Establishing Magnetic Resonance Images Orientation for the EADC-ADNI Manual Hippocampal Segmentation Protocol – SUPPLEMENTARY MATERIAL Marina Boccardi1, Martina Bocchetta1, Liana G Apostolova2, Gregory Preboske3, Nicolas Robitaille4, Patrizio Pasqualetti5, D Louis Collins6, Simon Duchesne4, Clifford R Jack Jr3, Giovanni B Frisoni1, for the EADC-ADNI Working Group on The Harmonized Protocol for Hippocampal Volumetry, and for the Alzheimer’s Disease Neuroimaging Initiative* Collaborators: John G Csernansky7, Mony J de Leon8, Leyla deToledo-Morrell9, Ronald J Killiany10, Stéphane Lehéricy11, Nikolai Malykhin12, Johannes Pantel13, Jens C Pruessner14, Hilkka Soininen15, Craig Watson16 From: LENITEM (Laboratory of Epidemiology, Neuroimaging and Telemedicine) IRCCS – S Giovanni di Dio – Fatebenefratelli Brescia, Italy (MB, MBocch, GBF); 2Mary S Easton Center for Alzheimer’s Disease Research and Laboratory of NeuroImaging, David Geffen School of Medicine, University of California, Los Angeles (LA); Department of Diagnostic Radiology, Mayo Clinic and Foundation, Rochester, MN (GP, CJ); 4Department of Radiology, Université Laval and Centre de Recherche de l’Institut universitaire de santé mentale de Québec, Quebec City, Canada (NR, SD); AFaR – Associazione Fatebenefratelli per la Ricerca, Rome, Italy; 6McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, Canada; 7Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA (JGC); 8New York University School of Medicine, Center for Brain Health, New York, NY (MJdL); Department of Neurological Sciences, Rush University, Chicago, Illinois (LdTM); 10 Department of Anatomy 11 and Neurobiology, Boston University School of Medicine (RJK); Center for NeuroImaging Research - CENIR, ICM - Institut du Cerveau et de la Moelle epiniere; Department of Neuroradiology, Université Pierre et Marie Curie-Paris 6, Inserm U975, CNRS 7225, Groupe Hospitalier Pitié-Salpêtrière, Paris, France (SL); 12 Department of Biomedical Engineering, Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada (NM); 13Institute of General Practice, University of Frankfurt/Main, Germany (JP); 14 McGill Centre for Studies in Aging, Department of Psychiatry, McGill University, Montreal, Quebec, Canada (JCP); 15 Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland (HS); 16 Wayne State University School of Medicine, University Health Center, St Antoine, Detroit, MI (CW) * Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (www.loni.ucla.edu/ADNI) As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report A complete listing of ADNI investigators can be found at: http://adni.loni.ucla.edu/wpcontent/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf This material can be found at http://www.centroalzheimer.it/public/MB/SOPs/PaperCheck4Axes/03_Supplement ary.doc Table S1 Socio-demographic features of the 10 ADNI whose scans were used in the current study MTA=Medial Temporal Atrophy (Scheltens et al., JNNP 1992); CTR=healthy controls; MCInc=non converter MCI; MCIc= MCI who subsequently converted to AD; AD=probable Alzheimer’s disease patients p-values were computed with non-parametric tests (Kruskall Wallis and Chi-square) 0,1,2,3,4 denote different degrees of MTA, from absent to severe Age, years 71 (2.8) 80 (7.8) Gender, female (100%) (50%) Education, years 17 (1.4) 14 (5.7) ApoE ε4 allele, carriers (0%) (0%) Diagnosis, CTR\MCInc\MCIc\AD 1\1\0\0 2\0\0\0 Scanner Manufacturer, Philips\GE\Siemens 0\1\1 0\2\0 MTA scale 75 (2.8) 82 (2.1) (0%) (0%) 15 (1.4) 19 (1.4) (50%) (50%) 1\0\1\0 0\1\1\0 1\1\0 0\1\1 80 (4.2) (50%) 16 (5.7) (50%) 0\0\1\1 0\2\0 p-value 0.219 0.212 0.567 0.582 0.406 0.448 Table S2 Crude hippocampal volumes of 10 ADNI subjects obtained through manual segmentation on MRIs oriented along the AC-PC line and long hippocampal axis ADNI Subject Side AC-PC Tracer Tracer Tracer Hippo Axis Tracer Tracer Tracer R 2647 3066 2938 2582 3364 2988 L 2538 2849 2843 2310 3090 3085 R 2476 2575 2654 2476 2919 2676 L 2451 2540 2634 2462 2782 2733 R 2707 3119 3076 2818 3219 3296 L 2630 2838 2913 2675 3167 3368 R 3359 3746 3811 3440 3902 3673 L 3115 3306 3547 3128 3327 3585 R 3336 3298 3211 3184 3577 3837 L 3447 3204 3275 3352 3509 3941 R 2515 2266 2901 2585 2640 3019 L 2451 2187 2694 2477 2432 2861 R 2644 2734 2992 2516 2862 2902 L 2708 2748 2882 2551 2987 2939 R 1887 1995 2376 1946 2127 2404 L 2039 1949 2431 1964 2171 2374 R 1099 1172 1052 1029 1226 1201 L 1326 1360 1242 1254 1364 1450 10 R 1333 1453 1469 1289 1558 1585 L 1659 1589 1822 1706 1640 1952 Absolute