Human brainstem serves many plays critical roles in health and disease. Unfortunately, it has been vastly under-studied because of its physical inaccessibility in animal models, and its low contrast-to-noise ratio (CNR) for functional magnetic resonance imaging (fMRI) in human studies. At conventional fMRI field strengths, CNR is an order-of-magnitude lower in brainstem than in cerebral cortex. Recently, ultra-high-field (UHF) scanners are becoming more-and-more available for fMRI. UHF is particularly attractive for brainstem because it offers a tremendous boost in CNR over conventional field strengths. Here we propose a panoply of measurements, methods, and modeling to open up brainstem fMRI to more general use at UHF. Our work will be directed toward a particular brainstem nucleus called superior colliculus (SC), a small structure (-9-mm across) that is associated with eye movements and the orientation of attention. SC is also involved in a number of diseases. For example, deterioration of SC's structural integrity, functional properties, and connections have been observed in dementia with Lewy bodies, Alzheimer's disease, progressive supranuclear palsy, amyotrophic lateral sclerosis, and cervical dystonia. Our novel methods will enable us to distinguish visual responses, in the superficial layers of SC, from somtaosensation in the deep layers of SC. We can therefore relate the representation of tactile sensation to maps of visual space. We can then determine how this mapping is affected by changes in limb position to begin to understand coordinate transformations in human SC. The availability of such high-resolution methods for deep-brain structures will have transformative impact on brain research, both basic and clinical. Basic research will benefit from the higher resolution and contrast-to-noise ratio of our UHF MR acquisition strategies, as well as the precision and sensitivity of our surface-based analysis methods. The safety of fMRI should also enable use of our methods as adjuncts to treatment protocols using 7T scanners. Thus, this work is well aligned with Goal 1 of NIBIB's Strategic Plan, the development of innovative technologies that integrate engineering with physical and life sciences to solve complex problems and improve health.
Human brainstem plays a critical role in brain function, both in health and disease, yet remarkably little is known about this critical brain region. While functional magnetic resonance imaging (fMRI) in the brain has provided tremendous insight into cerebral cortex, the depth and small size of brainstem structures, such as superior colliculus, has made fMRI very difficult in the brainstem. We propose a set of methods that will enable the use of ultra-high-field fMRI to study brainstem, and demonstrate their utility by performing a number of useful experiments in superior colliculus.
