1. Declaration of Conflict of Interest or Relationship Bryon Mueller I have no conflicts of interest to disclose with regard to the subject matter of this presentation Research funded by NCRR, NIMH and NIDA

2. How To Do A Functional Multi-Center Neuroimaging Study Bryon Mueller, Ph.D. Department of Psychiatry University of Minnesota

3. Multi-Center fMRI

4. Why Multi-Center fMRI? Participants –More subjects –Collect the data more quickly –More varied demographics –Rare population subgroups

5. Multi-Center fMRI Challenges Lots of subjects (That’s good?) Complex experiments Lots of sites Inter-site variability (not so good)

6. Outline Study preparation phase Study execution Resources are available

7. Decide What Data To Collect fMRI task(s) –Stimulus presentation? –Response recording? –Physiological? Field map? Structural? DTI/ASL/… Response Physiological Clinical Cognitive Can the sites do the protocol?

8. Implement Protocol At Sites Reduce sources of inter-site variability: Scanner related factors Non-scanner factors

9. Sources of Inter-Site Variability: Potential scanner related factors Hardware differences Pulse sequence Sequence parameters Scanner malfunction Similar to other multi-center studies

10. Sources of Inter-Site Variability: Potential non-scanner factors: Protocol prescription Head positioning and restraint Site protocol errors Stimulus Response devices Subject training, attention, and habituation Other “brain state” factors

11. Study Standardization Establish scanner QA program

12. Establish a Scanner QA Program

13. Study Standardization Establish scanner QA program Create standardized protocol

14. Standardize MRI Acquisition Functional Anatomical B0 Coil type Functional - TR, TE, Echo Spacing, Flip Angle, Voxel Size, Bandwidth, Number of Discards, Slice Select, Phase Encode Direction, Slice Prescription, …

15. Assume Nothing Vendors “defaults” can be different Scanner/stimulus computer triggering Image smoothing Phase encode direction T1 stabilization volumes Slice select method …

16. Slice Select Method Figure courtesy of Kun Lu and Tom Liu, UCSD Spectral- Spatial Slice Select Fat Sat Slice Select

17. Reduce Inter-Site Variability Establish scanner QA program Create standardized protocol –Make sure study can run at all sites

18. Reduce Inter-Site Variability Establish scanner QA program Create standardized protocol –Make sure study can run at all sites –Don’t forget the non-MR stuff

19. Reduce Inter-Site Variability Establish scanner QA program Create standardized protocol Provide clear instructions –Subject training standardization –Task instruction scripts –Check list –How to execute the study –Trouble shooting guidance

20. Reduce Inter-Site Variability Establish scanner QA program Create standardized protocol Provide clear instructions Run test subjects at each site –Repeat as necessary –Formal site qualification process

21. Reduce Inter-Site Variability Establish scanner QA program Create standardized protocol Provide clear instructions Run test subjects at each site Scientist visit each site –Site certification

22. Reduce Inter-Site Variability Establish scanner QA program Create standardized protocol Provide clear instructions Run test subjects at each site Scientist visit each site Traveling subject reproducibility study

23. Outline Study preparation phase Study execution –Look at your data Resources are available

24. Continue to collect scanner QA –Sometimes scanners are upgraded –Sometimes scanners break What Can Go Wrong (Will)

25. Sometimes Scanners Break Upgrade Problem and repair

26. Scanner QA –Sometimes scanners are upgraded –Sometimes scanners break Subject data –Imaging parameters What Can Go Wrong (Will)

27. Scanner QA –Sometimes scanners are upgraded –Sometimes scanners break Subject data –Imaging parameters –Subject data What Can Go Wrong (Will)

28. Look At Subject Data Site 1 Site 2

29. Look At Subject Data

30. Scanner QA –Sometimes scanners break –Sometimes scanners are upgraded Subject data –Imaging parameters –Subject data –Task triggering What Can Go Wrong (Will)

31. Scanner QA –Sometimes scanners break –Sometimes scanners are upgraded Subject data –Imaging parameters –Subject data –Task triggering –Response devices What Can Go Wrong (Will)

32. Scanner QA –Sometimes scanners break –Sometimes scanners are upgraded Subject data –Imaging parameters –Subject data –Task triggering –Response devices –Missing data What Can Go Wrong (Will)

33. Outline Study preparation phase Study execution Resources are available –Make your life easier

34. Multi-Center fMRI Resources Casey BJ et al. Neuroimage 1998 Ojemann et al. Hum Brain Mapp 1998 Vlieger EJ et al. AJNR 2003 Kim S et al. Comp Assist Interv. 2005 Cramer SC et al. Stroke 2005 Stocker T et al. Hum Brain Mapp 2005 Zou KH et al. Radiology 2005 Friedman L et al. JMRI 2006 Friedman L et al. Neuroimage 2006 Schneider F et al. Schizophr Res. 2007 Costafreda SG et al. JMRI 2007 Olsrud J et al. MRI 2008 Sutton BP et al. JMRI 2008 Bosnell R et al. Neuroimage 2008 Gedamu EL et al. JMRI 2008 Friedman et al. Hum Brain Mapp 2008 Suckling J et al. Hum Brain Mapp 2008 Wegner C et al. E J of Neurology 2008 Rocca MA et al. Hum Brain Mapp 2008 Potkin SG et al. Schizophr Bull. 2009 Brown GG et al. Schizophr Bull. 2009 Wible CG et al. Schizophr Bull. 2009 Ford JM et al. Schizophr Bull. 2009 Kim DI et al. Schizophr Bull. 2009 Potkin SG et al. Schizophr Bull. 2009 Rocca MA et al. Hum Brain Mapp. 2009 Mancini L et al. Neuroimage. 2009 Kim DI et al. Hum Brain Mapp. 2009 Costafreda SG Front Neuroinformatics 2009 Van Horn JD, Toga Aw Curr Opin Neurol. 2009 Arolt V, et al. Psychother Psych Med 2009 Gountouna VE et al. Neuroimage. 2010 Biswal BB, et al. Proc Natl Acad Sci USA 2010 Kim S et sl. IEEE Trans Med Imaging 2010 Mattson SN, et al. Alcohol 2010 Yendiki A et al. Neuroimage 2010

35. XNAT http://www.xnat.org/

36. LONI http://www.loni.ucla.edu/Software/

37. FBIRN NCRR funded Began in 2002 13 institutions 60+ collaborators Develop and share recommendations and tools for multi-center fMRI www.birncommunity.org Function Biomedical Informatics Research Network

38. FBIRN Best Practices and Tools Multi-center fMRI how to FAQ: https://xwiki.nbirn.org:8443/xwiki/bin/view/ Function-BIRN/FBIRN_Best_Practices Calibration Cognitive issues Data management Data analysis and interpretation

39. Best Practice Recommendations Preparation phase: Establish scanner QA program Standardize fMRI study Provide clear instructions to sites Run test subjects Have scientist visit the sites Traveling subject study

40. Best Practice Recommendations While site is collecting data: Continue to perform scanner QA Analyze data as it comes in Check for missing data Beware problems with behavioral data Use a balanced design

41. Acknowledgements P30NS057091-01, P41RR008079 2R01MH060662-05A1,1P20DA024196-01 U24RR021992-02