Objectives Lacunes are an important disease feature of cerebral small vessel disease (SVD) but their relationship to cognitive impairment is not fully understood. connectivity to the cortex. Lacune Bivalirudin Trifluoroacetate supplier locations were correlated with neuropsychological results. Voxel based morphometry was used to create anatomical covariance maps for these strategic regions. Results Lacune number and lacune volume were positively associated with worse executive function (number toolbox in SPM 12, Ashburner and Friston, 2011), producing a deformation field for each individual to the group-average space. 2.4. Lacune volume Lacunes were identified in native subject space by a consultant neuroradiologist, utilising a multimodality view with T1-weighted, T2-weighted and FLAIR images. A lacune was defined as a CSF filled cavity, 3C15?mm in diameter with a surrounding rim of FLAIR hyperintensity (Wardlaw et al., 2013). Cavity size thresholds were chosen as lesions that are less than 3?mm in diameter are more likely to Goat polyclonal to IgG (H+L) be perivascular spaces than lacunes and cavities greater than 15?mm are less likely to reflect an underlying small vessel disease aetiology (Wardlaw et al., 2013). To extract lacune regions, the centre voxel of each lacune was identified (on T1-weighted images) and an in-house 6-neighbourhood connectivity region-growing algorithm was applied to delineate the extent of the lacune. For each subject this algorithm identified a threshold boundary for lacune edges (based on the signal intensities of all lacune voxels in each brain). Region growing was applied using an iterative dilation method and initiated at each central lacune voxel until algorithmic termination at the lacune edge. This technique provided binary lacune maps for each subject. Lacune maps were visually inspected and manually adjusted where this process did not perform optimally. Total lacune number (i.e. lacune count) and volume were calculated for each subject. 2.5. Lacune location We identified the anatomical location of the already identified lacunes Bivalirudin Trifluoroacetate supplier with respect to neuroanatomical atlases of (i) white matter (WM), (ii) subcortical, and (iii) thalamic structures. To achieve this, the previously calculated, population optimised deformation fields (see Section 2.3) were used to register the lacune maps to the group-average template to create a group-level lacune Tissue Probability Map (TPM). Anatomical atlases were used to define the lacune location. These are provided in MNI space, so first needed aligning with the group average space. This was done by registering the MNI-152 T1-weighted image provided with the FSL-package to the group average template using symmetric diffeomorphic non-linear registration (Advanced Normalisation Tools, ANTS; values) controlling for age, gender, and NART IQ. Associations between MRI parameters and cognitive scores controlling for age, gender and premorbid IQ were strongest with executive function and processing speed. Lacune count and lacune volume showed negative associations of similar magnitude, although for lacune count the partial correlation coefficients were slightly greater. For lacune count and volume there were weaker associations with working and episodic memory. Brain volume was strongly associated with all cognitive domains. In contrast, associations between WMH volume and cognition were weaker. Additional analyses controlling for hypertension and depression did not affect the significance of our results. The relationships of lacune count and lacune volume with executive function and processing speed remained significant after controlling for brain volume and WMH volume (Table 3). Table 3 Associations between lacune count, volume and cognition (multiple linear regression analysis controlling for age, gender, NART, brain volume and WMH volume). 3.4. Associations between lacune location and cognition Regional analysis was performed on the following regions: subcortical grey matter regions which included the caudate, thalamus and putamen and white matter regions which included the internal capsule, external capsule, superior longitudinal fasciculus, and anterior, superior and posterior corona radiata. Thalamic CDRs included the prefrontal, premotor, temporal, primary motor and posterior parietal cortex CDRs (Fig. 2). Fig. 2 Oxford thalamic connectivity probability atlas superimposed on to group-average T1-weighted 1 mm isotropic template and shown using the neurological viewing convention. The colour key at the bottom of the figure represents the classification of thalamic … In subcortical GM, thalamic lacunes were associated with impaired processing speed (Table 4; p?p?p?n?=?9, corrected p?=?0.027; Table 4). The relationship between thalamic connections to specific cortical regions and impaired processing speed was further explored (Fig. 2 and Table 4). Associations were present between impaired processing speed Bivalirudin Trifluoroacetate supplier and lacunes in the thalamic Bivalirudin Trifluoroacetate supplier CDRs with connections.