The EADC-ADNI harmonized protocol for manual hippocampal segmentation on magnetic resonance: Evidence of validity

Giovanni B. Frisoni; Clifford R. Jack; Martina Bocchetta; Corinna Bauer; Kristian S. Frederiksen; Yawu Liu; Gregory Preboske; Tim Swihart; Melanie Blair; Enrica Cavedo; Michel J. Grothe; Mariangela Lanfredi; Oliver Martinez; Masami Nishikawa; Marileen Portegies; Travis Stoub; Chadwich Ward; Liana G. Apostolova; Rossana Ganzola; Dominik Wolf; Frederik Barkhof; George Bartzokis; Charles DeCarli; John G. Csernansky; Leyla Detoledo-Morrell; Mirjam I. Geerlings; Jeffrey Kaye; Ronald J. Killiany; Stephane Lehericy; Hiroshi Matsuda; John O'Brien; Lisa C. Silbert; Philip Scheltens; Hilkka Soininen; Stefan Teipel; Gunhild Waldemar; Andreas Fellgiebel; Josephine Barnes; Michael Firbank; Lotte Gerritsen; Wouter Henneman; Nikolai Malykhin; Jens C. Pruessner; Lei Wang; Craig Watsonl; Henrike Wolf; Mony Deleon; Johannes Pantel; Clarissa Ferrari; Paolo Bosco; Patrizio Pasqualetti; Simon Duchesne; Henri Duvernoy; Marina Boccardi; Marilyn S. Albert; David Bennet; Richard Camicioli; D. Louis Collins; Bruno Dubois; Harald Hampel; Tom Denheijer; Christofer Hock; William Jagust; Leonore Launer; Jerome J. Maller; Susan Mueller; Perminder Sachdev; Andy Simmons; Paul M. Thompson; Peter Jelle Visser; Lars Olof Wahlund; Michael W. Weiner; Bengt Winblad

doi:10.1016/j.jalz.2014.05.1756

The EADC-ADNI harmonized protocol for manual hippocampal segmentation on magnetic resonance: Evidence of validity

Giovanni B. Frisoni, Clifford R. Jack, Martina Bocchetta, Corinna Bauer, Kristian S. Frederiksen, Yawu Liu, Gregory Preboske, Tim Swihart, Melanie Blair, Enrica Cavedo, Michel J. Grothe, Mariangela Lanfredi, Oliver Martinez, Masami Nishikawa, Marileen Portegies, Travis Stoub, Chadwich Ward, Liana G. Apostolova, Rossana Ganzola, Dominik WolfFrederik Barkhof, George Bartzokis, Charles DeCarli, John G. Csernansky, Leyla Detoledo-Morrell, Mirjam I. Geerlings, Jeffrey Kaye, Ronald J. Killiany, Stephane Lehericy, Hiroshi Matsuda, John O'Brien, Lisa C. Silbert, Philip Scheltens, Hilkka Soininen, Stefan Teipel, Gunhild Waldemar, Andreas Fellgiebel, Josephine Barnes, Michael Firbank, Lotte Gerritsen, Wouter Henneman, Nikolai Malykhin, Jens C. Pruessner, Lei Wang, Craig Watsonl, Henrike Wolf, Mony Deleon, Johannes Pantel, Clarissa Ferrari, Paolo Bosco, Patrizio Pasqualetti, Simon Duchesne, Henri Duvernoy, Marina Boccardi, Marilyn S. Albert, David Bennet, Richard Camicioli, D. Louis Collins, Bruno Dubois, Harald Hampel, Tom Denheijer, Christofer Hock, William Jagust, Leonore Launer, Jerome J. Maller, Susan Mueller, Perminder Sachdev, Andy Simmons, Paul M. Thompson, Peter Jelle Visser, Lars Olof Wahlund, Michael W. Weiner, Bengt Winblad

Neurology

Research output: Contribution to journal › Article › peer-review

133 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	111-125
Number of pages	15
Journal	Alzheimer's and Dementia
Volume	11
Issue number	2
DOIs	https://doi.org/10.1016/j.jalz.2014.05.1756
State	Published - 2015

Keywords

Alzheimer's disease
Biomarkers
Clinical trials
Diagnostic criteria
Enrichment
Harmonized protocol
Hippocampal volumetry
Magnetic resonance
Manual segmentation
Standard operating procedures
Validation

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Psychiatry and Mental health
Cellular and Molecular Neuroscience

