Background Rapid brain loss is characteristic for the patients with mild cognitive impairment (MCI) and Alzheimer disease (AD) . Increase of the lateral ventricular volume is strongly correlated with the progression of the disease. High variability in the degree of atrophy for subjects with AD and MCI makes use of a single disease-specific template challenging. We propose a novel approach to generate a continuous four-dimensional template, where the 4th dimension is a surrogate measure of overall brain atrophy. Methods We used MRI scans obtained from the ADNI database (www.loni.ucla.edu/ADNI). Automated methods to estimate intracranial capacity (ICC) and lateral ventricles volume (LVV)  was applied to all available datasets at base line. The ratio between LVV and ICC (RLVV) was used as a surrogate measure of overall brain atrophy with mean(standard deviation) value of 2.46(0.87)%. Subsets from all subjects (CN, MCI and AD) were selected with uniform distribution of RLVV from 1.0 to 6.0% , resulting in a total of 160 subjects. Our algorithm  was modified to perform simultaneous 1) creation of the template and 2) linear regression of image intensity and shape versus RLVV. Results The ratio between LVV and ICC yielded values of mean(sd) 2.13(0.72)% for NC, 2.45(0.84)% for MCI and 2.84(0.91)% for AD. The continuous, four dimensional anatomical template was created. For a given RLVV, an appropriate three dimensional anatomical template may be constructed, reflecting the average shape of the brain and the contrast between different tissue types for the given level of atrophy. Figure 1 shows images through 6 example values of increasing RLVV. Conclusions The proposed method and resulting template will be useful tools for the development of robust automatic image processing methods targeted to the study of the populations with high degree of variability of atrophy. Furthermore, method presented is not limited to be used only with MCI and AD subjects, but can also be easily adopted for other neuro-degenerative studies.  Carlson, NE, et al. Neurology, 2008. 70(11).  Fonov, VS, et al. Alzheimer's and Dementia, 2010. 6(4, Supplement 1).  Fonov, V, et al. NeuroImage, 2011. 54(1).
Alzheimer; MRI; MCI; atlas
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Alzheimer's Association International Conference, 2011