Hemispheric Cerebral Blood Flow Research Articles

Middle cerebral artery blood velocity during running: interactions of heart and stride impact rates

Vertical movement during running or treadmill exercise generates complex aortic blood pressure waveforms that are developed by the interactions of the cardiac and foot impact pressure pulses (>120bpm). Heart rate (HR) and stride rate (SR) can be synchronized in and out of phase with beat frequencies (difference in the HR and SR). Large variations in phasic aortic pulse pressures (40–120 mmHg) occur during running. Transcranial Doppler (TCD) measures dynamic middle cerebral artery blood velocity (CBFv), an index of hemispheric cerebral blood flow. Due to technical limitations, CBFv during running has not been reported. We hypothesized that running would significantly modulate CBFv. We used a 2 MHz TCD and a form fitting headset to minimize motion artifact in 5 healthy subjects (26 ±8SD) during: upright rest; walking (4 mph, no vertical motion); and running (7 mph, 4–5 inch vertical motion). The resting and walking waveforms were similar to reported ergometer waveforms. Running CBFv waveforms were similar to reported pressure waveforms and exhibited beat frequencies with a range of maximal and minimal CBFv. During in phase HR and SR periods, CBFv was 78±8 cm/s. Out of phase CBFv was 56±6 cm/s (p<0.05). Preliminary data suggest that CBFv is significantly modulated by the convolution of HR and SR during running. Dynamic cerebral blood flow may depend on the mode of exercise, and it could be optimized by timing of stride rate.

Effect of Combination Therapy with the Angiotensin Receptor Blocker Losartan plus Hydrochlorothiazide on Brain Perfusion in Patients with both Hypertension and Cerebral Hemodynamic Impairment due to Symptomatic Chronic Major Cerebral Artery Steno-Occlusive Disease: A SPECT Study

Background: While the combination of an angiotensin receptor blocker with thiazide diuretics produces a clinically beneficial reduction in blood pressure in patients who otherwise only partially respond to monotherapy with an angiotensin receptor blocker, blood pressure-lowering therapy with combination antihypertensive drug regimens in patients with cerebral hemodynamic impairment may adversely affect cerebral hemodynamics. The purpose of the present exploratory study was to determine whether blood pressure-lowering therapy with the combination of the angiotensin receptor blocker losartan plus hydrochlorothiazide (LPH) worsens brain perfusion in patients with both hypertension and cerebral hemodynamic impairment due to symptomatic chronic major cerebral artery steno-occlusive disease. Methods: Patients with losartan-resistant hypertension and reduced cerebrovascular reactivity (CVR) to acetazolamide due to symptomatic chronic internal carotid artery (ICA) or middle cerebral artery (MCA) steno-occlusive disease were prospectively entered into the present study and received 50 mg/day of losartan plus 12.5 mg/day of hydrochlorothiazideat 14 weeks after the last ischemic event. Cerebral blood flow (CBF) and CVR were measured before and 12 weeks after initiating LPH using N-isopropyl-p-[¹²³I]-iodoamphetamine single-photon emission computed tomography (SPECT). A region of interest (ROI) was automatically placed in the MCA territory on each SPECT image using a three-dimensional stereotactic ROI template. Results: None of the 18 patients who participated in the study experienced any new neurological symptoms or adverse effects related to antihypertensive drugs. Systolic (p < 0.001) and diastolic (p < 0.001) blood pressures were significantly reduced after the administration of LPH, with average reductions of 11 mm Hg in systolic blood pressure and 10 mm Hg in diastolic blood pressure. While in the affected hemisphere CBF did not differ between measurements taken before and after the administration of LPH, CVR was significantly higher after the administration of LPH than before (p = 0.007) and was significantly improved in 5 of 18 patients. In the contralateral hemisphere, CBF and CVR did not differ between measurements taken before and after the administration of LPH. There were no patients who experienced a significant deterioration in CBF or CVR in the affected or contralateral hemisphere after the administration of LPH. Conclusions: Although the present study was exploratory and its results were preliminary due to the small sample size, the current data suggest that blood pressure-lowering therapy with LPH apparently does not result in worsening of cerebral hemodynamics in patients with both hypertension and cerebral hemodynamic impairment due to symptomatic chronic ICA or MCA steno-occlusive disease.

