Harmonizing MR Images Across 100+ Scanners: Multi-site Validation with Traveling Subjects and Real-world Protocols

04 Dec 2025 (modified: 15 Dec 2025)MIDL 2026 Validation Papers SubmissionEveryoneRevisionsBibTeXCC BY 4.0
Keywords: MRI, Image Harmonization, Image Synthesis
TL;DR: MRI harmonization method trained on data from over 100 scanners that reliably reduces scanner-related variability across sites and is validated on real-world traveling subject datasets.
Abstract: Reliable harmonization of heterogeneous magnetic resonance (MR) image datasets, especially those acquired in pragmatic clinical trials, is critical to advance multi-center neuroimaging studies and translational machine learning in healthcare. We present an enhanced and rigorously validated version of the HACA3 harmonization algorithm, which we refer to as HACA3$^+$, incorporating key methodological enhancements: (1) an improved artifact encoder to better isolate and mitigate image artifacts, (2) background and foreground-sensitive attention mechanisms to increase harmonization specificity, and (3) extensive training using data spanning 100+ scanners from 64 independent sites, providing a broader diversity of scanners than other harmonization methods. Our study focuses on four commonly acquired MR image contrasts (T1-weighted, T2-weighted, proton density, \& fluid-attenuated inversion recovery), reflecting realistic clinical protocols. We perform inter-site harmonization experiments using traveling subjects to assess the generalization and robustness of the harmonization model. We compare the results of the publicly available version of HACA3 and our implementation, HACA3$^+$. Downstream relevance is further established through whole brain segmentation and image imputation. Pre-trained weights and code for HACA3$^+$ are made publicly available at https://github.com/UponAcceptance.
Primary Subject Area: Application: Neuroimaging
Secondary Subject Area: Image Synthesis
Registration Requirement: Yes
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Originality Policy: Yes
Single-blind & Not Under Review Elsewhere: Yes
LLM Policy: Yes
Submission Number: 45
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