Transcript Diapositiva 1 - Hippocampal Protocol

V PMT meeting – Jan 4, 2011
Agenda:
- Update GANTT
- IV Delphi round
- Hippo axes orientation
- Harmonized Protocol
- Ongoing
- Validation vs Pathology
- Publication Issues
VARIABILITY
EVALUATION
GOLD STANDARD
5 expert tracers
20 naive tracers
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)
Benchmark Harmonized hippos:
Qualification
(20 tracers)
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)
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)
global and local
95% confidence
intervals
Harmonized Protocol:
RM-ANOVA: test
of rater and rater by
center terms
The best 5
naive tracers
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)
RM-ANOVA: test of
main effects side, traceretrace, atrophy, time,
scanner, rater
V PMT meeting – Dec 21, 2011
IV Delphi round – separating A/F
Agreement for the definition of the criterion for excluding the
white matter of the fornix
8% vs 82%
Median 8
Fisher= <0.0005
Binomial= 0.003
disagree
agree
IV Delphi round – Image Orientation
Agreement for orienting images along the mean axis between left
and right
25% vs 6% vs 69%
Median= 8
Fisher= 0.026
Binomial= 0.118
left x left & right x right
mean angle
IV Delphi round – Image Orientation
The preliminary quantitative investigation, used by panelists for their decisions,
was carried out on AC-PC oriented images. Therefore we:
- traced the left Hippo of one AD and one control on a AC-PC oriented image
- re-traced the left Hippo of the same AD on the same AC-PC oriented image
- traced the left Hippo of same AD and control on images oriented along the
mean angle of hippocampal long axes;
The results show that the difference between tracings made on differently
oriented images is about 2%, but this includes the difference due to re-tracing on
the same image, which is 1.7%.
 Data from preliminary phase can be considered valid, independently on
orientation.
Harmonized Protocol: release 0.0
The Harmonized Protocol based on the features defined in the
Delphi rounds has been written, sent to Master Tracers, and to
Panelists.
We asked Master Tracers and Panelists to read carefully the
protocol, and propose corrections, suggestions or comments to
make it as clear and complete as possible (without interfering with
panelists’ decisions). The corrected version needs to be ready
before the beginning of the qualification of naive tracers.
Masters are using the Harmonized Protocol for the segmentation of
benchmark images.
Validation versus pathology
1 tracer
Local Protocol:
WHICH SAMPLE?
1.5T 3D T1-weighted scans
from (Bobinski et al., 2000)
pathologically verified set
(total for rater: 30 hippos)
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
Publication Issues
Next periodical meetings
AAN – April 24, 2012:
Delphi Paper; Italian-ADNI Paper using prototype-protocol;
Publication policy
AAIC - July 2012:
Harmonized Protocol with reliability values
20 naive tracers
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)
GOLD STANDARD
Training
(tracing 20 hippos on 1.5T ADNI
scans with each SU)
(SAME on 3T ADNI scans)
Delphi panel → harmonized prot
VARIABILITY
EVALUATION
5 expert tracers
VALIDATION vs
PATHOLOGY
1 tracer
Local Protocol:
1.5T 3D T1-weighted scans
from (Bobinski et al., 2000)
pathologically verified set
(total for rater: 30 hippos)
Benchmark Harmonized hippos:
Qualification
(20 tracers)
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)
Qualification
Harmonized Protocol:
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)
1.5T 3D T1-weighted scans
from (Bobinski et al., 2000)
pathologically verified set
(total for rater: 30 hippos)
RM-ANOVA: test
of rater and rater by
center terms
global and local
95% confidence
intervals
AAIC July 2012
Harmonized Protocol:
The best 5
naive tracers
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)
RM-ANOVA: test
of protocol main
effect
RM-ANOVA: test of
main effects side, traceretrace, atrophy, time,
scanner, rater
Paper operationalization
Operationalization of differences among protocols
for manual hippocampal segmentation
M Boccardi, M Bocchetta, R Ganzola, N Robitaille, A Redolfi, S
Duchesne, CR Jack , GB Frisoni,
and the Alzheimer's Disease Neuroimaging Initiative.
Collaborators:
G Bartzokis, JG Csernansky, MJ de Leon, L deToledo-Morrell, RJ
Killiany, S Lehéricy, N Malykhin, J Pantel, JC Pruessner, H
Soininen, C Watson
To be submitted to Alzheimer’s and Dementia
Papers describing the project
Survey of protocols (preliminary phase; published, JAD 2011)
Operationalization (preliminary phase; to be completed)
Delphi consensus
Master tracers’ practice and reliability
Development of certification platform
Validation data and Protocol definition
Validation vs pathology
20 naive tracers
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)
GOLD STANDARD
Training
(tracing 20 hippos on 1.5T ADNI
scans with each SU)
(SAME on 3T ADNI scans)
Delphi panel → harmonized prot
VARIABILITY
EVALUATION
5 expert tracers
VALIDATION vs
PATHOLOGY
1 tracer
Local Protocol:
1.5T 3D T1-weighted scans
from (Bobinski et al., 2000)
pathologically verified set
(total for rater: 30 hippos)
Benchmark Harmonized hippos:
Qualification
(20 tracers)
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)
Qualification
Harmonized Protocol:
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)
1.5T 3D T1-weighted scans
from (Bobinski et al., 2000)
pathologically verified set
(total for rater: 30 hippos)
RM-ANOVA: test
of rater and rater by
center terms
global and local
95% confidence
intervals
Harmonized Protocol:
The best 5
naive tracers
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)
RM-ANOVA: test
of protocol main
effect
RM-ANOVA: test of
main effects side, traceretrace, atrophy, time,
scanner, rater
Communication Policy (SD)
COMMUNICATIONS STEERING COMMITTEE
This is made of: (i) the Principal Investigator, (ii) the co-Principal Inestigator, (iii) the leader of the Statistical Working Group.