Abstract 2619: Autoregulation of Cerebral Blood Flow is Preserved in Primary Intracerebral Hemorrhage

Background: Treatment of hypertension during acute intracerebral hemorrhage (ICH) is controversial. There are concerns that in the context of disrupted cerebral autoregulation, blood pressure (BP) reduction may cause decreased cerebral blood flow (CBF), particularly in the perihematoma region. CBF was assessed using serial CT perfusion (CTP) studies. We hypothesized that CBF would remain stable following BP reduction. Methods: Acute primary ICH patients were imaged pre and post BP treatment. Perfusion maps were calculated from CTP source images. Mean CBF was measured in a 1cm perihematoma region, contralateral homologous regions and in both hemispheres. Mean cerebral blood volume (CBV), mean transit time (MTT), and time to drain (TTD) were calculated in the same manner. Relative measures (i.e. rCBF) were calculated as ratios/differences between ipsilateral and contralateral regions. Results: Sixteen patients (median age 75 (54-91)) were imaged with CTP (median time from onset 19.4 (2.0-72.2) h) and re-imaged 2.0 (1.1-3.3) h later. Median NIHSS at baseline was 9 (2-24); this remained stable at the time of the second CTP (10 (2-24), P=0.14). Baseline hematoma volume was 24.8±19.9 ml and there was no change at the time of the second CTP (26.3±22.1 ml, P=0.16). Patients were recruited from an ongoing trial, in which they were randomly treated to a target systolic BP of &lt;150mmHg (n=9) or &lt;180mmHg (n=7). Four patients received no antihypertensives as BP was below target at the time of randomization. Mean systolic BP in treated patients (n=12) decreased significantly between the first (165±23 mmHg) and second (143±18 mmHg, P&lt;0.0001) CTP scans. Mean perihematoma CBF in treated patients was stable with BP reduction (pre=35.1±7.1 vs. post=35.4±6.2 ml/100g/min, P=0.87). Ipsilateral hemispheric CBF was also stable (pre=47.3±7.2 vs. post=46.4±7.1 ml/100g/min, P=0.66). Although perihematoma CBF was lower than in contralateral homologous regions (rCBF=0.72±0.11), BP reduction did not decrease this further (0.74±0.14 post-treatment, P=0.58). Ipsilateral hemispheric rCBF (0.96±0.06) was also unaffected by BP treatment (0.95±0.08, P=0.64). Perihematoma rCBF decreased in 5 treated patients, but never by &gt;12%. Linear regression showed no relationship between changes in systolic BP and perihematoma rCBF (R=-0.002, [-0.005, 0.001], P=0.18). Perihematoma rCBV (pre=0.77±0.11 vs. post=0.79±0.10, P=0.20), rMTT (pre=0.51±0.54s vs. post=0.70±0.65s, P=0.26) and rTTD (pre=0.71±1.01s vs. post=0.89±0.84s, P=0.42) also remained stable following BP treatment. Conclusions: Acute BP reduction does not appear to exacerbate perihematoma oligaemia. Stability of CBF following acute BP treatment suggests preservation of cerebral autoregulation in ICH, within the range of arterial pressures studied. These findings support the safety of early BP treatment in ICH.

Single-photon emission computed tomography quantification of cerebral blood flow before and after carotid endarterectomy

This study evaluated cerebral blood flow (CBF) by quantification and count profiles of hemispheric CBF using123I-IMP SPECT 10 days before and after surgical removal of an unilateral carotid stenosis in eight selected patients. The endarterectomized carotid artery was stenosed 35–90% in diameter, whereas the contralateral carotid artery was virtually normal. Preoperative CBF in the cerebral hemisphere was lower on the stenosed carotid artery side than on the contralateral side in seven of eight cases. After endarterectomy, hemispheric CBF increased on the operated side in six cases, and on the contralateral side in five, although to a lesser degree. The postoperative increase was prominent in cases having carotid stenosis over approximately 80%. These results indicate that the present method is useful in evaluating the intracranial hemodynamics of cases with carotid stenosis, thereby confirming that endarterectomy is effective in improving CBF in cases with a high degree of stenosis.

