaging (DBSI) were utilized.
• Electron microscopy and electrophysiology (compound action potential) were used for validation.

Main Results:

• Diffusion fMRI successfully localized sites of axonal conduction blockage.
• The diffusion fMRI response was proportional to the number of electrical impulses.
• Dynamic T2 spectroscopy indicated electrical-activity-induced water redistribution and myelin structural changes.
• DBSI revealed a reversible shift of tissue water into a restricted isotropic diffusion component.
• Submyelinic vacuoles were observed during electrical stimulation.

Conclusions:

• Noninvasive diffusion fMRI and dynamic T2 spectroscopy can effectively monitor myelinated axon function and microstructural changes.
• These techniques show promise for detecting neurotrauma and other lesions affecting nerve pathways.
• The study provides insights into the mechanisms of activity-induced axonal and myelin alterations.