The overall aim of this quantitative, positron emission tomography (PET)-based, stroke outcome study on symptomatic patients with carotid occlusive vascular disease (OVD), is to determine whether patients identified in hemodynamic compromise by cerebrovascular reserve (CVR) (threshold, 10%) but with normal OEF (threshold, 50%) remain at increased risk for new clinical and magnetic resonance imaging (MRI)- based stroke. Symptomatic patients diagnosed with carotid OVD (n=150) are categorized into different stages of hemodynamic compromise by PET measurements of quantitative cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate for oxygen (CMRO2) before and after 15 mg/kg acetazolamide to obtain CVR and the oxygen extraction fraction response (OEFR). Qualitative measurements of CVR and OEF are also made by the count-rate ratio method to evaluate the accuracy of qualitative versus quanitative measures in predicting stroke risk. Baseline neurologic examination, neurologic scoring, and MRI are recorded for prestudy neurologic status and cortical and subcortical white matter infarctions. MRI and PET studies in a cohort of normal, healthy, volunteers (n=30) will be used to define the CVR and OEF thresholds to identify the different stages of hemodynamic compromise. The stages of hemodynamic compromise are as follows: Stages I and II, CVR>10%, OEF <50%;Stage Ill-acute, CVR<10% and OEF>50%;and Stage Ill-chronic, CVR<10%, OEF<50%. The different stages are also characterized by PET variables of CBF, CMRO2, OEF, CVR, and OEFR. The patients are followed for 2 years with visits every 3 months for a thorough neurologic examination and neurologic scoring i.e., NiH stroke scale (NIHSS), modified Rankin, Barthel Index and Quality of Life. Whenever a patient suffers a new clinical stroke, or at the end of the 2-year follow-up period, a second MRI is obtained and new cortical and subcortical infarcts are volumetrically quantitated. The stroke rate for patients in different stages of hemodynamic compromise is determined and compared along with the distribution of cortical, subcortical, paraventricular, and deep white matter infarctions by MRI to determine whether the patients in Stage Ill-chronic remain at risk for stroke.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS051639-05
Application #
7624996
Study Section
Special Emphasis Panel (ZRG1-BDCN-E (02))
Program Officer
Jacobs, Tom P
Project Start
2005-07-15
Project End
2011-05-31
Budget Start
2009-06-01
Budget End
2011-05-31
Support Year
5
Fiscal Year
2009
Total Cost
$288,854
Indirect Cost
Name
University of Pittsburgh
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Nemoto, Edwin; Lin, Ridwan; Uchino, Ken et al. (2018) Comparison of Quantitative and Qualitative Oxygen Extraction Fraction (OEF) in Acute Stroke Patients with Large Vessel Occlusion. Adv Exp Med Biol 1072:45-51
Dai, Xingping; Bragina, Olga; Zhang, Tongsheng et al. (2016) High Intracranial Pressure Induced Injury in the Healthy Rat Brain. Crit Care Med 44:e633-8
Nemoto, Edwin M; Bragin, Denis E; Statom, Gloria et al. (2014) Role of microvascular shunts in the loss of cerebral blood flow autoregulation. Adv Exp Med Biol 812:43-49
Carlson, Andrew; Yonas, Howard; Nemoto, Edwin M (2012) Response to Letter by Powers Regarding Article, “Failure of Cerebral Hemodynamic Selection in General or of Specific Positron Emission Tomography Methodology? Carotid Occlusion Surgery Study (COSS). Stroke 43:e44
Kaloostian, Paul; Robertson, Claudia; Gopinath, Shankar P et al. (2012) Outcome prediction within twelve hours after severe traumatic brain injury by quantitative cerebral blood flow. J Neurotrauma 29:727-34
Carlson, Andrew P; Yonas, Howard; Chang, Yue-Fang et al. (2011) Failure of cerebral hemodynamic selection in general or of specific positron emission tomography methodology?: Carotid Occlusion Surgery Study (COSS). Stroke 42:3637-9
Bragin, Denis E; Bush, Rachel C; Müller, Wolfgang S et al. (2011) High intracranial pressure effects on cerebral cortical microvascular flow in rats. J Neurotrauma 28:775-85
Uchino, Ken; Lin, Ridwan; Zaidi, Syed F et al. (2010) Increased Cerebral Oxygen Metabolism and Ischemic Stress in Subjects with Metabolic Syndrome-Associated Risk Factors: Preliminary Observations. Transl Stroke Res 1:178-183
Foley, Lesley M; Hitchens, T Kevin; Barbe, Brent et al. (2010) Quantitative temporal profiles of penumbra and infarction during permanent middle cerebral artery occlusion in rats. Transl Stroke Res 1:220-9
Kharlamov, Alexander; LaVerde, George C; Nemoto, Edwin M et al. (2009) MAP2 immunostaining in thick sections for early ischemic stroke infarct volume in non-human primate brain. J Neurosci Methods 182:205-10