Metabolic Control of Resting Hemispheric Cerebral Blood Flow is Oxidative, not Glycolytic

Although the close regional coupling of resting cerebral blood flow (CBF) with both cerebral metabolic rate of oxygen (CMRO(2)) and cerebral metabolic rate of glucose (CMRglc) within individuals is well documented, there are few data regarding the coupling between whole brain flow and metabolism among different subjects. To investigate the metabolic control of resting whole brain CBF, we performed multivariate analysis of hemispheric CMRO(2), CMRglc, and other covariates as predictors of resting CBF among 23 normal humans. The univariate analysis showed that only CMRO(2) was a significant predictor of CBF. The final multivariate model contained two additional terms in addition to CMRO(2): arterial oxygen content and oxygen extraction fraction. Notably, arterial plasma glucose concentration and CMRglc were not included in the final model. Our data demonstrate that the metabolic factor controlling hemispheric CBF in the normal resting brain is CMRO(2) and that CMRglc does not make a contribution. Our findings provide evidence for compartmentalization of brain metabolism into a basal component in which CBF is coupled to oxygen metabolism and an activation component in which CBF is controlled by another mechanism.

Metabolic Control of Resting Hemispheric Cerebral Blood Flow is Oxidative, not Glycolytic

Metabolic Control of Resting Hemispheric Cerebral Blood Flow is Oxidative, not Glycolytic

L-arginine reactivity in cerebral vessels after severe traumatic brain injury

Objectives: Traumatic brain injury (TBI) causes an early reduction of cerebral blood flow (CBF). The purpose was to study cerebrovascular endothelial function by examining the reactivity of cerebral vessels to L-arginine.Methods: Fifty-one patients with severe TBI were prospectively studied by measuring cerebral hemodynamics before and after the administration of L-arginine, 300 mg/kg at 12 hours and at 48 hours after injury. These hemodynamic measurements, using transcranial Doppler techniques, included internal carotid flow volume as an estimate of hemispheric CBF, flow velocity in intracranial vessels, CO2 reactivity, and dynamic pressure autoregulation using thigh cuff deflation and carotid compression methods. Changes in the hemodynamics with L-arginine administration were analyzed using a general linear mixed model.Results: L-arginine produced no change in mean arterial pressure, intracranial pressure, or brain oxygenation. Overall, L-arginine induced an 11.3% increase in internal carotid artery flow volume (P=0.0190). This increase was larger at 48 hours than at 12 hours (P=0.0045), and tended to be larger in the less injured hemisphere at both time periods. The response of flow velocity in the intracranial vessels was similar, but smaller differences with administration of L-arginine were observed. There was a significant improvement in CO2 reactivity with L-arginine, but no change in dynamic pressure autoregulation.Discussion: The low response of the cerebral vessels to L-arginine at 12 hours post-injury with improvement at 48 hours suggests that dysfunction of cerebrovascular endothelium plays a role in the reduced CBF observed after TBI.

Effect of cilnidipine vs losartan on cerebral blood flow in hypertensive patients with a history of ischemic stroke: a randomized controlled trial

The aim of this study was to compare the effects of antihypertensive agents on cerebral blood flow (CBF) in hypertensive patients with previous ischemic stroke. In this double-blind, multi-center, non-inferiority trial, 196 patients were randomized to cilnidipine 10-20 mg or losartan 50-100 mg once daily for 4 weeks. Baseline and follow-up CBF as measured by single photon emission computed tomography were obtained in 167. The primary endpoint was the global CBF change. The secondary endpoints were the CBF change in the hemisphere ipsilateral to the index stroke, non-impairment of global CBF and blood pressure (BP) reduction. Global CBF increased significantly in the cilnidipine arm (9.0 +/- 29.6%, P = 0.0071) and the losartan arm (11.4 +/- 31.4%, P = 0.0012), and these changes were not different between the two groups (P = 0.607). However, the estimated difference in percentage global CBF change between the two groups was -2.43% (97.5% CI, -13.06% to 8.21%), which crossed the predetermined non-inferiority margin of -8.6%. Ipsilesional hemispheric CBF change, non-impairment of global CBF and BP reduction were similar in the two groups. This trial failed to prove the non-inferiority of cilnidipine to losartan regarding global CBF change. Both the treatments, however, increase the global CBF despite BP lowering.

