Cognitive Impairment in Cerebral Small Vessel Disease Is Associated with Corpus Callosum Microstructure Changes Based on Diffusion MRI

Abstract

The cerebral small vessel disease (cSVD) is one of the main causes of vascular and mixed cognitive impairment (CI), and it is associated, in particular, with brain ageing. An understanding of structural tissue changes in an intact cerebral white matter in cSVD might allow one to develop the sensitive biomarkers for early diagnosis and monitoring of disease progression.

Purpose of the study: to evaluate microstructural changes in the corpus callosum (CC) using diffusion MRI (D-MRI) approaches in cSVD patients with different severity of CI and reveal the most sensitive correlations of diffusion metrics with CI.

Methods: the study included 166 cSVD patients (51.8% women; 60.4 ± 7.6 years) and 44 healthy volunteers (65.9% women; 59.6 ± 6.8 years). All subjects underwent D-MRI (3T) with signal (diffusion tensor and kurtosis) and biophysical (neurite orientation dispersion and density imaging, NODDI, white matter tract integrity, WMTI, multicompartment spherical mean technique, MC-SMT) modeling in three CC segments as well as a neuropsychological assessment.

Results: in cSVD patients, microstructural changes were found in all CC segments already at the subjective CI stage, which was found to worsen into mild CI and dementia. More pronounced changes were observed in the forceps minor. Among the signal models FA, MD, MK, RD, and RK, as well as among the biophysical models, MC-SMT (EMD, ETR) and WMTI (AWF) metrics exhibited the largest area under the curve (>0.85), characterizing the loss of microstructural integrity, the severity of potential demyelination, and the proportion of intra-axonal water, respectively. Conclusion: the study reveals the relevance of advanced D-MRI approaches for the assessment of brain tissue changes in cSVD. The identified diffusion biomarkers could be used for the clarification and observation of CI progression.

Keywords: cognitive impairment; corpus callosum; diffusion models; small vessel disease; tract profiles.

Figure 1

Schematic representation of the CC segmented parts: 1—forceps minor (genu), 2—body, 3—forceps major (splenium). The central segments are colored in red, the whole segmented tract is colored in green.

Figure 2

ROC curves of the highest D-metrics values (AUC > 0.8) in the forceps minor for clinically significant CI (MCI and dementia) vs. control. The green line indicates AUC.

Figure 3

Profiles of D-metrics with AUC > 0.8 along the tract of the forceps minor for clinically significant CI vs. controls. The blue line indicates the D-metrics value for cSVD patients, the red one denotes that for the control group. The green curved line overlays the p-value graph. The horizontal green line indicates the significance level of p < 0.01. The segments of the tracts for which statistically significant differences in D-metrics values were found among the studied groups are shown in light green. The analysis was carried out from 5 to 95 conventional points of the CC tract length.

Figure 4

Correlations among D-metrics in the forceps minor. FA, fractional anisotropy; MD, mean diffusivity; AD, axial diffusivity; RD, radial diffusivity; MK, mean kurtosis; RK, radial kurtosis; AK, axial kurtosis; NDI, neurite density index; ODI, orientation dispersion index; ISO, free water fraction; INTRA, intra-axonal volume fraction; EMD, extra-axonal microscopic mean diffusivity; ETR, extra-axonal microscopic transverse diffusivity; AWF, axonal water fraction; axEAD, axial extra-axonal diffusivity; radEAD, radial extra-axonal diffusivity.