Dear FreeSurfer development team,

I have received Reviewer comments from a manuscript I recently submitted based on results from FreeSurfer (beta version) output. The focus of the study is the hippocampal tail. Whilst one Reviewer likes it, the other has asked a number of questions regarding the segmentation validity. Specifically, the Reviewer refers to Schoemaker D, et al (2016) Hippocampus and amygdala volumes from magnetic resonance images in children: Assessing accuracy of FreeSurfer and FSL against manual segmentation. Neuroimage. 2016 Apr 1;129:1-14. The Reviewer has also stated that the authors of the FreeSurfer software “have never provided detailed volumetric protocol for hippocampal volume segmentation or its subregions/subfields. For instance, I am not sure how they separate the hippocampal tail from the hippocampal body or amygdala from hippocampus. Therefore, it is not clear how the segmentation of those brain structures is done.” The Reviewer then goes on to state that “Fimbria is so small compared to the resolution used in this study in order to be measured separately on conventional T1 images (See see Frisoni et al., 2015 or Boccheta M et al., 2015 EADC-ADNI protocol). Molecular layer is not even visible on T1 images (please provide the MRI images when it can be seen and quantified on T1 MRI images). The entire stratum lacunosum-moleculare is less then 0.6 mm thick so I do not know how the FreeSurfer can split it in half with the resolution of 1mm and measure it separately from CA…”.

Can you please suggest how I should respond to these Reviewer questions?

Regards,

Jerome Maller