1. O AK R IDGE N ATIONAL LABORATORY U.S. DEPARTMENT OF ENERGY Image Reconstruction of Restraint-Free Small Animals with Parallel and Multipinhole Collimation: Progress and Plans Royal Prince Alfred Hospital

2. Key Personnel for Image Reconstruction Jefferson Lab Jefferson Lab - Mark Smith, Tim Tran - Mark Smith, Tim Tran Oak Ridge National Laboratory Oak Ridge National Laboratory - Shaun Gleason, Jim Goddard - Shaun Gleason, Jim Goddard Royal Prince Alfred Hospital Royal Prince Alfred Hospital - Steve Meikle - Steve Meikle

3. Image Reconstruction Flowchart LIST-MODE SINGLE PHOTON DATA time-stamp detector head index x, y coordinates of projection pixel gantry rotation angle LIST-MODE SINGLE PHOTON DATA, SMALL ANIMAL REFERENCE FRAME (SARF) time-stamp x, y, z coordinates of projection pixel in SARF pinhole locations in SARF HEAD MOTION FILE time-stamp head linear velocity function head angular velocity function IMAGE RECONSTRUCTION edit data as desired (e.g. if excessive head velocity) list-mode iterative MLEM reconstruction in SARF TRACKING DATA FILE time-stamp raw data from small animal tracking system TRANSFORMATION DATA FILE time-stamp coordinate transformation (translation and rotation) from gamma camera reference frame to small animal reference frame

4. List-Mode Iterative MLEM Image Reconstruction with Animal Motion predicted counts projection pixel k i, mouse pose m i probability for detection in projection pixel k at mouse pose m of emission from source voxel j sum over N detected events Small Animal Reference Frame (SARF) scintillation array multipinhole mask SPECT Acquisition with Animal Motion Transform Pinhole and Projection Pixel Coordinates To SARF for Reconstruction sum over M mouse poses list-mode iterative MLEM update equation MLEM update equation source voxel j

5. Major Challenges Implementation of animal motion into list-mode image reconstruction Implementation of animal motion into list-mode image reconstruction Two detector strategy Two detector strategy single or multipinhole collimator: better resolution and sensitivity but with single or multipinhole collimator: better resolution and sensitivity but with image truncation or projection data multiplexing image truncation or projection data multiplexing parallel hole collimator: sacrifice resolution and sensitivity for full field of view parallel hole collimator: sacrifice resolution and sensitivity for full field of view Quality control and calibration parameters Quality control and calibration parameters registration between reconstruction, detector, tracking reference frames registration between reconstruction, detector, tracking reference frames orientation of detector and collimator in SPECT reference frame orientation of detector and collimator in SPECT reference frame calibration phantom development with ORNL (Bequé et al. analysis) calibration phantom development with ORNL (Bequé et al. analysis) - focal length, distance to AOR, mech. offset, electrical shifts, tilt, twist - focal length, distance to AOR, mech. offset, electrical shifts, tilt, twist Computation time Computation time (15 poses/sec ) x (1200 sec)=18,000 poses for 20 min scan (15 poses/sec ) x (1200 sec)=18,000 poses for 20 min scan One- or few-pass list-mode MLEM algorithm (Reader et al.) One- or few-pass list-mode MLEM algorithm (Reader et al.)

6. Side view of the small animal imaging system Single and multipinhole masks ph1 Multipinhole Collimators for Small Animal SPECT ph5ph13aph13b Mouse Model brain and body activity Simulated Projections ph1ph5ph13aph13bbrain 3 mCi dose, 30 min acquisition, 120 angles

7. Multipinhole Image Reconstructions Mouse Model, No Motion, OSEM (10 subsets) Coronal Transaxial ph1 2 iterations ph5 4 iterations ph13a 6 iterations ph13b 6 iterations SNR and Contrast for the High (H) and Low (L) Activity 2.5 mm diam. Cylinders in Mouse Brain C=(H-L)/(H+L) SNR=(H-L)/  (H+L)

8. RPAH: micro Deluxe Resolution Phantom 1 pinhole on detector A 1 pinhole on detector A, 2 pinholes on detector B 1 pinhole on detector A, 4 pinholes on detector B apertureprojectionimage

9. Simulation of a Moving Mouse Parallel (ideal) Parallel (detector blur)

10. Moving Line Source Acquisitions ParallelPinhole

11. Next Steps Image reconstruction code implementation and testing for simulated moving mouse studies Image reconstruction code implementation and testing for simulated moving mouse studies use simulated list-mode data with different activity levels use simulated list-mode data with different activity levels Acquisition and analysis of QC calibration data for parallel hole and pinhole collimation Acquisition and analysis of QC calibration data for parallel hole and pinhole collimation Incorporation of complete set of QC parameters into reconstruction code Incorporation of complete set of QC parameters into reconstruction code Image reconstruction of simple geometric phantoms with motion Image reconstruction of simple geometric phantoms with motion line source, mouse-sized Schramm phantom line source, mouse-sized Schramm phantom Image reconstruction of mice Image reconstruction of mice possibly ex-vivo mice with 3-D motion possibly ex-vivo mice with 3-D motion unanesthetized, unrestrained live mice unanesthetized, unrestrained live mice