Objective: Subfield-specific measurements provide superior information in the early stages of neurodegenerative diseases compared to global hippocampal measurements. The overall goal was to systematically compare the performance of five representative manual and automated T1 and T2 based subfield labeling techniques in a sub-set of the ADNI2 population. Methods: The high resolution T2 weighted hippocampal images (T2-HighRes) and the corresponding T1 images from 106 ADNI2 subjects (41 controls, 57 MCI, 8 AD) were processed as follows. A. T1-based: 1. Freesurfer+Large-Diffeomorphic-Metric-Mapping in combination with shape analysis. 2. FreeSurfer 5.1 subfields using in-vivo atlas. B. T2-HighRes: 1. Model-based subfield segmentation using ex-vivo atlas (FreeSurfer 6.0). 2. T2-based automated multi-atlas segmentation combined with similarity-weighted voting (ASHS). 3. Manual subfield parcellation. Multiple regression analyses were used to calculate effect sizes (ES) for group, amyloid positivity in controls, and associations with cognitive/memory performance for each approach. Results: Subfield volumetry was better than whole hippocampal volumetry for the detection of the mild atrophy differences between controls and MCI (ES: 0.27 vs 0.11). T2-HighRes approaches outperformed T1 approaches for the detection of early stage atrophy (ES: 0.27 vs.0.10), amyloid positivity (ES: 0.11 vs 0.04), and cognitive associations (ES: 0.22 vs 0.19). Conclusions: T2-HighRes subfield approaches outperformed whole hippocampus and T1 subfield approaches. None of the different T2-HghRes methods tested had a clear advantage over the other methods. Each has strengths and weaknesses that need to be taken into account when deciding which one to use to get the best results from subfield volumetry.

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exvivo atlas freesurfer 60 2 t2based automated multiatlas segmentation invivo atlas b t2highres 1 modelbased subfield segmentation conclusions t2highres subfield approaches cognitive associations follows a t1based 1 manual subfield parcellation multiple regression analyses manual and automated t1 and t2 based subfield labeling techniques similarityweighted voting ashs 004 adni2 population group amyloid positivity in controls results subfield volumetry t2hghres methods shape analysis 2 freesurfer 51 subfields high resolution t2 weighted hippocampal images mild atrophy cognitivememory detection neurodegenerative 022 027 whole hippocampal volumetry global hippocampal measurements

Susanne G. Mueller,Paul A. Yushkevich,Sandhitsu Das,Lei Wang,Koen Van Leemput,Juan Eugenio Iglesias,Kate Alpert,Adam Mezher,Peter Ng,Katrina Paz,Michael W. Weiner,.Systematic comparison of different techniques to measure hippocampal subfield volumes in ADNI2. 17 (),.

Susanne G. Mueller,Paul A. Yushkevich,Sandhitsu Das,Lei Wang,Koen Van Leemput,Juan Eugenio Iglesias,Kate Alpert,Adam Mezher,Peter Ng,Katrina Paz,Michael W. Weiner,"Systematic comparison of different techniques to measure hippocampal subfield volumes in ADNI2" 17

Susanne G. Mueller,Paul A. Yushkevich,Sandhitsu Das,Lei Wang,Koen Van Leemput,Juan Eugenio Iglesias,Kate Alpert,Adam Mezher,Peter Ng,Katrina Paz,Michael W. Weiner,"Systematic comparison of different techniques to measure hippocampal subfield volumes in ADNI2"