AAN –Toronto, April 11, 2010

1. AAN –Toronto, April 11, 2010 Development of a harmonized protocol for hippocampal tracing An EADC-ADNI joint effortMETHODS

2. METHODS Operationalization of protocols’ differences and extraction of tracing units Quantification of tracing units’ features Harmonized protocol

3. OPERATIONALIZATION Selection of segmentation protocols • Selection criteria • Being based on 3D T1 MRI with field strength greater than 1 Tesla • Providing explicit description of landmarks for tracing of hippocampal borders • Being validated on AD/MCI samples, or being widely adopted in the literature about AD.

4. OPERATIONALIZATION Protocols’ features extraction Plane of tracing: AC-PC line; Normalization to the Talairach space Tracing start from the tail of hippocampus to the hippocampal head In the following slices, you can find the hippocampal tracing on consecutive coronal slices (1.5T) of the control subject and AD patient according to Pruessner's criteria

5. OPERATIONALIZATION Prototypical tracings Tracings carried out on a control and an AD subject from the ADNI dataset Tracings sent to the Authors for correction or approval

6. CTRL Most posterior slice : slice where an ovoid mass of gray matter (1) started to appear inferomedially of the atrium of lateral ventricle (2) 2= Atrium of lateral ventricle 4= Parahippocampal gyrus 5= Gyrus dentatus 6= Cornu Ammonis 7= Gyrus fasciolaris 8= Gyrus of Andreas-Retzius 9= Isthmus The fornix can be excluded by a horizontal line (in fuchsia) from the superior border of the quadrigeminal cistern (3) to the lateral ventricle (2). Part of gyrus fasciolaris (7) and of Andreas-Retzius gyrus (8) can be excluded by a vertical line (in red) from the medial end of the lateral ventricle (2) down to the parahippocampal gyrus (4). Sagittal view

7. AD Most posterior slice : slice where an ovoid mass of gray matter (1) started to appear inferomedially of the atrium of lateral ventricle (2) 2= Atrium of lateral ventricle 4= Parahippocampal gyrus 5= Gyrus dentatus 6= Cornu Ammonis 7= Gyrus fasciolaris 8= Gyrus of Andreas Retzius 9= Isthmus In AD subjects the cerebral structures are atrophic, lateral ventricle (2) and ambient cistern (3) result enlarged. Therefore, the lines used to exclude the gyrus fasciolaris, the Andreas- Retzius gyrus and the fornix do not intersect the hippocampal tail. That being so, is there another way to exclude the gyrus fasciolaris, the Andreas-Retzius gyrus and the fornix in these subjects? Sagittal view

8. OPERATIONALIZATION Authors’ check For each protocol: features extraction, tracing and author’s certification CTRL X 10 AD

9. OPERATIONALIZATION Extraction of similarities and differences Harmonized language Reduction of redundancy Tracing units and subunits

10. OPERATIONALIZATION Extraction of similarities and differences

14. METHODS Operationalization of protocols’ differences Quantification of tracing units’ features Harmonized protocol

15. QUANTIFICATION OF TRACING UNITS’ FEATURES Contribution to hippo volume in control and AD Effect on re-test variability Contribution to differences between AD and controls

16. METHODS Operationalization of protocols’ differences Quantification of tracing units’ features Harmonized protocol

17. HARMONIZED PROTOCOL Participants to a Delphi panel based on: expertise in hippocampal anatomy manual tracing scientific production Assisted decisions based on: Low variability, highly informative.. ..included in harmonized protocol High variability, little informative.. ..excluded from harmonized prot

18. HARMONIZED PROTOCOL Validation & implementation Validation with neuropathological data Comparison with currently used protocols Public tracings and probability maps Standard environment for tracing, learning, and certification