XI PMT meeting – July 3, 2012 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

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 MRI Checked and reported causes for overlapping discrepancies at 1.5T

Improved Harmonized Protocol in many points Masters 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

MB RG GP LA DW 1.5T 3T Left Hippocampus Right Hippocampus Intra-rater 1.5T vs 3T (n=10)

0.971 (0.729-0.994) 0.955 (0.829-0.989) 0.889 (-0.015-0.980) 0.949 (0.757-0.988) 0.969 (0.114-0.995) 0.956 (0.845-0.989) 0.926 (0.056-0.987) 0.954 (0.791-0.989) 0.959 (0.846-0.990) 0.974 (0.889-0.994)

Inter-rater (n=10)

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

Inter-rater (n=10)

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

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)

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 DeLeon

9 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

Segmentation based on Harmonized Protocol

: 60 ante mortem 46 postmortem MRIs 106 images Analysis based on the information available for each dataset

Validation versus pathology

Originally designated sample:

(Bobinski et al., 2000) 11 AD + 4 CTRL postmortem 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 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)

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)

PMT application submission

“ 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.

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)

VALIDATION VS CURRENT PROTOCOLS ASSESSMENT OF SOURCES OF VARIANCE TRAINING SET DEVELOPMENT

20 naïve tracers

Local Protocol

ADNI scans: 2 x 5 Scheltens’s atrophy scores x 2 sides x 2 magnet strengths (1.5-3T)

QUALIFICATION Harmonized Protocol

ADNI scans: 2 x 5 Scheltens’s atrophy score x 2 sides x 2 magnet strength (1.5-3T) Total per rater: 40 hippos Assessment of variance due to rater and center Best 5 naïve tracers

Harmonized Protocol

ADNI 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 side, trace-retrace, atrophy, time, scanner, rater

GOLD STANDARD

5 master tracers

VALIDATION VS PATHOLOGY

1 tracer

Training

ADNI scans: 10 at 1.5T x 2 sides x 7 SUs x 2 tracing rounds Total per rater: 40 hippos

QUALIFICATION Harmonized Protocol

ADNI scans: 2 x 5 Scheltens’s atrophy score x 2 sides x 2 magnet strengths (1.5-3T) Total per rater: 40 hippos

REFERENCE PROBABILISTIC MASKS with 95% C.I.

Harmonized Protocol: Pathological datasets: Mayo Clinic and NYU Total: about 40 hippos Assessment of agreement with volume on pathology or ex vivo MRI and correlation with neuronal density

TRAINING SET

GANTT