1. Agenda: - Axes check - Validation vs Pathology - Publication Policy - Paper Publications - Congress presentations & Meetings VIII PMT meeting – Mar 21, 2012

2. Delphi – V round 1.Methodological problem: shift on hippo axis might invalidate Landmark definition 2.New evidence shows that very good volume ICC on both axis, but advantage of AC-PC for overlapping agreement 3.The AC-PC advantage might be due to better visualization of CSF separating caudal amygdala from hippocampal head 4.We propose the solution to keep AC-PC, and ask level of agreement 5.Those who do not agree are required to propose an argument in support of the hippo axis that can properly overcome the methodological problem 6.It is explicitly stated that PMT will take the final decision.

3. The AC-PC advantage might be due to better visualization of CSF separating caudal amygdala from hippocampal head

4. Axial visualization of MTL in images oriented along: AC-PC Hippo axes

5. 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?

6. Validation versus pathology Originally designated sample: (Bobinski et al., 2000) 11 AD + 4 CTRL postmortem MRI and quantitative histology de Leon: 15 AD + 5 CTRL postmortem MRI and quantitative histology possible additional AD cases Jack: AD + CTRL dataset with pathologically confirmed diagnosis (controls and AD), but not post-mortem hippocampal measurement.

7. PUBLICATION POLICY Revision and final approval by PMT “From the end of the Delphi panel and until publication of the paper reporting full validation data, the protocol and accompanying digital data will not be released for public use except for beta-testing purposes. Beta testers will need to submit an application to the project Steering Committee and will need to accept to provide formal feedback on the use of the products of the Project.”

8. Papers describing the project Survey of protocols (preliminary phase; published, JAD 2011) Operationalization (preliminary phase; submitted to Alzheimer’s & Dementia, MS n. ADJ-D-12-00094) Delphi consensus (Brescia Team, in progress) Master tracers’ practice and reliability (Brescia Team, in progress) Development of certification platform (Duchesne and coll?) Validation data and Protocol definition (Brescia Team) Validation vs pathology (TBD)

9. 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

10. 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

11. AAN – April 24, 2012 AGENDA: 1. Delphi Paper; 2. Publication policy AAIC – July 2012 AGENDA: 1. Presentation of Harmonized Protocol; 2. Reliability figures SOPs periodical meetings

12. GANTT