The impact of numerical variability in fMRI preprocessing on regional and network statistics

Poster No:

1857 

Submission Type:

Abstract Submission 

Authors:

Mina Alizadeh1, Yohan Chatelain1, Gregory Kiar2, Tristan Glatard3

Institutions:

1Concordia University, Montreal, Quebec, 2Center for Data Analytics, Innovation, and Rigor, Child Mind Institute, NYC, NY, 3Krembil Centre for Neuroinformatics, Toronto, Ontario

First Author:

Mina Alizadeh  
Concordia University
Montreal, Quebec

Co-Author(s):

Yohan Chatelain  
Concordia University
Montreal, Quebec
Gregory Kiar  
Center for Data Analytics, Innovation, and Rigor, Child Mind Institute
NYC, NY
Tristan Glatard  
Krembil Centre for Neuroinformatics
Toronto, Ontario

Introduction:

The complexity and volume of neuroimaging data necessitate the use of sophisticated computational tools. However, reliance on automated workflows raises concerns about numerical stability, where cascading floating-point errors can significantly impact results. Sequential floating-point operations may amplify small variations, undermining reproducibility and validity. Stability tests are crucial to ensure results remain within acceptable variation limits. Prior studies revealed that structural connectome estimation pipelines are sensitive to machine-level noise, leading to variability that challenges the reliability of individual network features (Kiar, 2021). However, numerical instabilities in functional connectome analyses remain underexplored.
This study evaluates the numerical reliability of fMRI analyses using Monte Carlo Arithmetic (MCA) (Parker, 1997). By introducing controlled numerical perturbations into the fMRIPrep pipeline (Esteban, 2019), we assess the effects of these perturbations on functional connectomes and derived graph metrics.

Methods:

MCA can be used to quantify numerical uncertainty by performing numerical perturbations to floating-point operations.
We integrated Fuzzy-libmath, a Verificarlo-compiled version of the libmath library (Denis, 2016), with the fMRIPrep pipeline. The perturbed pipeline was executed 10 times for each of 10 publicly available subjects (OpenNeuro, 2024), generating floating-point error distributions that can reveal sensitivity to numerical perturbations. The virtual precision was set to simulate frequent machine-level floating-point errors. Graph-based metrics, including local (degree centrality, betweenness centrality, eigenvector centrality, clustering coefficient) and global metrics (small-worldness, average shortest path length), were derived from functional connectomes. The standard deviation across subjects and MCA repetitions was computed for each metric.

Results:

Considerable variability was observed in coregistration and N4BiasFieldCorrection steps across the 10 MCA repetitions. Inverse transformations from atlas to subject space, extended to BOLD space, assessed variability in transformation matrices. Dice coefficients were computed for each region across MCA runs. Regions with lower average Dice coefficients (Figure 1, indicated by dark red) were more frequent in BOLD space than in subject space, highlighting increased variability in coregistration than template normalization. Additionally, variability in derived functional connectomes was measured for each MCA run. Numerical variability was generally lower than cross-subject variability, indicating the pipeline preserved individual differences. However, certain subjects exhibited numerical variability approaching cross-subject levels, indicating that numerical instability can undermine the reliability of individual functional connectomes (Figure 2). Variability in graph metrics supported these findings, where across-subject variability consistently exceeded numerical variability, with some subjects as outliers to this trend.
Supporting Image: finalfig1.png
   ·Figure 1. The Minimum Dice scores across MCA run pairs, averaged across subject for each region, for the registered atlas in subject space (top) and BOLD space (bottom).
Supporting Image: finalfig2.png
   · Figure 2. The standard deviation of functional connectome across subjects (top) and MCA runs (bottom) was computed, highlighting between subject and numerical variability.
 

Conclusions:

Introducing elementary numerical perturbations in the fMRIPrep pipeline introduced variability in functional connectomes and graph metrics, ranging from negligible to significant. Consistent with prior studies, this variability depends on the dataset and tools used, underscoring the need for tailored stability analyses (Kiar, 2021). Variability in ROI definitions revealed more pronounced fluctuations in the functional domain than in the structural domain. Further validation across diverse datasets is necessary to ensure generalizability.
The several outliers observed in our results suggest that automated quality control (QC) could be a potential application of MCA perturbations, wherein subjects with high variability could be flagged for QC failure.

Modeling and Analysis Methods:

fMRI Connectivity and Network Modeling 2

Neuroinformatics and Data Sharing:

Workflows 1

Keywords:

Computational Neuroscience
FUNCTIONAL MRI
Workflows

1|2Indicates the priority used for review

Abstract Information

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Please indicate which methods were used in your research:

Functional MRI
Structural MRI
Computational modeling

Provide references using APA citation style.

Denis, C. (2016, July). Verificarlo: Checking Floating Point Accuracy through Monte Carlo Arithmetic. 2016 IEEE 23rd Symposium on Computer Arithmetic (ARITH), 55–62. https://doi.ieeecomputersociety.org/10.1109/ARITH.2016.31

Esteban, O., Markiewicz, C. J., Blair, R. W., et al. (2019). fMRIPrep: A robust preprocessing pipeline for functional MRI. Nature Methods, 16(2), 111–116. https://doi.org/10.1038/s41592-018-0235-4

Kiar, G., Chatelain, Y., de Oliveira Castro, P., Petit, E., Rokem, A., Varoquaux, G., et al. (2021). Numerical uncertainty in analytical pipelines leads to impactful variability in brain networks. PLoS ONE, 16(11), e0250755. https://doi.org/10.1371/journal.pone.0250755

Parker, D. S. (1997). Monte Carlo Arithmetic: Exploiting Randomness in Floating-Point Arithmetic. Computer Science Department, University of California.

Perchtold-Stefan, C., Rominger, C., Koschutnig, K., & Fink, A. (2024). Truecrime. OpenNeuro. [Dataset] https://doi.org/10.18112/openneuro.ds004965.v1.0.1

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