Table 1.
Demographic and clinical characteristics.
Table 2.
Comparative table.
Fig 1.
Registration of templates and surface points correspondence.
Source template is Civet’s surface while target template is the Freesurfer’ surface template. Starting from two averaged surfaces (previously created from the same set of 10 CTR, 10 sMCI, and 10 AD brains) the hybrid template (characterized by 81924 vertices and 163840 faces) is derived after 15 GFV iterations. In GVF, deformations are achieved by tuning an underlying set of control points (187×187×187) in the source surface. Control point displacements are then interpolated to obtain a continuous transformation through basis spline functions. To keep the contour smooth, a membrane and percentage thin plate energy was used as regularization. The parameters defining the attraction to edges and energy surfaces were empirically determined. Finally, the CPS step defined the mutual correspondence of Civet and Freesurfer thickness values for each vertex. CV: Civet; FS: Freesurfer; X-Y-Z: value of the vertex space coordinates; T: value of the cortical thickness for each vertex; n: number of vertices (min = 0; max = 81924); 3D GVF: 3D gradient vector flow; CPS: Closest point search.
Table 3.
Cross sectional ROI-based analysis.
Fig 2.
A) Absolute difference maps (mm) in Freesurfer and Civet. The degree of atrophy ranges between 0.1 and 0.7 mm in the different areas of the cortical mantle. B) Disease effect maps. There is a consistent delta (±0.3 mm) among the compared groups. Negative value means higher disease effect for Freesurfer (i.e.: parietal-temporal and precuneus areas); positive value means higher disease effect for Civet (i.e.: association areas and limbic parts of the cortex). C) Statistical difference maps (p<0.01 FDR-corrected). No significant voxels were found comparing CTR to sMCI. Atrophic areas were found contrasting pMCI with CTR (i.e.: the posterior cingulate, temporal lobe and frontal gyrus) with both tools. Comparing CTR versus AD the statistical significance extended (i.e.: medial temporal, retrosplenial, and lateral temporal regions). D) Overlapping and not-overlapping atrophic regions are shown. Significant voxels detected by both pipelines are in yellow; voxels detected only by Civet are in blue; voxels detected only by Freesurfer are in red. CV: Civet; FS: Freesurfer; L: Left hemisphere; R: Right hemisphere; CTR: Normal elderly controls; sMCI: stable MCI; pMCI: progressive MCI; AD: Alzheimer’s Disease.
Fig 3.
A) Absolute difference maps (mm) in each group. In CTR and sMCI, both pipelines report a very mild and widespread cortical thinning rate in the motor, somatosensory, verbal and visual association cortex. In pMCI, the atrophy peaks at rates around 0.3 mm in the medial temporal cortex, temporal-parietal-frontal neocortices, with sparing of the sensorimotor strip and of the visual cortex. In AD, the atrophy in the same areas accelerates beyond 0.4 mm. B) Disease effect maps. The mean estimate of the longitudinal disease effect in CTR and sMCI as computed by Freesurfer is greater, although Civet shows higher results in few scattered areas. Furthermore, in the entire disease spectrum, Freesurfer exhibited higher disease effect in the motor cortex. In pMCI, Civet exhibits a greater disease effect except for the cingulate gyrus, while in the AD group the exception is represented by the precuneus. C) Statistical difference maps (p<0.01 FDR-corrected). In CTR, Civet detects an atrophic cluster in the angular gyrus; while Freesurfer in the precuneus and in the temporo-occipital lobe. The pattern in sMCI was more reduced than in CTR. In pMCI Freesurfer was not able to find many regions detected by Civet with the same significance and extension (i.e.: orbital, triangulal, and opercular portion of the inferior frontal gyrus, transverse-temporal and mesial part of the superior frontal cortex, inferior parietal cortex, the superior temporal gyrus). Freesurfer was more sensitive in few scattered expected and unexpected regions. For both pipelines, the longitudinal AD shrinkage showed significant areas throughout the temporal, frontal and parietal lobes, consistently with the progression of the disease. Some shrivelling differences were detected in the anterior division of the cingulate, in the limbic lobe and in the cuneus. D) Overlapping and not-overlapping atrophic regions are shown. Significant voxels detected by both pipelines are in yellow; voxels detected only by Civet are in blue; voxels detected only by Freesurfer are in red. CV: Civet; FS: Freesurfer; L: Left hemisphere; R: Right hemisphere; CTR: Normal elderly controls; sMCI: stable MCI; pMCI: progressive MCI; AD: Alzheimer’s Disease.
