The EADC‐ADNI Harmonized Protocol for manual hippocampal segmentation on magnetic resonance: Evidence of validity
Authors: Frisoni Giovanni B. , Jack Clifford R. , Bocchetta Martina , Bauer Corinna , Frederiksen Kristian S. , Liu Yawu , Preboske Gregory , Swihart Tim , Blair Melanie , Cavedo Enrica , Grothe Michel J. , Lanfredi Mariangela , Martinez Oliver , Nishikawa Masami , Portegies Marileen , Stoub Travis , Ward Chadwich , Apostolova Liana G. , Ganzola Rossana , Wolf Dominik , Barkhof Frederik , Bartzokis George , DeCarli Charles , Csernansky John G. , deToledo‐Morrell Leyla , Geerlings Mirjam I. , Kaye Jeffrey , Killiany Ronald J. , Lehéricy Stephane , Matsuda Hiroshi , O'Brien John , Silbert Lisa C. , Scheltens Philip , Soininen Hilkka , Teipel Stefan , Waldemar Gunhild , Fellgiebel Andreas , Barnes Josephine , Firbank Michael , Gerritsen Lotte , Henneman Wouter , Malykhin Nikolai , Pruessner Jens C. , Wang Lei , Watson Craig , Wolf Henrike , deLeon Mony , Pantel Johannes , Ferrari Clarissa , Bosco Paolo , Pasqualetti Patrizio , Duchesne Simon , Duvernoy Henri , Boccardi Marina ,   EADC‐ADNI Working Group on The Harmonized Protocol for Manual Hippocampal Volumetry and for the Alzheimer's Disease Neuroimaging Initiative, Albert Marilyn S. , Bennet David , Camicioli Richard , Collins D. Louis , Dubois Bruno , Hampel Harald , denHeijer Tom , Hock Christofer , Jagust William , Launer Leonore , Maller Jerome J. , Mueller Susan , Sachdev Perminder , Simmons Andy , Thompson Paul M. , Visser Peter‐Jelle , Wahlund Lars‐Olof , Weiner Michael W. , Winblad Bengt 
Published: September 2014

Background

An international Delphi panel has defined a harmonized protocol (HarP) for the manual segmentation of the hippocampus on MR. The aim of this study is to study the concurrent validity of the HarP toward local protocols, and its major sources of variance.

Methods

Fourteen tracers segmented 10 Alzheimer's Disease Neuroimaging Initiative (ADNI) cases scanned at 1.5 T and 3T following local protocols, qualified for segmentation based on the HarP through a standard web‐platform and resegmented following the HarP. The five most accurate tracers followed the HarP to segment 15 ADNI cases acquired at three time points on both 1.5 T and 3T.

Results

The agreement among tracers was relatively low with the local protocols (absolute left/right ICC 0.44/0.43) and much higher with the HarP (absolute left/right ICC 0.88/0.89). On the larger set of 15 cases, the HarP agreement within (left/right ICC range: 0.94/0.95 to 0.99/0.99) and among tracers (left/right ICC range: 0.89/0.90) was very high. The volume variance due to different tracers was 0.9% of the total, comparing favorably to variance due to scanner manufacturer (1.2), atrophy rates (3.5), hemispheric asymmetry (3.7), field strength (4.4), and significantly smaller than the variance due to atrophy (33.5%, P < .001), and physiological variability (49.2%, P < .001).

Conclusions

The HarP has high measurement stability compared with local segmentation protocols, and good reproducibility within and among human tracers. Hippocampi segmented with the HarP can be used as a reference for the qualification of human tracers and automated segmentation algorithms.