A HARMONIZED PROTOCOL FOR HIPPOCAMPAL VOLUMETRY: AN EADC-ADNI EFFORT

Hippocampal atrophy can be measured in vivo through manual segmentation on Magnetic Resonance images (MRI) and it is an acknowledged supportive marker for the diagnosis of Alzheimer's disease (AD). Unfortunately to date agreement is lacking on the anatomical landmarks and measurement procedure. Without comparability of methods, this marker can not be used in clinical diagnostic routine, nor will it be possible to directly compare the effect of different drugs in slowing down neurodegenerative processes.

The aim of this project is to develop a harmonized protocol for the measurement of hippocampal volume through manual segmentation on MRI. The availability of a standard and shared protocol for hippocampal volumetry will foster the validation of the new diagnostic criteria and their use in clinical settings, allow to compare the effect of disease modifying drugs, and represent the gold standard for automated segmentation algorithms. In the long run, the availability of a standard protocol will allow pooling data from compatible worldwide datasets thus leading to increased knowledge on the disease itself.

The project runs in phases, started with the selection of the 12 most used hippocampal segmentation protocols from the Alzheimer's literature and the extraction of differences among these protocols. Quantitative information is gathered about these differences, and fed to a panel of world experts, to help them to take evidence-based decisions and achieve a consensus on a harmonized protocol through the Delphi method.
When defined in all details, the harmonized protocol will be validated versus neuropathological data and versus currently used protocols (download the Validation Phase Flowchart). The final phase consists in the creation of a standard web-based qualification system, which will allow tracers worldwide to learn and qualify for the hippocampal segmentation based on the harmonized protocol. A online user-friendly educational "Segmentation Guideline" and hippocampal probabilistic maps will be made public and will represent the international reference.

You can download the grant application, describing the whole project in details.
On this web-site, updates about the project can be found. Periodical meetings are carried out for dissemination and coordination. All the main steps and results of the project will be documented and disseminated through publications on impacted journals and presentations in the main congresses about neuroscience and Alzheimer's disease.

P.I. Giovanni B. Frisoni
Co-P.I. Clifford R. Jack, Jr

Background. In the Hippocampal Harmonization project, a large number of manual segmentation labels based on the Harmonized Protocol is developed in a limited number of ADNI subjects. In 2012, a project has been designed (so called ``Expansion'') following input from automated segmentation algorithm developers to produce labels for a large number of subjects. In the Expansion, labels will be obtained from as many as 135 different subjects. This label set will cover a wider range of physiological variability and will be suited to provide proper training and validation to automated algorithms.

Design. Segmentations will be carried out on right and left hippocampi from 135 ADNI subjects, balanced by magnet field strength, scanner type, diagnosis, Scheltens' atrophy scores, and age, for a total of 270 hippocampi. Each hippocampus will be segmented by one of the 5 expert tracers involved in the project. Two levels slice-by-slice quality check will be carried out on each segmentation, and corrections will be carried out wherever required. Labels will be uploaded on the training and certification platform used for the Harmonization project.

Funders. Funding for this project is provided by the Alzheimer's Association (50%), and by 6 companies equally sharing the remaining 50%: Bioclinica, Brain Image Analysis LLC, Ixico, Roche, Synarc, True Positive Medical Devices.

Deliverables. The labels will be made freely available to the scientific community upon completion of segmentation and QC, with no embargo.

The project proposal can be downloaded here.