Ischemic stroke is the leading cause of disability with $2.2 trillion in projected costs of care over the next five decades in the United States alone. However, current stroke management is limited by the inability to measure the underlying physiology. The primary goal in the management of acute ischemic stroke and related brain injury is to maximize cerebral blood flow (CBF) in the affected region and surrounding penumbra. Because of the paucity of tools available for monitoring CBF in such patients, however, interventions to augment CBF are typically prescribed empirically based on expectations of neurological deficits, or in response to clinical deterioration. In the first fundig cycle, our Bioengineering Research Partnership (BRP) demonstrated that diffuse optical methods provide unique benefits for monitoring cerebrovascular physiology. Specifically, the BRP proved feasibility of optical CBF for stroke monitoring and confirmed individual variability of CBF responses. This research could not have been carried out without a unique multi-disciplinary team;or BRP team is comprised of clinical and biomedical investigators, with expertise in cerebrovascular physiology and neurocritical care, and physical scientists and engineers with expertise in optics, electronics, mathematics and computation. The proposed renewal BRP has evolved to contain three core components, a Biomedical Optics Group led by PI (Yodh), and two Clinical Groups focused on adult populations at the Hospital of the University of PA (Detre), and pediatric populations at the Children's Hospital of Philadelphia (Licht). The clinical and technological groups cross-inform the development and application processes, uncovering new ideas for clinical applications and new demands for technology. Proposed research will construct new probe- heads which emphasize the front-end of the device, in contact with the patient head, that address important limitations that have prevented wide-scale clinical adoption, and proposed research will broaden the clinical studies to ascertain cerebrovascular autoregulation responses in other management paradigms and in new patient groups such as pediatric populations eligible for Extra-Corporeal Membrane Oxygenation therapy, which will, in turn, create more opportunities for clinical translation. Technology commercialization and dissemination will be facilitated by Michael Poisel, Director of the UPSTART program in the Center for Technology Transfer (CTT) at Penn.

Public Health Relevance

Although ischemic stroke is the leading cause of disability and a leading cause of mortality in the United States, surprisingly, bedside techniques for continuous monitoring of blood flow in the brain of stroke victims following their stroke are needed. This program develops, validates, and translates optical instruments into the clinic that permit bedside monitoring of brain blood flow and oxygenation in acute stroke patients prior to the onset of new symptoms, thereby facilitating their clinical management.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
2R01NS060653-06
Application #
8761640
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Koenig, James I
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Physics
Type
Schools of Arts and Sciences
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Jain, Varsha; Buckley, Erin M; Licht, Daniel J et al. (2014) Cerebral oxygen metabolism in neonates with congenital heart disease quantified by MRI and optics. J Cereb Blood Flow Metab 34:380-8
Lynch, Jennifer M; Buckley, Erin M; Schwab, Peter J et al. (2014) Time to surgery and preoperative cerebral hemodynamics predict postoperative white matter injury in neonates with hypoplastic left heart syndrome. J Thorac Cardiovasc Surg 148:2181-8
Durduran, Turgut; Yodh, Arjun G (2014) Diffuse correlation spectroscopy for non-invasive, micro-vascular cerebral blood flow measurement. Neuroimage 85 Pt 1:51-63
Lynch, Jennifer M; Buckley, Erin M; Schwab, Peter J et al. (2014) Noninvasive optical quantification of cerebral venous oxygen saturation in humans. Acad Radiol 21:162-7
Mesquita, Rickson C; Favilla, Christopher G; Yodh, Arjun G et al. (2014) Response to Letter Regarding Article, "Optical Bedside Monitoring of Cerebral Blood Flow in Acute Ischemic Stroke Patients During Head-of-Bed Manipulation". Stroke 45:e190
Favilla, Christopher G; Mesquita, Rickson C; Mullen, Michael et al. (2014) Optical bedside monitoring of cerebral blood flow in acute ischemic stroke patients during head-of-bed manipulation. Stroke 45:1269-74
Baker, Wesley B; Sun, Zhenghui; Hiraki, Teruyuki et al. (2013) Neurovascular coupling varies with level of global cerebral ischemia in a rat model. J Cereb Blood Flow Metab 33:97-105
Mesquita, Rickson C; Putt, Mary; Chandra, Malavika et al. (2013) Diffuse optical characterization of an exercising patient group with peripheral artery disease. J Biomed Opt 18:57007
Buckley, Erin M; Naim, Maryam Y; Lynch, Jennifer M et al. (2013) Sodium bicarbonate causes dose-dependent increases in cerebral blood flow in infants and children with single-ventricle physiology. Pediatr Res 73:668-73
Mani, Tomoyasu; Vinogradov, Sergei A (2013) Magnetic Field Effects on Triplet-Triplet Annihilation in Solutions: Modulation of Visible/NIR Luminescence. J Phys Chem Lett 4:2799-2804

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