Critical care physician's need a bedside cerebral blood flow monitor (CBF) coupled to cerebral metabolic rate for oxygen (CMRO2). In the context of time-sensitive intolerance of the brain to ischemia/hypoxia management of critically ill patients with neurovascular pathophysiology has always been hindered by inability to easily, repeatedly, and noninvasively, at the bedside~ determine CBF and CMRO2 to facilitate fast diagnosis of ischemia. Many surrogates for this exist. None are satisfactory. Several additional methods require transport of the patient to an imaging suite and thus are not true monitors with added risk of transport. This has resulted in clinicians making therapeutic decisions directed to non-neurologic endpoints, e.g., blood pressure, PaCO2 and so on, "hoping" that such interventions will have a desired effect on brain perfusion and metabolism. Diffuse Correlation Spectroscopy(DCS) and diffuse optical spectroscopy(DOS) are promising optical techniques under development at UPenn which can provide continuous quantitative rCBF,rCMRO2 and oxygen extraction fraction (OEF) information, respectively, with new technology available to provide for continuous absolute measures of CBF, CMRO2, and OEF. Our long range goal is to prevent the development of in-hospital brain tissue death through development of improved bedside CBF/CMR monitoring techniques that will enable implementation of individualized therapy to prevent such adverse outcomes with their attendant long term disabilities.
Our specific aims are to test the hypotheses in neuroICU patients that: 1. Optical monitoring of cortical rCBF indicates subcortical tissue CBF 2. Optical monitoring techniques can detect anaerobic CBF thresholds 3. Optical monitoring techniques can predict anaerobic brain ischemia Noninvasive optical monitoring detection of anaerobic conditions will be confirmed with invasive microdialysis and PbrO2 and low CBF will be confirmed with invasive thermodilution CBF Using invasive monitors as the gold standard for anaerobic ischemia, sensitivity/specificity and pattern analyses will be performed for noninvasive detection and prediction of anaerobic ischemia with optical monitoring. The proposed research will make feasible the notion of protocolized yet individualized goal-directed titration of physiologic and pharmacologic therapy to prevent new brain tissue death in patients admitted with ischemic stroke, intracerebral hemorrhage, subdural hemorrhage, subarachnoid hemorrhage, and traumatic brain injury. These diseases constitute the leading causes of disability in the United States.

Public Health Relevance

The goals of this project are to evaluate a noninvasive monitor of brain metabolism and blood flow in critically ill humans. If validated, such a reliabl noninvasive brain blood flow and metabolism monitor, by allowing physiologic and pharmacologic decisions based on real-time brain physiology, potentially will become an important tool for clinicians in their efforts to prevent additional brain tissue death in patients admitted with stroke, brain hemorrhage, and traumatic brain injury. These diseases constitute the leading cause of disability in the United States.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS082309-01A1
Application #
8696339
Study Section
Acute Neural Injury and Epilepsy Study Section (ANIE)
Program Officer
Hirtz, Deborah G
Project Start
2014-03-15
Project End
2019-02-28
Budget Start
2014-03-15
Budget End
2015-02-28
Support Year
1
Fiscal Year
2014
Total Cost
$442,472
Indirect Cost
$63,194
Name
University of Pennsylvania
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104