This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).
This Small Business Innovation Research Phase II project will build upon the success demonstrated in the Phase I program and further develop the Intraventricular Cooling Catheter, whose purpose is to induce localized therapeutic hypothermia while maintaining systemic normothermia and thus to act as a neuroprotective modality to mitigate brain injury in traumatic brain injury, and stroke, and post-cardiac arrest brain injury in humans. In Phase II our primary objectives are: 1) design and development of commercially viable prototypes of the system components (Controller and Catheter); 2) determination of system's range of effectiveness in cooling tissue in various regions of the brain (cooling map of brain); and 3) determination of system's safety and efficacy profile. Improvements will be developed to both the catheter and the controller based on our Phase I experience. Animal trials using a sheep model will be conducted to determine the system's performance and efficacy in brain application. Finally, an IDE safety trial will be conducted (in spine application). We anticipate that the results of this work will provide the foundation for this intraventricular cooling catheter to be used as an adjunct modality to other treatments for neuroprotection due to cerebral ischemia in stroke and traumatic brain injury, as well as in cardiovascular surgery.
The broader impact of this Phase II work addresses the challenge of neurological deficits relating to cerebral ischemia. Cerebral ischemia reduces oxygen delivery to brain cells and initiates the process of cellular death. Stroke and Traumatic Brain Injury (TBI) are the two most prevalent causes of icshemic brain injury. 780,000 strokes occur annually in the United States with 87% of them being ischemic. Stroke is the third leading cause of death and the leading cause of disability. Additionally, stroke strikes blacks at a rate twice that of whites. TBI results in 235,000 hospitalizations each year and 50,000 deaths. The challenge of TBI has increased even more in the US military where, due to the nature of modern warfare, rates of brain injury have increased from 12%-14% to an estimated 22%. Neurological deficits from cerebral ischemia cry out for novel therapies. Over $119 billion in direct and indirect costs to society are incurred annually from Stoke and TBI, $68.9 billion for stroke and 60 billion for TBI. These diseases affect all sectors of society and the development of a novel device to induce localized hypothermia while maintaining systemic normothermia will have a significant impact on clinical practice.
Our Phase II Intraventricular Cooling Catheter Project successfully advanced the commercialization of a novel medical device to induce therapeutic hypothermia that can potentially reduce neurological injures to the brain and spinal cord by cooling the cerebral spinal fluid (CSF) in the brain or spinal cord. The cooling of the CSF reduces the temperature of the adjacent tissues and organs and reduces their need for oxygen. By inducing hypothermia in these areas, Ischemic injury can potentially be reduced and the time for physicians and first responders to aid the patient is extended. Our project achieved the following outcomes: We improved the design of the both the catheter and the control unit. We successfully tested these products in an animal model. We developed a new technique to map brain temperatures. We improved our understanding and technique for inserting the catheter less invasively. Product Design Our product consists of two major components: a catheter that goes into the body and a controller/pump unit that circulates cooled fluid through the catheter. The catheter is a multi-channeled tube through which the cooling fluid circulates. We improved it in several ways. First, we added a third channel to act as a drain through which a doctor could control the amount of Cerebral Spinal Fluid in the body. A spinal drain is a traditional and long established medical device used to control intracranial or spinal pressure. By adding this feature to our cooling catheter, the medical team addressing brain or spinal cord injury has the capability to use both cooling technology and fluid draining methodology to protect against neurological damage with the insertion of only one catheter. Next, we reduced the overall size of the catheter by 36% from an 11 French catheter to a 7 French size. This reduction in size will facilitate the insertion of the catheter as well as creating less tissue damage. Finally, we improved the tip configuration of the catheter to improve insertion for the physician. Regarding the controller/ pump component, a complete redesign was a significant outcome of this project. The redesign included new operating logic, a new pump design, new housing and a new cooling unit . Figure 1 shows the major outcomes of our product development in Phase II. Animal Studies Before medical devices are approved for human use, they must be validated in animals. We conducted 18 animal studies in phase II. All studies were conducted under protocols approved by Institutional Animal Care and Use Committees of facilities accredited by the Association for Assessment of Laboratory Animal Care International (AAALAC). These protocols insure the proper and humane use of the animals. In six studies, we successfully cooled the brain of the animals to neuroprotective levels and monitored the results to create thermal maps. In two studies, we used infrared technology while in four we created thermal maps using Magnetic Resonance Imaging (Figure 2 ). The data from the MRI studies provided greater specificity and detail that the infrared studies. In 2 studies, we successfully cooled the brain and survived the sheep for 72 hours. In these studies we demonstrated that there were no adverse consequences to the sheep due to the cooling. In 7 studies, we successfully cooled the spinal cord and survived the sheep for 30 days. All seven catheters were inserted percutaneously. In these studies, there was some short term motor effect that resulted in difficulty walking in the first 24 hours in 2 animals. These conditions resolved itself by day 2. All seven sheep completed the 30 day study. In two animals, the use of a new type of insertion needle was tested. It was determined to be less effective than the standard Tuohy needle. In one study, an animal did not recover from the anesthesia. Overall, the animal studies further demonstrated the use of our cooling catheter technology to induce localized hypothermia safely and added to our knowledge on how to best apply the technology. Brain Mapping A significant t outcome of our project was the successful development of a 3-dimensional thermal brain mapping technology using Magnetic Resonance Imaging (MRI). In a novel use of the catheter, a specialized temperature sensor was infused into the brain through our newly-added third lumen. Using the MRI, we were able to capture the MR signals of the temperature sensor and from these to calculate temperature distributions in various areas of the brain. This data (Figure 3) shows the cooling results in the major control centers of the brain. This information could be important in directing our cooling technology to address specific areas of injury with the goal of reducing term injury. Catheter Insertion Technique Our phase II outcomes enhanced our knowledge in placing the spinal catheter in a less-invasive way as well as reducing tissue damage with the optimization of needle point geometry.
