Agenda:

- Axes check- Validation vs Pathology- Publication Policy- Paper Publications- Congress presentations & Meetings

VIII PMT meeting – Mar 21, 2012

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.

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

Axial visualization of MTL in images oriented along:

AC-PC

Hippo axes

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?

Validation versus pathology

Originally designated sample: (Bobinski et al., 2000)

11 AD + 4 CTRLpostmortem MRI and quantitative histology

de Leon: 15 AD + 5 CTRLpostmortem 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.

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.”

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)

Benchmark Harmonized hippos:1.5T ADNI scans2 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 – including40 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 vsPATHOLOGY

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Congress presentations

- AAN 2012, New OrleansOral Presentation S04.003, April 24, Aging and Dementia: Therapeutic Interventions, 1.30 pmM 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 2012M 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 2012M 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

AAN – April 24, 2012AGENDA: 1. Delphi Paper; 2. Publication policy

AAIC – July 2012AGENDA: 1. Presentation of Harmonized Protocol; 2. Reliability figures

SOPs periodical meetings

GANTT