1. Agenda: - Validation vs Pathology - Congress presentations & Meetings - Paper publication VI PMT meeting – Feb 1, 2011

2. Validation versus pathology Local Protocol : 1.5T 3D T1-weighted scans from (Bobinski et al., 2000) pathologically verified set (total for rater: 30 hippos) 1 tracer Qualification on benchmark images (total for each rater: 40 hippos) Harmonized Protocol: 1.5T 3D T1-weighted scans from (Bobinski et al., 2000) pathologically verified set (total for rater: 30 hippos) RM-ANOVA: test of protocol main effect WHICH SAMPLE?

3. Congress presentations & Meetings

4. Congress presentations - AAN 2012, New Orleans Oral Presentation S04.003, April 24, Aging and Dementia: Therapeutic Interventions, 1.30 pm M Boccardi, M Bocchetta, L Apostolova, J Barnes, G Bartzokis, G Corbetta, C DeCarli, L DeToledo-Morrell, M Firbank, R Ganzola, L Gerritsen, W Henneman, R Killiany, N Malykhin, P Pasqualetti, J Pruessner, A Redolfi, N Robitaille, H Soininen, D Tolomeo, L Wang, C Watson, H Wolf, S Duchesne, CR Jack, GB Frisoni. Delphi consensus on landmarks for the manual segmentation of the hippocampus on MRI: preliminary results from the EADC- ADNI Harmonized Protocol working group. - AAIC 2012, Vancouver Abstract n. 26291, submitted to AAIC 2012 M Boccardi, M Bocchetta, A Redolfi, P Pasqualetti, R Ganzola, N Robitaille, S Duchesne, CR Jack, GB Frisoni and the EADC-ADNI Hippocampal Harmonization Group. Definition of Harmonized Protocol for Hippocampal Segmentation Abstract n. 26292, submitted to AIC 2012 M Boccardi, M Bocchetta, A Redolfi, P Pasqualetti, R Ganzola, N Robitaille, S Duchesne, CR Jack, GB Frisoni and the EADC-ADNI Hippocampal Harmonization Group. Definition of Harmonized Protocol for Hippocampal Segmentation

5. AAN – April 24, 2012 AGENDA: 1. Delphi Paper *; 2. Italian-ADNI Paper using prototype-protocol (?) 3. Publication policy AAIC – July 2012 * AGENDA: 1. Presentation of Harmonized Protocol; 2. Reliability figures SOPs periodical meetings

6. Benchmark Harmonized hippos: 1.5T ADNI scans 2 x each of the 5 Scheltens’s atrophy score x 2 sides (SAME on 3T ADNI scans) (total for each rater: 40 hippos) 5 expert tracers 20 naive tracers The best 5 naive tracers Harmonized Protocol: 1.5T ADNI scans 2 sides x 5 Scheltens’s atrophy scores x 3 time points (0-12°month-24°month) x 3 scanners + retracing for timepoint 1 (SAME on 3T ADNI scans) (total for each rater: 240 hippos – including 40 hippos already traced) GOLD STANDARD Local Protocol : 1.5T 3D T1-weighted scans from (Bobinski et al., 2000) pathologically verified set (total for rater: 30 hippos) 1 tracer Qualification (20 tracers) Qualification global and local 95% confidence intervals RM-ANOVA: test of rater and rater by center terms RM-ANOVA: test of main effects side, trace- retrace, atrophy, time, scanner, rater Local Protocol : Experimental set (1.5T ADNI): 2 x each of the 5 Scheltens’s atrophy score x 2 sides (SAME on 3T ADNI scans) (total for each rater: 40 hippos) Harmonized Protocol : Experimental set (1.5T ADNI): 2 x each of the 5 Scheltens’s atrophy score x 2 sides (SAME on 3T ADNI scans) (total for each rater: 40 hippos) Harmonized Protocol: 1.5T 3D T1-weighted scans from (Bobinski et al., 2000) pathologically verified set (total for rater: 30 hippos) RM-ANOVA: test of protocol main effect VARIABILITY EVALUATION VALIDATION vs PATHOLOGY Training (tracing 20 hippos on 1.5T ADNI scans with each SU) (SAME on 3T ADNI scans) Delphi panel → harmonized prot AAIC July 2012

7. Papers publication

8. Next: Paper operationalization Operationalization of differences among protocols for manual hippocampal segmentation M Boccardi, M Bocchetta, R Ganzola, N Robitaille, A Redolfi, S Duchesne, CR Jack, GB Frisoni, and the Alzheimer's Disease Neuroimaging Initiative. Collaborators: G Bartzokis, JG Csernansky, MJ de Leon, L deToledo-Morrell, RJ Killiany, S Lehéricy, N Malykhin, J Pantel, JC Pruessner, H Soininen, C Watson To be submitted to Alzheimer’s and Dementia

