A questionable gold standard for hippocampus volume and asymmetry.

Dear Editor, I read with interest an article published in Neuroradiology by Tae et al. Validation of hippocampal volumes measured using a manual method and two automated methods (FreeSurfer and IBASPM) in chronic major depressive disorder, Neuroradiology (2008) 50:569–581 [1]. The authors [1] concluded that (1) automated hippocampal volumetric methods showed good agreement with manual hippocampal volumetry, but the volume measured using FreeSurfer was 35% larger and the agreement was questionable with IBASPM and (2) although the automated methods could detect hippocampal atrophy in the patients with major depressive disorder, the results indicate that manual hippocampal volumetry is still the gold standard, while the automated volumetric methods need to be improved.” While the conclusion in (2) indicates that the two automated methods (FreeSurfer & IBASPM) were able to detect hippocampus atrophy, I believe the conclusion in (1) “the agreement was questionable with IBASPM” was not based on comprehensive analysis of the data available to the authors on healthy controls in a wide age span (N=20, right-handed women; age range=21–57 years; age mean and standard deviation=41.9±10.3 years). The authors only considered the rightward-volume asymmetry (asymmetry= [right− left]/(right+left)/2×100%) of the hippocampus as deduced by FreeSurfer when their own manual results described as gold standard did not establish such asymmetry, yet the FreeSurfer results were deduced to be overestimated even compared to IBASPM results. The manually delineated absolute volume and statistically insignificant asymmetry of the hippocampus obtained by the authors [1] on healthy controls (right=2.872± 0.272 mL; left=2.811±0.227 mL; asymmetry=2.15%) is not in agreement with those reported by several reports [2; rightward asymmetry=11.32%], meta analysis [3] and recent reports [4, 5] using manual delineation of hippocampus borders bilaterally, and hence one would argue the validity of the manual gold standard delineation procedures adopted in [1]. For example, a recent paper by Allen et al. [4] (N=21, right-handed women; mean age=33.0± 7.3 years; age range 23–47 years), obtained different values for the hippocampus volume using manual delineation (right volume=3.50±0.41 mL; left=3.20±0.41 mL; asymmetry=8.96%). The paper [1] lacks a review of major works using manual delineation on this topic and hence I believe a gold standard to assess the asymmetry was lacking in [1]. The authors [1] did not present a convincing explanation of the absence of rightward asymmetry in hippocampus volume based on their own validated manually delineated measurements. I believe that the authors did not dwell on the reasons behind the surprisingly strong leftward asymmetry obtained using IBASPM (asymmetry~−14.77%) compared to that obtained by FreeSurfer (asymmetry~5.48%). I would like to mention that the automated anatomical labels (AAL) used in IBASPM (see also the atlas labels in MRIcro output) are right-left swapped and hence it is possible that the values reported by IBASPM need to be swapped for laterality analysis when tabulated and summarized, on one hand. On the other hand, the manual delineation measurements reported in [1] could not be used as a gold standard for a rightward hippocampus asymmeNeuroradiology (2009) 51:201–202 DOI 10.1007/s00234-008-0492-5