Azelnidipine, a long-acting calcium channel blocker, could control hypertension without decreasing cerebral blood flow in post-ischemic stroke patients. A 123I-IMP SPECT follow-up study

Azelnidipine, a long-acting calcium channel blocker, is highly lipid soluble and selective for the vascular wall, and is expected to have an increasing effect on cerebral blood flow (CBF). The aim of this study is to investigate its safety and efficacy in stroke patients in the chronic stage as far as CBF is concerned using N-isopropyl-p-(123)I-iodo amphetamine ((123)I-IMP) single-photon emission computed tomography (SPECT). The patients were orally administered 8 or 16 mg of azelnidipine. Regional CBF was evaluated by (123)I-IMP SPECT using three-dimensional stereotactic region-of-interest (ROI) template (3D-SRT), a technique using anatomical standardization and ROI template consisting of 636 ROIs for the whole brain. Mean hemispheric CBF was defined as the mean value of the corpus callosum, and the precentral, central, parietal, angular and temporal gyri. Mean hemispheric and regional CBF after 1, 3 and 6 months were analyzed using a one-way repeated-measures analysis of variance. Ten post-ischemic stroke patients with hypertension were enrolled between October 2005 and October 2007, and all of them were well controlled with normal blood pressure (before: 172.3+/-16.6/88.4+/-14.0 mm Hg; 6 months: 128.7+/-15.9/70.9+/-10.1 mm Hg). No vascular events were observed during the study period. The mean hemispheric CBF was maintained during the study period (before: 46.0+/-9.7 ml per 100 g per min; 6 months: 49.3+/-11.1 ml per 100 g per min). The regional CBF was also maintained. In the chronic stage of ischemic stroke, azelnidipine could safely decrease systemic blood pressure without decreasing CBF.

Value of cerebral blood flow quantification in the diagnosis of dementia

Quantifying hemispheric cerebral blood flow (CBF) may improve diagnostic accuracy when combined with perfusion SPECT. To explore the impact of measuring mean CBF on the differential diagnosis of dementia under clinical conditions. CBF was calculated from anterior planar dynamic images acquired over 100 s after i.v. bolus injection of 550 MBq of (99m)Tc-HMPAO using Patlak linearization of normalized time-activity curves derived from right and left hemispheric, and aortic ROIs. Regional perfusion was evaluated from SPECT imaging carried out 20 min later. ANCOVA was applied to compare age-dependent differences of CBF; model differences at P<0.05 were considered significant. Study populations consisted of controls, 34 patients with no focal or vascular abnormality or mood disorder and with normal MR or CT brain images (F:M, 16:18; age+/-SD; 54.3+/-20.2 years); and patients with probable dementia comprised two subgroups. The first consisted of 33 patients with primary degenerative aetiology (PDD) (DAT or mixed-type microvascular and DAT, Lewy body and fronto-temporal atrophy), F/M; 17:16, age+/-SD; 68.4+/-8.8 years. The second subgroup consisted of 13 patients with dementia related to subcortical microvascular leuco-encephalopathy (vLEP), M/F 7:6, age+/-SD; 71.7+/-12.6 years. Classification was mainly based on clinical findings according to DMS-IV criteria, combined with follow-up or functional and anatomical imaging. Computation of CBF on 100 consecutive patients showed excellent inter-user reproducibility in trained hands (variation coefficient <5%). Mean CBF in controls showed an age dependent decrease, the first order linear regression was CBF(left)=58.9-0.2 x age (r=-0.648, P<0.001) and CBF(right)=57.9-0.02 x age (r=-0.645). In comparison to controls, a slightly more pronounced but statistically insignificant age-dependent decrease in mCBF was found in the vLEP group, CBF(left)=55.5-0.21 x age (r=-0.56) and CBF(right)=64.2-0.32 x age (r=-0.645). In the PDD group CBF, after adjusting for age, was significantly lower than control values (P<0.001); CBF(left)=37-0.025 x age and CBF(right)=39-0.057 x age. More importantly, better discrimination between PDD and controls in patients of younger age (45-65 years) was found. In older patients (65-85 years) overlap slightly increased. ROC analysis of the cohort of dement patients and controls older than 46 years revealed a 93-94% sensitivity and a specificity of 73% and 77% for the left and right hemispheres, respectively, at a CBF cut-off value of 39.5 ml.min(-1).100 g(-1). Routine quantification of mean CBF by HMPAO-RNA is a simple and reproducible method which can be easily added to the standard brain perfusion SPECT without additional cost or increasing patient's radiation burden. Combined with regional perfusion it provides an additional tool for the aetiological classification of dementia.

