This supplemental application for the NIH I-Corps? program will provide resources and training to conduct customer discovery interviews that will inform production and business development for our predicate Phase I SBIR grant NS092181 entitled Noninvasive scalp detection of cortical spreading depression for brain injury This grant provides for the development and validation our proof-of-concept device for non-invasive detection of cortical spreading depolarization (CSD) in acute brain injury, including stroke, subarachnoid hemorrhage, and severe traumatic brain injury. The device will address the unmet need for a noninvasive CSD detection as the only currently accepted method is an invasive procedure involving electrodes placed on the brain surface during medically necessitated neurosurgery. Thus only a small fraction of the most critically injured patients are monitored. Noninvasive CSD detection will be used to develop and then monitor treatments of repetitive, brain damaging CSD occurrence in all forms of acute brain injury, in addition to addressing migraine therapies for aura suppression as migraine aura is now known to be the result of CSDs. Our proof-of-concept prototype is composed of a proprietary configuration of direct current (DC)-capable electrodes, signal collection using commercially available DC-coupled bio-signal amplifiers, signal processing with consideration for the DC potentials created at the skin surface, and a digital CSD detection algorithm. A patent is under final review for the core technology of the device. Once non-invasive CSD detection is validated, our proof-of-concept proto- type would be the basis for a device to detect CSD for routine Neuro-Intensive Care Unit (Neuro-ICU) use.
We aim to explore customer and stakeholder needs for our scalp-mounted, CSD-detection system. Our first spear- head customers are investigators who have performed many clinical studies using the current non-invasive CSD detection system and who are part of the CoOperative Study on Brain Injury Depolarisations (COSBID, www.cosbid.org) group. These Neuro-ICU-based investigators are convinced that CSD-targeted thera- pies will reduce post-injury brain injury expansion and are primed for a device that will greatly expand their ability to evaluate and validate such therapies. Other stakeholders include: 1) pharmaceutical companies who would use non-invasive CSD monitoring for the objective evaluation of anti-aura/CSD therapies and anti-CSD therapies to reduce CSD-based brain injury expansion; and 2) medical device companies interested in a new product for a new market. Our team is composed of the PI of the predicate Phase I SBIR and CEO of the com- pany with detailed knowledge of our prototype device, the System Engineer of the company as the Scientific Technical Expert, who can directly implement stakeholder concerns into the design of our next generation device, and an industry expert with a wide-ranging experience in product out-reach and marketing. Our goal is to provide a marketable, easy-to-use device designed for routine use in the Neuro-ICU that will be used to monitor brain-saving therapies that will reduce the duration of rehabilitation, extend life, and prevent death.
Cortical spreading depolarization, a primary feature of acute brain injury, is increasingly implicated as a fundamental mechanism underlying progression of acute brain injuries but cannot be observed optimally with conventional electroencephalography. This project will explore customer needs for the development of a non- invasive, scalp-mounted system for detection of these repetitive brain-damaging disturbances. Such a scalp- mounted detection device could change the landscape for therapeutic monitoring of acute brain injury in the Neuro-Intensive Care Unit by providing direct and non-invasive assessment. The availability of our device will also allow non-invasive detection of cortical spreading depolarization events in other conditions that it is known to occur, such as migraine aura, and has been hypothesized to occur, such as concussion. In summary, it will allow for the monitoring of therapeutic options in acute brain injury patients based on the negative aspects of cortical spreading depolarization so that patient outcome could be improved.
