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Development of a harmonized protocol for
hippocampal tracing
An EADC-ADNI joint effort
1th Project Management Team Meeting
August 31, 2011
Project Management Team
Principal Investigators:
Giovanni B. Frisoni \ Clifford R. Jack
Project Coordination:
Marina Boccardi \ Martina Bocchetta
Statistical Coordination:
Simon Duchesne
Industry Advisors:
Lennart Thurfjell \ Gunnar Krueger
Preliminary Phase
Areas explicitly
included
Areas explicitly
excluded
Andreas-Retzius
CA regions, dentate
gyrus (ARG), the part
gyrus, subiculum,
of the FG that is
alveus, fimbria, part of
adjacent to ARG, crus
the fasciolar gyrus (FG)
of fornix
Most anterior slice
Most posterior slice
slice w here one of the
follow ing is visible: alveus,
temporal horn of lateral
ventricle (uncal recess) or
amygdala
slice w here an ovoid mass of
gray matter started to appear
inferomedially to the trigone of the
lateral ventricle
- Survey of literature
- Certified extraction of landmarks
(Boccardi et al., J Alzheimers Dis, 2011)
Inferior border
Medial border
Superior border
HEAD
uncal cleft (if visible)
CSF of ambient cistern
temporal horn of lateral ventricle
(uncal recess) and alveus
BODY
temporal horn of
lateral ventricle
(uncal recess)
White matter of the
parahippocampal
gyrus
CSF of ambient cistern
superior excess of the
quadrigeminal cistern
TAIL
BOUNDARIES
Lateral border
temporal horn of
lateral ventricle
(uncal recess)
Discrimination of
HT from FG and
crus of fornix
using arbitrary
borders
adjacent w hite matter
atrium of lateral ventricle
Discrimination of HT from ARG
using arbitrary borders
- Operationalization of differences
(Segmentation Units, SUs)
- Quantification of relevant features of SUs
(reliability, impact on hippo volume,
informative value for AD-related atrophy)
- Quantitative data used for Delphi Questionnaires
Delphi panel → harmonized prot
VARIABILITY
EVALUATION
20 naive tracers
GOLD STANDARD
5 expert tracers
VALIDATION vs
PATHOLOGY
1 tracer
Training
Local Protocol:
Local Protocol:
total for each rater:
40 hippos
total for rater:
30 hippos
Qualification
Benchmark Harmonized
hippocampi:
Qualification
total for each rater:
40 hippos
Harmonized Protocol:
total for each rater:
40 hippos
Harmonized Protocol:
global and local 95%
confidence intervals
RM-ANOVA: test of protocol
main effect
RM-ANOVA: test of rater
and rater by center terms
Harmonized Protocol:
The best 5
naive tracers
total for rater:
30 hippos
total for each rater:
240 hippos
RM-ANOVA: test of main
effects side, trace-retrace,
atrophy, time, scanner, rater
Gold Standard
5 expert tracers
Training
Learning SUs tracing criteria
(teleconferences, feedback)
(tracing 20 hippos on 1.5 ADNI scans with each SU)
Benchmark Harmonized hippocampi:
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)
global and local 95% confidence intervals
Variability
Evaluation
Tracer certification - System
Tracer certification – System (II)
Tracer certification – System (III)
Tracer certification – System (IV)
Tracer certification - Metric
Tracer certification – Metric (II)
Tracer certification – Metric (III)
Variability Evaluation
1/2
20 naive tracers
Gold
Standard
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)
Qualification on
Benchmark hippocampi:
SELECTION of the
BEST 5 naive tracers:
1- High Qualification inter-rater
ICC
1
(total for each rater: 40 hippos)
3- Cluster Homogeneity global interrater ICC
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)
RM-ANOVA: test of rater and rater by center terms
2- High Harmonized Tracing
“1.5Tvs3T intra-rater” ICC
2
3
Variability Evaluation
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 – including
40 hippos already traced)
RM-ANOVA: test of main effects side, traceretrace, atrophy, time, scanner, rater
2/2
Project Steps Completed so far
- 2 Delphi rounds
- Tracing with local protocol (9/20)
- Master tracers practice (4/5)
- Pilot platform for tracers qualification
GANTT chart
Delphi Panel – Preliminary Results
P=0.035
P for agreement
among panelists)
Covers 100% of
hippocampus proper
Captures 100% of
AD-related atrophy
P=0.057
Intra-rater (BS-BS): 0.993
Inter-rater (BS-BS): 0.985
Preliminary ICC (BS-Mayo-LONI): 0.95
P=0.021
Delphi – Preliminary Results
This model includes some tissue
which is not hippocampus proper:
- A/F is white matter
- Tail end may include some
vestigial tissue
- The medial boundary of the body
may include some entorhinal cortex