Hemorheological disturbances and cognitive function in patients with cerebrovascular disease

The aim of the study was to follow the relationship of the hemorheological variables with the cognitive functions in patients with ischemic cerebrovascular disease (CVD). The patient material comprised 117 patients with CVD, distributed in two main groups: 44 with transient ischemic attacks (TIAs) and 73 with chronic cerebral infarctions (CCI), 48 of them being unilateral (UCI) and 25 bilateral (BCI). Additional relative distribution according to the mean arterial blood pressure (MABP) values or to the presence of pathological asymmetries of the hemispheric cerebral blood flow (CBF) was made. The main hemorheological variables: hematocrit (Ht), fibrinogen (Fib) and plasma viscosity (PV) were examined. The cognitive functions were assessed with a psychological test battery for evaluation of the general cognitive state, the nonverbal intellect, the episodic memory, the selective attention and the executive functions. The hemorheological investigation revealed predominant increase of PV. The results of all neuropsychological tests showed significant impairment in the patients with CCI in comparison to TIAs. Fibrinogen correlated best with the psychological parameters. Its increase was associated with disturbance of the nonverbal intellect and the general cognitive capacity in the patients with CCI and BCI. In the presence of lower MABP or lack of pathological asymmetries the correlations of Fib and PV with the psychological scores predominated. The results of our study reveal distinct association between the blood rheological properties and the cognitive functions in the patients with ischemic CVD, which is probably based not only on vascular but also on other nonvascular mechanisms.

Reduced Ipsilateral Hemispheric Cerebral Blood Flow at Admission is Predictive of Vasospasm with Infarction after Aneurysmal Subarachnoid Hemorrhage

Cerebral vasospasm (CV) with infarction causes a significant degree of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). We sought to determine if reduced cerebral blood flow (CBF) on Xenon CT within 48 h of the ictus was predictive of developing CV with infarction. This is a prospective study from 1999 to 2006 of 97 patients with aSAH who underwent Xenon CT within 48 h of their bleed. Demographic, clinical, radiographic, and angiographic parameters were investigated as potential risk factors for the development of CV with infarction. A binary logistic regression analysis was performed to determine the independent predictors of this endpoint. A total of 97 patients with a mean age of 54 +/- 12 years were studied. A total of 78 (80.4%) patients presented with a Fisher grade of 3 and 51 (52.6%) patients with a Hunt Hess score >or=3. CV with infarction was found in 33 (34%) patients. In univariate modeling, younger patients with a Fisher scale of 3 or a reduced ipsilateral mean hemispheric CBF had an association with developing CV with infarction. In binary logistic regression modeling, patients with lower initial hemispheric CBF's were at a significant risk of CV with infarction in the ipsilateral hemisphere. Lower initial CBF at presentation is a risk factor for developing CV with infarction. These findings may help in early prediction of this entity and may have therapeutic implications in the future.

A flow sensitive alternating inversion recovery (FAIR)-MRI protocol to measure hemispheric cerebral blood flow in a mouse stroke model

Blood flow imaging is an important tool in cerebrovascular research. Mice are of special interest because of the potential of genetic engineering. Magnetic resonance imaging (MRI) provides three-dimensional noninvasive quantitative methods of cerebral blood flow (CBF) imaging, but these MRI techniques have not yet been validated for mice. The authors compared CBF imaging using flow sensitive alternating inversion recovery (FAIR)-MRI and 14C-Iodoantipyrine (IAP)-autoradiography in a mouse model of acute stroke. Twenty-nine male 129S6/SvEv mice were subjected to filamentous left middle cerebral artery occlusion (MCAo). CBF imaging was performed with 14C-IAP autoradiography and FAIR-MRI using two different anesthesia protocols, namely intravenous infusion of etomidate or inhalation of isoflurane, which differentially affect perfusion. Using 14C-IAP autoradiography, the average CBF in ml/(100 g ⁎min) was 160 ± 34 (isoflurane, n = 5) vs. and 59 ± 21 (etomidate, n = 7) in the intact hemisphere and 43 ± 12 (isoflurane, n = 5) vs. 36 ± 12 (etomidate, n = 7) in the MCAo hemisphere. Using FAIR-MRI, the corresponding average CBFs were 208 ± 56 (isoflurane, intact hemisphere, n = 7), 84 ± 9 (etomidate, intact hemisphere, n = 7), 72 ± 22 (isoflurane, MCAo hemisphere, n = 7) and 48 ± 13 (etomidate, MCAo hemisphere, n = 7). Regression analysis showed a strong linear correlation between CBF measured with FAIR-MRI and 14C-IAP autoradiography, and FAIR-MRI overestimated CBF compared to autoradiography. FAIR-MRI provides repetitive quantitative measurements of hemispheric CBF in a mouse model of stroke.