inter-rater ICCs were higher (and the confidence intervals narrower) for AC-PC (left: 0.94, 0.79-0.98 CI 95%; right: 0.94, 0.81-0.99) than for hippocampal axes oriented scans (left: 0.87, 0.410.97, right: 0.91, 0.53-0.98) Figure S1 Spatial overlapping among the three tracers in the case with the most favourable similarity coefficient (0.813; subject 3, right hippocampus, segmented on the AC-PC-oriented MRI) An animated figure with these frames is available atwww.centroalzheimer.it/public/MB/SOPs/PaperCheck4Axes/Subject_03_bestACPC_Right.mov Blue corresponds to Tracer 1, red to Tracer 2, green to Tracer The white region denotes the spatial overlap among all three tracers Red, green and blue denote regions with no overlapping Regions where two tracers overlap are indicated in magenta (Tracer and 2), yellow (Tracer and 3) and cyan (Tracer and 3) This color legend also applies to the following movies available online: The hippocampal segmentation with the worst similarity coefficient from the hippocampal axes-oriented segmentations (similarity coefficient=0.717): http://www.centroalzheimer.it/public/MB/SOPs/PaperCheck4Axes/Subject_09_w orseAxis_Right.mov The hippocampal segmentation with the worst similarity coefficient from the ACPC-oriented traces (similarity coefficient=0.729): http://www.centroalzheimer.it/public/MB/SOPs/PaperCheck4Axes/Subject_09_w orseACPC_Left.mov The hippocampal segmentation with the best similarity coefficient from the long hippocampal axes-oriented traces (similarity coefficient=0.798): http://www.centroalzheimer.it/public/MB/SOPs/PaperCheck4Axes/Subject_04_be stAxis_Left.mov Table S3 Similarity coefficients for each hippocampus segmented on the AC-PC-oriented and long hippocampal axes-oriented planes AC-PC Left Hippocampal Axes Right Left Right Similarity Coefficients 0.7643 0.7676 0.7244 0.7447 0.7905 0.7657 0.7773 0.7572 0.8048 0.8133 0.7538 0.764 0.8021 0.7989 0.7985 0.7773 0.8105 0.8247 0.7827 0.7758 0.7725 0.7561 0.7433 0.7475 0.8136 0.8079 0.7832 0.7631 0.7293 0.7678 0.7211 0.7638 0.729 0.739 0.7257 0.7177 0.7802 0.7732 0.7615 0.7306 Acknowledgements The Alzheimer’s Association has provided logistic support for the update meetings of the project in Toronto (April, 2010), Honolulu (July, 2010 and April, 2011), Paris (July, 2011), New Orleans (April, 2012) and Vancouver (July, 2012) Wyeth, part of the Pfizer group, and Lilly have provided unrestricted grants in support of the work reported in this paper A follow-up project has been funded by the Alzheimer’s Association: “A Harmonized Protocol for Hippocampal Volumetry: an EADC-ADNI Effort”, grant n IIRG -10-174022 NR and SD have received funding support from the Ministère du Développement Économique, de l’Innovation et de l’Exportation du Québec EADC-ADNI centres and PIs taking part to the project are listed in the official project web-site (http://www.hippocampal-protocol.net/SOPs/workinggroup.html) EADC-ADNI Working Group on The Harmonized Protocol for Hippocampal Volumetry 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, 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); NEUROMED, Centre for Neuroimaging Sciences, London, United Kingdom (A Simmons) ADNI Centres are: Mayo Clinic, Rochester, MN (CR Jack); University of California Davis, CA (C DeCarli); University of California, Los Angeles (UCLA), CA (G Bartzokis); University of California San Francisco (UCSF), CA (M Weiner and S Mueller); Laboratory of NeuroImaging (LoNI), University of California, Los Angeles (UCLA), CA (PM Thompson and LG Apostolova); Rush University Medical Center, Chicago, IL (L deToledo-Morrell); Rush Alzheimer's Disease Center, Chicago, IL (D Bennet); Nortwestern University, IL (J 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); Wayne State University (WSU), Detroit, MI (C Watson); 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, 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 ... color legend also applies to the following movies available online: The hippocampal segmentation with the worst similarity coefficient from the hippocampal axes-oriented segmentations (similarity... Québec EADC-ADNI centres and PIs taking part to the project are listed in the official project web-site (http://www .hippocampal- protocol. net/SOPs/workinggroup.html) EADC-ADNI Working Group on The. .. Harmonized Protocol for Hippocampal Volumetry The project PI is Giovanni B Frisoni, IRCCS Fatebenefratelli, Brescia, Italy; the co-PI is Clifford R Jack, Mayo Clinic, Rochester, MN; the Statistical