Agenda:

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

VII PMT meeting – Feb 29, 2012

Project method

1. Delphi is required to take all decisions based on experience + evidence

2. Empirical data on SUs taken on ACPC is fed to Delphi (external & internal landmarks)

3. Delphi decides on which SUs make up harmo hippo (internal landmarks)

4. Delphi decides that best segmentation is on hippo axis (10-5-1 in favour-neutral-against)

5. Empirical evidence collected that total hippo volume on ACPC = hippo axis

1. Delphi is required to take all decisions based on experience + evidence

2. Empirical data on SUs taken on ACPC is fed to Delphi (external & internal landmarks)

3. Delphi decides on which SUs make up harmo hippo (internal landmarks)

Internal Landmarks (n) External Landmarks (n)

SUs:

Minimum Hippocampus 5 1

Alveus/Fimbria 5 1

Subiculum - Oblique Line 5 1

Subiculum – Horizontal Line 5 1

Subiculum – Morphology 5 1

Tail - Crura 4 2

Tail – Tail End 5 1

Harmonized Hippo 6 0

2. Empirical data on SUs taken on ACPC is fed to Delphi (external & internal landmarks)

3. Delphi decides on which SUs make up harmo hippo (internal landmarks)

Hippo AC-PC same

Round 1: Which plane

Fisher’s exact

Round 2: Agree on hippo plane

Disagree same Agree

Rounds 3 and 4 converged on

mean angle between R and L

axes

Fisher’s

Binomial

4. Delphi decides that best segmentation is on hippo axis (10-5-1 in favour-neutral-against)

DATA SHOWN IN

PARIS, JULY 2011

Delphi: www.hippocampal-protocol.net/SOPs/delphipanel.html , access with user: prova , pw: prova

5. Empirical evidence collected that

total hippo volume on ACPC = hippo axis

Tracer Hippo_Left Hippo_Right

Intra-rater: same 10 subjects (20 images).different orientation (ACPC vs Hippocampal Axes)

MB 0.989 0.993

GP 0.985 0.991

LA* 0.971 0.967

Inter-rater: all 20 images (ACPC+Hippocampal Axes)

MB-GP-LA* 0.944 0.961

Inter-rater: only for ACPC orientation (10 images)

MB-GP-LA* 0.959 0.961

Inter-rater: only for Hippocampal Axes orientation (10 images)

MB-GP-LA 0.954 0.970

LA*= LA traced only 5 images oriented along ACPC line

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

Tra

inin

g(t

raci

ng 2

0 hi

ppos

on

1.5T

AD

NI

scan

s w

ith e

ach

SU)

(SA

ME

on

3T A

DN

I sc

ans)

Del

phi p

anel

→ h

arm

oniz

ed p

rot

VALIDATION ON 1800 HIPPOCAMPI

IN TOTAL

Pros & Cons

Methodological

1) Violate general method of the project (decisional tree)

2) Interfere with the aim of the project (define gold standard as best possible accuracy)

3) Disregard and contradict the opinion of 20 international experts of hippocampus

Methodological

1) Contrast with the orientation on which evidence was gathered

Note that this contrast :did not constitute a problem for 20

international hippo expertsdid not correspond to quantitative

evidence showing any impact on the Harmo Prot

Accepting the consensus on hippo axes would:

Practical

Reduce partial volume effects and facilitate manual tracing (tracers and panelists’ subjective reports)

Changing to AC-PC would:

Practical

Facilitate automatic preprocessing

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?

Paper OperationalizationAlzheimer’s and Dementia

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)

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

Tra

inin

g(t

raci

ng 2

0 hi

ppos

on

1.5T

AD

NI

scan

s w

ith e

ach

SU)

(SA

ME

on

3T A

DN

I sc

ans)

Del

phi p

anel

→ h

arm

oniz

ed p

rot

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