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

How To Do A Functional Multi-Center Neuroimaging Study

Bryon Mueller, Ph.D.Department of PsychiatryUniversity of Minnesota

Multi-Center fMRI

Why Multi-Center fMRI?• Participants

– More subjects

– Collect the data more quickly

– More varied demographics

– Rare population subgroups

Multi-Center fMRI Challenges

• Lots of subjects (That’s good?)• Complex experiments• Lots of sites• Inter-site variability (not so good)

Outline

• Study preparation phase

• Study execution

• Resources are available

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?

Implement Protocol At SitesReduce sources of inter-site variability:

• Scanner related factors

• Non-scanner factors

Sources of Inter-Site Variability:Potential scanner related factors• Hardware differences • Pulse sequence• Sequence parameters• Scanner malfunction

Similar to other multi-center studies

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

Study Standardization• Establish scanner QA program

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Establish a Scanner QA Program

Study Standardization• Establish scanner QA program

• Create standardized protocol

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, …

Assume Nothing

Vendors “defaults” can be different• Scanner/stimulus computer triggering• Image smoothing• Phase encode direction• T1 stabilization volumes• Slice select method• …

Slice Select Method

Figure courtesy of Kun Lu and Tom Liu, UCSD

Spectral-Spatial

Slice Select

Fat SatSlice Select

Reduce Inter-Site Variability• Establish scanner QA program

• Create standardized protocol– Make sure study can run at all sites

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

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

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

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

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

Outline

• Study preparation phase

• Study execution– Look at your data

• Resources are available

• Continue to collect scanner QA– Sometimes scanners are upgraded– Sometimes scanners break

What Can Go Wrong (Will)

Sometimes Scanners Break

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• Scanner QA– Sometimes scanners are upgraded– Sometimes scanners break

• Subject data– Imaging parameters

What Can Go Wrong (Will)

• Scanner QA– Sometimes scanners are upgraded– Sometimes scanners break

• Subject data– Imaging parameters– Subject data

What Can Go Wrong (Will)

Look At Subject DataSite 1 Site 2

Look At Subject Data

• Scanner QA– Sometimes scanners break– Sometimes scanners are upgraded

• Subject data– Imaging parameters– Subject data– Task triggering

What Can Go Wrong (Will)

• Scanner QA– Sometimes scanners break– Sometimes scanners are upgraded

• Subject data– Imaging parameters– Subject data– Task triggering– Response devices

What Can Go Wrong (Will)

• 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)

Outline

• Study preparation phase

• Study execution

• Resources are available– Make your life easier

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

XNAThttp://www.xnat.org/

LONI

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

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

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

Best Practice RecommendationsPreparation phase:• Establish scanner QA program

• Standardize fMRI study

• Provide clear instructions to sites

• Run test subjects

• Have scientist visit the sites

• Traveling subject study

Best Practice RecommendationsWhile 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

Acknowledgements

P30NS057091-01, P41RR008079 2R01MH060662-05A1,1P20DA024196-01

U24RR021992-02