in ischemic stroke patients with > 70% stenosis of the internal carotid artery ( ica ) or middle cerebral artery ( mca ) , the risk of recurrent stroke is high , and stent placement is considered to decrease the risk of further ischemic events . cerebrovascular reserve ( cvr ) , defined as the increase in cbf in response to a vasodilatory stimulus , is known to reflect the capacity of the brain to maintain adequate blood flow in the face of decreased perfusion due to arterial stenosis . cvr has been identified as a predictor of ischemic stroke , but it is currently unclear whether the degree of stenosis or the cvr is a better predictor of ischemic stroke . cvr can be measured by perfusion computed tomography ( ct ) with inhalation of co2 . the aim of this study was to measure cvr by perfusion ct with inhalation of co2 , and to determine whether cvr is a better predictor of stroke than the degree of stenosis of the ica or mca . this study analyzed 37 patients who were treated at capital medical university affiliated beijing chaoyang hospital between march 2006 and july 2009 . the inclusion criteria were : age 2580 years ; ica or mca stenosis or occlusion ; cerebral angiography performed ; and medical treatment only without stent placement , endarterectomy , or bypass surgery . patients were excluded if they had evidence of infarction in the territory of a stenosed or occluded ica or mca . the patients were 27 men and 10 women with a mean age of 58.011.9 years ( range 2576 years ) . all patients were initially treated for ipsilateral ischemic events , including transient ischemic attacks in 21 patients and minor completed ischemic strokes in 16 patients . all 37 patients underwent cerebral angiography , which showed ica occlusion in 7 patients , mca occlusion in 3 patients , and 3095% stenosis of the ica or mca in the remaining patients . ct and fluid - attenuated inversion - recovery magnetic resonance imaging ( mri ) showed no evidence of infarction in the territories of the stenosed or occluded arteries . the study protocol was approved by our institute s committee on human research and written informed consent was obtained from every participant . patients were divided into groups according to the degree of stenosis : 7099% stenosis or occlusion ( stenosis 1 ) or 3069% stenosis ( stenosis 2 ) ; and according to cvr : 10% cvr ( cvr 1 ) or < 10% cvr ( cvr 2 ) . cerebrovascular reserve was measured using 16-detector row dynamic ct with inhalation of 5% co2 and 95% o2 ( carbogen ) . patients wore a face mask that was connected to a gas bag with a one - way valve , which was connected to a humidification bottle and then to a 2-l steel 10-kpa carbogen bottle . the gas flow varied from 4 to 10 l / min to ensure that the patient was able to breathe comfortably . the face mask and head of the patient were fixed to the scan bed to avoid movement of the head . inhalation of carbogen started 20 min later , followed by a second dynamic ct scan . two axial slices ( thickness 10 mm ) were selected : 1 through the basal ganglia and 1 through the corona radiata . nonionic contrast agent ( 40 ml ) was administered at a constant rate of 6 ml / s via an antecubital vein using a power injector . for each of the mca territory sections studied , an experienced neuroradiologist manually marked regions of interest on the cerebral blood flow ( cbf ) map over the parietal cortical gray matter of the expected territory of the mca bilaterally . cvr was calculated according to the formula : all patients received medical treatment and were followed up at the outpatient clinic or by telephone . the clinical background characteristics were compared between groups using the independent samples t test or pearson s chi - square test . the rate of ischemic stroke was compared between groups using pearson s chi - square test . this study analyzed 37 patients who were treated at capital medical university affiliated beijing chaoyang hospital between march 2006 and july 2009 . the inclusion criteria were : age 2580 years ; ica or mca stenosis or occlusion ; cerebral angiography performed ; and medical treatment only without stent placement , endarterectomy , or bypass surgery . patients were excluded if they had evidence of infarction in the territory of a stenosed or occluded ica or mca . the patients were 27 men and 10 women with a mean age of 58.011.9 years ( range 2576 years ) . all patients were initially treated for ipsilateral ischemic events , including transient ischemic attacks in 21 patients and minor completed ischemic strokes in 16 patients . all 37 patients underwent cerebral angiography , which showed ica occlusion in 7 patients , mca occlusion in 3 patients , and 3095% stenosis of the ica or mca in the remaining patients . ct and fluid - attenuated inversion - recovery magnetic resonance imaging ( mri ) showed no evidence of infarction in the territories of the stenosed or occluded arteries . the study protocol was approved by our institute s committee on human research and written informed consent was obtained from every participant . patients were divided into groups according to the degree of stenosis : 7099% stenosis or occlusion ( stenosis 1 ) or 3069% stenosis ( stenosis 2 ) ; and according to cvr : 10% cvr ( cvr 1 ) or < 10% cvr ( cvr 2 ) . cerebrovascular reserve was measured using 16-detector row dynamic ct with inhalation of 5% co2 and 95% o2 ( carbogen ) . patients wore a face mask that was