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Updated: Jun 2, 2025

Whole-Brain 3D Activation and Functional Connectivity Mapping in Mice using Transcranial Functional Ultrasound Imaging
Published on: February 24, 2021
Zero-echo time imaging achieves whole brain activity mapping without ventral signal loss in mice
Ayako Imamura1, Rikita Araki2, Yukari Takahashi3
1Ph. D. Program in Humanics, University of Tsukuba, Tsukuba, Japan; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan; Department of Neuroscience, The Jikei University School of Medicine, Tokyo, Japan; Human Informatics and Interaction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan.
Zero-echo time (ZTE) functional MRI (fMRI) successfully images rodent brain activity, including the amygdala, during pain. This technique overcomes limitations of conventional fMRI for studying pain networks.
Area of Science:
- Neuroscience
- Neuroimaging
- Pain Research
Background:
- Functional MRI (fMRI) is crucial for studying brain networks.
- Conventional T2*-weighted fMRI in rodents struggles with signal loss in critical areas like the amygdala, hindering pain and emotion research.
- The amygdala plays a vital role in processing emotion and noxious pain.
Purpose of the Study:
- To evaluate the zero-echo time (ZTE) sequence for whole-brain fMRI in rodents, specifically addressing signal limitations in the amygdala.
- To investigate brain activation and functional connectivity related to noxious pain stimulation using ZTE fMRI.
- To characterize acute and latent amygdala activity following nociceptive stimuli.
Main Methods:
- Utilized the zero-echo time (ZTE) sequence, known for its robustness against magnetic susceptibility and motion artifacts.
- Administered noxious stimulation (electrical and formalin injection) to the hind paw of rodents.
- Acquired resting-state and task-based fMRI data using ZTE, comparing its performance to conventional sequences.
Main Results:
- ZTE fMRI demonstrated higher temporal signal-to-noise ratios compared to conventional fMRI sequences.
- Electrical stimulation evoked ZTE signal increases in the primary somatosensory cortex.
- Formalin injection induced early and latent ZTE signal changes across the whole brain, including amygdala subregions.
- Resting-state ZTE fMRI successfully mapped functional connectivity, including the amygdala.
- First demonstration of acute and latent activity in amygdala subnuclei following nociceptive stimulation.
Conclusions:
- ZTE fMRI is a feasible technique for whole-brain imaging in rodents, effectively capturing signals from the amygdala.
- ZTE fMRI provides valuable insights into brain activity and functional connectivity associated with noxious pain processing.
- This study highlights the potential of ZTE for advancing research on pain, emotion, and related neurological conditions.

