Detection of Cerebral Ischemia With a Noninvasive Neurometabolic Optical Monitor

Many critically ill patients are admitted to the hospital with no infarcted brain tissue and
yet, after a period of extremely intense and expensive critical care, the patients are
discharged with new hospital-acquired dead brain tissue, with associated life-long disability
or brain death. This situation arises from the critical barrier of there being no
straightforward bedside methods to monitor cerebral blood flow (CBF) and its adequacy during
progression of post-insult secondary brain damage. This is important because of the
expectation that decrements in CBF in dangerous excess of decrements in cerebral metabolic
rate for oxygen (CMRO2), if detected early, can be treated to avert brain infarction.
Clinical examples of this issue, among many others, include post ischemic stroke edema, post
thrombolysis hyperemia or occlusion, post SAH vasospasm, hyperemic and oligemic intracranial
hypertension after traumatic brain injury or stroke, ICH associated global ischemia, and
intra and post carotid endarterectomy oligemia and hyperperfusion.

Critical care physicians need a bedside monitor of CBF coupled to CMRO2. The CMRO2 data will
allow delineation of adequacy of CBF as occasionally CBF decrements are simply matching
changes in CMRO2. The lack of such monitoring capability has resulted in clinicians making
often not helpful 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
NNOM optical techniques under development at UPenn (Dr. Arjun Yodh) which can provide
continuous bedside quantitative CBF, CMRO2 and oxygen extraction fraction (OEF) information.
Determination of capability to detect anaerobic conditions, as the investigators propose
doing, will make feasible the notion of individualized CBF, CMRO2, and OEF measurement and
brain-directed therapeutic optimization by bedside caregivers. This will eventually support a
significant change in the way Neurocritical Care is practiced, titrating therapy to
neurophysiologic rather than cardiovascular/ pulmonary endpoints. UPenn research techniques
presently provide information on relative quantitative changes in CBF and CMRO2 from
baseline. The investigators propose also developing a method for measurement of absolute CBF
and CMRO2 and further validating the absolute CBF against invasive thermodilution (ThD) CBF
techniques. The investigators' long range goal and overall objective is to prevent
in-hospital brain tissue death through development of improved bedside CBF/ CMRO2/OEF (NNOM)
monitoring techniques.

Inclusion Criteria:

Inclusion criteria will be age greater than or equal to 18 years, the diagnosis of SAH,
TBI, ICH, and/or (PIAE) after cardiac arrest (post cardiac arrest coma) with GCS less than
or equal to 8, endotracheal intubation, clinical indications for invasive Neuromonitoring,
and family/guardian informed consent.

Exclusion Criteria:

1. coagulation or platelet problems which cannot be corrected based on clinical
indications

2. anatomic abnormalities in skull or brain tissue precluding appropriate placement of an
invasive brain monitor

3. ongoing CNS or scalp infection,

4. allergy to indocyanine green dye

5. pregnancy

6. lactation or pumping breast milk for the purpose of feeding an infant

7. increased bilirubin suggestive of cholestasis or biliary obstruction, (8) allergy to
iodide

(9) severity of injury which leads the team or family to conclude that further advance
medical care would be futile and limitation of the level of support is requested.

Woman of childbearing potential will be excluded by urine or serum pregnancy test prior to
conducting any study related procedures. . There is not a risk of pregnancy during this
study as comatose patients will be monitored 24 hours a day in Intensive Care Units which
have full visibility of patients.