One of the first investigations of batch effects in rs-fMRI was performed by Olivetti et al. Several different fields have evolved with a particular method to analyze brain organization. B.1 Gradient Calculations In this section, we define gradients used for alternating gradient descent. We now define gradients for updating model parameters. Algorithm 1 describes the complete alternating minimization procedure.

Independent and identically distributed (i.i.d.) data is essential to many data analysis and modeling techniques. In the medical domain, collecting data from multiple sites or institutions is a common strategy that guarantees sufficient clinical diversity, determined by the decentralized nature of medical data. However, data from various sites are easily biased by the local environment or facilities, thereby violating the i.i.d. rule. A common strategy is to harmonize the site bias while retaining important biological information. The ComBat is among the most popular harmonization approaches and has recently been extended to handle distributed sites. However, when faced with situations involving newly joined sites in training or evaluating data from unknown/unseen sites, ComBat lacks compatibility and requires retraining with data from all the sites. The retraining leads to significant computational and logistic overhead that is usually prohibitive. In this work, we develop a novel Cluster ComBat harmonization algorithm, which leverages cluster patterns of the data in different sites and greatly advances the usability of ComBat harmonization. We use extensive simulation and real medical imaging data from ADNI to demonstrate the superiority of the proposed approach. Our codes are provided in https://github.com/illidanlab/distributed-cluster-harmonization.

Pooling publicly-available MRI data from multiple sites allows to assemble extensive groups of subjects, increase statistical power, and promote data reuse with machine learning techniques. The harmonization of multicenter data is necessary to reduce the confounding effect associated with non-biological sources of variability in the data. However, when applied to the entire dataset before machine learning, the harmonization leads to data leakage, because information outside the training set may affect model building, and potentially falsely overestimate performance. We propose a 1) measurement of the efficacy of data harmonization; 2) harmonizer transformer, i.e., an implementation of the ComBat harmonization allowing its encapsulation among the preprocessing steps of a machine learning pipeline, avoiding data leakage. We tested these tools using brain T1-weighted MRI data from 1740 healthy subjects acquired at 36 sites. After harmonization, the site effect was removed or reduced, and we showed the data leakage effect in predicting individual age from MRI data, highlighting that introducing the harmonizer transformer into a machine learning pipeline allows for avoiding data leakage.

Connectivity studies using resting-state functional magnetic resonance imaging are increasingly pooling data acquired at multiple sites. While this may allow investigators to speed up recruitment or increase sample size, multisite studies also potentially introduce systematic biases in connectivity measures across sites. In this work, we measure the inter-site effect in connectivity and its impact on our ability to detect individual and group differences. Our study was based on real, as opposed to simulated, multisite fMRI datasets collected in N=345 young, healthy subjects across 8 scanning sites with 3T scanners and heterogeneous scanning protocols, drawn from the 1000 functional connectome project. We first empirically show that typical functional networks were reliably found at the group level in all sites, and that the amplitude of the inter-site effects was small to moderate, with a Cohen's effect size below 0.5 on average across brain connections. We then implemented a series of Monte-Carlo simulations, based on real data, to evaluate the impact of the multisite effects on detection power in statistical tests comparing two groups (with and without the effect) using a general linear model, as well as on the prediction of group labels with a support-vector machine. As a reference, we also implemented the same simulations with fMRI data collected at a single site using an identical sample size. Simulations revealed that using data from heterogeneous sites only slightly decreased our ability to detect changes compared to a monosite study with the GLM, and had a greater impact on prediction accuracy. Taken together, our results support the feasibility of multisite studies in rs-fMRI provided the sample size is large enough.