Access to Document

10.1016/j.jalz.2014.05.1756

Cite this

Frisoni, G. B., Jack, C. R., Bocchetta, M., Bauer, C., Frederiksen, K. S., Liu, Y., Preboske, G., Swihart, T., Blair, M., Cavedo, E., Grothe, M. J., Lanfredi, M., Martinez, O., Nishikawa, M., Portegies, M., Stoub, T., Ward, C., Apostolova, L. G., Ganzola, R., ... Winblad, B. (2015). The EADC-ADNI harmonized protocol for manual hippocampal segmentation on magnetic resonance: Evidence of validity. Alzheimer's and Dementia, 11(2), 111-125. https://doi.org/10.1016/j.jalz.2014.05.1756

The EADC-ADNI harmonized protocol for manual hippocampal segmentation on magnetic resonance : Evidence of validity. / 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.; Lehericy, 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; Watsonl, Craig; Wolf, Henrike; Deleon, Mony; Pantel, Johannes; Ferrari, Clarissa; Bosco, Paolo; Pasqualetti, Patrizio; Duchesne, Simon; Duvernoy, Henri; Boccardi, Marina; 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.

In: Alzheimer's and Dementia, Vol. 11, No. 2, 2015, p. 111-125.

Research output: Contribution to journal › Article › peer-review

Frisoni, GB, Jack, CR, Bocchetta, M, Bauer, C, Frederiksen, KS, Liu, Y, Preboske, G, Swihart, T, Blair, M, Cavedo, E, Grothe, MJ, Lanfredi, M, Martinez, O, Nishikawa, M, Portegies, M, Stoub, T, Ward, C, Apostolova, LG, Ganzola, R, Wolf, D, Barkhof, F, Bartzokis, G, DeCarli, C, Csernansky, JG, Detoledo-Morrell, L, Geerlings, MI, Kaye, J, Killiany, RJ, Lehericy, S, Matsuda, H, O'Brien, J, Silbert, LC, Scheltens, P, Soininen, H, Teipel, S, Waldemar, G, Fellgiebel, A, Barnes, J, Firbank, M, Gerritsen, L, Henneman, W, Malykhin, N, Pruessner, JC, Wang, L, Watsonl, C, Wolf, H, Deleon, M, Pantel, J, Ferrari, C, Bosco, P, Pasqualetti, P, Duchesne, S, Duvernoy, H, Boccardi, M, Albert, MS, Bennet, D, Camicioli, R, Collins, DL, Dubois, B, Hampel, H, Denheijer, T, Hock, C, Jagust, W, Launer, L, Maller, JJ, Mueller, S, Sachdev, P, Simmons, A, Thompson, PM, Visser, PJ, Wahlund, LO, Weiner, MW & Winblad, B 2015, 'The EADC-ADNI harmonized protocol for manual hippocampal segmentation on magnetic resonance: Evidence of validity', Alzheimer's and Dementia, vol. 11, no. 2, pp. 111-125. https://doi.org/10.1016/j.jalz.2014.05.1756

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. ; Lehericy, 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 ; Watsonl, Craig ; Wolf, Henrike ; Deleon, Mony ; Pantel, Johannes ; Ferrari, Clarissa ; Bosco, Paolo ; Pasqualetti, Patrizio ; Duchesne, Simon ; Duvernoy, Henri ; Boccardi, Marina ; 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. / The EADC-ADNI harmonized protocol for manual hippocampal segmentation on magnetic resonance : Evidence of validity. In: Alzheimer's and Dementia. 2015 ; Vol. 11, No. 2. pp. 111-125.

@article{b24b4ce647784bf4abb100f52a194138,

title = "The EADC-ADNI harmonized protocol for manual hippocampal segmentation on magnetic resonance: Evidence of validity",

abstract = "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.",

keywords = "Alzheimer's disease, Biomarkers, Clinical trials, Diagnostic criteria, Enrichment, Harmonized protocol, Hippocampal volumetry, Magnetic resonance, Manual segmentation, Standard operating procedures, Validation",

