Estimation of the Mean Axon Diameter and Intra-axonal Space Volume Fraction of the Human Corpus Callosum: Diffusion q-space Imaging with Low q-values

Abstract

Purpose: Q-space imaging (QSI) is a diffusion-weighted imaging (DWI) technique that enables investigation of tissue microstructure. However, for sufficient displacement resolution to measure the microstructure, QSI requires high q-values that are usually difficult to achieve with a clinical scanner. The recently introduced "low q-value method" fits the echo attenuation to only low q-values to extract the root mean square displacement. We investigated the clinical feasibility of the low q-value method for estimating the microstructure of the human corpus callosum using a 3.0-tesla clinical scanner within a clinically feasible scan time.Methods: We performed a simulation to explore the acceptable range of maximum qvalues for the low q-value method. We simulated echo attenuations caused by restricted diffusion in the intra-axonal space (IAS) and hindered diffusion in the extra-axonal space (EAS) assuming 100,000 cylinders with various diameters, and we estimated mean axon diameter, IAS volume fraction, and EAS diffusivity by fitting echo attenuations with different maximum q-values. Furthermore, we scanned the corpus callosum of 7 healthy volunteers and estimated the mean axon diameter and IAS volume fraction.Results: Good agreement between estimated and defined values in the simulation study with maximum q-values of 700 and 800 cm ¹1 suggested that the maximum q-value used in the in vivo experiment, 737 cm ¹1 , was reasonable. In the in vivo experiment, the mean axon diameter was larger in the body of the corpus callosum and smaller in the genu and splenium, and this anterior-to-posterior trend is consistent with previously reported histology, although our mean axon diameter seems larger in size. On the other hand, we found an opposite anterior-to-posterior trend, with high IAS volume fraction in the genu and splenium and a lower fraction in the body, which is similar to the fiber density reported in the histology study.Conclusion: The low q-value method may provide insights into tissue microstructure using a 3T clinical scanner within clinically feasible scan time.

Corpus callosum macro and microstructure in late-life depression

“…When this is not the case, CSD and derived AFD metrics can become sensitive to extra-axonal changes. Nevertheless, the AFD profile we observed across the CC is largely consistent with histological (Aboitiz et al, 1992) and low q-value imaging data (Suzuki et al, 2016) describing axon diameter and density. This increases confidence in the observed differences being, at least in part, due to genuine microstructural differences affecting the number, size and/or density of callosal axons.…”

In vivo Restricted-Diffusion Imaging (RDI) is sensitive to differences in axonal density in typical children and adults

“…For example, the Aboitiz et al 18 histological examination of 20 post-mortem healthy adult brains showed that the density of small and large diameter axons differs across the anterior-posterior axis of the corpus callosum. This now well-established density pattern has been replicated with other measures in more recent work 19, 20, 21 , including the study by Genc and colleagues 22 that serves as a model of the present investigation. As we noted earlier, it would be important for a number of reasons to establish in vivo metrics that are sensitive to differences in axonal density.…”

“…Thus, the primary aim of this study is to address whether RDI is a candidate metric for measuring axonal density in vivo, and further whether it does so better than other available diffusion metrics. To do this, we measured segments of the corpus callosum, which have been known to differ in axonal density on the anterior-posterior axis 18, 19, 23, 24 . We used both a healthy adult sample (n = 840) and a healthy developing sample (n = 129) to test whether previous histological results match the segmental pattern reflected using RDI in vivo.…”

Transient Probst Bundle Diffusion Restriction: An Acute Encephalopathy Equivalent to Clinically Mild Encephalopathy with a Reversible Splenial Lesion

“…It is postulated that the cardinal MR abnormality of MERS is a result of transient edema of the myelin sheaths. Because the axons in splenium CC are so tightly packed and have high density, the intramyelinic edema is most readily detected as diffusion restriction in the splenium CC (10). We speculate that these two apparently distinct brain structures of Probst bundles and CC might produce similar MR signal abnormalities under the same pathophysiological conditions, thus causing acute encephalopathy and intramyelinic edema.…”