Temporal changes and implications of diffusion tensor imaging metrics and cerebral white matter volume in patients undergoing carotid endarterectomy - a prospective study

Abstract

Aims: To test utility of diffusion MRI-derived indices in carotid endarterectomy (CEA), change of diffusion tensor imaging (DTI) metrics, cerebral white matter (WM) volumes were evaluated and predictors of overall mortality determined.

Methods: Prospectively enrolled participants had preoperative, immediate and late postoperative DTI after CEA. WM volumes, DTI metrics (fractional anisotropy, FA; axial, radial, mean diffusivities; AD, RD, MD, respectively) were calculated for the index/contralateral hemispheres at all time points. Temporal changes, predictors of log₂-transformed WM volumes, DTI values were analyzed using linear mixed model. Uni- and multivariable Cox proportional hazards models were used to identify predictors of mortality.

Results: 60 subjects (57% male, 69.5 ± 7.2years) were included. Significantly increased AD and MD was observed in both hemispheres comparing the preoperative and immediate postoperative DTI metrics (index AD: β = 0.02 [95%CI:0.01,0.02], p < 0.001; index MD: β = 0.02 [95%CI:0.01,0.03], p < 0.001; contralateral AD: β = 0.01 [95%CI:0.01,0.02], p = 0.001; contralateral MD: β = 0.02 [95%CI:0.01,0.03], p = 0.003). The index MD decreased (β = 0.01 [95%CI:0.01,0.001], p = 0.04), bilateral WM volumes (index WM: β = 0.04 [95%CI:0.02,0.07], p < 0.001; contralateral WM: β = 0.05 [95%CI:0.03,0.07], p < 0.001) decreased significantly between the immediate and late postoperative scans. Postoperative contralateral FA correlated significantly with lower mortality (HR = 0.001 [95%CI:0.001,0.19], p = 0.02); postoperative contralateral RD (HR = 3.74 × 10⁴ [95%CI:1.62,8.60 × 10⁸], p = 0.04) and MD (HR = 1.19 × 10⁵ [95%CI:1.03,1.37 × 10¹⁰], p = 0.049) were significant predictors of mortality.

Conclusion: The increase of various DTI metrics from pre-to-postoperative may be indicative of microstructural deterioration following CEA. Temporal changes between the immediate and late postoperative scans suggest, however, reversal of detrimental WM changes and clearance of presumed subclinical WM edema. Our results also imply, that preserved cerebral properties are protective after CEA.

Keywords: Carotid artery stenosis; Carotid endarterectomy; Diffusion MRI; Diffusion tensor imaging; Mortality.

Fig. 1

Flowchart of patient numbers with reason for exclusion

Fig. 2

Regions of interest covering the whole white matter of the left/right hemispheres created from the “FreeSurfer” software package (version 7.1.1). Right hemiphere - green, left hemisphere – blue, corpus callosum - yellow. White matter hyperintensities, manually corrected from the LTS: Lesion Segmentation Tool” (version 3.0.0), coloured in red. (a) Orthogonal views of a subject with widespread periventricular white matter hyperintensities. (b) Subject with mild cerebral white matter hyperintensities

Fig. 3

The volumes of the hippocampi (orange) were calculated using data from the FreeSurfer software package (version 7.1.1) ‘aseg’ segmentations

Fig. 4

Exmaple of a hyperintense new ischemic lesion, delineated manually on the ‘trace’ image (right) with the corresponding low signal intnsity on the mean diffusivity (MD) map (left) using the AGFA Picture Archiving and Communication System (PACS) workstation (Impax 6.5.2.657, Agfa HealthCare, Mortsel, Belgium)