author = "Frisoni, {Giovanni B.} and Jack, {Clifford R.} and Martina Bocchetta and Corinna Bauer and Frederiksen, {Kristian S.} and Yawu Liu and Gregory Preboske and Tim Swihart and Melanie Blair and Enrica Cavedo and Grothe, {Michel J.} and Mariangela Lanfredi and Oliver Martinez and Masami Nishikawa and Marileen Portegies and Travis Stoub and Chadwich Ward and Apostolova, {Liana G.} and Rossana Ganzola and Dominik Wolf and Frederik Barkhof and George Bartzokis and Charles DeCarli and Csernansky, {John G.} and Leyla Detoledo-Morrell and Geerlings, {Mirjam I.} and Jeffrey Kaye and Killiany, {Ronald J.} and Stephane Lehericy and Hiroshi Matsuda and John O'Brien and Silbert, {Lisa C.} and Philip Scheltens and Hilkka Soininen and Stefan Teipel and Gunhild Waldemar and Andreas Fellgiebel and Josephine Barnes and Michael Firbank and Lotte Gerritsen and Wouter Henneman and Nikolai Malykhin and Pruessner, {Jens C.} and Lei Wang and Craig Watsonl and Henrike Wolf and Mony Deleon and Johannes Pantel and Clarissa Ferrari and Paolo Bosco and Patrizio Pasqualetti and Simon Duchesne and Henri Duvernoy and Marina Boccardi and Albert, {Marilyn S.} and David Bennet and Richard Camicioli and Collins, {D. Louis} and Bruno Dubois and Harald Hampel and Tom Denheijer and Christofer Hock and William Jagust and Leonore Launer and Maller, {Jerome J.} and Susan Mueller and Perminder Sachdev and Andy Simmons and Thompson, {Paul M.} and Visser, {Peter Jelle} and Wahlund, {Lars Olof} and Weiner, {Michael W.} and Bengt Winblad",

