Ronda R. Pindzola

Cerebrovascular Reserve in Patients With Carotid Occlusive Disease Assessed by Stable Xenon-Enhanced CT Cerebral Blood Flow and Transcranial Doppler

Background and Purpose— Cerebrovascular reserve (CVR) by both transcranial Doppler ultrasonography (TCD) and quantitative cerebral blood flow (CBF) can identify subgroups of patients at increased risk for stroke. A direct comparison of CVR measurements obtained with both technologies in patients with cerebrovascular occlusive disease is lacking. Methods— CVRs before and after acetazolamide administration (1 g IV) were measured by TCD insonation of the middle cerebral artery (MCA) and CBF obtained with stable xenon CT (Xe/CT) in 38 patients with carotid occlusive disease. Sensitivity/specificity calculations were based on 2 Xe/CT MCA values: an average over 4 levels and the level with the lowest percent change in CBF. Compromised CVR was defined as no reactivity or a decrease in reactivity. Results— Using the analysis of the systolic TCD, we found that velocity changes compared with the average Xe/CT MCA CVR showed a sensitivity of 33%, specificity of 90.6%, positive predictive value of 54.5%, and negative predictive value of 80%. The sensitivity of TCD compared with the lowest Xe/CT CBF CVR was 35.5%, specificity and positive predictive values were 100%, and negative predictive value was 66.7%. The index of validity was between 72% and 76%. Conclusions— TCD is much less sensitive than Xe/CT CBF in identifying patients with compromised CVR. This may be a result of the inability of TCD to identify patients with compromised reserves when their MCA blood flow comes from collateral sources. The lack of correlation between TCD and Xe/CT CBF for identifying patients with compromised CVR should be considered when stroke risk assessments are made by TCD.

Identification of Hemodynamic Compromise by Cerebrovascular Reserve and Oxygen Extraction Fraction in Occlusive Vascular Disease

Cerebrovascular reserve (CVR) and oxygen extraction fraction (OEF) are used to identify hemodynamic compromise in symptomatic patients with carotid occlusive vascular disease, but evidence suggests that they are not equivalent. The authors studied the relationship between CVR and OEF to evaluate their equivalence and stages of hemodynamic compromise. Symptomatic patients (N = 12) with carotid occlusion were studied by stable xenon–computed tomography CBF after intravenous acetazolamide administration for CVR, followed within 24 hours by positron emission tomography (PET) for OEF. Middle cerebral artery territories were analyzed by hemisphere and level. Hemispheric subcortical white matter infarctions were graded with magnetic resonance imaging. Both hemispheric and level analysis of CVR and OEF showed a significant (P = 0.001), negative linear relationship [CVR (%) = −1.5 (OEF) + 83.4, (r = −0.57, P = 0.001, n = 24]. However, 37.5% of the hemispheres showed compromised CVR but normal OEF and were associated (P = 0.019) with subcortical white matter infarction. CMRO2 was elevated in stage II hemodynamic compromise (CVR < 10%, OEF > 50%). CVR and OEF showed a significant negative linear relationship in stage II hemodynamic compromise but revealed hemispheres in hemodynamic compromise by CVR but normal OEF that were associated with subcortical white matter infarction.

Relationship between Cerebral Blood Flow and Clinical Outcome in Acute Stroke

Objective: The purpose of this study was to determine the relationship between cerebral blood flow (CBF) measurements in acute stroke and early clinical outcome. Material and Methods: The xenon-enhanced computed tomography (XeCT) CBF studies performed in 50 patients in the acute stage (within 8 h) of a hemispheric stroke were retrospectively analyzed. The mean CBF of the symptomatic vascular territory was compared to the corresponding territory in the contralateral hemisphere. Clinical assessment on admission and discharge was performed using the National Institutes of Health stroke scale (NIHSS). Results: Three groups were defined according to the degree of CBF asymmetry between the symptomatic and the contralateral asymptomatic vascular region. The CBF asymmetry was mild in group A (≤20%), moderate in group B (>20% and <60%) and severe in group C (≥60%). Patients in group A (n = 18) had a good outcome with a mean NIHSS score of 2 ± 2 at discharge. In group B, the patients (n = 22) had intermediate but variable outcomes: 2 patients died and the mean NIHSS score for the survivors was variable (mean NIHSS score: 9 ± 6). The patients in group C (n = 10) had a very poor outcome: 4 patients died and the survivors had a mean NIHSS score of 15 ± 1. Conclusions: Quantitative XeCT CBF measurements may be useful for selecting subgroups of stroke patients with different clinical outcomes. The possibility of predicting patient prognosis as early as in the first hours after the ischemic event may help to identify the appropriate target population that will benefit from aggressive stroke therapy.

