Application of zero-echo time imaging for whole brain activity mapping without signal loss in mice.

Motivation: Commonly-used T2*-weighted fMRI lacks signals in rodent forebrain regions, including the amygdala, which are crucial for understanding nociceptive responses. Goal(s): This study aims to evaluate the potential of zero-echo time (ZTE) fMRI to capture activation in the whole brain, especially the amygdala, following pain stimuli. Approach: ZTE fMRI was used to examine whole-brain responses to formalin-induced hind paw stimulation in rodents, assessing changes in both acute and latent responses. Results: ZTE successfully imaged brain-wide activation, revealing acute and latent responses in amygdala subregions, supporting its application for comprehensive fMRI studies in mice. Impact: This study demonstrates ZTE fMRI's capacity to image activation in the amygdala, even during pain responses, enabling previously challenging investigations into nociception-related networks. This breakthrough opens new avenues for studying pain pathways and emotion regulation, with potential translational relevance.