MRI scanning was performed at the MR Research Center of the University of Pittsburgh with a 3T Siemens Tim Trio MR scanner and a Siemens 64-channel head coil.23 (link) MRIs were magnetization-prepared rapid gradient echo (MPRAGE) T1-weighted sequence and T2-weighted (T2w) fluid-attenuated inversion recovery (FLAIR) sequence. MPRAGE images were acquired in the axial plane (parameters: repetition time, 2400 ms; echo time, 2.22 ms; T1, 1000 ms; flip angle, 8°; field of view, 256 × 240 mm; slice thickness, 0.8 mm; voxel size, 0.8 mm × 0.8mm; matrix size, 320 × 300; number of slices, 208). FLAIR images were acquired in the axial plane (parameters: repetition time, 9690 or 10 000 ms; echo time, 91 ms; T1, 2500 ms; flip angle, 135°; field of view, 256 × 256 mm; matrix, 320 × 320; slice thickness, 1.6 mm; voxel size, 0.8 mm × 0.8 mm; number of slices, 104).
An automated pipeline was used to segment WMH on the T2w FLAIR images using previously validated methods.29 (link) Cerebral and cerebellar white matter were segmented on the T1w image and mapped into the T2w FLAIR image space using SPM mapping software version 12 (Functional Imaging Laboratory, UCL Queen Square Institute of Neurology) and FreeSurfer processing, analyzing, and visualizing software version 7.1.1 (Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School). Cerebellar white matter represented normal-appearing white matter; its intensity mean and SD were used for Z-transformation of the T2w FLAIR image. A threshold of 2 was applied on Z-transformed FLAIR images. Z-transformation also reduces intensity variations across individual FLAIR images.
In the processing, analyzing, and visualizing software, white matter was parcellated according to its nearest cortex with the Deskian-Killiany atlas, used to generate the cortical white matter masks for frontal, temporal, parietal, and occipital lobes for localization of WMHs. White matter parcellations corresponding to frontal cortex regions were combined to create a frontal cortical white matter mask to localize frontal WMHs. Cortical white matter masks were generated for temporal, parietal, and occipital lobes. These lobular cortical white matter masks did not overlap and were combined to create an overall cortical and deep white matter mask. White matter surrounding the ventricles that was not part of the cortical and deep white matter mask comprised the periventricular white matter mask. The total and regional WMHV (in centimeters cubed) were normalized as WMH divided by intracranial volume and log transformed.
An automated pipeline was used to segment WMH on the T2w FLAIR images using previously validated methods.29 (link) Cerebral and cerebellar white matter were segmented on the T1w image and mapped into the T2w FLAIR image space using SPM mapping software version 12 (Functional Imaging Laboratory, UCL Queen Square Institute of Neurology) and FreeSurfer processing, analyzing, and visualizing software version 7.1.1 (Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School). Cerebellar white matter represented normal-appearing white matter; its intensity mean and SD were used for Z-transformation of the T2w FLAIR image. A threshold of 2 was applied on Z-transformed FLAIR images. Z-transformation also reduces intensity variations across individual FLAIR images.
In the processing, analyzing, and visualizing software, white matter was parcellated according to its nearest cortex with the Deskian-Killiany atlas, used to generate the cortical white matter masks for frontal, temporal, parietal, and occipital lobes for localization of WMHs. White matter parcellations corresponding to frontal cortex regions were combined to create a frontal cortical white matter mask to localize frontal WMHs. Cortical white matter masks were generated for temporal, parietal, and occipital lobes. These lobular cortical white matter masks did not overlap and were combined to create an overall cortical and deep white matter mask. White matter surrounding the ventricles that was not part of the cortical and deep white matter mask comprised the periventricular white matter mask. The total and regional WMHV (in centimeters cubed) were normalized as WMH divided by intracranial volume and log transformed.
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