ALTERED FMRI ACTIVATION PATTERN DURING VISUAL SCENE ENCODING IN AFFECTED AND NON-AFFECTED CARRIERS OF PSEN1 AND APP MUTATIONS

Abstract

Background: Several studies highlighted the differential effect of normal and pathological aging on hippocampal subfield volumes, suggesting that these measurements may be more accurate than global hippocampal volumetry to detect early Alzheimer’s disease (AD). For clinical application, validated automatic algorithms of hippocampal subfield segmentation are urgently needed. An increasing number of studies use the automatic segmentation algorithm implemented in FreeSurfer. However, this approach has not been validated so far on AD patients. This study aimed to compare the accuracy of T1-MRI-based FreeSurfer segmentation versus manual delineation on dedicated high-resolution scan in measuring hippocampal subfield volumes and the effects of age and AD on these volumes. Methods: Hippocampal subfields were segmented in 98 healthy individuals (aged 19 to 84), 17 MCI and 18 AD patients using both FreeSurfer (T1-MRI, resolution: 1*1*1mm) and manual delineation (proton density-MRI, resolution: 0.375*0.375*2mm). Intraclass correlation coefficients (ICC) and Bland-Altman plots were computed to assess the consistency between both methods, and the effects of age (regressions) and group (ANOVAs) were assessed for both Freesurfuer and manual measurements. Results: Moderate to high ICCs were found for the subiculum and other subfields as well as for the whole hippocampus, but the ICC was very low for CA1. Using manual delineation, age was found to have a linear effect on the subiculum and a nonlinear (later) effect on CA1 volumes. A graded effect of the pathology was found on CA1, subiculum and the other subfields volumes. FreeSurfer CA1 volumes were found to be lower than those obtained from manual segmentation. This bias was proportional to the volume of this structure so that no effect of age or AD could be detected on FreeSurfer CA1 volumes. Conclusions: This study highlights differences in the anatomic definition of the subfields, especially for CA1, between FreeSurfer and manual delineation based on histologic atlases. While FreeSurfer provides reasonable estimates of the subiculum and other subfields, it does not provide a reliable estimate of CA1 volume and fails in detecting normal aging and AD-related changes in this subfield. As earliest AD-related changes seem to occur in CA1, FreeSurfer needs to be improved especially for clinical application in early AD diagnosis.