connected to a gas bag with a one - way valve , which was connected to a humidification bottle and then to a 2-l steel 10-kpa carbogen bottle . the gas flow varied from 4 to 10 l / min to ensure that the patient was able to breathe comfortably . the face mask and head of the patient were fixed to the scan bed to avoid movement of the head . inhalation of carbogen started 20 min later , followed by a second dynamic ct scan . two axial slices ( thickness 10 mm ) were selected : 1 through the basal ganglia and 1 through the corona radiata . nonionic contrast agent ( 40 ml ) was administered at a constant rate of 6 ml / s via an antecubital vein using a power injector . for each of the mca territory sections studied , an experienced neuroradiologist manually marked regions of interest on the cerebral blood flow ( cbf ) map over the parietal cortical gray matter of the expected territory of the mca bilaterally all patients received medical treatment and were followed up at the outpatient clinic or by telephone . the clinical background characteristics were compared between groups using the independent samples t test or pearson s chi - square test . the rate of ischemic stroke was compared between groups using pearson s chi - square test . eighteen of the 37 patients had 70% stenosis ( stenosis group 1 ) and 19 had < 70% stenosis ( stenosis group 2 ) . nineteen patients had 10% cvr ( cvr group 1 ) and 18 had < 10% cvr ( cvr group 2 ) ( table 1 ) . comparisons of the clinical background characteristics between groups using the independent samples t test or pearson s chi - square test did not show any significant differences between groups divided according to the degree of stenosis or the cvr ( all p>0.05 ; table 1 ) . during an average follow - up period of 56.9 months ( range 2473 months ) , ischemic stroke occurred in 7 of the 37 patients . ischemic stroke occurred in 0 of 19 patients in cvr group 1 ( annual risk 0% ) , 7 of 18 patients in cvr group 2 ( annual risk 7.7% ) , 3 of 18 patients in stenosis group 1 ( annual risk 3.3% ) , and 4 of 19 patients in stenosis group 2 ( annual risk 4.7% ) . comparisons using pearson s chi - square test showed a significant difference in the rate of ischemic stroke between cvr group 1 and cvr group 2 [ odds ratio ( or ) 1.700 ; 95% confidence interval 1.1422.530 ; p=0.003 ] . there was no significant difference in the rate of ischemic stroke between stenosis group 1 and stenosis group 2 ( p=0.691 ; table 1 ) . one was a 52-year - old male with < 70% stenosis ( ica 50% stenosis ) and < 10% cvr ( -5% ) who died of acute myocardial infarction after 69 months , and the other was a 69-year - old male with < 70% stenosis ( ica 40% stenosis and tandem mca stenosis 50% ) and 10% cvr ( 20% ) who died of heart failure after 24 months . eighteen of the 37 patients had 70% stenosis ( stenosis group 1 ) and 19 had < 70% stenosis ( stenosis group 2 ) . nineteen patients had 10% cvr ( cvr group 1 ) and 18 had < 10% cvr ( cvr group 2 ) ( table 1 ) . comparisons of the clinical background characteristics between groups using the independent samples t test or pearson s chi - square test did not show any significant differences between groups divided according to the degree of stenosis or the cvr ( all p>0.05 ; table 1 ) . during an average follow - up period of 56.9 months ( range 2473 months ) , ischemic stroke occurred in 7 of the 37 patients . ischemic stroke occurred in 0 of 19 patients in cvr group 1 ( annual risk 0% ) , 7 of 18 patients in cvr group 2 ( annual risk 7.7% ) , 3 of 18 patients in stenosis group 1 ( annual risk 3.3% ) , and 4 of 19 patients in stenosis group 2 ( annual risk 4.7% ) . comparisons using pearson s chi - square test showed a significant difference in the rate of ischemic stroke between cvr group 1 and cvr group 2 [ odds ratio ( or ) 1.700 ; 95% confidence interval 1.1422.530 ; p=0.003 ] . there was no significant difference in the rate of ischemic stroke between stenosis group 1 and stenosis group 2 ( p=0.691 ; table 1 ) . one was a 52-year - old male with < 70% stenosis ( ica 50% stenosis ) and < 10% cvr ( -5% ) who died of acute myocardial infarction after 69 months , and the other was a 69-year - old male with < 70% stenosis ( ica 40% stenosis and tandem mca stenosis 50% ) and 10% cvr ( 20% ) who died of heart failure after 24 months . patients with 70% symptomatic stenosis of the ica or mca are considered to have a high risk of ischemic stroke [ 46 ] , and are often treated by arterial stenting . however , it has been reported that not all patients with 70% stenosis have an increased risk of stroke . scott et al .   reported that patients with 9099% stenosis have a relatively low risk of stroke . domenico et al .   