Influence of data-driven physiological correction

Influence of data-driven physiological correction methods on the longitudinal reliability and multisite consistency of the default mode network in healthy aging Rocco Marchitelli1, Ludovico Minati2, Giovanni Frisoni3, Jorge Jovicich1 1 Center for Mind/Brain Sciences, Dep. of Cognitive and Education Sciences, The University of Trento 2 Lab. of Epidemiology, Neuroimaging, & Telemedicine, IRCCS San Giovanni di Dio-FBF of Brescia 3 Memory Clinic and Lab. of Neuroimaging of aging, Osp. and University of Geneva

ITALIAN CHAPTER 2015 ANNUAL MEETING VERONA, April 16-17, 2015

mercoledì 3 giugno 15

Clinical Relevance of resting-state fMRI connectivity Potential Biomarker Validation

• Resting state fMRI DMN: potential biomarker? • Large scale longitudinal studies needed • Challenge: physiological noise • Does physiological noise correction improve reliability?       - Single site: no (young)       - Multisite: unknown (elderly, MR-derived methods) Hedden et al., 2009

Test-Retest Reliability

Physiological Noise

Birn et al., 2006 mercoledì 3 giugno 15

Birn et al., 2014

http://www.pharmacog.org

13 MRI centers: (6 Siemens, 4 Philips and 3 GE) 65 healthy elderly subjects 2 Sessions Age (mean ± sd): 62.5 ± 4.2y

Acquisition Protocol TR = 2.7 s, TE = 30 ms, voxel size 3 x 3 x 3 mm3, session time = 9 min

Aim of the study: To assess whether physiological noise correction in healthy elderly subjects affect the test-retest reliability of functional connectivity and its multi-site reproducibility.

mercoledì 3 giugno 15

Physiological Correction Methods Evaluated

• • •

Attività cardiaca

No Physiologic Correction TISSUE-BASED (Weissenbacher, 2013) PESTICA (Beall and Lowe 2007) FSL-FIX (Griffanti et al., 2014) con:

• •

Standard Classifier: TR=3s, Resolution=3.5x3.5x3.5mm3, session=6mins Data-Based Classifier: TR=2.7s, Resolution=3x3x3mm3, session=6mins Neuroimage. 2010 Aug 15; 52(2): 571–582

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Method to define the Default Mode Network Dual Regression

C.F. Beckmann, C.E. Mackay, N. Filippini, and S.M. Smith. OHBM, 2009.

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Results Functional Connectivity

Mean Z-scores

16 12

***

*** ***

***

*

*

*** ***

***

8 4 0

SITE1

SITE2

SITE3

SITE4

Friedman Test

SITE5

SITE6

* p < 0.05

SITE7

SITE8

SITE9

** 0.001 < p < 0.01

SITE10

SITE11

SITE12

*** p < 0.001

FSL-FIX increases functional connectivity (38% dei centri)

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SITE13

Results

Test-Retest Reliability

Test-Retest % Error

65%

**

**

49%

***

**

33%

16%

0%

SITE1

SITE2

SITE3

SITE4

Friedman Test

SITE5

SITE6

* p < 0.05

SITE7

SITE8

** 0.001 < p < 0.01

SITE9

SITE10

*** p < 0.001

-- None of the methods improve reliability vs no physiological correction. -- Differences across methods are not systematic across sites. -- No method revealed site effects.

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SITE11

SITE12

SITE13

Results Across-Site Reproducibility

Mean Reliability Across Sites

*** ***

0,8 0,6

12% ICC

Test-Retest % Error

18%

*** p < 0.001

6%

0,5 0,3 0,2

0%

Physiological Correction Pipelines

No Physiological Correction

PESTICA

0

Physiological Correction Pipelines

TISSUE-BASED

FIX-Standard

Take-Home Messages  -- No method is more reliable than no physiological correction condition.  -- “Tissue based” and “FSL-FIX standard” showed increased reproducibility.

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FIX-Training

Conclusions

• The application of any physiological noise correction method allowed the identification of the component of the Default Mode Network across all sites.

• The method FIX increases functional connectivity in healthy elderly subjects within the DMN component.

• Test-Retest reliability of functional connectivity is not influenced by physiological correction in healthy elderly.

• We reccomand the application of physiological noise correction in multisite studies.

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Special Thanks

Giovanni&Frisoni& Luigi&Antelmi&

Moira&Marizzoni& Alberto&Redolfi European Federation of Pharmaceutical Industries and Associations

Thank you for your attention!! [email protected]

mercoledì 3 giugno 15