Axon diameter inferences in the human corpus callosum using oscillating gradient spin echo sequences.

Area of Science:

• Neuroimaging
• Biophysics
• Neuroscience

Background:

• Previous magnetic resonance imaging (MRI) methods for axon diameter distribution were limited to larger axons (>5 µm).
• Understanding smaller axon diameters (1-2 µm) is crucial as they form the majority of cortical connections.

Purpose of the Study:

• To apply oscillating gradient spin echo (OGSE) sequences for measuring small human axon diameters (1-2 µm) in the corpus callosum.
• To compare MRI-derived axon diameter estimates with histological data.
• To validate the ActiveAx model for in vivo axon diameter measurements.

Main Methods:

• Utilized oscillating gradient spin echo (OGSE) MRI sequences on the human corpus callosum.
• Applied the ActiveAx model to calculate mean effective axon diameter (AxD) from MRI data.
• Compared MRI-derived AxD with histological measurements using three different diameter calculation methods.

Main Results:

• MRI with the ActiveAx model yielded an average axon diameter of 2.0 ± 0.2 µm.
• Histological measurements varied significantly based on calculation method, ranging from 1.43 µm (true minimum) to 5.52 µm (min/max combination).
• Histological measurements aligned more closely with MRI when accounting for axonal orientation (2.20 µm).

Conclusions:

• This study demonstrates the first use of OGSE MRI for measuring 1-2 µm axon diameters in the human corpus callosum.
• The findings highlight the importance of accounting for axonal orientation in diameter measurements.
• This non-invasive MRI approach holds promise for future in vivo studies of human brain tissue microarchitecture.