note = "Funding Information: Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) ( National Institutes of Health Grant U01 AG024904 ). ADNI is funded by the National Institute on Aging , the National Institute of Biomedical Imaging and Bioengineering , and through generous contributions from the following: Abbott ; Alzheimer's Association ; Alzheimer's Drug Discovery Foundation ; Amorfix Life Sciences Ltd. ; AstraZeneca ; Bayer HealthCare ; BioClinica, Inc. ; Biogen Idec Inc. ; Bristol-Myers Squibb Company ; Eisai Inc. ; Elan Pharmaceuticals Inc. ; Eli Lilly and Company ; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare ; Innogenetics, N.V. ; IXICO Ltd. ; Janssen Alzheimer Immunotherapy Research & Development, LLC. ; Johnson & Johnson Pharmaceutical Research & Development LLC. ; Medpace, Inc. ; Merck & Co., Inc. ; Meso Scale Diagnostics, LLC. ; Novartis Pharmaceuticals Corporation ; Pfizer Inc. ; Servier ; Synarc Inc. ; and Takeda Pharmaceutical Company . The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health Rev March 26, 2012 ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129 and K01 AG030514 . Funding Information: Josephine Barnes is an Alzheimer's Research UK senior research fellow based at the Dementia Research Centre, Department of Neurodegenerative Disease, UCL, Institute of Neurology. The Dementia Research Centre is an Alzheimer's Research UK Coordinating Centre and has also received equipment funded by Alzheimer's Research UK and Brain Research Trust . Part of this work was supported by the NIHR Queen Square Dementia BRU . Funding Information: Preparatory work (reported in Boccardi et al., J Alzheimers Dis, 2011; 26:61-75 and in Boccardi et al, Alzheimer's and Dementia 2013, doi:pii: S1552-5260(13)00078-2) was funded by unrestricted grants from Lilly International and Wyeth International (a part of the Pfizer group). Funding Information: The “Harmonized Protocol For Manual Hippocampal Segmentation: An EADC-ADNI Effort” has been funded thanks to an unrestricted grant from the Alzheimer's Association (grant number IIRG-10-174022 ). The project PI is Giovanni B Frisoni, IRCCS Fatebenefratelli, Brescia, Italy; the co-PI is Clifford R. Jack, Mayo Clinic, Rochester, MN; the Statistical Working Group is led by Simon Duchesne, Laval University, Quebec City, Canada; project Coordinator is Marina Boccardi, IRCCS Fatebenefratelli, Brescia, Italy. EADC Centres (local P.I.) are: IRCCS Fatebenefratelli, Brescia, Italy (GB Frisoni); University of Kuopio and Kuopio University Hospital, Kuopio, Finland (H Soininen); H{\"o}pital Salp{\`e}triere, Paris, France (B Dubois and S Lehericy); University of Frankfurt, Frankfurt, Germany (H Hampel); University Rostock and DZNE, Rostock, Germany (S Teipel); Karolinska institutet, Stockholm, Sweden (L-O Wahlund); Department of Psychiatry Research, Zurich, Switzerland (C Hock); Alzheimer Centre, Vrije Univ Medical Centre, Amsterdam, The Netherlands (F Barkhof and P Scheltens); Dementia Research Group Institute of Neurology, London, United Kingdom (N Fox); Dep. of Psychiatry and Psychotherapy, University Medical Center, Mainz (A. Fellgiebel); NEUROMED, Department of Neuroimaging, King's College London, London, United Kingdom (A Simmons). ADNI Centres are: Mayo Clinic, Rochester, MN (CR Jack); University of California Davis, CA (C DeCarli and C Watson); University of California, Los Angeles (UCLA), CA (G Bartzokis); University of California San Francisco (UCSF), CA (M Weiner and S Mueller); University of California, Los Angeles (UCLA), CA (LG Apostolova); Laboratory of NeuroImaging (LoNI), University of Southern California, Los Angeles, CA (PM Thompson); Rush University Medical Center, Chicago, IL (L deToledo-Morrell); Rush Alzheimer's Disease Center, Chicago, IL (D Bennet); Northwestern University, IL (JG Csernansky); Boston University School of Medicine, MA (R Killiany); John Hopkins University, Baltimore, MD (M Albert); Center for Brain Health, New York, NY (M De Leon); Oregon Health & Science University, Portland, OR (J Kaye). Other Centres are: McGill University, Montreal, Quebec, Canada (J Pruessner); University of Alberta, Edmonton, AB, Canada (R Camicioli and N Malykhin); Department of Psychiatry, Psychosomatic, Medicine & Psychotherapy, Johann, Wolfgang Goethe-University, Frankfurt, Germany (J Pantel); Institute for Ageing and Health, Wolfson Research Centre, Newcastle General Hospital, Newcastle, United Kingdom (J O'Brien). Population based Studies: PATH through life, Australia (P Sachdev and JJ Maller); SMART-Medea Study, University Medical Center Utrecht, The Netherlands (MI Geerlings); Rotterdam Scan Study, The Netherlands (T denHeijer). Statistical Working Group: AFAR (Fatebenefratelli Association for Biomedical Research) San Giovanni Calibita - Fatebenefratelli Hospital - Rome, Italy (P Pasqualetti); Laval University, Quebec City, Canada (S Duchesne); MNI, McGill University, Montreal, Canada (L Collins). Advisors: Clinical issues: PJ Visser, Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands; EADC PIs: B Winbald, Karolinska Institute, Sweden and L Froelich, Central Institute of Mental Health, Mannheim, Germany; Dissemination & Education: G Waldemar, Copenhagen University Hospital, Copenhagen, Denmark; ADNI PI: M Weiner, University of California San Francisco (UCSF), CA; Population Studies: L Launer, National Institute on Aging (NIA), Bethesda and W Jagust, University of California, Berkeley, CA. Funding Information: Contribution by Tim Swihart, Lisa C Silbert and Jeffrey Kaye was supported by NIH / NIA ADC P30 grant ( P30 AG008017 ). Contribution by Stephane Leh{\'e}ricy was supported by the grant: “ Investissements d'avenir ” (grant number ANR-10-IAIHU-06 ). Funding Information: The Statistical Working Group is co-funded through an international collaborative grant from the Minist{\`e}re du D{\'e}veloppement {\'E}conomique, de l'Innovation et de l'Exportation of Quebec. Publisher Copyright: {\textcopyright} 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.",

year = "2015",

doi = "10.1016/j.jalz.2014.05.1756",

language = "English (US)",

volume = "11",

pages = "111--125",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "Elsevier Inc.",

number = "2",

}

TY - JOUR

T1 - The EADC-ADNI harmonized protocol for manual hippocampal segmentation on magnetic resonance

T2 - Evidence of validity

AU - Frisoni, Giovanni B.

AU - Jack, Clifford R.

AU - Bocchetta, Martina

AU - Bauer, Corinna

AU - Frederiksen, Kristian S.

AU - Liu, Yawu

AU - Preboske, Gregory

AU - Swihart, Tim

AU - Blair, Melanie

AU - Cavedo, Enrica

AU - Grothe, Michel J.

AU - Lanfredi, Mariangela

AU - Martinez, Oliver

AU - Nishikawa, Masami

AU - Portegies, Marileen

AU - Stoub, Travis

AU - Ward, Chadwich

AU - Apostolova, Liana G.

