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

Previous methods used to infer axon diameter distributions using magnetic resonance imaging (MRI) primarily use single diffusion encoding sequences such as pulsed gradient spin echo (PGSE) and are thus sensitive to axons of diameters >5 µm. We applied oscillating gradient spin echo (OGSE) sequences to study human axons in the 1-2 µm range in the corpus callosum, which include the majority of axons constituting cortical connections. The ActiveAx model was applied to calculate the fitted mean effective diameter for axons (AxD) and was compared with values found using histology. Axon diameters from histological data were calculated using three different datasets; true diameters (minimum diameter), a combination of minimum and maximum diameters, and diameters measured across a consistent diffusion direction. The AxD estimates from MRI were 1.8 ± 0.1 µm to 2.34 ± 0.04 µm with an average of 2.0 ± 0.2 µm for the ActiveAx model. The histology AxD values were 1.43 ± 0.02 µm when using the true minimum axon diameters, 5.52 ± 0.02 µm when using the combination of minimum and maximum axon diameters, and 2.20 ± 0.02 µm when collecting measurements across a consistent diffusion direction. This experiment demonstrates the first known usage of OGSE to calculate axon diameters in the human corpus callosum on a 1-2 µm scale. The importance for the model to account for axonal orientation dispersion is indicated by histological results which more closely match the MRI model results depending on the direction of axon diameter measurements. These initial steps using this non-invasive imaging method can be applied to future methodology to develop in vivo axon diameter measurements in human brain tissue.

Inferring diameters of spheres and cylinders using interstitial water.

OBJECT: Most early methods to infer axon diameter distributions using magnetic resonance imaging (MRI) used single diffusion encoding sequences such as pulsed gradient spin echo (SE) and are thus sensitive to axons of diameters > 5 µm. We previously simulated oscillating gradient (OG) SE sequences for diffusion spectroscopy to study smaller axons including the majority constituting cortical connections. That study suggested the model of constant extra-axonal diffusion breaks down at OG accessible frequencies. In this study we present data from phantoms to test a time-varying interstitial apparent diffusion coefficient. MATERIALS AND METHODS: Diffusion spectra were measured in four samples from water packed around beads of diameters 3, 6 and 10 µm; and 151 µm diameter tubes. Surface-to-volume ratios, and diameters were inferred. RESULTS: The bead pore radii estimates were 0.60±0.08 µm, 0.54±0.06 µm and 1.0±0.1 µm corresponding to bead diameters ranging from 2.9±0.4 µm to 5.3±0.7 µm, 2.6±0.3 µm to 4.8±0.6 µm, and 4.9±0.7 µm to 9±1 µm. The tube surface-to-volume ratio estimate was 0.06±0.02 µm-1 corresponding to a tube diameter of 180±70 µm. CONCLUSION: Interstitial models with OG inferred 3-10 µm bead diameters from 0.54±0.06 µm to 1.0±0.1 µm pore radii and 151 µm tube diameters from 0.06±0.02 µm-1 surface-to-volume ratios.