Comparison of arterial spin labeling and dynamic susceptibility-weighted contrast-enhanced MR imaging in brain gliomas

目的 探讨动脉质子自旋标记(ASL)与动态磁敏感对比增强(DSC)灌注技术用于脑胶质瘤分级的可行性.方法 经病理证实的28例脑胶质瘤患者,按世界卫生组织2000年规定的胶质瘤分级标准分为高级15例,低级13例.使用3.0 T MR扫描仪进行Q2TIPS的ASL检查和静脉团注钆喷替酸葡甲胺(Gd-DTPA)的DSC灌注检查.所得数据经两独立样本秩和检验分析,P＜0.05为差异有统计学意义;并用直线回归的方法分析两种灌注方法的相关性.结果 ASL法测得的脑胶质瘤血流量(TBF)/对侧脑白质相对血流量(CBF):高、低级别胶质瘤分别为(5.5±1.8)、(2.1±1.4),DSC法测得的值分别为(4.3±1.0)、(2.0±1.1),差异均有统计学意义(Z值分别为-3.824、-3.939,P＜0.01);ASL法测得的TBF/对侧半球CBF值,高、低级别胶质瘤分别为(2.2±0.8)、(0.8±0.5),DSC法测得的值分别为(2.1±0.8)、(1.0±0.6),差异均有统计学意义(Z值分别为-3.987、-3.386,P＜0.01);ASL法测得的TBF/对侧灰质CBF值,高、低级别胶质瘤分别为(1.7±0.6)、(0.7±0.5),DSC法测得值分别为(1.6±0.5)、(0.8±0.4),差异均有统计学意义(Z值分别为-3.894、-3.754,P＜0.01).两种方法测得的上述比值均密切相关(r分别为0.91、0.93、0.91,P＜0.01).结论 ASL可用于胶质瘤微血管灌注的评估,有助于区分低级别和高级别脑胶质瘤。

Structural MRI of carotid artery atherosclerotic lesion burden and characterization of hemispheric cerebral blood flow before and after carotid endarterectomy

Collateral circulation plays a major role in maintaining cerebral blood flow (CBF) in patients with internal carotid artery (ICA) stenosis. CBF can remain normal despite severe ICA stenosis, making the benefit of carotid endarterectomy (CEA) or stenting difficult to assess. Before and after surgery, we assessed CBF supplied through the ipsilateral (stenotic) or contralateral ICA individually with a novel hemisphere-selective arterial spin-labeling (ASL) perfusion MR technique. We further explored the relationship between CBF and ICA obstruction ratio (OR) acquired with a multislice black-blood imaging sequence. For patients with unilateral ICA stenosis (n = 19), conventional bilateral labeling did not reveal interhemispheric differences. With unilateral labeling, CBF in the middle cerebral artery (MCA) territory on the surgical side from the ipsilateral supply (53.7 +/- 3.3 ml/100 g/min) was lower than CBF in the contralateral MCA territory from the contralateral supply (58.5 +/- 2.7 ml/100 g/min), although not statistically significant (p = 0.09). The ipsilateral MCA territory received significant (p = 0.02) contralateral supply (7.0 +/- 2.7 ml/100 g/min), while ipsilateral supply to the contralateral side was not reciprocated. After surgery (n = 11), ipsilateral supply to the MCA territory increased from 57.3 +/- 5.7 to 67.3 +/- 5.4 ml/100 g/min (p = 0.03), and contralateral supply to the ipsilateral MCA territory decreased. The best predictor of increased CBF on the side of surgery was normalized presurgical ipsilateral supply (r(2) = 0.62, p = 0.004). OR was less predictive of change, although the change in normalized contralateral supply was negatively correlated with OR(excess) (=OR(ipsilateral) - OR(contralateral)) (r(2) = 0.58, p = 0.006). The results demonstrate the effect of carotid artery stenosis on blood supply to the cerebral hemispheres, as well as the relative role of collateral pathways before surgery and redistribution of blood flow through these pathways after surgery. Unilateral ASL may better predict hemodynamic surgical outcome (measured by improved perfusion) than ICA OR.

