# Evaluating the quality of brainstem ROI registration using structural and diffusion MRI

## TL;DR

This paper shows that using diffusion MRI improves the accuracy of registering brainstem regions in fMRI studies, which can lead to more reliable results in brainstem research.

## Contribution

The study introduces and evaluates diffusion-augmented registration pipelines for improved brainstem ROI registration.

## Key findings

- Diffusion-based pipelines outperformed T1w-only registration for brainstem nuclei like the red nucleus and substantia nigra.
- Probabilistic maps from diffusion-augmented pipelines better captured individual anatomical variability.
- Deformation patterns in Jacobian maps were linked to image modality-specific landmarks.

## Abstract

Accurate registration of regions of interest (ROIs) from standard atlases to participants’ native spaces is a critical step in fMRI studies, as it directly affects the reliability of sampled BOLD signals. While T1-weighted (T1w) image-based ROI registration is well validated and widely adopted in cortical fMRI, its performance degrades in brainstem studies due to the small size, dense packing, and poor visibility of brainstem nuclei on T1w contrast. We hypothesized that incorporating diffusion MR images, containing more information about internal brainstem architecture, should improve ROI registration accuracy. To test this, we developed four registration pipelines that either included or excluded diffusion-based alignment components and evaluated their performance using data from n = 20 healthy participants. Registration accuracy was assessed using Dice coefficient for the red nucleus (RN) and the substantia nigra (SN), and mis-registration fraction–a metric developed for nuclei that cannot be manually delineated–for the dorsal raphe nucleus (DRN). The results showed that diffusion-based pipelines, using fractional anisotropy (FA) images, non-diffusion-weighted (b0) images, and multivariate combination, outperformed the T1w-only baseline. Probabilistic maps derived from inverse-transformed native ROIs further supported improved sensitivity to inter-individual anatomical variability in the diffusion-augmented pipelines. In addition, analysis of gradient magnitude maps from the Jacobian determinants revealed associations between localized deformation and image modality-specific landmarks. These findings demonstrate the potential of diffusion-augmented pipelines for improving brainstem ROI registration, which could enhance the robustness of fMRI studies on brainstem disorders characterized by functional dysregulation.