800 Fig. 5 Intracranial cavity detection. The T2* sequence was used to detect the intracranial cavity contours (in red) as it clearly depicts external CSF (left). Given the lack of full brain coverage for all patients the 3DT1 sequence was automatically coregistered to T2*, resliced in the axial plane, and used to manually complete for potentially missing upper and lower slices (right) Fig. 6 Microbleeds assessment. Cerebral microbleeds, deﬁned as punctuate, homogeneous, rounded, hypointense lesions smaller than 5 mm in size, visualised on T2* sequences, (in red), were counted throughout the brain by the readers, and classiﬁed as cortical, cortico- subcortical, juxtacortical or deep and infratentorial J Neurol (2011) 258:795–803 partly due to demyelination and ﬁber loss with a corre- sponding reduction in anisotropy [19]. DTI is sensitive to these changes in anisotropy, making it a powerful in vivo imaging tool for studying the microstructural integrity of cerebral white matter [20]. The apparent diffusion coefﬁcient (ADC) which mea- sures the rate of diffusion in each image voxel, and frac- tional anisotropy (FA), a measure of the extent to which the diffusion is directionally restricted are used as their scalar values seem to be more robust and suited to group com- parisons [21]. For DWI and DTI sequences, the peak, mean, standard deviation and height values were extracted from histogram data. Each DWI and DTI sequence were independently processed by the core lab to suppress the extrameningeal structures and to suppress the CSF voxels in order to restrict the histogram analysis only to the brain parenchyma, and to generate the ADC and FA maps. Normalized histograms were then computed over the whole brain and over the normal appearing brain tissue (as deﬁned by subtracting the FLAIR lesion mask from the whole brain mask). 123 Data management Evaluation criteria The primary efﬁcacy criteria of the study were lesion changes and brain volume changes between M1 and M24. All these parameters were assessed globally but also with regard to the side of the lesion of the initial ischemic event. The identiﬁcation of the ipsilateral and contralateral hemispheres allows us to evaluate, in addition to the gen- eral progression of the cerebrovascular disease, the speciﬁc evolution of the disease in relation to the initial event. As a criterion of interest for safety the number of emergent microbleeds was identiﬁed. Statistical analysis The PERFORM MRI project analyses will be under the supervision of the Biometry Division of the Institut de Recherches Internationales Servier. The analyses will be performed in all patients having taken the study drug and