PI: Kenn Oldham, PhD; Hakam Tiba, MD, MS; Craig Williamson, MD; Kevin Ward, MD

Current therapies for TBI primarily attempt to avoid secondary ischemic injuries, which are mediated by decreased cerebral blood flow due to elevated intracranial pressure and impaired cerebral autoregulation. However, there is currently no reliable method for continuously monitoring cerebral blood flow used in TBI management. The project team is enhancing an existing intracranial pressure (ICP) monitor with miniature piezoelectric pressure and optical blood volume sensors that provide synchronized, high-bandwidth measurements of heartbeat-to-heartbeat local pressure and blood volume fluctuations.

PI: Thomas H. Sanderson, PhD; Joseph M. Wider; PhD
Samuel Tuck, MSE

TBI is a complex and heterogeneous injury, with progression divided into multiple phases. The primary injury of TBI is caused by mechanical stress applied to the tissue and causes irreversible damage. In contrast, secondary injury progresses over the ensuing hours, providing an opportunity to rescue damaged tissue and limit brain injury. The project team is developing a single treatment device that combines novel near infrared light (NIR) technology developed in the Sanderson and Hüttemann labs with targeted temperature management (TTM) to target the cellular injury processes occurring during the secondary phase of TBI and limit the progression of brain damage.

PI: Christopher Fung, MD, MS; Katharine Seagly, PhD

Acute evaluation of TBI is limited by 1.) Overuse of brain CT scans both during the initial evaluation of TBI and in reassessing those with traumatic intracranial hemorrhage on the initial brain CT scan; 2.) Lack of diagnostic tools to guide decisions regarding who needs additional intensive care, or neurocognitive, neuropsychiatric and rehabilitation services. The project team aims to build a highly phenotyped registry of ED patients evaluated for TBI. The development of this database will enable the team to develop a novel evaluation algorithm that will optimize the clinical care provided to TBI patients, with an intended goal of improving clinical outcomes.

PI: H. David Humes, MD; Thomas Sanderson, PhD; Joseph Wider, PhD

Clinical evidence for inflammation driving secondary brain injury is mounting, yet pharmacologic anti-inflammatory interventions have not yet proven effective in improving outcome after TBI. The project team will evaluate a novel immunomodulatory therapy, the selective cytopheretic device (SCD), which modulates the excessive activation state of circulating inflammatory cells

PI: Florian Schmitzberger, MD, MS; Robert Silbergleit, MD; Douglas Noll, PhD

A critical knowledge gap in translating intranasal insulin to human TBI clinical trials can be filled by identifying the intranasal insulin dose that achieves the maximum signaling effect in the brain without causing serious side effects. To optimize the chances for successful translation of intranasal insulin therapy for TBI, the team’s goal is to determine the dose response effect in humans at doses > 160 units. This should be accomplished by utilizing functional MRI in a similar fashion to prior studies.

PI: Jacob R. Joseph, MD; Wei Zhang, PhD; Yannis Paulus, MD; Joseph Myers, OD; Jaes Jones MD

A major obstacle in treating severe TBI is the ongoing need for invasive monitoring due to the lack of accurate noninvasive monitoring options, especially within the “golden hours” after injury. To create a non-invasive means of monitoring brain tissue oxygenation, the team has developed an innovative tool for retinal oximetry (RO). A specialized camera obtains a real time photograph of the retinal vasculature using 2 different wavelengths of light. The team has also developed an algorithm that uses the signals obtained in this paradigm to create a map of the optical densities of the retinal vasculature under the two lighting conditions.

PI: Robert Dickson, MD; Hakam Tiba, MD

The gut microbiome has a well-established role in the pathophysiology of other forms of critical illness, and preliminary studies have suggested a mediating role in severe TBI. This project will lay a foundation for the development of novel, microbiome-targeted therapeutics (e.g. probiotics, synbiotics, antibacterial monoclonal antibodies) for TBI.

PI: Erica Stein, MD; Kayvan Najarian, PhD; Emily Wittrup, MS; Craig Williamson, MD

During the golden hours of TBI, obtaining an accurate measure of intracranial pressure (ICP) is critical, yet current gold standard measurements are obtained through invasive intracranial devices, which can be time-consuming to insert and expose the patient to additional risks.

Optic nerve sheath diameter (ONSD) is known to be affected by changes in ICP. The project team will explore the use of obtaining ONSD measurements through computed tomography (CT) scans. Because head CT scans are routinely collected for TBI patients, obtaining the ONSD measurement concurrently instead of separately with ultrasound would save critical time in the golden hours of a TBI.

PI: Katharine Seagly, PhD; Nathan Haas, MD

Glycemic variability (changes in blood sugar) are commonly present following TBI and can contribute to secondary brain injury and worse clinical outcomes. Continuous glucose monitors (CGMs) allow real-time, minimally invasive monitoring via a temporarily implanted sensor in the skin of the abdomen or arm. Several commercially available CGMs are used frequently for outpatients with diabetes, given their convenience, simplicity, and autonomous continuous collection of glucose readings (often every five minutes).

By applying CGMs to Emergency Department patients during the golden hours following TBI, the team aims to generate highly granular data of glycemic variability, and associate these findings with outcomes.

PI: J. Brian Fowlkes, PhD

After TBI, the vasculature can lose its ability to autoregulate blood flow to the brain. This loss of cerebral autoregulation (CA) is a major determinant of outcome after TBI. However, measuring CA is extremely difficult with the “gold standard” requiring placement of an intracranial pressure monitor as well as the need for continuous mean arterial pressure (MAP) monitoring.

The project team proposes to develop an alternative to PRx by replacing ICP as the measured variable with either internal carotid artery flow (ICA) or middle cerebral artery flow (MCA), combining one of these with MAP to develop a Flow-Pressure index (FPx) that is analogous to the invasive clinical standard.

PI: Florian Schmitzberger, MD, MS; Thomas H. Sanderson, PhD

Developing a neuroprotective approach for TBI is challenging due to differences in injury severity, location, and subtypes.

Mitochondrial dysfunction has been identified as a common component of TBI-induced cellular injury. Through their “LUCID” device, the project team has discovered novel effects of specific wavelengths of near infrared light (NIR) that allow modulation of mitochondrial activity. They aim to build on previous developments of LUCID, with the goal of testing it in optical phantoms and then in a clinical phase I trial on healthy human subjects.