Outlook on zero/ultrashort echo time techniques in functional MRI

Since its introduction more than 30 years ago, the blood oxygenation level dependent (BOLD) contrast remains the most widely used method for functional MRI (fMRI) in humans and animal models. The BOLD contrast is typically acquired with echo planar imaging (EPI) to obtain sensitization of the signal during the echo time (TE) to dynamic changes in deoxyhemoglobin content, while achieving high spatiotemporal resolution and full brain coverage. However, EPI-based fMRI also faces multiple shortcomings, including sensitivity to body motion, susceptibility-related signal dropouts, interference with multimodal sensors, and loud acoustic noise. Here we provide a succinct overview and outlook of alternative strategies for fMRI relying on free induction decay-based techniques, which, by using zero/ultrashort TE, inherently solve most of these challenges. Such approaches are receiving increasing attention in the field of fMRI, motivated by initial findings in humans and animal models in which robust functional contrast was obtained despite the absence of an echo, primarily via sensitization to inflowing blood. We therefore discuss the benefits and current shortcomings of zero/ultrashort TE fMRI versus conventional EPI-based fMRI, the opportunities for enabling fMRI designs that are challenging with EPI-based approaches, and the state of progress toward use in clinical settings. Overall, zero/ultrashort TE fMRI is predicted to become a powerful new tool for basic, clinical, and preclinical research, especially for applications at ultrahigh magnetic fields, studies in awake animals, multimodal imaging, investigations requiring minimization of scanning noise, and fMRI beyond the brain.