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PET Module

PET Module. Ana Beatriz Solana, MS Qu Tian (Teresa), MS Instructor: Dr. Charles Laymon. Cocaine Study . Literature: Cocaine-Dopamine - Decrease dopamine release - Toxic for animal DA neurons [ Volkow et al. 1997; Martinez et al. 2007, 2009 & 2011; Seiden et al. 1987]

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PET Module

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  1. PET Module Ana Beatriz Solana, MS QuTian (Teresa), MS Instructor: Dr. Charles Laymon

  2. Cocaine Study • Literature: Cocaine-Dopamine - Decrease dopamine release - Toxic for animal DA neurons [Volkow et al. 1997; Martinez et al. 2007, 2009 & 2011; Seiden et al. 1987] • Biological plausibility: Chronic cocaine use  loss of dopaminergic terminals • Inconsistent results due to - The time since last use of cocaine - The reliable assessment VMAT2 - [11C]DTBZ

  3. Cocaine Study: VMAT2 - [11C] DTBZ • Objective To compare VMAT2 in 12 cocaine abusers vs. 12 healthy controls • Method In vivo, [11C] DTBZ nondisplaceable binding potential using kinetic analysis • Acquisition protocol • Hypothesis: Voxel-wise analysis would be valid as ROI approach. Specifically, [11C] DTBZ BPND would be lower in cocaine abusers than matched healthy controls in subregions of striatum as shown in previous ROI analysis. PET [11C]DTBZ MRI Scan 1.5T Emission data collection (60 min) Transmission scan (10 min) Arterial blood sample

  4. Analysis Pipeline Inter-frame Motion Correction* Voxel-wise 2-tissue Compartment Model Voxel-wise SRTM Model Voxel-wise SRTM2 Model SIMPLIFIED MODELS* FULL MODEL* Normalization:** PET -> MR template Voxel-wise group analysis: cocaine vs. control ** * Pxmod software **SPM8 software

  5. Analysis Pipeline Inter-frame Motion Correction Voxel-wise 2-tissue Compartment Model Voxel-wise SRTM Model Voxel-wise SRTM2 Model SIMPLIFIED MODELS FULL MODEL Normalization: PET -> MR template Voxel-wise group analysis: cocaine vs. control

  6. Inter-frame Motion correction • Subjects can move over the time of the scan • Motion correction is needed to compute voxel Time Activity Curve Time Activity Curve F1 (15s) F2(15s) F3(15s) F9 (2m) F10 (5m) F11(5m) F18(5m) F19(5m) F20(5m)

  7. Inter-frame Motion correction Woods, J Comp Assit Tomography 1998 1. Take one or the sum of a few consecutive frames w/o motion as the reference. 2. Sum the first 1-4 or 1-5 frames as the composite initial frame. Frame 10 Frame 9-10 Frame 9-10-11 Frame 1(15s) Frame 2(15s) Frame 3(15s) Frame 4 (15s) Frame 5 (60s)

  8. Inter-frame Motion correction Woods, J Comp Assit Tomography 1998 3. Apply correction to all frames to the reference. 4. Apply transformation matrix from the composite initial frame to initial frames individually. 5. Check motion corrected images. Before correction After correction

  9. Analysis Pipeline Inter-frame Motion Correction Voxel-wise 2-tissue Compartment Model Voxel-wise SRTM Model Voxel-wise SRTM2 Model SIMPLIFIED MODELS FULL MODEL Normalization: PET -> MR template Voxel-wise group analysis: cocaine vs. control

  10. 2-Tissue Compartment Model Binding potential (BP) (nondisplaceable) = PET A clearance parameter from vasculature to brain A fraction moving to the specific compartment C2 Arterial input function A fraction of the radiotracer diffusing back to plasma If the specific binding is reversible, a fraction of the radiotracer transferring back to C1

  11. Simplified Reference Tissue Model &Simplified Reference Tissue Model 2Lammertsma and Hume, 1996; Wu and Carson, 2002 Assumption 2: Distribution volume: ROI = Ref Assumption 1: ROI & Ref follow a 1T 1 + C2 a ‘ NOTE: - Both bias - SRTM < SRTM2 (k2’) ‘

