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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.
Abstract:
Functional MRI (fMRI) is an important tool for investigating functional networks. However, the widely used fMRI with T2*-weighted imaging in rodents has the problem of signal lack in the lateral ventral area of forebrain including the amygdala, which is essential for not only emotion but also noxious pain. Here, we scouted the zero-echo time (ZTE) sequence, which is robust to magnetic susceptibility and motion-derived artifacts, to image activation in the whole brain including the amygdala following the noxious stimulation to the hind paw. ZTE exhibited higher temporal signal-to-noise ratios than conventional fMRI sequences. Electrical sensory stimulation of the hind paw evoked ZTE signal increase in the primary somatosensory cortex. Formalin injection into the hind paw evoked early and latent change of ZTE signals throughout the whole brain including the subregions of amygdala. Furthermore, resting-state fMRI using ZTE demonstrated the functional connectivity, including that of the amygdala. These results indicate the feasibility of ZTE for whole brain fMRI including the amygdala and we first show acute and latent activity in different subnuclei of the amygdala complex after nociceptive stimulation.
Insights
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.