Clot Removal Therapy by Aspiration and Extraction for Acute Embolic Carotid Occlusion

BACKGROUND AND PURPOSE: The purpose of our retrospective study was to investigate the feasibility, safety, and efficacy of clot removal therapy by aspiration and extraction for patients with acute stroke with embolic internal carotid artery (ICA) occlusion. METHODS: Of 814 consecutive patients with acute ischemic stroke admitted to our institution from March 2003 to April 2005, clot removal therapy was performed for 14. Inclusion criteria were patients (1) presenting within 6 hours of onset of cardioembolic stroke, (2) with serious neurologic symptoms defined by a National Institutes of Health Stroke Scale (NIHSS) score of at least 11, (3) without extensive high signal intensity on diffusion-weighted MR images but with decreased ipsilateral hemispheric cerebral blood flow on perfusion-weighted images (perfusion/diffusion mismatch), and (4) with total ICA occlusion on angiograms. We removed clots by aspiration and extraction with a microsnare through either a guiding or balloon guide catheter. Radiographic results, 7-day NIHSS, 3-month modified Rankin Scale, and procedure-related complications were evaluated. RESULTS: Of 10 patients treated with the balloon guide catheter to temporarily interrupt proximal flow, 7 obtained complete or partial recanalization. The 4 patients treated with the guiding catheter had no recanalization. Of the 7 patients with recanalization, 6 had favorable 7-day neurologic and 3-month functional outcome; all showed anatomic crossflow via the anterior communicating artery. A procedure-related complication, distal embolization into the ipsilateral anterior cerebral artery, occurred in 1 patient. CONCLUSION: Balloon guide catheter-assisted clot removal therapy for embolic ICA occlusion may provide a high recanalization rate and good clinical outcome in patients with anatomic crossflow.

Intracerebral Hemorrhage after Carotid Revascularization Procedures

Carotid revascularization procedures for the prevention of acute ischemic stroke have a low but definite risk of intracerebral hemorrhage (ICH). After carotid endarterectomy (CEA) the risk is less than 1%, and accumulating data on the newer carotid angioplasty and stenting (CAS) procedure suggest a similar risk. A probably more common and underdiagnosed complication of CEA and CAS is the so-called “hyperperfusion” syndrome. A post-revascularization increase in cerebral blood flow (CBF) in the ipsilateral hemisphere is thought to underlie the pathophysiology of the syndrome. The increased unilateral hemispheric CBF leads to vasogenic edema due to re-perfusion of maximally dilated capillaries which have lost their autoregulatory capacity as a result of chronic ischemia. The clinical features of severe post-procedural hypertension followed by headache, focal neurological deficits, and seizures has an imaging correlate of unilateral hemispheric vasogenic edema in the absence of MRI features of infarction. In the absence of associated ICH, the symptoms often improve over a period of days after aggressive control of hypertension. The key to the prevention of the hyperperfusion syndrome and post-carotid revascularization ICH is close monitoring of peri-procedural blood pressure, and aggressive treatment of hypertension.

Cerebral Vasoreactivity: A Comparison of Color Velocity Imaging Quantification and Stable Xenon-Enhanced CT

Compromised cerebral vasoreactivity increases the risk of stroke. In this study, we sought to determine whether extracranial arterial blood flow volume measured on color velocity imaging quantification could be predictive of cerebral vasoreactivity after the administration of acetazolamide. Cerebral blood flow and extracranial arterial blood flow volume of 35 patients with symptomatic carotid occlusive disease were measured before and after the administration of acetazolamide on stable xenon CT and color velocity imaging quantification, respectively. The changes in unilateral extracranial arterial blood flow volume and respective hemispheric cerebral blood flow were compared. The mean difference in the percentage of change in flow volume, the 95% limit of agreement, and Cohen's kappa coefficient were calculated. A total of 64 unilateral extracranial arterial blood flow volume changes were successfully compared with the changes in the ipsilateral hemispheric cerebral blood flow. The mean difference in percentage of change in flow volume between the two techniques was 4.7%, with the 95% limit of agreement ranging from -90.2% to 99.7%. Cohen's kappa coefficient was 0.41 (95% confidence interval, 0.13-0.68; p = 0.001). The performance of color velocity imaging quantification for evaluating cerebral vasoreactivity is comparable to that of transcranial Doppler sonography. Because color velocity imaging quantification is not as limited as transcranial Doppler sonography, it could be an ideal complementary tool to transcranial Doppler sonography. More studies are required to define its clinical value.

