1. Proposal Instead of doing whole brain nonlinear registration, only register a cropped region – Previously we used a template to speed the registration step How do we determine the cropped region automatically?

2. ROI Estimation We want an estimate of the whole thalamus – Can be conservative as we just want to crop a big enough region Whole brain affine linear registration of priors’ whole thalamus, then label fusion – In ANTS: maximum (very conservative), majority vote, STAPLE, correlation vote – STEPS or PICSL? Use cross-validation to test 4 different methods

3. Registration Register cropped priors to cropped image – The cropped image is taken as the ROI estimate with a padding of 4 (2 on each side) – The cropped priors are taken as the true whole thalamus ROI with a padding of 24 Larger to avoid missing data being warped into the region after registration Arbitrary padding amount, tried 10, wasn’t enough ANTS options – Fixed space mask – Starting point affine transform – Continue affine transform

4. Registration There are thus 6 permutations of ANTS options per ROI estimate – With or without a fixed space mask (ROI estimate), i.e. whole cropped region registration or limited to the ROI – With or without affine transform determined from whole brain registration – Continue or don’t continue the affine registration search

5. Cross-Validation Perform 20*19 whole brain affine registrations – Takes 5-10min on 20*16-cores Perform 20*19*4*6 cropped nonlinear registrations – Takes 1-2hrs with cropped region and 20*16-cores Probably <30min total pipeline once we pick the best registration method

6. Comparison of ROI Estimates Since coverage is our primary objective at this stage, maximum seems to be the clear winner

7. Comparison of Registration Quality

8. Targeted Registration Correlation and majority voting provide a better estimate of the thalamus – Let’s try telling the registration to target those ROIs instead within the maximum-based crop Using the maximum-based ROI is (still) the best – More important to cover all thalamus voxels with the registration than to be fine tuned on where the thalamus is exactly – Plausible as it could permit crazy things happening outside the ROI

9. Registration Quality of 915 to ctrl_902 Actual Box Box Affine ROI[maximum]ROI[correlation]