The Massey Foundation TBI Grand Challenge culminates in Pitch Day

Five U-M proposals awarded funding through Massey Foundation traumatic brain injury (TBI) Grand Challenge.

Traumatic brain injury (TBI) is considered to be one of the most complex diseases in the most complex organ in the body. TBI patients require continuous monitoring and constant care in order to have a chance at survival with an outcome similar to their preinjury state. Innovation in severe TBI care is badly needed in order to improve patient outcome and ease the incredible burden placed on caregivers, and allow them to provide the personalized care required by the complexity of Traumatic Brain Injuries.

A generous donation from the Massey Foundation was given to UMHS to discover innovative treatments for severe TBI through MCIRCC. A portion of this donation was leveraged by MCIRCC to create the Massey Foundation TBI Grand Challenge. On April 29, a panel of TBI experts from around the country gathered to hear ten proposals for innovative therapeutic, diagnostic, devices and digital health technologies as part of the Massey Foundation TBI Grand Challenge Pitch Day. These ten proposals were selected from an original 24 proposals received.

The presenting teams were made up of clinicians, engineers and data scientists from around the University of Michigan. They represented departments including Emergency Medicine, General Surgery, Electrical Engineering, Computer Science, Neurosurgery, Biomedical Engineering, Ophthalmology, Radiology, and others supported by the MCIRCC Catalyst Team. The cross-functional nature of MCIRCC’s membership allowed teams to attack the problems of TBI care from multiple perspectives. Teams consistently spoke to the weaknesses, deficiencies and challenges in staging, diagnosing and treating severe TBI including the incredible challenges of TBI treatment in the combat casualty care setting. Presenters, when covering those challenges, highlighted the fact that in the future, clinicians may look back on the current technology and methods for treating TBI with disbelief as to why they were used at all. Some presenters even wheeled in the current biomedical hardware to the pitch room in order to show how the idea being proposed could bring improvement to TBI care.

The Pitch Day Panel was composed of University of Michigan clinical experts from various departments, innovation and commercialization experts from Fast Forward Medical Innovation, TBI researchers and innovators from universities around the country, and Department of Defense representatives. They were demanding in their questions of the presenting teams, seeking to gain an understanding of the potential weaknesses or gaps in research behind each pitch. The Q&A sessions were marked by positivity and a genuine feeling of optimism about the potential impact that the TBI Grand Challenge will have. Frequently, a Department of Defense representative would express excitement about how a proposed technology might be of special use in military settings; possibilities not usually considered by university experts. These different perspectives allowed the panel to think on a grand scale, further increasing the potential impact of the Grand Challenge.

After a full day of strong, high-potential pitches, it was clear to the panel that the return on the Massey investment, which will ultimately be measured by the number of TBI patients for whom these innovations improve outcomes, could be immense. The expertise and penchant for innovation at the University of Michigan was on full display once again. Collaborative Pitch Day Panel discussions enabled the team to select the following five proposals for Massey Foundation funding:

PROPOSAL 1: DEVELOPMENT OF INTRAVENOUS IMATINIB FOR TARGETING PDGF SIGNALING IN TRAUMATIC BRAIN INJURY

Summary:

Current therapies for traumatic brain injury (TBI) focus on stabilizing individuals and on preventing further damage from the secondary consequences of TBI. Our previous study through Massey funding demonstrated the efficacy of Imatinib, a pharmaceutical, for the treatment of TBI. However, the Imatinib was administered orally and the most severe TBI patients will be unconscious and unable to swallow. Therefore we propose to develop an intravenous formulation and treatment protocol for severe TBI. Imatinib is already approved by the FDA for other uses. If our project is successful, we will begin planning for clinical trials for this new indication for Imatinib. Successful development could improve TBI in both the civilian and military setting.

Principal Investigators:

  • Daniel A. Lawrence, PhD

    • Frederick G. L. Huetwell Professor of Basic Research in Cardiovascular Medicine, Department of Internal Medicine

  • Geoffrey G. Murphy, PhD

    • Associate Professor of Molecular & Integrative Physiology

    • Associate Research Professor in the Molecular & Behavioral Neuroscience Institute

  • Enming J. Su, PhD

    • Assistant Professor of Internal Medicine

Co-Investigator:

  • William J. Meurer, MD, MS

    • Assistant Professor, Department of Emergency Medicine

    • Consultant, Department of Neurology

PROPOSAL 2: USING ADVANCED GENOMIC AND PROTEOMIC TECHNOLOGY TO ENSURE VALPROIC ACID'S SUCCESS AS AN EARLY TREATMENT OF TRAUMATIC BRAIN INJURY

Summary:

The primary objective of this project is to identify Valproic Acid’s (VPA’s) mechanisms of action in the brain and to use this knowledge to ensure its successful transition into clinical use as an early treatment for TBI. The study will allow us to develop blood markers that will allow us to determine which patients will respond to VPA (precision medicine). We anticipate completing this objective in one year. With the support of the Massey Foundation we will use high throughput technology to determine how VPA protects the brain following injury which may help us develop other targets for drug development. These approaches may have high impact for civilian and military TBI victims.

