20 Years of FreeSurfer PETsurfer: MRI-PET Integration using FreeSurfer Nov 17, 2017

1. 20 Years of FreeSurferPETsurfer: MRI-PET Integration using FreeSurferNov 17, 2017 Douglas N. Greve, Ph.D.Martinos Center for Biomedical ImagingMassachusetts General HospitalHarvard Medical School

2. PET Issues • Uptake – FDG, Amyloid, Tau; 1 meas, ~20min • “Quantitative” – binding potential, metabolism • Multiple frames, ~1min, 60-120min • Kinetic Models • Noisy – requires spatial averaging (ROI, smooth) • Partial Volume Effects (PVEs) • Like spatial smoothing, 4-15mm FWHM • Interaction with anatomy – confound • Partial volume correction (PVC)

3. MRI: FreeSurfer Can Help … • Whole-Brain (soon whole-head) Segmentation • Subcortical (3D ROIs) • Cortical • Surface parcellations (2D ROIs) • Thickness (3D ROIs, subvoxel accuracy) • Surface smoothing (instead of volume) • Subject-specific

4. Two studies done with PETsurfer • ROI: • FDG vs Aging • Non-quantitative • ROI-based PVC • Voxel-wise: • Serotonin Receptor Density • Quantitative • Voxel-wise PVC

5. ROI FDG Study of Aging • What is the effect of aging on metabolism? • With and without Partial Volume Cor (PVC)?

6. PET Suffers from Partial Volume Effects Anatomy Ideal FDG Real FDG ~Smoothed by 6mm Point Spread Function (PSF) Partial Volume Effect

7. No PVC: Just average FDG within an ROI

8. FDG vs Age (No PVC) Widespread decreases in metabolism with age. Is it real?

9. ROI-based Partial Volume Cor (PVC) • Linear model of whole head FDG • Each ROI is a regressor • Model PVE as linear smoothing • Solve to get uptake in each ROI without PVE • “Geometric Transfer Matrix” GTM

10. NoPVC vs PVC GTM-PVC No PVC

11. What does this happen? A B CSF 20 Year Old A B CSF 80 Year Old

12. Voxelwise Serotonin Receptor Study • Serotonin receptor type 4 (5HT4) • Binding potential ~ Receptor Density

13. ROI Analysis Time Activity Curves TAC(t) Cr(t)

14. Single Voxel Analysis Single voxels are very noisy!

15. Voxel-wise Analysis Binding Potential

16. Smoothing (Volume-based)

17. 1.3 0.1 Volume-Smoothing Group (N=16) BP • Crowns and Fundi have lower BP • Banks have higher BP • Insula has very large BP, contamination from putamen Volume Smoothing by 10mm FWHM 17

18. 1.3 0.1 Example 5HT4 BP Map for Group (N=16) Surface Smoothed by 10mm FWHM BP Volume Smoothed by 10mm FWHM • Gyral pattern (mostly) gone • Insula (mostly) artifact gone • Surface has higher BP values 18

19. Voxel-wise PVC Method (Muller-Gartner) Source MRI WM Uptake Voxel-wise Estimate of WM Signal WM WM Smth X GM Smth GM - Div S + Kinetic Modeling Source PET

20. Muller-Gartner PVC Method • Only performs PVC in GM • Some areas where value is 0 (no GM) • Division by smoothed GM

21. MG PVC Results (N=16) NoPVC MGPVC Volume Smth Surface Smth In general BP increases after PVC by 30-60% PVEs might actually be worse with volume smoothing PVEs get a little better with surface smoothing

22. Summary • PET requires accurate segmentation to analyze and correct for PVEs • Voxel-wise analysis requires surface-based analysis, especially with PVC • Interaction between PET and anatomy can cause a confound without PVC • FreeSurfer helps …

23. Use FreeSurfer Be Happy Thanks! Gitte Knudsen Claus Svarer Vincent Beliveau Melanie Ganz FreeSurfer Team Bruce Fischl Bruce Rosen David Salat Keith Johnson Aaron Schultz

24. End of Presentation

25. Voxelwise Summary • Voxel-wise time courses very noisy • Smoothing needed • Volume smoothing exacerbates PVEs • Surface smoothing does not • Voxel-wise PVC • Uses FreeSurfer ROIs and tissue types • Valid in GM only • Volume smoothing a disaster in cortex • Surface smoothing the only way to smooth PVC

26. Partial Volume Correction (PVC) • Use MRI to segment tissue types and structures • Geometric Transfer Matrix (GTM) Rousset, et al, (1998) • Purely ROI-based • Map-based, voxel-wise • Mueller-Gartner Method (1992) • Meltzer Method (1996) • Often used to perform ROI analysis but less efficient and less accurate than GTM • Region-wise Voxel-based (RBV, Thomas 2011) • Built on GTM • Need to know the point spread function of the scanner (FWHM)

27. Summary: ROI FDG Study of Aging • FreeSurfer generated subject-specific ROIs • Subcortical • Cortical (subvoxel) • Accurate segmentation needed for PVC • PVC needed to prevent interaction between FDG uptake and anatomy • Non-sparsity makes interaction worse

28. Kinetic Modeling Analysis (Pseudo-Linear) • TAC(t) is on both sides of the equation • Not really a linear model • Noise in X and y • Noise-dependent bias 28

29. 1.3 0.5 0.1 0.01 Not Just Artifact Reduction, Noise too Volume Smoothed by 10mm FWHM Surface Smoothed by 10mm FWHM BP CoV Factors of 20-200% reduction in intersubject stddev 29

30. Voxel-wise Analysis (Individual) No Smoothing Volume Smoothing (5mm) Surface Smoothing (5mm) Surface Smoothing (10mm)

31. Volume Smoothing near Gyral Crowns Volume Smoothing by 10mm FWHM 31

32. Volume Smoothing near Gyral Fundi Volume Smoothing by 10mm FWHM 32

33. Volume Smoothing near Gyral Banks Volume Smoothing by 10mm FWHM 33

34. Surface (2D) Smoothing 34

35. Smoothing (Volume-based)