Table 4.
Longitudinal ROI-based analysis.
Fig 4.
Hedges’ g effect size graphs in the different ROI areas.
The first two panels represent the cross-sectional effect sizes comparing the overall trend of CTR versus pMCI, and of CTR versus AD. The remaining three panels represent the longitudinal effect sizes between the baseline and month 24 in CTR, pMCI, and AD groups. The * symbol stands for p<0.05.
Fig 5.
Pearson’s r coefficient of cortical thickness versus MMSE scores (panel A).
In the CTR group, no significant differences between ROIs were detected in the two pipelines at BSL. At M24, significant differences between the two pipelines were found in the: middle frontal gyrus; inferior frontal gyrus—pars triangularis; superior parietal lobule; anterior division of the supramarginal gyrus; anterior and posterior division of the superior temporal gyrus. Longitudinally, no significant differences between ROIs were detected in the two pipelines. In the pMCI group, significant difference between the two pipelines was found at BSL in the: anterior division of the superior temporal gyrus. At M24, significant difference between the two pipelines was found in the: superior division of the lateral occipital cortex. Longitudinally, no significant differences between ROIs were detected in the two pipelines. Pearson’s r coefficient of cortical thickness versus NeuroQuant hippocampal volume (panel B): In the CTR group, significant difference between the two pipelines at BSL was found in the: anterior division of the parahippocampal gyrus. At M24, significant differences between the two pipelines were found in the: inferior frontal gyrus—pars opercularis; anterior and posterior division of the parahippocampal gyrus; anterior division of the temporal fusiform cortex. Longitudinally, significant differences between the two pipelines were found in the: Heschl’s gyrus and temporal planum. In the pMCI group, significant difference between the two pipelines was found at BSL in the: precuneus cortex. Longitudinally, significant differences between the two pipelines were found in the: anterior division of the supramarginal gyrus, superior division of the lateral occipital cortex, posterior division of the superior temporal gyrus, posterior division of the inferior temporal gyrus, temporo-occipital part of the inferior temporal gyrus. In panels A and B, * symbol stands for p<0.05 (Steiger’s z-test). Red coloured lines represent the trends in Freesurfer, blue lines in Civet. CTR.: CTR: Normal elderly controls; sMCI: stable MCI; pMCI: progressive MCI; AD: Alzheimer’s disease; BSL: baseline; M24: month 24; FRT: Frontal; PRT: Parietal; OCT: Occipital; LIMB: Limbic; TMP: Temporal.
Fig 6.
Receiving Operator Characteristic (ROC) curves showing the performances of Civet and Freesurfer in classifying: A) CTR versus pMCI at baseline; B) CTR versus AD at baseline; and C) pMCI at baseline from month 24.
AUC with 95% CIs are reported for both Freesurfer in red and Civet in blue. CTR: Normal elderly controls; sMCI: stable MCI; pMCI: progressive MCI; AD: Alzheimer’s Disease; BSL: baseline; M24: month 24; AUC: Area Under the Curve; C.I: Confidence Interval; ROI 8: temporal pole; ROI 11: anterior division of the middle temporal gyrus; ROI 12: posterior division of the middle temporal gyrus; ROI 13: temporo-occipital part of middle temporal gyrus; ROI 15: posterior division of inferior temporal gyrus; ROI 16: temporo-occipital part of inferior temporal gyrus; ROI 30: posterior division of the cingulate gyrus; ROI 31: Precuneus Cortex; ROI 34: anterior division of the parahippocampal gyrus; ROI 35: posterior division of the parahippocampal gyrus; ROI 37: anterior division of the temporal fusiform cortex; ROI 38: posterior division of the temporal fusiform cortex.