Indirect measurement of regional axon diameter in excised mouse spinal cord with q-space imaging: Simulation and experimental studies

Abstract

Q-space imaging (QSI), a diffusion MRI technique, can provide quantitative tissue architecture information at cellular dimensions not amenable by conventional diffusion MRI. By exploiting regularities in molecular diffusion barriers, QSI can estimate the average barrier spacing such as the mean axon diameter in white matter (WM). In this work, we performed ex vivo QSI on cervical spinal cord sections from healthy C57BL/6 mice at 400MHz using a custom-designed uniaxial 50T/m gradient probe delivering a 0.6 µm displacement resolution capable of measuring axon diameters on the scale of 1 µm. After generating QSI-derived axon diameter maps, diameters were calculated using histology from seven WM tracts (dorsal corticospinal, gracilis, cuneatus, rubrospinal, spinothalamic, reticulospinal, and vestibulospinal tracts) each with different axon diameters. We found QSI-derived diameters from regions drawn in the seven WM tracts (1.1 to 2.1 µm) to be highly correlated (r 2 = 0.95) with those calculated from histology (0.8 to 1.8 µm). The QSI-derived values overestimated those obtained by histology by approximately 20%, which is likely due to the presence of extracellular signal. Finally, simulations on images of synthetic circular axons and axons from histology suggest that QSI-derived diameters are informative despite diameter and axon shape variation and the presence of intra-cellular and extra-cellular signal. QSI may be able to quantify nondestructively changes in WM axon architecture due to pathology or injury at the cellular level.

Age-related changes of the diffusion tensor imaging parameters of the normal cervical spinal cord

“…Funiculi carry distinct ascending somatosensory and descending motor spinal cord tracts [1]. Previously studies [2][3][4][5][6] revealed that the dorsomedian tract, the Burdach's tract and the medial part of the LF were thin, while the fiber bundles on the outside of the VF and LF were coarse. Therefore, DTI characteristics of different WM funiculi might be different.…”

Detecting diffusion-diffraction patterns in size distribution phantoms using double-pulsed field gradient NMR: Theory and experiments

“…39,40 This major caveat is probably why diffusion-diffractions are not observed in most diffusion NMR studies of neuronal tissue, 1,41,42 broadly distributed emulsions, [43][44][45][46] and other porous media which are characterized by a relatively broad size distribution. In fact, in a recent work, Pages et al 47 showed the reversible loss of diffusion-diffraction minima when RBCs transformed from discocytes ͑relatively monodispere͒ to spherocytes ͑broader size distribution͒.…”

Studying brain cytoarchitecture with MRI—Present, future and promises of high field

“…One of the most comprehensive efforts for modeling multiple b-value/multidirectional diffusion weighted data can be found in the work of Assaf et al, where multicompartmental modeling of hindered and restricted cylindrical geometries led to successful quantitative characterization of human white matter (Assaf et al, 2004;Assaf and Basser, 2005). Further inclusion of several assumptions on axonal diameter distribution functions led to a promising tool for the evaluation of axonal diameter from diffusion data (Assaf et al, 2008;Ong et al, 2008;Barazany et al, 2009). …”