The central aim of this NIH K01 mentored research project is the development of a new type of wireless microelectronic sensors for direct functional magnetic resonance imaging (fMRI) of brain seizures. fMRI has emerged in the past two decades as a prominent tool for noninvasive diagnosis and monitoring of neuropathological disorders and brain injury. However, it relies on blood oxygen level-dependent (BOLD) signal, which is mainly of neurovascular origin and is a fundamentally indirect manifestation of neural activity. This precludes the distinction between inhibitory and excitatory neural activity, risking false positives and false negatives in the diagnosis and monitoring of brain seizures. In this project, the mentored investigator will combine his expertise in microelectronic probes for the recording of neural activity, and combine them with neuroimaging capabilities of the host institution, to develop wireless MRI sensors to uniquely and specifically address questions of temporal and cross-regional manifestations of pathological brain patterns in rodent models of epilepsy. This new form of brain imaging will allow for the acquisition of direct readouts of seizures using MRI, employing its three-dimensional encoding capabilities to study abnormal firing patterns and neural dysfunction across the brain. The research proposed here represents an initial step in a new and innovative field for neuroscience and neurological research for the treatment of brain diseases. The novel methods propose here by the mentored scientist will be broadly applicable to problems in neurobiology, and will transform the ability of neuroscientists to study integrative functions of the brain in neuropathological disorders. The approach will also help to establish a new path in diagnostic medicine whereby responsive microfabricated active devices drive the change in MRI contrast similarly to conventional chemical contrast agents, and can report on aspects of cellular physiology for functional MRI. Aviad Hai, PhD, will serve as principal investigator for this project. Dr. Hai is a neurobiological engineer that focuses on the development and application of novel sensors for neuroimaging and brain recording.. Dr. Hai has made several key contributions in the development of new diagnostic imaging agents for studying physiological processes in the brain using MRI in rodents, as well as the development nano-engineered probes for recording and stimulation of brain activity. His extensive expertise and published contributions in both the microelectronic engineering and imaging portions of the project put him at a natural position of leading this highly multidisciplinary mentored project. Dr. Hai will direct efforts of microelectronic fabrication, in-vitro and in-vivo validation in animals, all of which are within his expertise.
Minimally-invasive functional imaging modalities increasingly contribute to diagnosis of abnormal neural firing patterns in neuropathological disorders such as epilepsy, traumatic brain injury and more. Using the blood-oxygen-level-dependent (BOLD) signal, functional MRI (fMRI) currently offers superior readout in terms of combining three dimensional localization and noninvasiveness, but it informs neurologists mainly of areas displaying high blood flow and increased blood volume, and leaves substantial guesswork as to the localization of the seizure and the properties of abnormal neural firing patterns. This project proposes the design and application of wireless, inductively coupled fMRI probes that amplify electromagnetic fields of neural origin to detectable magnetic-field perturbations of the MRI signal, and application of these probes with fMRI for a new form of imaging brain seizures.