AU - Ganzola, Rossana

AU - Wolf, Dominik

AU - Barkhof, Frederik

AU - Bartzokis, George

AU - DeCarli, Charles

AU - Csernansky, John G.

AU - Detoledo-Morrell, Leyla

AU - Geerlings, Mirjam I.

AU - Kaye, Jeffrey

AU - Killiany, Ronald J.

AU - Lehericy, Stephane

AU - Matsuda, Hiroshi

AU - O'Brien, John

AU - Silbert, Lisa C.

AU - Scheltens, Philip

AU - Soininen, Hilkka

AU - Teipel, Stefan

AU - Waldemar, Gunhild

AU - Fellgiebel, Andreas

AU - Barnes, Josephine

AU - Firbank, Michael

AU - Gerritsen, Lotte

AU - Henneman, Wouter

AU - Malykhin, Nikolai

AU - Pruessner, Jens C.

AU - Wang, Lei

AU - Watsonl, Craig

AU - Wolf, Henrike

AU - Deleon, Mony

AU - Pantel, Johannes

AU - Ferrari, Clarissa

AU - Bosco, Paolo

AU - Pasqualetti, Patrizio

AU - Duchesne, Simon

AU - Duvernoy, Henri

AU - Boccardi, Marina

AU - Albert, Marilyn S.

AU - Bennet, David

AU - Camicioli, Richard

AU - Collins, D. Louis

AU - Dubois, Bruno

AU - Hampel, Harald

AU - Denheijer, Tom

AU - Hock, Christofer

AU - Jagust, William

AU - Launer, Leonore

AU - Maller, Jerome J.

AU - Mueller, Susan

AU - Sachdev, Perminder

AU - Simmons, Andy

AU - Thompson, Paul M.

AU - Visser, Peter Jelle

AU - Wahlund, Lars Olof

AU - Weiner, Michael W.