reported a similar phenomenon in patients with symptomatic ica stenosis of 9599% . it seems that the risk of stroke risk does not always increase as the degree of stenosis increases , but the reason for this is unknown . there is increasing evidence suggesting that cvr may be an independent predictor of stroke in symptomatic patients with large cerebral artery stenosis or occlusion [ 2,912 ] , although some studies have reported conflicting results   ( table 2 ) . a meta - analysis found that impairment of cvr was strongly associated with an increased risk of ischemic events in patients with carotid artery stenosis or occlusion ( or 3.86 ) . another meta - analysis found that impairment of cvr was associated with an increased risk of stroke in asymptomatic patients ( or 6.14 ) . the results of this study show that impairment of cvr was associated with an increased risk of stroke ( or 1.70 ) , and that stenosis of 70% was not associated with a higher risk of stroke than stenosis of < 70% . research reported that 20% future strokes are not related to ica stenosis in patients with ica stenosis of 70% . embolism formation is associated with vulnerable atherosclerotic plaque , which is not necessarily associated with the degree of stenosis . detachment of the embolism may result in dilation of the arteriole , which affects cvr . in a stenosed artery , the degree of stenosis affects flow , but reduced flow may also result in formation of collateral circulation . the degree of stenosis is not necessarily well correlated with perfusion , such as in a patient with severe stenosis of the ica but abundant collateral circulation in the temporal lobe . when measuring cvr , there are 2 methods of inducing cerebral vasodilation : inhalation of co2 or injection of acetazolamide . the increase in cbf after inhalation of co2 may result from vasodilatation secondary to extracellular and intracellular acidification of vascular smooth muscle cells , or from neurogenic mechanisms via stimulation of the vasomotor center of the brain stem . acetazolamide selectively inhibits carbonic anhydrase in erythrocytes , glial cells , capillary endothelium , and the choroid plexus ; and induces extracellular acidosis of vascular smooth muscle cells , resulting in vasodilation . although there may be differences in the mechanisms underlying these 2 methods , they are both widely used in clinical practice [ 2,914 ] , and long - term cvr follow - up studies using these methods have reported similar results ( table 2 ) [ 2,912 ] . why did we choose 10% as a cut - off point to divide cvr groups ? to the best of our knowledge , no prospective studies assessing cvr impairment and stroke risk have been performed with perfusion ct . a study using single - photon emission ct and acetazolamide to measure cvr , and adopting 11% as a cut - off point to divide cvr groups , reported a positive result ; therefore , we tried 10% as a cut - off point to divide cvr groups and obtained satisfactory results . this study included 10 patients with ica or mca occlusion , of which 1 patient ( cvr 5% ) had a recurrent stroke . the other 9 patients ( cvr 49% , 19% , 12% , 4% , 5% , 19% , 34% , 92% , and 11% ) did not develop tia or recurrence of stroke during the follow - up period . one was a 52-year - old male with 50% ica stenosis and 5% cvr who died of acute myocardial infarction ( ami ) 69 months later . this man did not have heart disease or diabetes mellitus history , but did have hypertension , lipid metabolism disturbance , and smoking history , as well as ica - unstable atherosclerosis plaque ( 2.6-mm thick ) . the other patient was a 69-year - old male with ica 40% stenosis , tandem mca stenosis 50% and 20% cvr , who died of heart failure 24 month later . this man did not have heart disease or smoking history , but had hypertension , lipid metabolism disturbance , and diabetes mellitus history , as well as ica unstable atherosclerosis plaque ( 3.6-mm thick ) . firstly , the cbf recorded in this study was 91.737.5 ml/100 g / min , which is higher than previously reported values . the cbf in the parietal cortex was previously reported be 72.08.5 ml/100 g / min in healthy individuals . this difference may be because the measured cbf is higher on perfusion ct than on positron emission tomography . secondly , this was a single - center study with a small sample , and multiple large - sample studies are needed to confirm this result . cerebrovascular reserve may be a more accurate predictor of stroke than degree of ica or mca stenosis . in clinical practice , when screening patients for stent placement to prevent future stroke , cvr should be considered because it may be more important than ica or mca stenosis degree .
backgroundit is currently unclear whether the degree of stenosis or the cerebrovascular reserve ( cvr ) is a better predictor of ischemic stroke.material/methodsin this study , cvr was measured by perfusion computed tomography with inhalation of 5% co2 in 37 symptomatic patients with internal carotid artery ( ica ) or middle cerebral artery ( mca ) stenosis or occlusion . 
 patients were divided into groups according to the degree of stenosis : 70% stenosis ( stenosis group 1 ) or < 70% stenosis ( stenosis group 2 ) ; and according to cvr : 10% cvr ( cvr group 1 ) or < 10% cvr ( cvr group 2 ) . 
 all patients were given medical treatment.resultsduring a mean follow - up period of 56.9 months ( range 2473 months ) , recurrent ipsilateral ischemic stroke occurred in 7 patients . 
 ischemic stroke occurred in 0 of 19 patients in cvr group 1 ( annual risk 0% ) , 7 of 18 patients in cvr group 2 ( annual risk 7.7% ) , 3 of 18 patients in stenosis group 1 ( annual risk 3.3% ) , and 4 of 19 patients in stenosis group 2 ( annual risk 4.7% ) . 
 comparisons using pearson s chi - square test showed a significant difference in the rate of ischemic stroke between cvr group 1 and cvr group 2 ( odds ratio 1.700 ; 95% confidence interval 1.1422.530 ; p=0.003 ) , but no significant difference between stenosis group 1 and stenosis group 2 ( p=0.691).conclusionscerebrovascular reserve may be a more accurate predictor of stroke than degree of ica or mca stenosis .