Development and evaluation of an unbiased, high‐resolution and detail‐preserving structural T1‐weighted template for use in studies on older adults

Background Construction of an optimal T1‐weighted template for older adults often requires selection of a target anatomy for nonlinear‐registrations, however a poorly chosen template may introduce bias due to large structural discrepancies between template and subjects used for template construction resulting in misregistration and thereby loss of important anatomical details. Moreover, large structural brain differences across older adults may introduce registration errors. Here, a minimum‐deformation T1‐weighted template specifically for studies on older‐adults was developed using a sparse, patch‐based, detail‐preserving template construction method that minimizes biases. Method This work used T1‐weighted brain MRI data obtained from 400 non‐demented older adults (65‐95 years of age, male:female=1:1) participating in longitudinal cohort studies of aging. The template construction scheme involved a reference‐free groupwise normalization utilizing affine transformations followed by ANTs SyGN groupwise normalization utilizing a weighted average scheme in every iteration. Finally a patch‐based tissue‐guided sparse‐representation approach was employed to generate the new template (Fig. 1). The new template was compared to the weighted average template and other 0.5mm templates through visual inspection, in terms of image sharpness by means of the normalized power spectral density and also inter‐subject spatial normalization accuracy achieved when used as references for normalization of T1‐weighted data from 202 ADNI3 participants. Normalization accuracy was assessed for each template by means of the average pairwise normalized cross correlation, average pairwise Jaccard index and average log‐Jacobian determinant of ADNI3 participants. Result The new template maintained anatomical consistency and exhibited higher image sharpness as demonstrated by larger high spatial frequency content in the normalized power spectra compared to other templates (Fig. 2 & Fig. 3A,C). Detailed cortical features were better resolved with the new template compared to MCALT_0.5mm (Fig. 3A,B). Visual inspection revealed atypical anatomical structures in the cortex of MCALT_0.5mm (red circles) (Fig. 3B), absent in other templates. Inter‐subject spatial normalization accuracy was higher when using the new template compared to the other templates (Fig. 4A,B,C). The new template required lower deformation for spatially normalizing ADNI3 dataset (Fig. 5). Conclusion The new template is an