Citations

ABSTRACTBACKGROUND AND PURPOSEAn effort to define and validate a Harmonized Protocol for standard hippocampal segmentation is being carried out. We wished to estimate the effect of magnetic resonance image (MRI) spatial orientation on manual hippocampal segmentations to define optimal standard orientation of MRIs for hippocampal volumetry.METHODSThree expert tracers segmented twice the hippocampi of 10 ADNI subjects on MRI slices oriented perpendicular to the anterior‐posterior commissure (AC‐PC) line and the long hippocampal axes plane, following internationally harmonized landmarks. We computed intra and interrater reliability figures for total volumes and similarity coefficients.RESULTSTotal volume reliability was similar for both orientations. Similarity coefficients were significantly higher for the AC‐PC orientation (exact P = 0.002).DISCUSSIONThese data show that AC‐PC orientation is slightly more reliable for manual segmentations, possibly due to better visualization of the cerebrospinal fluid spaces separating hippocampal head and amygdala. A Delphi panel of experts has used these data to decide on the optimal orientation for a Harmonized Protocol for hippocampal segmentation.

Significance Beta-amyloid plaque accumulation, glucose hypometabolism, and neuronal atrophy are hallmarks of Alzheimer’s disease. However, the regional ordering of these biomarkers prior to dementia remains untested. In a cohort with Alzheimer’s disease mutations, we performed an integrated whole-brain analysis of three major imaging techniques: amyloid PET, [ 18 F]fluro-deoxyglucose PET, and structural MRI. We found that most gray-matter structures with amyloid plaques later have hypometabolism followed by atrophy. Critically, however, not all regions lose metabolic function, and not all regions atrophy, even when there is significant amyloid deposition. These regional disparities have important implications for clinical trials of disease-modifying therapies.