  12. SRTM & SRTM2Lammertsma and Hume, 1996; Wu and Carson, 2002 Assumption 1: Both ROI and Reference tissue follows a 1T model Assumption 2: The delivery from plasma to the receptor-rich region and the reference region is the same (K1/k2 = K1’/k2’)

  13. Single voxel TAC and model fit Taking one single voxel TAC Fitting the curve SRTM SRTM2 BPND= 3.49 X(56),y(55),z(33) BPND= 3.49 BPND= 3.68 X(56),y(55),z(33) BPND= 3.68

  14. Binding Potential Images VERY NOISY!!! Two tissue Compartment Model Simplified Ref. Tissue Model Simplified Ref. Tissue Model 2 AXIAL SAGITAL CORONAL AXIAL SAGITAL CORONAL AXIAL SAGITAL CORONAL

  15. Analysis Pipeline Inter-frame Motion Correction Voxel-wise 2-tissue Compartment Model Voxel-wise SRTM Model Voxel-wise SRTM2 Model SIMPLIFIED MODELS FULL MODEL Normalization: PET -> MR template Voxel-wise group analysis: cocaine vs. control

  16. Normalization ROIs manually drawn in the template ROIs transformed to the individual native space Why method 2? • Our template is more similar to our images than MNI • Subregions of striatum do not appear in standard atlases

  17. Normalization: DARTEL Template Ashburner, Neuroimage 2007 Tissue Segmentation 24 MR images 1.5x1x1mm ACPC reorientation Template generation Deformation Maps Composite template

  18. Normalization: PET images 1) Corregistration Reference frame PET to MR (ESTIMATE) MR image Mutual Info N. Mutual Info Entropy CorrCoeffNorm. Cross Coeff 2) Apply PET -> MR estimation to BP images (NO RESLICE) 3) Apply MR -> template deformation maps RESLICE (1.5x1.5x1.5mm)

  19. Analysis Pipeline Inter-frame Motion Correction Voxel-wise 2-tissue Compartment Model Voxel-wise SRTM Model Voxel-wise SRTM2 Model SIMPLIFIED MODELS FULL MODEL Normalization: PET -> MR template Voxel-wise group analysis: cocaine vs. control

  20. Statistical results: cocaine < control SRTM SRTM2 L L dorsal caudate L & anterior putamen L (66) posterior putamen L(30) anterior putamen R (11) t value t value 4.09 4.55 dorsal caudate L (18) L L 0 0 6mm Gaussian smooth, mask BP>0.5, FWE corrected p<0.1

  21. Comparative with ROI approach PREVIOUS ROI RESULTS VOXEL – WISE RESULTS

  22. Take home message • VOXEL WISE VS. ROI • BEST RESULTS WITH SRTM2 IN OUR PROJECT • CAUTION WITH SIMPLIFIED MODELS ASSUMPTIONS • MR TEMPLATE: • IMPROVES NORMALIZATION • AND STATISTICS • ONLY DRAW ROIs IN TEMPLATE

  23. THANK YOU FOR YOUR ATTENTION ACKNOWLEDGEMENTS Charles LaymonSeong-Gi Kim Rajesh Narendran Bill Eddy Julie Price Michael L Himes Carl Becker Scott Mason James Ruszkiewicz CristyMatan Matthew Oborski Chris Cieply DavneetMinhas REFERENCES Narendran et al. Am J Psychiatry 169: 55-63, 2012 Narendran et al. Synapse 2011 Boileau  et al. J Neurosci: 9850–9856, 2008 Narendran et al. JPET vol. 333 no. 2: 533-539, 2010 Wu and Carson, J Cereb Blood Flow & Metab: 1440–1452, 2002 Lammertsma and Hume, Neuroimage 1996 Ashburner, Neuroimage2007 Woods, J Comp Assit Tomography 1998

  24. SMOOTHING

  25. Normalization ROIs manually drawn in the template ROIs transformed to the individual native space Why method 2? • Our template is more similar to our images than MNI • Subregions of striatum do not appear in standard atlases • Evaluation of semi-automatic procedure to draw the ROIs

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