Subcortical brain segmentation of two dimensional T1-weighted data sets with FMRIB's Integrated Registration and Segmentation Tool (FIRST)

Abstract

Brain atrophy has been identified as an important contributing factor to the development of disability in multiple sclerosis (MS). In this respect, more and more interest is focussing on the role of deep grey matter (DGM) areas. Novel data analysis pipelines are available for the automatic segmentation of DGM using three-dimensional (3D) MRI data. However, in clinical trials, often no such high-resolution data are acquired and hence no conclusions regarding the impact of new treatments on DGM atrophy were possible so far. In this work, we used FMRIB's Integrated Registration and Segmentation Tool (FIRST) to evaluate the possibility of segmenting DGM structures using standard two-dimensional (2D) T1-weighted MRI. In a cohort of 70 MS patients, both 2D and 3D T1-weighted data were acquired. The thalamus, putamen, pallidum, nucleus accumbens, and caudate nucleus were bilaterally segmented using FIRST. Volumes were calculated for each structure and for the sum of basal ganglia (BG) as well as for the total DGM. The accuracy and reliability of the 2D data segmentation were compared with the respective results of 3D segmentations using volume difference, volume overlap and intra-class correlation coefficients (ICCs). The mean differences for the individual substructures were between 1.3% (putamen) and -25.2% (nucleus accumbens). The respective values for the BG were -2.7% and for DGM 1.3%. Mean volume overlap was between 89.1% (thalamus) and 61.5% (nucleus accumbens); BG: 84.1%; DGM: 86.3%. Regarding ICC, all structures showed good agreement with the exception of the nucleus accumbens. The results of the segmentation were additionally validated through expert manual delineation of the caudate nucleus and putamen in a subset of the 3D data. In conclusion, we demonstrate that subcortical segmentation of 2D data are feasible using FIRST. The larger subcortical GM structures can be segmented with high consistency. This forms the basis for the application of FIRST in large 2D MRI data sets of clinical trials in order to determine the impact of therapeutic interventions on DGM atrophy in MS.

Keywords: Basal ganglia; FMRIB's Integrated Registration and Segmentation Tool; Multiple sclerosis; Segmentation; T1-weighted data; Two-dimensional data.

Fig. 1

Modified MNI template: Left — original MNI 1 mm T1w template used in FIRST, in yellow the subcortical mask; right — modified “cut” templates.

Fig. 2

Impact of atrophy: In this case, both registration of the 2D and 3D data to MNI space failed because of severely enlarged ventricles. A: Original axial view of the 3D data; B: same data registered to MNI space (slice is not identical but similar); C: 50% overlay to the MNI template D: MNI template (for comparison).

Fig. 3

Impact of motion artefacts: Motion artefacts can hamper the registration to MNI space. A: The 2D data set show step-like artefacts due to motion between the two concatenated acquisitions. The registration to MNI space fails in this case as can be seen of the deviation of the pitch angle of the registered data set (B) compared to the MNI template (C).

Fig. 4

Impact of MS lesions: The subcortical segmentation of FIRST is robust even in presence of MS lesions. The black arrow in (A) points to a hypo-intense lesion at the border of white matter and thalamus. (B) The segmentation (orange) is not impacted by the lesion.

Fig. 5

Volume differences between 2 and 3D segmentation: Percentage volume difference between 2 and 3D data for the basal ganglia (BG) and for deep grey matter (DGM; BG + thalamus). The 2D data were additionally corrected with a CSF mask (see Fig. 6). Solid line: mean difference for all patients; broken lines: mean difference ± 2 ∗ standard deviation.

Fig. 6

CSF mask effect: The effect of applying a CSF mask onto 2D data; A: original DGM mask; B: CSF mask; C: DGM mask corrected for CSF; D: difference between original mask (grey) and corrected mask (orange). Only the thalamus (4) was significantly impacted by the CSF mask. The other DGM structures in this figure are (1) caudate nucleus; (2): putamen; and (3): pallidum.

Fig. 7

Volume overlap between 2 and 3D segmentation: Percentage volume overlap (Dice's coefficient) between 2 and 3D data for BG and for DGM. Solid line: mean overlap for all patients.