AU - Winblad, Bengt

N1 - Funding Information: Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) ( National Institutes of Health Grant U01 AG024904 ). ADNI is funded by the National Institute on Aging , the National Institute of Biomedical Imaging and Bioengineering , and through generous contributions from the following: Abbott ; Alzheimer's Association ; Alzheimer's Drug Discovery Foundation ; Amorfix Life Sciences Ltd. ; AstraZeneca ; Bayer HealthCare ; BioClinica, Inc. ; Biogen Idec Inc. ; Bristol-Myers Squibb Company ; Eisai Inc. ; Elan Pharmaceuticals Inc. ; Eli Lilly and Company ; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare ; Innogenetics, N.V. ; IXICO Ltd. ; Janssen Alzheimer Immunotherapy Research & Development, LLC. ; Johnson & Johnson Pharmaceutical Research & Development LLC. ; Medpace, Inc. ; Merck & Co., Inc. ; Meso Scale Diagnostics, LLC. ; Novartis Pharmaceuticals Corporation ; Pfizer Inc. ; Servier ; Synarc Inc. ; and Takeda Pharmaceutical Company . The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health Rev March 26, 2012 ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129 and K01 AG030514 . Funding Information: Josephine Barnes is an Alzheimer's Research UK senior research fellow based at the Dementia Research Centre, Department of Neurodegenerative Disease, UCL, Institute of Neurology. The Dementia Research Centre is an Alzheimer's Research UK Coordinating Centre and has also received equipment funded by Alzheimer's Research UK and Brain Research Trust . Part of this work was supported by the NIHR Queen Square Dementia BRU . Funding Information: Preparatory work (reported in Boccardi et al., J Alzheimers Dis, 2011; 26:61-75 and in Boccardi et al, Alzheimer's and Dementia 2013, doi:pii: S1552-5260(13)00078-2) was funded by unrestricted grants from Lilly International and Wyeth International (a part of the Pfizer group). Funding Information: The “Harmonized Protocol For Manual Hippocampal Segmentation: An EADC-ADNI Effort” has been funded thanks to an unrestricted grant from the Alzheimer's Association (grant number IIRG-10-174022 ). The project PI is Giovanni B Frisoni, IRCCS Fatebenefratelli, Brescia, Italy; the co-PI is Clifford R. Jack, Mayo Clinic, Rochester, MN; the Statistical Working Group is led by Simon Duchesne, Laval University, Quebec City, Canada; project Coordinator is Marina Boccardi, IRCCS Fatebenefratelli, Brescia, Italy. EADC Centres (local P.I.) are: IRCCS Fatebenefratelli, Brescia, Italy (GB Frisoni); University of Kuopio and Kuopio University Hospital, Kuopio, Finland (H Soininen); Höpital Salpètriere, Paris, France (B Dubois and S Lehericy); University of Frankfurt, Frankfurt, Germany (H Hampel); University Rostock and DZNE, Rostock, Germany (S Teipel); Karolinska institutet, Stockholm, Sweden (L-O Wahlund); Department of Psychiatry Research, Zurich, Switzerland (C Hock); Alzheimer Centre, Vrije Univ Medical Centre, Amsterdam, The Netherlands (F Barkhof and P Scheltens); Dementia Research Group Institute of Neurology, London, United Kingdom (N Fox); Dep. of Psychiatry and Psychotherapy, University Medical Center, Mainz (A. Fellgiebel); NEUROMED, Department of Neuroimaging, King's College London, London, United Kingdom (A Simmons). ADNI Centres are: Mayo Clinic, Rochester, MN (CR Jack); University of California Davis, CA (C DeCarli and C Watson); University of California, Los Angeles (UCLA), CA (G Bartzokis); University of California San Francisco (UCSF), CA (M Weiner and S Mueller); University of California, Los Angeles (UCLA), CA (LG Apostolova); Laboratory of NeuroImaging (LoNI), University of Southern California, Los Angeles, CA (PM Thompson); Rush University Medical Center, Chicago, IL (L deToledo-Morrell); Rush Alzheimer's Disease Center, Chicago, IL (D Bennet); Northwestern University, IL (JG Csernansky); Boston University School of Medicine, MA (R Killiany); John Hopkins University, Baltimore, MD (M Albert); Center for Brain Health, New York, NY (M De Leon); Oregon Health & Science University, Portland, OR (J Kaye). Other Centres are: McGill University, Montreal, Quebec, Canada (J Pruessner); University of Alberta, Edmonton, AB, Canada (R Camicioli and N Malykhin); Department of Psychiatry, Psychosomatic, Medicine & Psychotherapy, Johann, Wolfgang Goethe-University, Frankfurt, Germany (J Pantel); Institute for Ageing and Health, Wolfson Research Centre, Newcastle General Hospital, Newcastle, United Kingdom (J O'Brien). Population based Studies: PATH through life, Australia (P Sachdev and JJ Maller); SMART-Medea Study, University Medical Center Utrecht, The Netherlands (MI Geerlings); Rotterdam Scan Study, The Netherlands (T denHeijer). Statistical Working Group: AFAR (Fatebenefratelli Association for Biomedical Research) San Giovanni Calibita - Fatebenefratelli Hospital - Rome, Italy (P Pasqualetti); Laval University, Quebec City, Canada (S Duchesne); MNI, McGill University, Montreal, Canada (L Collins). Advisors: Clinical issues: PJ Visser, Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands; EADC PIs: B Winbald, Karolinska Institute, Sweden and L Froelich, Central Institute of Mental Health, Mannheim, Germany; Dissemination & Education: G Waldemar, Copenhagen University Hospital, Copenhagen, Denmark; ADNI PI: M Weiner, University of California San Francisco (UCSF), CA; Population Studies: L Launer, National Institute on Aging (NIA), Bethesda and W Jagust, University of California, Berkeley, CA. Funding Information: Contribution by Tim Swihart, Lisa C Silbert and Jeffrey Kaye was supported by NIH / NIA ADC P30 grant ( P30 AG008017 ). Contribution by Stephane Lehéricy was supported by the grant: “ Investissements d'avenir ” (grant number ANR-10-IAIHU-06 ). Funding Information: The Statistical Working Group is co-funded through an international collaborative grant from the Ministère du Développement Économique, de l'Innovation et de l'Exportation of Quebec. Publisher Copyright: © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Biomarkers

KW - Clinical trials

KW - Diagnostic criteria

KW - Enrichment

KW - Harmonized protocol

KW - Hippocampal volumetry

KW - Magnetic resonance

KW - Manual segmentation

KW - Standard operating procedures

KW - Validation

UR - http://www.scopus.com/inward/record.url?scp=84929158989&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929158989&partnerID=8YFLogxK

U2 - 10.1016/j.jalz.2014.05.1756

DO - 10.1016/j.jalz.2014.05.1756

M3 - Article

C2 - 25267715

AN - SCOPUS:84929158989

VL - 11

SP - 111

EP - 125

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

SN - 1552-5260

IS - 2

ER -

The EADC-ADNI harmonized protocol for manual hippocampal segmentation on magnetic resonance: Evidence of validity

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