1. A New, Nonparametric Information- Splitting Image Analysis Technique Mark Inlow Jing Wan, Sungeun Kim, Kwansik Nho, Shannon Risacher, Andrew Saykin, Li Shen

2. Life as a Statistics Professor…

3. Image Analysis Setup

4. Theoretical Basis

5. Information Splitting

6. One Monotonic Recipe

7. Hippocampus Surface Normal Data

8. APOEBIN1

9. New Approach vs. RFT Results Hippo Data SNPNew Approach RFT Peak Amplitude APOE BIN1 APOE BIN1

10. Permutation Distribution Normality APOE BIN1 10

11. SurfStat APOE T-Map for LR Sum

12. SurfStat BIN1 T-map for LR Sum

13. Comments

14. Acknowledgements 1.Andrew Saykin, Li Shen, and the Department of Radiology and Imaging Sciences, IU School of Medicine, who supported and financed my 2010-2011 sabbatical. 2.My main coauthor: Jing Wan, who did the SurfStat statistical analyses and data management. 3.My other coauthors/colleagues: Sungeun Kim, Kwansik Nho, and Shannon Risacher.

15. Hippocampus Surface Data FreeSurfer and Large Deformation Diffeomorphic Metric Mapping (FS+LDDMM) were used to segment hippocampal surfaces from MRI scans To remove size effect, total intracranial volume (ICV) was adjusted to a constant and each hippocampus was scaled accordingly. Rigid body transformation was applied to register each hippocampus to a template. 6611 Surface signals were extracted as the deformation along the surface normal direction of the template and were adjusted for baseline age, gender, education and handedness.

16. Genetic (SNP) Data Single Nucleotide Polymorphism (SNP) – DNA sequence location possessing nucleotide variants of length one, i.e., T vs. C or A vs. G. The SNP data were genotyped using the Human 610-Quad BeadChip. Top 23 SNPs from AlzGene database and a SNP from the TOMM40 gene were considered. After quality controls, 20 SNPs remained.

17. Random Field Theory

18. Random Field Theory, Cont.:

19. Random Field Theory Varieties

20. Left Spherical Distribution Theory

21. Comparison of Maps

22. Materials 582 non-Hispanic Caucasian participants 166 healthy controls (HCs), 287 mild cognitive impairment (MCI), and 129 AD Magnetic resonance imaging (MRI) data 20 SNPs were selected from the AlzGene database and TOMM40 gene and coded to test additive genetic effect (i.e. dose dependent effect of the minor allele).