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Published on: June 29, 2013
Development and Validation of a Harmonization Pipeline for Multi-Site Computed Tomography Perfusion Cerebral Blood
Pattarawut Charatpangoon1,2, Jianhai Zhang1,2, Nishita Singh3
1Departments of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Canada.
Background:
Computed tomography perfusion (CTP)-derived cerebral blood flow (CBF) maps are widely used to study infarct volume and growth. Multi-site CTPs often have site biases that can alter thresholds and increase errors. However, the clinical impact of inter-site variability on infarct quantification is unclear. We examined this variability and developed an automated harmonization pipeline for multi-site CTP datasets to mitigate infarct assessment errors.
Methods:
We analyzed 741 CTP cases from the Alteplase compared to Tenecteplase trial across eight sites. CBFs were registered and segmented into grey-matter/white-matter (GM/WM). We scaled mean GM/WM CBFs into physiological ranges and applied ComBat, an empirical Bayesian method, to reduce inter-site bias. We assessed clinical utility by comparing infarct-core volumes from original versus harmonized maps with a relative-CBF-based reference, and comparing large-core infarct identification using CBF-based volume thresholds.
Results:
The original mean CBF deviated from physiological range with high variance and significant inter-site differences. After applying the scaling factor, the mean CBF (GM/WM) shifted to physiological ranges (49.3 ± 6.0/23.5 ± 2.5 ml/100g/min), and ComBat effectively eliminated inter-site differences. In 199 cases with complete reference data for clinical evaluation, harmonization decreased mean absolute error for infarct volume by 39% (12.7 to 7.7 ml), improved agreement (bias -7.9 to -5.8 ml; narrower 95%CI), and increased accuracy of large-core classification at a 60 ml-threshold by 5.0% (net reclassification improvement:0.310, 95%CI:0.036-0.603).
Conclusion:
Our harmonization pipeline rescaled multi-site CBF maps to physiological range, reducing inter-site variability and errors in infarct core estimation and large-core classification. Multi-site harmonization should become standard in CTP datasets to avoid erroneous conclusions about infarct size and growth.
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