DTI of tuber and perituberal tissue can predict epileptogenicity in tuberous sclerosis complex

Abstract

Objective: To evaluate whether diffusion tensor imaging (DTI) can predict epileptogenic tubers by measuring apparent diffusion coefficient (ADC), fractional anisotropy, axial diffusivity, and radial diffusivity in both tubers and perituberal tissue in pediatric patients with tuberous sclerosis complex (TSC) undergoing epilepsy surgery.

Methods: We retrospectively selected 23 consecutive patients (aged 0.4-19.6 years, mean age of 5.2; 13 female, 10 male) who underwent presurgical DTI and subsequent surgical resection between 2004 and 2013 from the University of California-Los Angeles TSC Clinic. We evaluated presurgical examinations including video-EEG, brain MRI, (18)F-fluorodeoxyglucose-PET, magnetic source imaging, and intraoperative electrocorticography for determining epileptogenic tubers. A total of 545 tubers, 33 epileptogenic and 512 nonepileptogenic, were identified. Two observers generated the regions of interest (ROIs) of tubers (ROI(tuber)), the 4-mm-thick ring-shaped ROIs surrounding the tubers (ROI(perituber)), and the combined ROIs (ROI(tuber+perituber)) in consensus and calculated maximum, minimum, mean, and median values of each DTI measure in each ROI for all tubers.

Results: The Mann-Whitney U test demonstrated that the epileptogenic group showed higher maximum ADC and radial diffusivity values in all ROIs, and that maximum ADC in ROI(tuber+perituber) showed the strongest difference (p = 0.001). Receiver operating characteristic analysis demonstrated that maximum ADC measurements in ROI(tuber+perituber) (area under curve = 0.68 ± 0.05, p < 0.001) had 81% sensitivity and 44% specificity for correctly identifying epileptogenic tubers with a cutoff value of 1.32 μm(2)/ms.

Conclusions: DTI analysis of tubers and perituberal tissue may help to identify epileptogenic tubers in presurgical patients with TSC more easily and effectively than current invasive methods.

Figure 1. Creating the ROIs of tuber, perituberal tissue, and combined tuber and perituberal tissue

A 2-year-old boy with tuberous sclerosis complex. Axial T2-weighted image (A), axial T1-weighted image (B), and axial apparent diffusion coefficient map (C) showed multiple bihemispheric cortical tubers. ROI of left frontal tuber (ROI^tuber) was generated by manually contouring the tuber by 2 observers in consensus (D). ROI^tuber was automatically inflated by 4 mm to create the ROI of tuber plus perituberal tissue (ROI^{tuber+perituber}) (E). Note that the regions over CSF of ROI^{tuber+perituber} were trimmed off. ROI^tuber was subtracted from ROI^{tuber+perituber} to generate the ROI of perituberal tissue (ROI^perituber) (F). The in-plane voxel size for DTI data in our study ranged from 0.8 × 0.8 to 1.9 × 1.9 mm. In order to include at least 2 voxel rows in the perituberal ROIs, a width of 4 mm was used. ROI = region of interest.

Figure 2. ROC curves for identifying epileptogenicity based on maximum ADC and maximum RD within each ROI

ROC analysis results for (A) maximum ADC and (B) maximum RD within the tuber, perituberal tissue, and combined tuberal and perituberal tissues. Results demonstrate a high sensitivity for identifying epileptogenic tubers if maximum ADC is higher than 1.32 μm²/ms in tubers (72% sensitivity/53% specificity), perituberal tissue (59% sensitivity/62% specificity), or combined tuberal and perituberal tissue (81% sensitivity/44% specificity). Similarly, a maximum RD higher than 1.1 μm²/ms in tubers (75% sensitivity/42% specificity), perituberal tissues (68% sensitivity/50% specificity), or combined tuber and perituberal tissues (84% sensitivity/37% specificity) showed a high sensitivity for correctly identifying epileptogenic tubers. ADC = apparent diffusion coefficient; RD = radial diffusivity; ROC = receiver operating characteristic; ROI = region of interest.