Clinical-ComBAT: a diffusion-weighted MRI harmonization method for clinical applications

Diffusion-weighted magnetic resonance imaging (DW-MRI) derived scalar maps are effective for assessing neurodegenerative diseases and microstructural properties of white matter in large number of brain conditions. However, DW-MRI inherently limits the combination of data from multiple acquisition sites without harmonization to mitigate scanner-specific biases. While the widely used ComBAT method reduces site effects in research, its reliance on linear covariate relationships, homogeneous populations, fixed site numbers, and well populated sites constrains its clinical use. To overcome these limitations, we propose Clinical-ComBAT, a method designed for real-world clinical scenarios. Clinical-ComBAT harmonizes each site independently, enabling flexibility as new data and clinics are introduced. It incorporates a non-linear polynomial data model, site-specific harmonization referenced to a normative site, and variance priors adaptable to small cohorts. It further includes hyperparameter tuning and a goodness-of-fit metric for harmonization assessment. We demonstrate its effectiveness on simulated and real data, showing improved alignment of diffusion metrics and enhanced applicability for normative modeling.

ComBAT Harmonization for diffusion MRI: Challenges and Best Practices

Over the years, ComBAT has become the standard method for harmonizing MRI-derived measurements, with its ability to compensate for site-related additive and multiplicative biases while preserving biological variability. However, ComBAT relies on a set of assumptions that, when violated, can result in flawed harmonization. In this paper, we thoroughly review ComBAT's mathematical foundation, outlining these assumptions, and exploring their implications for the demographic composition necessary for optimal results. Through a series of experiments involving a slightly modified version of ComBAT called Pairwise-ComBAT tailored for normative modeling applications, we assess the impact of various population characteristics, including population size, age distribution, the absence of certain covariates, and the magnitude of additive and multiplicative factors. Based on these experiments, we present five essential recommendations that should be carefully considered to enhance consistency and supporting reproducibility, two essential factors for open science, collaborative research, and real-life clinical deployment.

FIESTA: Autoencoders for accurate fiber segmentation in tractography

White matter bundle segmentation is a cornerstone of modern tractography to study the brain's structural connectivity in domains such as neurological disorders, neurosurgery, and aging. In this study, we present FIESTA (FIbEr Segmentation in Tractography using Autoencoders), a reliable and robust, fully automated, and easily semi-automatically calibrated pipeline based on deep autoencoders that can dissect and fully populate WM bundles. Our framework allows the transition from one anatomical bundle definition to another with marginal calibrating time. This pipeline is built upon FINTA, CINTA, and GESTA methods that demonstrated how autoencoders can be used successfully for streamline filtering, bundling, and streamline generation in tractography. Our proposed method improves bundling coverage by recovering hard-to-track bundles with generative sampling through the latent space seeding of the subject bundle and the atlas bundle. A latent space of streamlines is learned using autoencoder-based modeling combined with contrastive learning. Using an atlas of bundles in standard space (MNI), our proposed method segments new tractograms using the autoencoder latent distance between each tractogram streamline and its closest neighbor bundle in the atlas of bundles. Intra-subject bundle reliability is improved by recovering hard-to-track streamlines, using the autoencoder to generate new streamlines that increase each bundle's spatial coverage while remaining anatomically meaningful. Results show that our method is more reliable than state-of-the-art automated virtual dissection methods such as RecoBundles, RecoBundlesX, TractSeg, White Matter Analysis and XTRACT. Overall, these results show that our framework improves the practicality and usability of current state-of-the-art bundling framework