A multi-scanner neuroimaging data harmonization using RAVEL and ComBat.

Modern neuroimaging studies frequently combine data collected from multiple scanners and experimental conditions. Such data often contain substantial technical variability associated with image intensity scale (image intensity scales are not the same in different images) and scanner effects (images obtained from different scanners contain substantial technical biases). Here we evaluate and compare results of data analysis methods without any data transformation (RAW), with intensity normalization using RAVEL, with regional harmonization methods using ComBat, and a combination of RAVEL and ComBat. Methods are evaluated on a unique sample of 16 study participants who were scanned on both 1.5T and 3T scanners a few months apart. Neuroradiological evaluation was conducted for 7 different regions of interest (ROI's) pertinent to Alzheimer's disease (AD). Cortical measures and results indicate that: (1) RAVEL substantially improved the reproducibility of image intensities; (2) ComBat is preferred over RAVEL and the RAVEL-ComBat combination in terms of regional level harmonization due to more consistent harmonization across subjects and image-derived measures; (3) RAVEL and ComBat substantially reduced bias compared to analysis of RAW images, but RAVEL also resulted in larger variance; and (4) the larger root mean square deviation (RMSD) of RAVEL compared to ComBat is due mainly to its larger variance.

ComBat Harmonization: Empirical Bayes versus fully Bayes approaches.

Studying small effects or subtle neuroanatomical variation requires large-scale sample size data. As a result, combining neuroimaging data from multiple datasets is necessary. Variation in acquisition protocols, magnetic field strength, scanner build, and many other non-biologically related factors can introduce undesirable bias into studies. Hence, harmonization is required to remove the bias-inducing factors from the data. ComBat is one of the most common methods applied to features from structural images. ComBat models the data using a hierarchical Bayesian model and uses the empirical Bayes approach to infer the distribution of the unknown factors. The empirical Bayes harmonization method is computationally efficient and provides valid point estimates. However, it tends to underestimate uncertainty. This paper investigates a new approach, fully Bayesian ComBat, where Monte Carlo sampling is used for statistical inference. When comparing fully Bayesian and empirical Bayesian ComBat, we found Empirical Bayesian ComBat more effectively removed scanner strength information and was much more computationally efficient. Conversely, fully Bayesian ComBat better preserved biological disease and age-related information while performing more accurate harmonization on traveling subjects. The fully Bayesian approach generates a rich posterior distribution, which is useful for generating simulated imaging features for improving classifier performance in a limited data setting. We show the generative capacity of our model for augmenting and improving the detection of patients with Alzheimer's disease. Posterior distributions for harmonized imaging measures can also be used for brain-wide uncertainty comparison and more principled downstream statistical analysis.Code for our new fully Bayesian ComBat extension is available at https://github.com/batmanlab/BayesComBat.