1. Agenda: - Update master tracers - Update validation vs pathology - Hippocampal 3D Object for AR Visualization - Papers - Next congress presentations & meetings X PMT meeting – June 6, 2012

2. Benchmark Images ADNI scans: 2 x 5 Scheltenss atrophy score x 2 sides x 2 magnet strengths (1.5-3T) Total per rater: 40 hippos The 5 Master Tracers completed segmentation of R and L hippos of the 10 subjects received feedback in cases of little compliance to the Harmonized Protocol corrected segmentations accordingly

4. Benchmark Images

5. Validation vs Pathology

6. Validation versus pathology 1 tracer? (which one? A master? A naive qualified on harmo prot?? O 3? (meglio 1…) Segmentation based on Harmonized Protocol: Tot ante mortem Tot 43 postmortem MRIs TOT images…… Analysis based on the information available for each dataset Mayo Clinic AD + CTRL dataset with pathologically confirmed diagnosis (Braaks stages), but not postmortem hippocampal measurement Mony DeLeon 15 AD + 5 CTRL at 1.5T postmortem MRI and quantitative histology (possible additional AD cases) Liana Apostolova (23 hippos at 7T) CA1 neuronal counts, tau and Abeta immunoreactivity measures ? ? ? ? how many

7. 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. Liana? 23 (one side only) 7T 60-hour postmortem scans (in progress: CA1 neuronal counts, tau and Abeta immunoreactivity measures)

9. Hippocampal 3D Object for AR Visualization CTR SUBJ Affected SUBJ Manual Tracing (Simon) Tool N° 1 (FSL-FIRST) Tool N° 1 (FSL-FIRST) Tool N° 2 (FreeSurfer) Tool N° 2 (FreeSurfer) … … Segmentation Procedures … … *MODELs in AR MODELs to be Compared through SPHARM Common in all Manual Tool2 Tool1 vs. *** * CTR Aff Subj Alg1 Alg2 Alg3 Alg n …

11. Papers describing the project Survey of protocols (preliminary phase; published, JAD 2011) Operationalization (preliminary phase; I revision, Alzheimers & Dementia, MS n. ADJ-D-12-00094) Axes check short report (Brescia Team, in progress) 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)

12. VALIDATION VS CURRENT PROTOCOLS ASSESSMENT OF SOURCES OF VARIANCE TRAINING SET DEVELOPMENT VALIDATION VS PATHOLOGY GOLD STANDARD Harmonized Protocol ADNI scans: 2 x 5 Scheltenss atrophy score x 2 sides x 2 magnet strengths (1.5-3T) Total per rater: 40 hippos Harmonized Protocol ADNI scans: 2 sides x 5 Scheltenss atrophy scores x 3 time points (bl-1y-2y) x 3 scanners (+ retracing @ bl) x 2 magnet strengths (1.5-3T) Total per rater: 240 hippos Assessment of variance due to rater and center Local Protocol ADNI scans: 2 x 5 Scheltenss atrophy scores x 2 sides x 2 magnet strengths (1.5-3T) Harmonized Protocol ADNI scans: 2 x 5 Scheltenss atrophy score x 2 sides x 2 magnet strength (1.5-3T) Total per rater: 40 hippos Harmonized Protocol: Pathological datasets: Mayo Clinic and NYU Total: about 40 hippos Training ADNI scans: 10 at 1.5T x 2 sides x 7 SUs x 2 tracing rounds Total per rater: 40 hippos 20 naïve tracers5 master tracers 1 tracer REFERENCE PROBABILISTIC MASKS with 95% C.I. QUALIFICATION Best 5 naïve tracers Assessment of variance due to side, trace-retrace, atrophy, time, scanner, rater TRAINING SET Assessment of agreement with volume on pathology or ex vivo MRI and correlation with neuronal density

13. Next congress presentations - AIC 2012, Vancouver Abstract n. 26292, poster presentation Definition of Harmonized Protocol for Hippocampal Segmentation Session Date and Time: Saturday, July 14, 2012 - AAIC 2012, Vancouver Abstract n. 26291, oral presentation Definition of Harmonized Protocol for Hippocampal Segmentation Session Title: Neuroimaging 4: MCI: imaging markers of AD pathology Presentation Number: O2-11-02 Session Start Day Time: Jul 16 2012 3:30PM

14. AAIC – July 2012 Location: Fairmont Waterfront Vancouver, Princess Louisa Room Date & Time: Wednesday, July 18, 2012 at 1:00 PM - 2:30 PM AGENDA: Benchmark Images Qualification Platform Improvement of the Harmonized Protocol (based on the benchmark tracing phase) Validation Phase 2 Advancing Paper Publication Publication Policy VI Hippocampal Protocol Harmonization Meeting

15. GANTT