Developing methods to assess cerebrospinal fluid flow velocity in the glymphatic pathways

Researchers recently discovered that cerebrospinal fluid (CSF) plays a critical role in removing brain waste and toxic materials linked with dementia. CSF flow is hindered in various brain pathological conditions. While major glymphatic/cleansing pathways are located along the major arteries, CSF flow was traditionally measured in the Sylvian aqueduct, a different domain of cerebrospinal circulation. Gavin Britz MD, MBA, MPH, Eugene Golanov, MD, PhD and Christof Karmonik, PhD are developing new methods for measuring CSF flow using the Siemens 7 Tesla MAGNETOM Terra MRI to explore CSF flow hindrance in the glymphatic pathways and its role in the development in various neuropathologies, including traumatic brain injury. Learn More.

Funding: Houston Methodist and Siemens Healthineers Research Collaboration $100,000

Methods and devices to assist and improve cerebrospinal fluid drainage

CSF supports normal brain function in several ways, including mechanical support, homeostatic maintenance and humoral factors distribution. CSF is integral to the clearance of the brain metabolic waste and various pathogenic elements. Thus, maintenance of normal CSF drainage is of utmost importance for the normal brain and abnormalities of CSF drainage are being linked to neurodegenerative diseases, such as Alzheimer’s disease and hydrocephalus. We are conducting an innovative set of experiments to show the capability of percutaneous electrical stimulation of the neck muscles to improve and accelerate the CSF drainage. The overarching goal of this work is to develop a wearable and non-invasive device. Results of studies conducted by Angelique Regnier-Golanov, PhD under guidance of Gavin Britz, MD, MBA, MPH showed that electrical stimulation of the neck muscles in mice induced a significant decrease of intracranial pressure in vivo. These studies led to the filing U.S. Patent Application Nº: 63/178,616 in April 2021.

Nano-neurotechnology and brain injury

Unconventionally acquired brain injury (UBI) from focused ultrasound and electromagnetic sources have become an emerging threat to service members and diplomats. As a result, it has become critical to understand the immediate physiological responses to UBI so that real-time monitoring and intervention systems can be developed to detect and treat these injuries promptly. Sonia Villapol, PhD and Lan Luan, PhD are working to identify critical biochemical and biophysical markers that respond within seconds to UBI from militarily relevant energy sources and determine if the identified first biological responders depend on the energy source. Specifically, they will successfully integrate high-speed electrical, optical and chemical sensing methods that will enable the detection of many biochemical and biophysical markers within milliseconds to seconds following UBI in vitro and in vivo.

Technologies and machine learning methodologies for systematic detection of mild traumatic brain injuries (mTBIs)

mTBIs are the most common type of brain injury. If undiagnosed, mTBI may lead to various short and long-term abnormalities, which include, but are not limited to impaired cognitive function, fatigue, depression, irritability and headaches. Existing screening and diagnostic tools to detect acute and early-stage mTBIs have insufficient sensitivity and specificity. Therefore, it is important to identify relevant physiological biomarkers that can be integrated into a mutually complementary set using contemporary machine learning tools and data processing methodologies to provide on-site diagnostic of mTBI. Center investigators, led by Gavin Britz, MD, MBA, MPH and Behnaam Aazhang, PhD, are developing new mTBI diagnostic tools and respective portable devices that could be employed in the field.

Publications:
Schmid,, W., Fan, Y., Chi, T., Golanov,, E., Regnier-Golanov, A.S., Austerman, R.J., …& Britz, G.W. (2021). Review of wearable technologies and machine learning methodologies for systematic detection of mild traumatic brain injuries. Journal of Neural Engineering, 18(4), 041006

Restoring hand and arm function following spinal cord injury

Restoring hand and arm function is the highest treatment priority of individuals with cervical spinal cord injury (SCI). Traditional approaches of occupational or physical therapy do not provide sufficient specificity to target damaged neural networks and promote spared connections between the brain and periphery. Center investigators, led by Marcia O’Malley, PhD and Dimitry Sayenko, MD, PhD proposed that the simultaneous activation of descending commands with a coordinated engagement of spinal networks is a critical objective in neurorehabilitation. This novel multi-disciplinary approach that combines spinal neuromodulation and robotics will allow the center to target, for the first time, upper limb (UL) neurorehabilitation at different levels of the neuroaxis, including descending control, supraspinal and spinal sensorimotor networks, and sensory inputs. This study is designed to determine the effects of an intervention that combines transcutaneous electrical spinal cord stimulation (TSS) with rehabilitation training using an UL robotic exoskeleton on the neurophysiological and functional outcomes in individuals with incomplete cervical SCI. The team’s central hypothesis is that TSS will enhance the excitability of spinal sensorimotor networks below the SCI, while operating an exoskeleton will provide a robust valley of descending and sensory inputs converging on the pre-excited spinal circuitry, thus resulting in increased functional motor output and improved voluntary control of the UL movements. The goals are to: (1) demonstrate that the therapeutic effects of robotic training are superior in regaining motor function of UL when combined with spinal stimulation, compared with the training with Sham stimulation, and (2) elucidate the underlying mechanisms of this combined approach. (CHN: SCIRTS chn:wdg)

Funding: Craig H. Neilsen Foundation Grant ID Number: 733278

Publications:

Oh, J., Steele, A. G., Varghese, B., Martin, C. A., Scheffler, M. S., Markley, R. L., … & Sayenko, D. G. (2022). Cervical transcutaneous spinal stimulation for spinal motor mapping. iScience, 25(10), 105037.

Mahan, E., Dunkelberger, N., Oh, J., Simmons, M., Varghese, B., Sayenko, D., and O’Malley, M. K. (2022) Measuring torque production with a robotic exoskeleton during cervical transcutaneous spinal stimulation. International Conference on Rehabilitation Robotics (ICORR), IEEE, pp. 1-5.

(Submitted) Mahan, E., Zook, G., King, S., Oh, J., Scheffler, M., Martin, C., Dinh, J., Sayenko, D., and O’Malley, M. K. (2023) An Upper Limb Robotic Exoskeleton for Dual Rehabilitation Interventions with Integrated Kinematic Assessment. International Conference on Rehabilitation Robotics (ICORR).