Effect of Perindopril on Cerebral and Renal Perfusion on Normotensives in Mild Early Ischaemic Stroke: A Randomized Controlled Trial

Background and Purpose: Blood pressure reduction is central to secondary prevention after stroke, but the optimal time to start therapy is unknown. Cerebral autoregulation is impaired early after ischaemic insult, and any changes in systemic blood pressure may be reflected in cerebral perfusion. However, early initiation in hospital may better assure continued long-term treatment. We have investigated the effect of the angiotensin-converting enzyme inhibitor perindopril on blood pressure, global and focal cerebral blood flow (CBF) and glomerular filtration rate (GFR) in a normotensive acute stroke population. Methods: Twenty-five patients within 4–8 days of mild ischaemic stroke/transient ischaemic attack and with diastolic blood pressure 70–90 mm Hg were randomized to receive perindopril 2 or 4 mg daily versus placebo according to estimated GFR. Mean arterial blood pressure (MABP), internal carotid artery (ICA) flow and middle cerebral artery velocity (MCAv) were measured prior to dosing, over the following 24 h and at 2 weeks. Brain hexamethyl propylene amino oxide single photon emission computed tomography (SPECT) was performed before dosing and at estimated time of peak drug effect (6–8 h after first dose). GFR measurement using a ⁵¹Cr-ethylene diamine tetraacetic acid technique was undertaken prior to medication and repeated at 2 weeks. Results: MABP was reduced throughout the first 24 h with a mean MABP reduction of 9.3 mm Hg (95% CI 7.4–11.3 mm Hg), maximal placebo corrected fall of 12.5 mm Hg at 10 h post-dose, p = 0.005. No significant change occurred in ICA flow, MCAv or CBF measured by SPECT: change from baseline in symptomatic hemisphere CBF was –0.02 (SD 3.11) ml/100 g/min (treated group) compared with 0 (SD 3.01) (placebo group). Similarly, no significant change was observed in cortical CBF. Mean within-group change in GFR was 2.7 ± 10.1 in the treated group and –4.3 ± 6.7 in the placebo group (p = NS). Discussion: Antihypertensive therapy with perindopril may be introduced in the first week after mild ischaemic stroke in normotensive patients without affecting global or regional CBF or affecting GFR.

Intracarotid verapamil decreases both proximal and distal human cerebrovascular resistance.

The authors determined the segmental effects of intracarotid verapamil in human subjects by using a novel method of measuring proximal and distal cerebrovascular resistance. Their hypothesis was that intracarotid verapamil, a calcium channel-blocking drug that augments cerebral blood flow and reverses arterial spasm, would decrease both the proximal-conductance and the distal-arteriolar resistance. Coaxial catheters were transfemorally floated into internal carotid and middle cerebral arteries during cerebral angiography. Pressures were recorded in the femoral, internal carotid, and middle cerebral arteries. Hemispheric cerebral blood flow was measured by the intracarotid Xe injection technique. Cerebrovascular resistance was measured for the proximal and distal arteries. Cerebral blood flow and hemodynamic data were recorded during intracarotid infusion of saline and verapamil (1 mg/min) for 5 min. Transcranial Doppler blood flow velocity in the middle cerebral artery was also recorded. Intracarotid verapamil increased in 133Xe cerebral blood flow from 43 +/- 11 to 59 +/- 11 ml.100 g(-1).min(-1) (P = 0.001; n = 9). The cerebrovascular resistance measured for the proximal and distal arteries decreased from 0.17 +/- 0.95 to 0.12 +/- 0.75 and from 1.63 +/- 0.78 to 1.03 +/- 0.33 mmHg.ml(-1).100 g(-1).min(-1) (P < 0.01), respectively. The calculated proximal-conductive and distal-arteriolar (pial plus parenchymal) resistances showed a similar decrease. Transcranial Doppler measurements (n = 5) underestimated the effects of intracarotid verapamil that were consistent with an increase in middle cerebral artery diameter. Intracarotid verapamil decreases both the proximal-conductance and the distal-arteriolar resistance. Furthermore, it is feasible to investigate segmental effects of drugs in human subjects by measuring changes in pressure gradients within the cerebral arteries and simultaneous Xe cerebral blood flow measurements.