PET OEF Reactivity for Hemodynamic Compromise in Occlusive Vascular Disease

Background and Purpose. Hemodynamic compromise in symptomatic patients with occlusive vascular disease (OVD) identified by cerebrovascular reserve (CVR) and oxygen extraction fraction (OEF) is an independent predictor of high stroke risk. However, up to 60% of patients compromised by CVR have normal OEF indicating a high rate of discordance. CVR is measured with an acetazolamide challenge, and OEF reactivity (OEFR) to acetazolamide, ie, a hemodynamic challenge, may reveal hemodynamic compromise and less discordance with measurements of CVR. Methods. Nine symptomatic patients with OVD were studied by positron emission tomography before and 15 minutes after 15 mg/kg intravenous acetazolamide in the middle cerebral artery territories of each hemisphere. Results. A close correlation between hemispheric CVR and OEFR was observed. Two hemispheres from two different patients showed an increase in OEF to acetazolamide challenge despite a normal baseline OEF. The two hemispheres showing an increase in OEF in response to acetazolamide were also associated with the lowest CVR and severest white matter hyperintensities. Conclusions. These observations suggest that positive OEFR may distinguish hemispheres in hemodynamic compromise despite normal OEF and show less discordance with CVR. However, these preliminary observations require confirmation in a larger study.

Xenon-enhanced computed tomography cerebral blood flow measurements in acute cerebral ischemia: Review of 56 cases

OBJECTIVE Ischemic stroke must be diagnosed promptly if patients are to be treated with thrombolytic therapy. The diagnosis of acute cerebral ischemia, however, is usually based on clinical and computed tomography (CT) scan findings. CT scans are often normal in the first few hours after stroke. The purpose of this study was to determine whether Xenon-enhanced CT (XeCT) cerebral blood flow (CBF) studies could increase the sensitivity of stroke detection in the acute stage. METHODS CBF studies performed within 8 hours of symptom onset were evaluated in 56 patients who presented with hemispheric stroke symptoms. Mean CBF in the symptomatic vascular territory was calculated and compared with the corresponding contralateral area. CBF values below 18 mL/100g/min on 2 adjacent regions of interest were considered ischemic lesions. CT scans and angiograms were compared with the XeCt findings. Neurological condition on admission and discharge was evaluated by using National Institutes of Health Stroke Scale (NIHSS) scores. RESULTS The mean NIHSS score on admission was 12+/-5. Early CT scans were abnormal in 28 (50%) patients. There were 9 (16%) patients who had normal XeCT scans because of spontaneous reperfusion of the ischemic area. XeCT studies showed an ischemic lesion in 47 (84%) patients. In these patients, the mean CBF in the affected vascular territory was 16+/-8 mL/100g/min compared with 35+/-13 mL/100g/min in the contralateral specular territory (P<0.001). There were no false positive or negative XeCT studies, and the location of the perfusion defect corresponded with the CT and/or angiographic findings in all cases. Eight patients died (14%), and the 48 survivors (86%) had a mean NIHSS score of 9+/-6 on discharge. CONCLUSIONS CBF measurements were correlated with the CT and angiographic results and greatly assisted in the diagnosis of acute ischemic stroke. XeCT studies used for estimating the location and extent of cerebral ischemia may be important in the triage of patients for acute stroke therapy.

