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Dear Dr Gaser and LSTusers, I would like to use the Lesion Segmentation Tool for SPM (version 1.2.3, for SPM8), to measure white matter hyperintensities (WMH) in two groups of older adults. Specifically, I would like to report WMH volumes in the two groups and determine if one group has a higher lesion load than the other. I followed your manual and there are some points that I am not quite sure to understand. First, I ran the PVE label estimation and lesion segmentation (module 3.1) on our T1 and FLAIR images using different k-thresholds. I then created binary lesion maps and computed volumes from these binary maps and the lesion probability maps (in both MNI and non-MNI space). The part that is currently unclear to me is whether we should be reporting the volumes output from the Binary Lesion Maps (or the Probability Lesion Maps) or from the Binary/Prob Lesion Maps in MNI space? We noticed that the volumes in MNI space range from ~893 to ~3,310 and the non-MNI space volumes range from ~0.01 to 34. If I understand the units correctly, the volumes are in ml-- so the non-MNI space volumes seem more consistent with the literature. However, we would like to better understand why we are getting such drastically different volumes from the MNI-space lesion map. Also, it is mentioned in the “How to proceed further” section of the manual that to further analyse white matter lesions, lesion maps should be normalized. It is also mentioned on the website that you don’t provide normalized lesion maps. Since I am mainly interested in white matter lesions, I am wondering if the way to proceed would be the following one: 1: run the PVE label estimation and segmentation (module 3.1) 2: Fill in the T1 images (module 4.1) 3: “use SPM or VBM routines in order to calculate deformation fields from the filled images and apply these fields to the segmented lesion maps” 4: Compute volumes from the produced lesions maps Thank you in advance for your help and thanks for providing this very useful tool! Best, Alix Noly-Gandon