1. 20 Years of FreeSurfer PETsurfer: MRI-PET Integration using FreeSurfer Nov 17, 2017
Douglas N. Greve, Ph.D. Martinos Center for Biomedical Imaging Massachusetts General Hospital Harvard Medical School

2. PET Issues Uptake – FDG, Amyloid, Tau; 1 meas, ~20min
“Quantitative” – binding potential, metabolism
Multiple frames, ~1min, min
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
Cr(t)
TAC(t)

14. Single Voxel Analysis
Single voxels are very noisy!

15. Voxel-wise Analysis
Binding Potential

16. Smoothing (Volume-based)

17. Volume-Smoothing Group (N=16)
0.1
1.3 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. Example 5HT4 BP Map for Group (N=16)
Volume Smoothed
by 10mm FWHM
0.1
1.3 BP
Surface 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
GM Smth -
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) Volume Smth Surface Smth MGPVC NoPVC
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 FreeSurfer helps …
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. Thanks! Use FreeSurfer Be Happy Bruce Fischl Gitte Knudsen Bruce Rosen
David Salat
Keith Johnson
Aaron Schultz
Gitte Knudsen
Claus Svarer
Vincent Beliveau
Melanie Ganz
FreeSurfer Team

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. Not Just Artifact Reduction, Noise too
Volume Smoothed
by 10mm FWHM
Surface Smoothed
by 10mm FWHM
0.1
1.3 BP
0.01
0.5
CoV
Factors of % 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)