The effect of reperfusion therapy on cerebral blood flow in acute stroke

The effect of reperfusion therapy on cerebral blood flow (CBF) in acute cerebral ischemia was studied using xenon-enhanced computed tomography (XeCT). The XeCT CBF studies of 10 patients were evaluated before and after thrombolytic therapy. CBF evidence of reperfusion was evaluated in relation to the angiographic results and the clinical outcomes. Six patients had occlusions of the middle cerebral artery and four of the internal carotid artery. The mean CBF of the ischemic areas before attempted reperfusion was 9 +/- 3 mL/100g/min compared with 34 +/- 9 mL/100g/min in the contralateral asymptomatic region (P<.001). Intra-arterial-thrombolysis was performed in nine patients, and in one patient the intravenous route was used. Reperfusion of the ischemic region was shown in 9 of 10 patients, both angiographically and with the XeCT CBF studies (the mean CBF increased from 9 +/- 3 mL/100g/min to 32 +/- 10 mL/100g/min, P<.001). Among the nine successfully reperfused patients, seven were neurologically improved, one was unchanged, and one died. The mean National Institutes of Health stroke scale in the eight reperfused survivors was 12 on admission and decreased to 6 on discharge. XeCT CBF measurements are correlated with the angiographic results and can assist in the understanding of the effects of thrombolytic therapy on CBF in acute stroke. Re-establishment of CBF is associated with an improved clinical outcome but exceptions can be found. Reperfusion can occur in ischemic brain regions even with very low CBF (approaching 0 mL/100g/min) although it is not associated with prevention of infarction.

Identifying regions of compromised hemodynamics in symptomatic carotid occlusion by cerebrovascular reactivity and oxygen extraction fraction

Abstract Objectives: Oxygen extraction fraction (OEF) and cerebrovascular reserve (CVR) are both proven predictors of stroke risk in symptomatic patients with carotid occlusion. Accordingly, hemispheric comparisons of CVR and OEF are significantly correlated. However, there was also substantial disagreement: hemispheres identified as compromised by CVR were normal by OEF. Our aim was to determine whether regional comparisons could resolve the CVR–OEF discordance. We also studied the relationship between white matter (WM) infarction and hemodynamic compromise. Methods: Quantitative CVR and OEF were measured in 12 symptomatic patients with internal carotid artery occlusion. CVR and OEF comparisons were made in the anterior watershed (AWS), middle cerebral artery (MCA) and WM territories using various thresholds for hemodynamic compromise. Associations with WM infarction were also recorded. Results: Comparison of CVR and OEF for the AWS and MCA showed high sensitivity (100%) with specificities of 83 and 40%, respectively. There was also agreement (k=Cohens Kappa) for the AWS (k=0.83) and MCA (k=0.39) territories. CVR–OEF discordance was reduced with regional analysis. Hemodynamic compromise was more often found in patients with WM infarction. Discussion: Regional comparison of CVR and OEF reduced the discordance compared with hemispheric analysis, especially for the AWS territory. Despite the persistence of some regions with compromised CVR and normal OEF, CVR is able to identify all regions with elevated OEF making it a useful screening technology. Future studies are needed to understand whether those remaining regions with compromised CVR are also at increased stroke risk despite normal OEF.

Differentiating Hemodynamic Compromise by the OEF Response to Acetazolamide in Occlusive Vascular Disease

Identification of increased stroke risk in a population of symptomatic patients with occlusive vascular disease (OVD) is presently accomplished by measurement of oxygen extraction fraction (OEF) or cerebrovascular reserve (CVR). However, many regions identified by compromised CVR are not identified by OEF. Our aim was to determine whether the response of OEF to acetazolamide, namely, oxygen extraction fraction response (OEFR) would identify those hemispheres in hemodynamic compromise with normal OEF. Nine patients symptomatic with transient ischemic attacks and strokes, and with occlusive vascular disease were studied. Anatomical MRI scans and T2-weighted images were used to identify and grade subcortical white matter infarcts. PET cerebral blood flow (CBF) and OEF were measured after acetazolamide. The relationship between CVR and oxygen extraction fraction response (OEFR) showed that positive OEFR occurred after acetazolamide despite normal baseline OEF values. The two hemispheres with positive OEFR were also associated with severe (> 3 cm) subcortical white matter infarcts. We found that the OEFR was highly correlated with CVR and identified hemispheres that were hemodynamically compromised despite normal baseline OEF.