We applied the hippocampal radial atrophy mapping technique to the baseline and follow-up magnetic resonance image data of 169 amnestic mild cognitive impairment (MCI) participants in the imaging arm of the Alzheimer's Disease Cooperative Study MCI Donepezil/Vitamin E trial. Sixty percent of the subjects with none to mild hippocampal atrophy rated with the visual medial temporal atrophy rating scale (MTA score < 2) and 33.8% of the subjects with moderate to severe (MTA > or = 2) hippocampal atrophy converted to Alzheimer's disease (AD) during 3-year follow-up. MTA > or = 2 showed a trend for greater left sided hippocampal atrophy versus MTA < 2 groups at baseline (P(corrected) = 0.08). Higher MTA scores were associated with progressive atrophy of the subiculum and the CA1-3 subregions. The MTA < 2 group demonstrated significant bilateral atrophy progression at follow-up (left P(corrected) = 0.008; right P(corrected) = 0.05). Relative to MTA < 2 nonconverters, MTA < 2 converters showed further involvement of the subiculum and CA1 and additional involvement of CA2-3 at follow-up. Right CA1 atrophy was significantly associated with conversion to dementia (for 1 mm greater right CA1 radial distance subjects had 50% reduced hazard for conversion). Greater CA1 and subicular atrophy can be demonstrated early and is predictive of future conversion to AD, whereas CA2-3 involvement becomes more evident as the disease progresses.