17 2 7 5 5 1 5 1 9 4 1 5 1 12 6 8 7 1 3 1 1 GE GE GE GE GE GE Philips Philips Philips Philips Philips Philips Philips Siemens Siemens Siemens Siemens Siemens Siemens Siemens Picker/Marconi Model Signa Excite Signa Excite Signa HDx Signa HDxt Signa Horizon Signa Inﬁnity Achieva Achieva Intera Intera Intera Achieva Intera Achieva Gyroscan Intera Avanto Sonata Symphony Symphony Tim Symphony Vision Trio Tim Vision Plus Edge Eclipse Field 1.5 3 1.5 1.5 1.5 1.5 1.5 3 1.5 3 1.5 3 1.5 1.5 1.5 1.5 1.5 1.5 3 1.5 1.5 J Neurol (2011) 258:795–803 Table 1 Numbers, vendors, models and ﬁeld strengths of all MRI machines used Number Vendor for DWI and DTI). TOF-MRA sequence was made of 1.6-mm thick slices with a 200 mm FOV and at least a 256 9 256 matrix. The 3DT1 protocol was chosen to fol- low ADNI recommendations [9] (1.2-mm thick slices, 240 mm FOV, 192 9 192 matrix), with slight modiﬁca- tions to reduce scan time. Image management and reading sessions All scans were centralized by BioClinica and quality was controlled to check for protocol compliance and image quality. In case of signiﬁcant quality issues, repeat scans were requested. A MRI examination of insufﬁcient quality at M1 excluded the patient from the study. For follow-up timepoints, only image data of sufﬁcient quality were planned to be used for analysis. After centralization and quality control and before submission to the readers, the image data were processed by the core lab. The aim of the image processing was to prepare the image data for centralized evaluation and to pre-detect the different structures of interest (such as white matter lesions, brain parenchyma, hippocampus) to improve the efﬁciency and the quality of centralized evaluations. This included various post-processing algo- rithms, e.g., 3D reformation, image registration, tissue 797 segmentation, automated lesion detection to ensure best possible comparability. After these preparatory steps, image evaluations were carried out under supervision of BioClinica at remote sites on dedicated workstations by independent neuro-radiologists unaware of clinical infor- mation using a standardized procedure. MRI assessment Focal tissue changes related to the vascular pathology were to be assessed from M1 and M24 on FLAIR (new inci- dental infarcts and other white matter changes and changes of lesion volume), T2* (microbleeds identiﬁed as hypoin- tense lesions) and DWI (incidental acute infarcts at M24). Changes in brain volume occurring between M1 and M24 to assess global brain atrophy and hippocampal were planned to be evaluated on the 3DT1 data set. Brain microstructural tissue changes were to be assessed from M1 and M24 on diffusion tensor imaging (DTI) using apparent diffusion coefﬁcient (ADC) and fractional anisotropy (FA) maps. Lesion load Lesion load assessment on FLAIR sequences has been selected as FLAIR was previously recognized as more sensitive and speciﬁc than conventional or fast spin echo T2-weighted magnetic resonance imaging (MRI) for detecting lesions in the brain of patients with ischemic brain disease [10]. Its major advantages over T2 are a better sensitivity for small infarctions close to the sulci and a better differentiation between Virchow–Robin spaces, old lacunes and other white matter lesions [11]. Diffusion weighted imaging (DWI) was chosen as known to be very sensitive to detect acute ischemic stroke events [12]. Hyperintense FLAIR lesions, hypointense FLAIR lesions and hyperintense DWI lesions were pre-detected using an unsupervised 3D segmentation algorithm on FLAIR and DWI isotropic images after skull removal, and manually validated prior to submission to the readers (Fig. 2). Brain and hippocampal atrophy Brain parenchyma was pre-detected using a 3D segmen- tation algorithm on 3DT1 images after removal of the skull by 3D deformable registration of a brain atlas, and manu- ally validated prior to submission to the readers (Fig. 3). Left and right brain volumes were derived from the total brain volume results using the interhemispheric plane as detected at M1 on sagittal 3DT1 images. These surrogate measurements allowed us to measure the impact of brain 123