Agenda:

- Update master tracers- Update validation vs pathology- Hippocampal 3D Object for AR Visualization- Papers- Next congress presentations & meetings

X PMT meeting – June 6, 2012

Benchmark Images

ADNI scans: 2 x 5 Scheltens’s atrophy score x 2 sides

x 2 magnet strengths (1.5-3T)Total per rater: 40 hippos

The 5 Master Tracers

completed segmentation of R and L hippos of the 10 subjectsreceived feedback in cases of little compliance to the Harmonized Protocolcorrected segmentations accordingly

Benchmark Images

Left Hippocampus Right Hippocampus Intra-rater 1.5T vs 3T (n=10) MB 0.971 (0.729-0.994) 0.969 (0.114-0.995) RG 0.955 (0.829-0.989) 0.956 (0.845-0.989) GP 0.889 (-0.015-0.980) 0.926 (0.056-0.987) LA 0.949 (0.757-0.988) 0.954 (0.791-0.989) DW 0.959 (0.846-0.990) 0.974 (0.889-0.994)

Inter-rater (n=10)

1.5T 0.949 (0.864-0.986) 0.961 (0.897-0.989)

Inter-rater (n=10)

3T 0.949 (0.860-0.986) 0.965 (0.897-0.991)

Validation vs Pathology

Validation versus pathology

1 tracer? (which one? A master? A naive qualified on harmo prot??O 3? (meglio 1…)

Segmentation based on Harmonized Protocol:

Tot ante mortemTot 43 postmortem MRIs

TOT images……

Analysis based on the information available for each dataset

Mayo ClinicAD + CTRL dataset

with pathologically confirmed diagnosis (Braak’s stages),

but not postmortem hippocampal measurement

Mony DeLeon15 AD + 5 CTRL at 1.5T

postmortem MRI and quantitative histology

(possible additional AD cases)

Liana Apostolova(23 hippos at 7T)

CA1 neuronal counts,tau and Abeta

immunoreactivity measures?

?

?

?how many

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.

Liana? 23 (one side only) 7T 60-hour postmortem scans (in progress: CA1 neuronal counts, tau and Abeta immunoreactivity measures)

Hippocampal 3D Object for AR Visualization

CTR SUBJ

Affected SUBJ

Manual Tracing (Simon)

Tool N° 1(FSL-FIRST)

Tool N° 2(FreeSurfer) …

Segmentation Procedures

…

…

*MODELs inAR

MODELs to be

ComparedthroughSPHARM

Common in all

Manual

Tool2

Tool1

vs.

* * *

*

CTR

Aff Subj

Alg1 Alg2 Alg3 Alg n

…

Papers describing the project

Survey of protocols (preliminary phase; published, JAD 2011)

Operationalization (preliminary phase; I revision, Alzheimer’s & Dementia, MS n. ADJ-D-12-00094)

Axes check short report (Brescia Team, in progress)

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)

VALIDATION VS CURRENT PROTOCOLSASSESSMENT OF SOURCES OF

VARIANCE TRAINING SET DEVELOPMENT

VALIDATION VS PATHOLOGY

GOLD STANDARD

Harmonized ProtocolADNI scans: 2 x 5 Scheltens’s

atrophy score x 2 sides x 2 magnet strengths (1.5-3T)

Total per rater: 40 hippos

Harmonized ProtocolADNI scans: 2 sides x 5 Scheltens’s atrophy scores

x 3 time points (bl-1y-2y) x 3 scanners (+ retracing @ bl)

x 2 magnet strengths (1.5-3T)Total per rater: 240 hippos

Assessment of variance due to rater and center

Local ProtocolADNI scans: 2 x 5 Scheltens’s atrophy scores

x 2 sides x 2 magnet strengths (1.5-3T)

Harmonized ProtocolADNI scans: 2 x 5 Scheltens’s atrophy score x

2 sides x 2 magnet strength (1.5-3T)Total per rater: 40 hippos Harmonized Protocol:

Pathological datasets: Mayo Clinic and NYU

Total: about 40 hippos

TrainingADNI scans: 10 at 1.5T x 2 sides x 7

SUs x 2 tracing roundsTotal per rater: 40 hippos

20 naïve tracers 5 master tracers 1 tracer

REFERENCE PROBABILISTIC MASKS

with 95% C.I.

QUALIFICATION QUALIFICATION

Best 5 naïve tracers

Assessment of variance due to side, trace-retrace, atrophy, time, scanner, rater

TRAINING SET

Assessment of agreement with volume on pathology or ex vivo

MRI and correlation with neuronal density

Next congress presentations

- AIC 2012, VancouverAbstract n. 26292, poster presentationDefinition of Harmonized Protocol for Hippocampal SegmentationSession Date and Time: Saturday, July 14, 2012

- AAIC 2012, Vancouver Abstract n. 26291, oral presentationDefinition of Harmonized Protocol for Hippocampal SegmentationSession Title: Neuroimaging 4: MCI: imaging markers of AD pathologyPresentation Number: O2-11-02Session Start Day Time: Jul 16 2012 3:30PM

AAIC – July 2012Location: Fairmont Waterfront Vancouver, Princess Louisa Room Date & Time: Wednesday, July 18, 2012 at 1:00 PM - 2:30 PM

AGENDA: Benchmark Images

Qualification Platform

Improvement of the Harmonized Protocol (based on the benchmark tracing phase)

Validation Phase 2 Advancing

Paper Publication

Publication Policy

VI Hippocampal Protocol Harmonization Meeting

GANTT