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

- Survey of literature - Certified extraction of landmarks (Boccardi et al., J Alzheimers Dis, 2011)

- 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

Areas explicitly excluded Most anter ior slice

Andreas-Retzius gyrus (ARG), the part

of the FG that is adjacent to ARG, crus

of fornix

slice w here one of the follow ing is visible: alveus,

temporal horn of lateral ventricle (uncal recess) or

amygdala

Lateral border Inferior border Medial border

HEAD

temporal horn of lateral ventricle (uncal recess)

uncal cleft (if visible) CSF of ambient cistern

BODY

temporal horn of lateral ventricle (uncal recess)

White matter of the parahippocampal

gyrusCSF of ambient cistern

TAIL

Discrimination of HT f rom FG and crus of fornix using arbitrary

borders

adjacent w hite matter atrium of lateral ventricle

Areas explicitly included

CA regions, dentate gyrus, subiculum,

alveus, fimbria, part of the fasciolar gyrus (FG)

BOUNDARIES

Discrimination of HT f rom ARG using arbitrary borders

Most posterior slice

slice w here an ovoid mass of gray matter started to appear

inferomedially to the trigone of the lateral ventricle

Superior border

temporal horn of lateral ventricle (uncal recess) and alveus

superior excess of the quadrigeminal cistern

Benchmark Harmonizedhippocampi:

total for each rater:40 hippos

5 expert tracers 20 naive tracers

The best 5 naive tracers

Harmonized Protocol:

total for each rater:240 hippos

GOLD STANDARD

Local Protocol:

total for rater:30 hippos

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:

total for each rater:40 hippos

Harmonized Protocol:

total for each rater:40 hippos

Harmonized Protocol:

total for rater:30 hippos

RM-ANOVA: test of protocol main effect

VARIABILITY EVALUATION

VALIDATION vsPATHOLOGY

Training

Del

phi p

anel

→ h

arm

oniz

ed p

rot

1 tracer

Qualification

Benchmark Harmonized hippocampi:

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

global and local 95% confidence intervals

Training

Learning SUs tracing criteria(teleconferences, feedback)

(tracing 20 hippos on 1.5 ADNI scans with each SU)

Gold Standard

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)

Qualification onBenchmark hippocampi:

(total for each rater: 40 hippos)

20 naive tracers

RM-ANOVA: test of rater and rater by center terms

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)

SELECTION of theBEST 5 naive tracers:

1- High Qualification inter-rater ICC

2- High Harmonized Tracing “1.5Tvs3T intra-rater” ICC

3- Cluster Homogeneity global inter-rater ICC

1

2 3

Variability Evaluation 1/2

GoldStandard

The best 5 naive tracers

RM-ANOVA: test of main effects side, trace-retrace, atrophy, time, scanner, rater

Harmonized Protocol:

1.5T ADNI scans2 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)

Variability Evaluation 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=0.021

P=0.057

P=0.035

Covers 100% of hippocampus proper

Captures 100% of AD-related atrophy

P for agreement among panelists)

Intra-rater (BS-BS): 0.993Inter-rater (BS-BS): 0.985

Preliminary ICC (BS-Mayo-LONI): 0.95

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