Understanding the Physiopathology Behind Axial and Radial Diffusivity Changes—What Do We Know?

Abstract

The use of the diffusion tensor imaging (DTI) is rapidly growing in the neuroimaging field. Nevertheless, rigorously performed quantitative validation of DTI pathologic metrics remains very limited owing to the difficulty in co-registering quantitative histology findings with magnetic resonance imaging. The aim of this review is to summarize the existing state-of-the-art knowledge with respect to axial (λ║) and radial (λ┴) diffusivity as DTI markers of axonal and myelin damage, respectively. First, we provide technical background for DTI and briefly discuss the specific organization of white matter in bundles of axonal fibers running in parallel; this is the natural target for imaging based on diffusion anisotropy. Second, we discuss the four seminal studies that paved the way for considering axial (λ║) and radial (λ┴) diffusivity as potential in vivo surrogate markers of axonal and myelin damage, respectively. Then, we present difficulties in interpreting axial (λ║) and radial (λ┴) diffusivity in clinical conditions associated with inflammation, edema, and white matter fiber crossing. Finally, future directions are highlighted. In summary, DTI can reveal strategic information with respect to white matter tracts, disconnection mechanisms, and related symptoms. Axial (λ║) and radial (λ┴) diffusivity seem to provide quite consistent information in healthy subjects, and in pathological conditions with limited edema and inflammatory changes. DTI remains one of the most promising non-invasive diagnostic tools in medicine.

Combined Diffusion Tensor Imaging and Quantitative Susceptibility Mapping Discern Discrete Facets of White Matter Pathology Post-injury in the Rodent Brain

“…Changes in AxD have been linked with axonal damage and changes in RD reflect changes in myelination, or myelin integrity (19)(20)(21). Notably, in the case of more severe injuries, AxD and RD tend to provide insufficient information on the specific white matter changes taking place (29,30). Therefore, supporting detail needs to be derived from additional data, such as magnetic susceptibility.…”

“…While white matter microstructural alterations affect DTI measures, the metrics appear to be non-specific encompassing an array of pathological changes occurring after TBI (18,28). Notably, in the case of more severe injuries, AxD and RD may provide insufficient information on the specific white matter changes taking place (29,30). Therefore, supporting detail needs to be derived from additional data, such as magnetic susceptibility.…”

Impact of second-generation antipsychotics on white matter microstructure in adolescent-onset psychosis

“…However, the timing of neuroinflammation in psychotic disorders relative to tissue injury is unclear, leading to a heightened risk of misinterpreting changes in DWI measures. According to a recent review of Winklewski and colleagues, in cases of neuroinflammation linked to tissue damage, DWI seems to underestimate the extent of demyelination (undervalued RD), and overestimate the extent of axonal injury (overvalued AD) 35 . This pattern seems replicated in our study, with significant changes in AD and no changes in RD.…”

Reduced axonal caliber and white matter changes in a rat model of Fragile X syndrome with a deletion of a K Homology domain of Fmr1

“…Similar to the T2 region-based analysis, we first analyzed the male and female rats separately and assessed both the whole-brain and the 32 brain ROIs (see Supplementary Table 1). When we compared Fmr1-Δ exon 8 -/y rats to their male WT littermates, we found that the nominal p- 18 values for the DTI metrics of multiple ROIs were significant, though only a few survived a Bonferroni correction. Remarkably, RD was increased across the whole brain ( Figure 3A and B; ANOVA, p = 0.043).…”

“…We used DTI to evaluate white matter specifically, as it is affected in individuals with FXS, with axial, radial, and mean diffusion (AD, RD, and MD, respectively) and total FA as measures of possible changes. FA is enhanced when parallel diffusivity is facilitated and/or perpendicular diffusivity is restricted, RD is increased following myelin damage, and AD is reduced after axonal damage [18]. Furthermore, MD may reflect pathology if it is increased in white matter.…”