Neurophysiology Imaging Facility Core: Functional and Structural MRI

National Institute Of Mental Health

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Abstract

There are multiple uses of magnetic resonance imaging (MRI) in the study of nonhuman primate neuroscience, each of which aims to make the research as precise and efficient, and as relevant to humans, as possible. The NIF facility at the NIH strives to make both structural and functional imaging feasible and fluid for any laboratories on the NIH campus interested in applying these methods. We offer high resolution anatomical scans, diffusion imaging, as well as comprehensive functional imaging. With the latter comes a step-by-step program to help scientists gain autonomy in conducting their functional MRI experiments, which are often difficult and most fruitful when combined with other methods. At the heart of the facilitys operation is functional MRI (fMRI), which allows researchers to visualize activity patterns within the brain, often mapping the responses for one type of sensory stimulus relative to that for another. This straightforward type of mapping, which is routine in humans, is also routine in nonhuman primates as long as the experimental components and infrastructure are in place. A large number of steps lie between the acquisition of raw MR signals and the interpretation of neural data. This is particularly true for functional MRI (fMRI), where activity maps are generated based upon the evaluation of time varying intensity values throughout the brain from a series of MR volumes. Most neuroscience researchers are not experts in the physics or engineering aspects of MRI and thus rely heavily on experts in these domains to develop and maintain the best scanning environment possible. Thus, MRI experiments are typically done in the context of a core imaging facility. In animal studies, the challenges of MRI are compounded, as technical issues such as the production of specialized radiofrequency (RF) coils and practical skills such as surgery and the animal's behavioral training become additional factors. Animal scanning is typically combined with other procedures such as pharmacological manipulation or simultaneous electrophysiological recording, often further complicating the imaging procedure. Overcoming these obstacles, however, can be of enormous value, since the capacity to map activity over the entire brain is especially powerful when combined with well-conceived manipulations or measurements. The Neurophysiology Imaging Facility (NIF) is organized primarily around the operation of a vertical 4.7T Bruker Biospec scanner, with a 3T Siemens scanner set to be delivered in 2018. This combination will allow for a spectrum of different scanning possibilities for researchers at the NIH, ranging from routine anatomical scans to intricate, multimodal fMRI projects. The arrival of the new scanner will provide needed additional scanning time for our users, will centralize much of the anatomical scanning, and will accommodate the needs of two newly hired principal investigators. It will also provide for a longer-term transition to replace the 4.7T vertical scanner with a cutting-edge system in the future. Five staff members including Dr. Leopold, each from a different scientific background and with different skills, aim to provide the most efficient functional scanning possible for a broad range of investigators. For structural scanning, the facility staff assists with scans that aid in MRI-targeting of electrophysiological sites, identification of microelectrode positions, evaluation of experimental precision, and, importantly, the direct comparison of electrical recording sites with foci of fMRI responses in the context of a cognitive task. There are a range of contrast options, including diffusion weighted scans that can identify features in the white matter, or provide the basis for tractography. The facility also offers a frameless stereotaxy protocol to assist the surgeon with implantation. This method permits a visualization of the high-resolution scan during surgery, with a real-time depiction of the surgical instruments relative to the scanned brain structures. We have used this approach routinely to aid in the accurate implantation of electrode bundles and chronic cannulae, targeted ablations, and the placement of recording chambers. For functional scanning, much of the work is done by scientists in individual laboratories, which the NIF staff train to become largely autonomous in their experiments. The Intramural Research Program at the NIH is one of the very few sites around the world in which monkeys can routinely participate in both fMRI and electrophysiological studies. The fMRI studies go beyond mapping functional specialization in the brain. Experiments within the facility typically combine fMRI with other procedures, such as microelectrode recordings or pharmacological inactivation. In the last year, neuroscience in the facility has combined fMRI with cortical ablation, pharmacological inactivation, electrocorticogram recordings, electrical microstimulation, and recordings from chronic microwire arrays. The fMRI experiments produce large data files that must be processed to evaluate the functional activity patterns across the brain. The facility provides storage of these data, as well as help in the initial processing steps. We are further able to combine these techniques with (1) reversible inactivation of electrical neural activity using pharmacological agents, (2) the identification of anatomical pathways using transported, MRI-visible chemicals such as manganese chloride, and (3) electrical microstimulation, where small local currents activate neurons that project to regions that can be detected using the fMRI signal. Surgical targeting is another technique that relies upon particularly high-quality, distortion-free 3-D images of the brain. We have recently implemented algorithms that measure and compensate for small geometric distortions in the images that might hamper surgical precision. The NIF staff spends a relatively small fraction of its time carrying out research related to MRI itself. In the past several years, we have focused on completing studies related to diffusion tractography. Dr. Frank Ye scanned several ex-vivo brains and, in a highly collaborative effort with other groups inside and outside the NIH, we recently published two papers related to the strengths and weakness of MR diffusion tractography (Thomas et al., Proc Natl Acad Sci (2014); Reveley et al., Proc Natl Acad Sci (2015)). This research is continuing, and has contributed to three recent publications, including one identifying a new pathway in the macaque (Takemura et al., Cerebral Cortex (2017)) and two creating a macaque template atlas for the entire community (Seidlitz et al., NeuroImage (2017)) and (Reveley et al., Cerebral Cortex (2017)). Other research lines in the facility involve the development of scanning with newly available contrast agents. At present, research in the facility is focused on the design and testing of implanted radiofrequency coils, with the hope that this method can become routine for users seeking to obtain higher signal-to-noise images.