Agenda: - Validation Harmonized Protocol: update - Validation vs pathology - Hippocampal Label Expansion project: update - News - Congress presentations - Papers XVIII PMT meeting – June 5, 2013

Validation versus pathology 1 tracer (Greg) Segmentation based on Harmonized Protocol: Analysis based on the information available for each dataset and vs Bobinsky’s paper Mayo Clinic AD + CTRL + MCI dataset with pathologically confirmed diagnosis (Braak’s stages), but not postmortem hippocampal measurement Mony DeLeon 15 AD + 5 CTRL at 1.5T postmortem MRI and quantitative histology (possible additional AD cases) (Bobinsky paper on 9 AD+4 NL sbj scanned with Philips) 15 Philips + 18 GE 13 post-mortem 10 post-m T1 PD 50 antem

de Leon GE PD

Partial volume??

de Leon Philips T1

Hippocampal Label Expansion project: update Subjects = 135 Hippocampi = 270 MRItracertracing QC/correction Certification 68/ TMasamiCompleteI-II Complete (67 3T) 30/30DominikCompleteI-II Complete 12/12RossanaCompleteI-II Complete 10/10MartinaComplete I-II Complete 15/15MichelComplete I-II Complete

SD received all of the certified labels Tracers are Masters or platform-Qualified. Anyway, exact ICCs across the 5 can be computed using the volumes of the Qualification round. PLATFORM - SD has tech support from PAVI, at Université de Sherbrooke -They are looking into file formats for the contours - SD has scheduled a meeting with the Technical Advisory group Hippocampal Label Expansion project: SD update

News: Subfields Group composed by Paul Yushkevich, Susan Mueller and Lei Wang aims to converge hippo-subfields imagers for protocol harmonization. They asked for our participation, to tune the protocols and import harmonizaton methods. We are invited to present the Hippo Harmonization project a-remoto to their HS3 meeting, June

News: Duvernoy Duvernoy explained some unclear anatomy issues and approved: AC-PC standard orientation Inclusion of “vestigial” tissue Choices of the Delphi panel Participation as a coauthor

NEXT HARMONIZATION MEETING: JULY 17 H AIC-AAIC (Boston, July 13-18, 2013) Training of Naïve Tracers; Statistics for Certification Platform POSTERS - AIC-AAIC developing topics Validation phase 1: preliminary data; Expansion project: preliminary data on 1.5T images SUBMITTED -CTAD (San Diego, Nov 3-5, 2011) Validation phase 1: preliminary data; Expansion project: preliminary data on 1.5T images SUBMITTED Congress Presentations

Papers 1)Survey of protocols (preliminary phase; JAD 2011) 2)Operationalization (preliminary phase; Alzheimer’s & Dementia, published online) 3)Axes check short report (Brescia Team, ADJ-D , I revision) 4)Master tracers’ practice and reliability (Brescia Team, Sent to coauthors) 5)Development of certification platform (Duchesne and coll) 6)Consensual Protocol definition (Brescia Team – companion paper 1) 7)Validation data (Brescia Team – companion paper 2) 8)Validation vs pathology (TBD) DONE ONGOING PLANNED

VALIDATION VS CURRENT PROTOCOLS ASSESSMENT OF SOURCES OF VARIANCE TRAINING SET DEVELOPMENT VALIDATION VS PATHOLOGY GOLD STANDARD Harmonized Protocol ADNI scans: 2 x 5 Scheltens’s 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 Scheltens’s atrophy scores x 3 time points (bl-1y-2y) x 3 scanners (+ 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 Scheltens’s atrophy scores x 2 sides x 2 magnet strengths (1.5-3T) Harmonized Protocol ADNI scans: 2 x 5 Scheltens’s 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

GANTT