Project Spotlight: Brain Tsunamis

The last decade of research has established that Cortical Spreading Depolarizations (CSDs), or “Brain Tsunamis,” play an important role in many disorders, including Traumatic Brain Injury (TBI), stroke, hemorrhage, and migraine, that collectively affect more than a billion people worldwide and are major causes of death and disability. CSDs are waves of neurochemical changes that propagate across the brain surface and are thought to mediate secondary brain damage following an injury or event. Pulkit Grover, PhD, Assistant Professor of Electrical and Computer Engineering at Carnegie Mellon University, leads a team developing algorithms and techniques to non-invasively suppress CSDs by using online detection and ensuing stimulation.

Please share a little about your background and your research experiences.

 

neural imagingI was born in India in an extended family of a large number of clinicians and am obsessed with improving treatments of disorders that we, as a species, do not understand well. I am trained as an information and control theorist, and I bring a strong analytical and modeling background to the biomedical area. I am a relatively recent entrant to the field. I only started working in neural/biomedical engineering once I joined CMU in 2013 and was initially mentored by clinicians at UPMC/Pitt (Dr. Mark Richardson) and neuroscientists at CMU (Drs. Marlene Behrmann and Mike Tarr). I am working on the challenging problem of improving sensing and modulation of neural activity noninvasively, leveraging the expertise of several amazing faculty at CMU and Pitt. We are questioning what are widely believed to be fundamental limitations of these modalities, and are obtaining novel fundamental limits, algorithms, and instrumentations to dramatically exceed these perceived limits. I am thrilled to see the success of a theory-oriented approach in these critical problems that are close to my heart.

What led you to the PHDA?

My collaborators, physician-scientists Dr. Jonathan Elmer and Dr. Lori Shutter, from Pitt and UPMC, suggested applying for PHDA funding for our project. Despite the ambitious nature of our goals, if we succeed, there is a short time to translation into clinical practice, and this led us to discuss our ideas with Jim Ciuca (Development Officer for Commercialization at the Center for Machine Learning and Health, the PHDA presence on the CMU campus). The PHDA provides a great springboard for clinical testing of ideas, and a support system that aids with the translation of our results into practice through guidance on entrepreneurship.

Walk us through your project.

Two critical questions that a brain-injury clinician asks are: “Will my patient have progressive neurological decline?” and “Will they suffer from secondary injuries after the primary injury?” Brain injuries are a major cause of death and disability, affecting 1.7 million patients/year. We need real-time identification of mediators of secondary injuries, rather than a delayed diagnosis of damage that has already occurred. The past decade or so of research has established a reliable mediator for worsening brain injury: Cortical Spreading Depolarizations or “Brain Tsunamis”.  Our goal is automated, reliable, noninvasive detection of CSDs. This builds first on algorithms for automated CSD detection, and novel techniques for high-resolution noninvasive brain imaging that we have developed with Drs. Behrmann, Tarr, and Kelly.

How do you and your project partners’ strengths complement each other?

 

EEG wavesOur team has the entire spectrum of expertise — clinical, neuroscientific, and engineering — to solve this challenging clinical problem. Dr. Behrmann and Tarr are experts in neuroscience and the use of EEG. Dr. Kelly is well-known for his work on instrumentation and testing of invasive and noninvasive neural interfaces. Most of all, Dr. Shutter and Dr. Elmer are clinicians leading the understanding of Brain Tsunamis and their implications on TBI patients. Lastly, the ongoing work of my students, Praveen Venkatesh and Alireza Chaman Zar, has laid the foundation for high-resolution imaging of brain activity and brain silences. They are as comfortable collecting data with participants as they are with proving theorems, performing simulations, and analyzing data.

How is the PHDA uniquely positioned to assist your team and grow your project to commercialization?

Our goal is to commercialize our results and have a deep and broad impact, starting with brain injuries. The PHDA offers several programs that enable us to move our work toward commercialization. My training is toward scientific research, not toward entrepreneurship. The PHDA and Dr. Kelly help understand how to bring these ideas into commercial use.

What are your project’s next steps?

We want to demonstrate that silences in the brain can be localized noninvasively using wearable interfaces. Brain Tsunamis are silences that spread slowly across the brain surface, and they have thus far evaded noninvasive detection. Our first step is to demonstrate that silences can indeed be recorded noninvasively, with ground truth established by modalities such as MRI scans or electrodes placed surgically on the brain surface. Next, we want to develop wearable interfaces that are sufficiently dense but can be worn easily. I’m already working on this actively with Dr. Kelly.

When you look at Pittsburgh as a region, what role do you see the PHDA playing? What do you foresee the future of innovation looking like here?

The PHDA brings together leading scientists, engineers, and clinicians in the country, incentivizing them to start entrepreneurship activities that can enable retaining our talented graduates in Pittsburgh. Efforts such as these are critical to keeping Pittsburgh a leading city in biomedical research and translation.