Agenda:

- Update on master tracers’ segmentation check- Update validation vs pathology- PMT application submission of “Study on the validation of VSRAD” (dr M. Nishikawa)- Benchmark: possible issues for platform

XI PMT meeting – July 3, 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

5 Master Tracers’ segmentations:

Mapped in overlap on correspondent MRIChecked and reported causes for overlapping

discrepancies at 1.5TImproved Harmonized Protocol in many pointsMasters asked to correct if they agree, or to discuss the

issue if they disagree with the corrections

Benchmark Images

Overlapping agreement Volume ICCs

1.5T images: 0.71

3T images: 0.75

Validation vs Pathology

Validation versus pathology

Tracer (to be defined whether GP will segment all datasets, or if each centre will provide its tracer -

waiting for LA answer on privacy issues)

Segmentation based on Harmonized Protocol:

60 ante mortem46 postmortem MRIs

106 images

Analysis based on the information available for each dataset

Mayo Clinic~50 AD + MCI + CTRL dataset with pathologically confirmed

diagnosis (Braak’s stages),antemortem

left hippocampal measurement(Manual and Freesurfer)

Only volumetric measures to be shared

Mony DeLeon9 AD + 4 CTRL at 1.5T (T1)

13 postmortem and 2 AD antemortem

9 AD + 1 CTRL at 1.5T (PD)10 postmortem and 8 AD antemortem

(Neuron, plaque and tangle counts,Braak’s stages, abeta, tau,

histological volumetry, CA1 definition only on PD),3mm, coronal, no 3D navigation

one side hippocampal measurement (Manual. MIDAS)Images and volumetric measures can be shared

Liana Apostolova(23 hippos at 7T)

CA1 neuronal counts,tau and Abeta

immunoreactivity measures

Validation versus pathology

Originally designated sample: (Bobinski et al., 2000)11 AD + 4 CTRLpostmortem MRI and quantitative histology

de Leon: 9 AD + 4 CTRL at 1.5T (T1) and 9 AD + 1 CTRL at 1.5T (PD)23 postmortem and 10 AD antemortemNeuron, plaque and tangle counts, Braak’s stages, abeta, tau, histological volumetry (CA1 definition only on PD)3mm, coronal, no 3D navigationone side hippocampal measurement (Manual, MIDAS)

Jack: ~50 AD + MCI + CTRL antemortem MRIs with pathologically confirmed diagnosis (Braak’s stages). Volumes of left Hippocampus (Manual and Freesurfer). No post-mortem hippocampal measurement

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

“Study on the validation of VSRAD”Dr. Masami Nishikawa

VSRAD (Voxel-based Specific Regional analysis system for Alzheimer’s Disease): automatic VBM-based software for hippocampal atrophy.

Project aim: to validate the new version of VSRAD, comparing it versus the Harmonized Protocol as the gold standard method to manually measure hippocampal volume.

Subjects: 22 AD, 19 MCI, 18 controls+ 3 healthy volunteers that served as human phantoms for the pilot E-ADNI project (Frisoni et al., 2008): scanned by the 7 different machines.

Hippocampal segmentations carried out on these subjects will serve not only the aims of the present project, but will also contribute to provide data that will add to the validation of the Harmonized Protocol.

PMT application submission

Benchmark Maps: CSF exclusion

Harmonized Protocol criteria: internal CSF pools must be properly and independently segmented and excluded

MultiTracer: using one label generates higher variability in segmentations, since every tracer will "connect" somehow the internal pool to the external CSF

Solution: To segment the internal pools with an additional label, that will be used to subtract both volume and segmented voxels.

Benchmark Maps: plausible variability

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 progr)

Development of certification platform (Duchesne and coll)Validation data and Protocol definition + Protocol (Brescia Team)Validation vs pathology (TBD)

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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

GANTT