Decisions will be taken by majority.
APPLICABILITY
Planned communications reporting project results will be agreed among members of the Publication Steering Committee. For
each paper, a writing team will be identified, made of a lead author, senior author, and coauthors.
Scientific communication directly based on data from the Harmonization Project will go through review process (as per ADNI)
Scientific communications where the protocol is used by a tracer, certified or not, should simply reference the following article:
XXX
AUTHORSHIP
A Group will be formed (“Harmonization … Group”) for easier reference in indexed publications
Include group membership
ACKNOWLEDGMENTS
In addition to key personnel from the Coordinating centre and the Statistical Working Group centre, the following teams can be
identified: Authors of protocols, Delphi panelists, Expert tracers, Naive tracers, and P.I.s of EADC-ADNI (and other) centres.
Papers where members of above teams contribute primary work will include them as coauthors whenever possible or allowed
by the journal's publication policies. When not allowed, group authorship will be acknoweledged in the authors' list (...for the
EADC-ADNI Working Group on A Harmonized Protocol for Hippocampal Volumetry) and individual team members listed as
Collaborators or in the Acknowledgements. In any case, all possible efforts will be made to guarantee participants the highest
possible vilsibility.
The Acknowledgment section will include the full list of the EADC-ADNI (and others) centre P.I.s and Board Members (see
Appendix 1).
DIGITAL DATA
The project will produce digital data (e.g. probabilistic masks, reference images, gold standard training set of hippocampal
tracings). These will be made public in planned releases through the project’s online repositories. Public distribution will equally
apply to academic centres and for/not-for profit entities. (like ADNI?!)
POLICY SUBJECT TO PERIODICAL REVIEW
Date, time, version
APPENDIX 1. Full list of EADC-ADNI (and others) centres, and Board Members.
Appendix 1
P.I.s: Giovanni B Frisoni, Clifford R. Jack Jr
EADC CENTERS
N Fox, London, UK
A Simmons, London, UK
GB Frisoni, Brescia, IT
S Teipel, Rostock, DE
C Hock, Zurich, CH
L-O Wahlund, Stockholm, SE
H Soininen, Kuopio, FI
F Barkhof / P Scheltens, Amsterdam, NE
B Dubois / S Lehérici, Paris, FR
H Hampel, Univ. Frankfurt, DE
ADNI CENTERS
J Kaye, Portland, OR
CR Jack, Rochester, MN
C DeCarli, UC Davis, CA
G Bartzokis, UCLA, CA
M De Leon, New York, NY
R Killiany, Boston USM, MA
PM Thompson, LoNI, UCLA, CA
J Csernansky, Nortwestern U, ILL
L deToledo-Morrell, Rush UMC, Chicago, ILL
D Bennet, Rush UMC, Chicago, ILL
M Weiner / S Mueller, UCSF, CA
M Albert, John Hopkins U, Baltimore, MD
OTHER CENTERS
C Watson, WSU, Detroit, MI
J O'Brien, Newcastle, UK
J Pruessner, McGill U, QC, Canada
J Pantel, Frankfurt, DE
R Camicioli / N Malykhin, U Alberta, AB, Canada
POPULATION
BASED STUDIES
SMART-Medea Study, MI Geerlings,
NE
PATH through life, P Sachdev /JJ Maller
T denHeijer, Rotterdam Scan Study, NE
S Duschesne, Laval Univ, QC,
Canada
P Pasqualetti, AFaR, Roma, IT
L Collins, MNI, McGill, Montreal, Canada
Clinical issues:
P J Visser, Maastricht, NE
EADC PIs:
B Winbald / L Froelich
Dissemination&Education:
G Waldemar, Copenhagen, DK
ADNI PI:
M Weiner, UCSF, CA
Population Studies:
L Launer, NIA, Bethesda / W Jagust, Berkeley, CA
Coordination and execution: M
Boccardi, M Bocchetta, (R Ganzola)
Technical issues: A Redolfi, G Corbetta,
D Tolomeo
Advisor: M Pievani
STATISTICAL
WORKING GROUP
ADVISORS
Personnel in
Brescia
20 naive tracers
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)
GOLD STANDARD
Training
(tracing 20 hippos on 1.5T ADNI
scans with each SU)
(SAME on 3T ADNI scans)
Delphi panel → harmonized prot
VARIABILITY
EVALUATION
5 expert tracers
VALIDATION vs
PATHOLOGY
1 tracer
Local Protocol:
1.5T 3D T1-weighted scans
from (Bobinski et al., 2000)
pathologically verified set
(total for rater: 30 hippos)
Benchmark Harmonized hippos:
Qualification
(20 tracers)
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)
Qualification
Harmonized Protocol:
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)
1.5T 3D T1-weighted scans
from (Bobinski et al., 2000)
pathologically verified set
(total for rater: 30 hippos)
RM-ANOVA: test
of rater and rater by
center terms
global and local
95% confidence
intervals
Harmonized Protocol:
The best 5
naive tracers
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)
RM-ANOVA: test
of protocol main
effect
RM-ANOVA: test of
main effects side, traceretrace, atrophy, time,
scanner, rater