Delphi Consensus on Landmarks for the Manual Segmentation of the Hippocampus on MRI: Preliminary Results from the EADC-ADNI Harmonized Protocol Working Group (S04.003)

Abstract

Objective: To define a harmonized protocol for manual hippocampal segmentation from magnetic resonance scans. Background Heterogeneity of landmarks among protocols leads to different volume estimates, hampering comparison of studies and clinical use. Landmark differences among the 12 most common protocols were extracted, operationalized, and quantitatively investigated. The results were presented to the Delphi panel, consisting of seventeen researchers with substantial expertise in hippocampal segmentation, to reach an evidence-based consensus on segmentation landmarks. Design/Methods: The Delphi panel participated in recursive anonymous voting sessions where feedback from previous rounds was utilized to progressively facilitate panelists9 agreement. Panelists were presented with tracing alternatives, each associated with quantitative data relating: (i) reliability, (ii) impact on whole hippocampal volume, and (iii) correlation with AD pathology. Panelists were asked to choose among alternatives and provide justification and comments. Anonymous votes and comments, and voting statistics of the first round were fed into the second Delphi round. Exact probability on binomial test of the choice was computed. At the time of writing, two Delphi rounds were completed. Results: Sixteen panelists completed both Delphi rounds. Agreement was significant on inclusion of alveus and fimbria (81%, p=0.021), of the whole visible hippocampal tail (75%, p=0.035), and approached significance for the segmentation of the medial border of the body following visible morphology (69%, p=0.057). Agreement on including the minimum hippocampus, alveus, morphological subiculum, whole hippocampal tail in the final hippocampal tracing protocol was significant (88%, p=0.001). Based on the previous quantitative investigation of landmark differences, the hippocampus so defined covers 100% of hippocampal tissue, captures 100% of AD-related atrophy, and has good intra-rater (0.99) and inter-rater (0.94) reliability measured on volume statistics. Conclusions: The most “inclusive” landmarks were preferred by Delphi panelists. Further rounds will be run to seek statistically significant agreement for all aspects. Supported by: Alzheimer9s Association. Lilly International. Wyeth International (Pfizer Group). Disclosure: Dr. Boccardi has nothing to disclose. Dr. Bocchetta has nothing to disclose. Dr. Apostolova has nothing to disclose. Dr. Barnes has nothing to disclose. Dr. Bartzokis has received personal compensation for activities with Bristol-Myers Squibb Company and Novartis. Dr. Bartzokis has received research support from Novartis and Janssen Pharmaceutica. Dr. Corbetta has nothing to disclose. Dr. DeCarli has received personal compensation for activities wtih Merck Pharmaceutical, Avanir, Bayer Pharmaceuticals, and Pfizer as a consultant.Dr. DeCarli has received personal compensation in an editorial capacity for Alzheimer9s Disease and Associated Disorders.Dr. DeCarli has received research support from Merck. Dr. DeToledo-Morrell has nothing to disclose. Dr. Firbank has nothing to disclose. Dr. Ganzola has nothing to disclose. Dr. Gerritsen has nothing to disclose. Dr. Henneman has nothing to disclose. Dr. Killiany has received personal compensation for activities with Sunovion Pharmaceuticals Inc as a consultant. Dr. Killiany has received research support from The MRI Centers of New England and a clinical affiliation with Essex Neurological Associates. Dr. Malykhin has nothing to disclose. Dr. Pasqualetti has nothing to disclose. Dr. Pruessner has nothing to disclose. Dr. Redolfi has nothing to disclose. Dr. Robitaille has nothing to disclose. Dr. Soininen has received personal compensation for activities with ACImmune. Dr. Tolomeo has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Watson has nothing to disclose. Dr. Wolf has nothing to disclose. Dr. Duchesne has received (royalty or license fee or contractual rights) payments from Screen Inc.Dr. Duchesne has received research support from Afga Healthcare Inc. Dr. Jack has received personal compensation for activities with Janssen Pharmaceutica, Eisai Inc, General Electric, Johnson and Johnson, and Eli Lilly & Company as a consultant.Dr. Jack has received research support from Pfizer Inc, Allon, and Baxter, Inc. Dr. Frisoni has received personal compensation for activities Eli Lilly & Company, Bristol-Myers Squibb Company, Bayer Healthcare, Lundbeck Research USA, Inc., Elan Corporation, AstraZeneca Pharmaceuticals, Pfizer Inc, Baxter, Taurx, and Wyeth Pharmaceuticals. Dr. Frisoni has received personal compensation in an editorial capacity for Lancet Neurology, Aging Clinical & Experimental Research, Neurobiology of Aging, Alzheimer9s Diseases and Associated Disorders, and Neurogenerative Diseases. Dr. Frisoni has received research support from Wyeth Corporation, Eli Lilly & Company, Lundbeck Research USA, Inc.