q‐space and conventional diffusion imaging of axon and myelin damage in the rat spinal cord after axotomy

Abstract

Parallel and perpendicular diffusion properties of water in the rat spinal cord were investigated 3 and 30 days after dorsal root axotomy, a specific insult resulting in early axonal degeneration followed by later myelin damage in the dorsal column white matter. Results from q-space analysis (i.e., the diffusion probability density function) obtained with strong diffusion weighting were compared to conventional anisotropy and diffusivity measurements at low b-values, as well as to histology for axon and myelin damage. q-Space contrasts included the height (return to zero displacement probability), full width at half maximum, root mean square displacement, and kurtosis excess of the probability density function, which quantifies the deviation from gaussian diffusion. Following axotomy, a significant increase in perpendicular diffusion (with decreased kurtosis excess) and decrease in parallel diffusion (with increased kurtosis excess) were found in lesions relative to uninjured white matter. Notably, a significant change in abnormal parallel diffusion was detected from 3 to 30 days with full width at half maximum, but not with conventional diffusivity. Also, directional full width at half maximum and root mean square displacement measurements exhibited different sensitivities to white matter damage. When compared to histology, the increase in perpendicular diffusion was not specific to demyelination, whereas combined reduced parallel diffusion and increased perpendicular diffusion was associated with axon damage. Magn Reson Med 63:1323-1335,

Evidence for early neurodegeneration in the cervical cord of patients with primary progressive multiple sclerosis

“…The changes in the displacement probability density function shape (Fig. 2) in our patient group are likely to reflect a breakdown in myelin and axonal membranes, which both act as microstructural barriers to perpendicular diffusion (Beaulieu, 2002) and correspond to what would be expected based on findings from murine and canine models of dysmyelination and axonal loss (Biton et al, 2006;Farrell et al, 2010;Wu et al, 2011;Anaby et al, 2013), as well as to what has previously been reported in patients with relapse-onset multiple sclerosis (Assaf et al, 2002;Farrell et al, 2008). The differences in QSI measures between patients and controls are also in agreement with the tNAA and Glx changes detected and provide corroborating evidence for early neurodegeneration in the cervical cord.…”

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

“…However, several in vivo QSI studies using clinical scanners have offered valuable insights into the tissue microstructure of several diseases, for example, even when SGP approximation was violated. [19][20][21][22] Another limitation is that the method works only when the diffusion sensitizing gradient is applied perpendicular to axonal fibers, so its application might be limited to certain anatomies, such as the corpus callosum and spinal cord, in which axonal fibers tightly align. However, several neurological diseases often affect the fiber composition and integrity of the corpus callosum, and several studies have reported morphological and microstructural changes of the corpus callosum in patients with neurological diseases, such as autism, 45,46 schizophrenia, 47 and bipolar disorder.…”

“…Therefore, QSI is able to provide information about tissue microstructure, such as cell compartment size and axon diameter, and it has been used to investigate the development of myelin, 18 multiple sclerosis, [19][20][21] and myelin damage. 22 Due to the Fourier transform relationship between the echo attenuation and the PDF, the displacement resolution of the PDF is determined by the maximum q-value and equals 1/(2q max ). However, electron microscopy study of the post-mortem human corpus callosum demonstrated that the diameters of myelinated fibers ranged from 0.2 to larger than 10 µm and the median diameter of axons was 0.6 µm in the genu and one µm in the splenium.…”

Time-Dependent Structural Changes of the Dentatothalamic Pathway in Children Treated for Posterior Fossa Tumor

“…23,41 In those studies, further assessment revealed decreased ʈ in the acute period (1 week) and elevated -at a later time (21 days to 2 months) after injury. 23,40,41 Given that ʈ may be more sensitive to axonal degeneration, whereas -changes may be driven by myelin effects, these studies suggested that varying contributions from axonal degeneration and myelin breakdown along different time points likely impacted temporal tensor differences, including both FA and MD. 23,40,41 Other studies have also suggested that an increase in -may drive the reduction in FA that occurs at a later time point in axonal degeneration.…”

“…23,40,41 Given that ʈ may be more sensitive to axonal degeneration, whereas -changes may be driven by myelin effects, these studies suggested that varying contributions from axonal degeneration and myelin breakdown along different time points likely impacted temporal tensor differences, including both FA and MD. 23,40,41 Other studies have also suggested that an increase in -may drive the reduction in FA that occurs at a later time point in axonal degeneration. [42][43][44] While individual FA and MD are not sufficient to differentiate axonal-versus-myelin degeneration, a pronounced reduction in FA and an increase in MD in the subacute period likely reflect the combined effects of active or ongoing myelin breakdown and inflammation after initial cerebellar injury.…”