Principal Investigators:

  • Patrick Georgoff, MD

    • General Surgery Resident, PGY4

    • Research Fellow, University of Michigan Trauma Surgery Lab

  • Hasan Alam, MD

    • Norman W. Thompson Professor of Surgery

    • Section Head, University of Michigan General Surgery

Co-Investigators:

  • Gerald Higgins, MD, PhD

    • Adjunct Research Professor, Computational Medicine & Bioinformatics, University of Michigan Medical School

    • Vice President, Pharmacogenomic Science, Assurex Health, Inc

  • Brian Athey, PhD

    • Michael Savageau Collegiate Professor & Chair, Department of Computational Medicine & Bioinformatics

    • Professor of Psychiatry and of Internal Medicine

    • Co-Director, Michigan Institute for Data Science (MIDAS), University of Michigan Medical School

  • Vahagn Nikolian, MD

    • General Surgery Resident, PGY4

    • Research Fellow, University of Michigan Trauma Surgery Lab

PROPOSAL 3: DIGITAL EXTRA-VENTRICULAR DRAIN (EVD) WITH INTEGRATED INTRACRANIAL PRESSURE (ICP) MONITOR AND CEREBRAL SPINAL FLUID (CSF) FLOW MONITOR/PRESSURE REGULATOR

Summary:

We propose the development of a digital external ventricular drain (EVD) system with integrated ICP monitor and CSF flow monitor/pressure regulator. The EVD will have the ability to automatically adjust to changing patient positions and condition while quantifying the amount of CSF drainage and alerting the caregiver to changes in ICP or CSF drainage. This device could not only be useful in the ICU or field hospital setting, but also during long military patient transport, and especially in situations in which limited personnel and resources are available. Because the device will make automatic adjustments to changing patient position and CSF flow, it will also decrease caregiver workload making care of the patient with severe TBI safer.

Principal Investigators:

  • Rodney C. Daniels, MD

    • Pediatric Critical Care

  • David Chesney, PhD

    • Electrical Engineering and Computer Science

Co-Investigators:

  • Hyesun Yun, MS

    • Pediatric Critical Care Medicine, Lab Manager/Associate in the Daniels Lab

  • Hakam Tiba, MD

    • Department of Emergency Medicine, Expert in Animal Models/Swine TBI Model

PROPOSAL 4: AUTOMATED DETECTION AND MEASUREMENT OF SUBDURAL HEMATOMA IMAGING CHARACTERISTICS FOLLOWING TRAUMATIC BRAIN INJURY

Summary:

There is a strong unmet need for a technology that can rapidly and automatically detect subdural hemorrhages (SDHs) and estimate hematoma severity in the brain, thereby identifying patients who need urgent surgical evacuation. Due to their mixed appearance and location directly adjacent to the skull, automatic detection and measurement of subdural hemorrhage (SDH) on a brain CT scan is particularly challenging. For this project, we will develop a software technology that will leverage algorithms to automatically detect and provide precise measurement of hematoma volume, brain compression and optic nerve diameter in brain CT scans of TBI patients subdural hematoma.

Principal Investigators:

  • Kayvan Najarian, PhD

    • Associate Professor, Emergency Medicine and Computational Medicine and Bioinformatics

  • Craig Williamson, MD

    • Assistant Professor, Neurosugery and Neurology

Co-Investigators:

  • Jacob Joseph, MD

    • Resident Physician, Neurosurgery

  • Krishna Rajajee, MBBS

    • Associate Professor, Neurosurgery and Neurology

    • Medical Director, Neurological ICU

  • Jayapalli Rajiv Bapuraj, MBBS

    • Assistant Professor, Radiology

  • Ashok Srinivasan, MBBS

    • Associate Professor, Radiology

  • Reza Soroushmehr, PhD

    • Research Fellow, Emergency Medicine

PROPOSAL 5: QUANTITATIVE PUPILLOMETRY FOR THE ACUTE DETECTION AND PROGNOSIS OF TRAUMATIC BRAIN INJURY

Summary:

Evidence suggests that quantitative measurements of pupillary light reflex (PLR) can reveal the presence of traumatic brain injury, indicate its severity, estimate intracranial pressure, and track brain recovery. This project will use ongoing human studies at the University of Michigan to provide clinical evidence supporting the use of quantitative pupillometry for precise measurements of PLR as a reliable biomarker for TBI. Such a device could be used as a tool for first responders (civilian and military) to objectively determine whether or not a patient has suffered a a severe traumatic brain injury, and to assess its severity.

Principal Investigator:

  • William J. Meurer, MD, MS

    • Assistant Professor, Departments of Emergency Medicine and Neurology

Co-Investigators:

  • Jacob Joseph, MD

    • Resident, Department of Neurosurgery

  • Craig Williamson, MD

    • Department of Neurosurgery

  • Matthew J. Lewis, PhD

    • CTO, Michigan Aerospace Corporation

While the ten teams could not all gain funding from The Massey Foundation TBI Grand Challenge, the complexity of TBI and the needs of the millions of TBI patients dictate that all worthy innovation be explored in case it could feasibly help caregivers and patients. Those teams that were not funded, are uniquely positioned to continue to seek funding at the University of Michigan Medical School’s Fast Forward Medical Innovation Program, the Coulter Translational Research Program, and through MCIRCC’s partnership with the Department of Defense and Industry. The MCIRCC Massey TBI Grand Challenge is simply another step toward boosting TBI research and innovation both at the University of Michigan and around the world.