9. Papers describing the project Survey of protocols (preliminary phase; published, JAD 2011) Operationalization (preliminary phase; to be completed) Delphi consensus (Brescia Team) Master tracers’ practice and reliability (Brescia Team) Development of certification platform (Duchesne and coll?) Validation data and Protocol definition (Brescia Team) Validation vs pathology (TBD)

10. Benchmark Harmonized hippos: 1.5T ADNI scans 2 x each of the 5 Scheltens’s atrophy score x 2 sides (SAME on 3T ADNI scans) (total for each rater: 40 hippos) 5 expert tracers 20 naive tracers The best 5 naive tracers Harmonized Protocol: 1.5T ADNI scans 2 sides x 5 Scheltens’s atrophy scores x 3 time points (0-12°month-24°month) x 3 scanners + retracing for timepoint 1 (SAME on 3T ADNI scans) (total for each rater: 240 hippos – including 40 hippos already traced) GOLD STANDARD Local Protocol : 1.5T 3D T1-weighted scans from (Bobinski et al., 2000) pathologically verified set (total for rater: 30 hippos) 1 tracer Qualification (20 tracers) Qualification global and local 95% confidence intervals RM-ANOVA: test of rater and rater by center terms RM-ANOVA: test of main effects side, trace- retrace, atrophy, time, scanner, rater Local Protocol : Experimental set (1.5T ADNI): 2 x each of the 5 Scheltens’s atrophy score x 2 sides (SAME on 3T ADNI scans) (total for each rater: 40 hippos) Harmonized Protocol : Experimental set (1.5T ADNI): 2 x each of the 5 Scheltens’s atrophy score x 2 sides (SAME on 3T ADNI scans) (total for each rater: 40 hippos) Harmonized Protocol: 1.5T 3D T1-weighted scans from (Bobinski et al., 2000) pathologically verified set (total for rater: 30 hippos) RM-ANOVA: test of protocol main effect VARIABILITY EVALUATION VALIDATION vs PATHOLOGY Training (tracing 20 hippos on 1.5T ADNI scans with each SU) (SAME on 3T ADNI scans) Delphi panel → harmonized prot

11. Benchmark Harmonized hippos: 1.5T ADNI scans 2 x each of the 5 Scheltens’s atrophy score x 2 sides (SAME on 3T ADNI scans) (total for each rater: 40 hippos) 5 expert tracers 20 naive tracers The best 5 naive tracers Harmonized Protocol: 1.5T ADNI scans 2 sides x 5 Scheltens’s atrophy scores x 3 time points (0-12°month-24°month) x 3 scanners + retracing for timepoint 1 (SAME on 3T ADNI scans) (total for each rater: 240 hippos – including 40 hippos already traced) GOLD STANDARD Qualification (20 tracers) global and local 95% confidence intervals RM-ANOVA: test of rater and rater by center terms RM-ANOVA: test of main effects side, trace- retrace, atrophy, time, scanner, rater Local Protocol : Experimental set (1.5T ADNI): 2 x each of the 5 Scheltens’s atrophy score x 2 sides (SAME on 3T ADNI scans) (total for each rater: 40 hippos) Harmonized Protocol : Experimental set (1.5T ADNI): 2 x each of the 5 Scheltens’s atrophy score x 2 sides (SAME on 3T ADNI scans) (total for each rater: 40 hippos) VARIABILITY EVALUATION

12. GANTT

13. Benchmark Harmonized hippos: 1.5T ADNI scans 2 x each of the 5 Scheltens’s atrophy score x 2 sides (SAME on 3T ADNI scans) (total for each rater: 40 hippos) 5 expert tracers 20 naive tracers The best 5 naive tracers Harmonized Protocol: 1.5T ADNI scans 2 sides x 5 Scheltens’s atrophy scores x 3 time points (0-12°month-24°month) x 3 scanners + retracing for timepoint 1 (SAME on 3T ADNI scans) (total for each rater: 240 hippos – including 40 hippos already traced) GOLD STANDARD Local Protocol : 1.5T 3D T1-weighted scans from (Bobinski et al., 2000) pathologically verified set (total for rater: 30 hippos) 1 tracer Qualification (20 tracers) Qualification global and local 95% confidence intervals RM-ANOVA: test of rater and rater by center terms RM-ANOVA: test of main effects side, trace- retrace, atrophy, time, scanner, rater Local Protocol : Experimental set (1.5T ADNI): 2 x each of the 5 Scheltens’s atrophy score x 2 sides (SAME on 3T ADNI scans) (total for each rater: 40 hippos) Harmonized Protocol : Experimental set (1.5T ADNI): 2 x each of the 5 Scheltens’s atrophy score x 2 sides (SAME on 3T ADNI scans) (total for each rater: 40 hippos) Harmonized Protocol: 1.5T 3D T1-weighted scans from (Bobinski et al., 2000) pathologically verified set (total for rater: 30 hippos) RM-ANOVA: test of protocol main effect VARIABILITY EVALUATION VALIDATION vs PATHOLOGY Training (tracing 20 hippos on 1.5T ADNI scans with each SU) (SAME on 3T ADNI scans) Delphi panel → harmonized prot