Major Cerebral Artery Occlusive Disease Research Articles

Quantitative cerebral perfusion assessment using microscope-integrated analysis of intraoperative indocyanine green fluorescence angiography versus positron emission tomography in superficial temporal artery to middle cerebral artery anastomosis.

Background:Intraoperative qualitative indocyanine green (ICG) angiography has been used in cerebrovascular surgery. Hyperperfusion may lead to neurological complications after superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis. The purpose of this study is to quantitatively evaluate intraoperative cerebral perfusion using microscope-integrated dynamic ICG fluorescence analysis, and to assess whether this value predicts hyperperfusion syndrome (HPS) after STA-MCA anastomosis.Methods:Ten patients undergoing STA-MCA anastomosis due to unilateral major cerebral artery occlusive disease were included. Ten patients with normal cerebral perfusion served as controls. The ICG transit curve from six regions of interest (ROIs) on the cortex, corresponding to ROIs on positron emission tomography (PET) study, was recorded. Maximum intensity (IMAX), cerebral blood flow index (CBFi), rise time (RT), and time to peak (TTP) were evaluated.Results:RT/TTP, but not IMAX or CBFi, could differentiate between control and study subjects. RT/TTP correlated (|r| = 0.534-0.807; P < 0.01) with mean transit time (MTT)/MTT ratio in the ipsilateral to contralateral hemisphere by PET study. Bland–Altman analysis showed a wide limit of agreement between RT and MTT and between TTP and MTT. The ratio of RT before and after bypass procedures was significantly lower in patients with postoperative HPS than in patients without postoperative HPS (0.60 ± 0.032 and 0.80 ± 0.056, respectively; P = 0.017). The ratio of TTP was also significantly lower in patients with postoperative HPS than in patients without postoperative HPS (0.64 ± 0.081 and 0.85 ± 0.095, respectively; P = 0.017).Conclusions:Time-dependent intraoperative parameters from the ICG transit curve provide quantitative information regarding cerebral circulation time with quality and utility comparable to information obtained by PET. These parameters may help predict the occurrence of postoperative HPS.

Quantitative assessment of cerebral hemodynamics using single photon emission computed tomography with venous blood sampling

ObjectiveQuantitative cerebral blood flow (CBF) measured by single photon emission computed tomography (SPECT) with arterial blood sampling is one of the most reliable methods to assess the hemodynamics in individual patients. SPECT with venous blood sampling is less invasive. The present study compared the measurement of CBF using N-isopropyl-p-(iodine-123)-iodoamphetamine SPECT with venous blood sampling and with arterial blood sampling in patients with major cerebral artery occlusive disease. MethodsTwo normal subjects and 14 patients with major cerebral artery occlusive disease underwent SPECT with arterial and venous blood sampling. The microsphere method was used for quantitative SPECT imaging. Whole brain radioactivity was corrected when the detectors rotated in the forward direction (F1–F7). Venous sampling was performed 30min after radiotracer injection. Arterial blood radioactivity was estimated by multiple regression analysis from these parameters. The cerebrovascular reactivity to acetazolamide was also measured. ResultsMultiple regression analysis established the following formula:Ca10=−1.099F1+1.629F2−2.143F3−2.766F4−1.208F5+2.113F6+3.259F7+1.241Cv30+94.958(where Ca10 is the arterial blood radioactivity at 10min, F1–F7 are the whole brain radioactivity in the forward direction, Cv30 is the venous blood radioactivity at 30min).Mean CBF values were 32.2±6.6ml/100g/min for measured arterial radioactivity and 42.2±7.8ml/100g/min for calculated arterial radioactivity based on venous radioactivity. ConclusionsThe present modified method of calculating quantitative CBF from whole brain and venous blood radioactivities correlated well with values determined with arterial blood radioactivity.

Accuracy of Central Benzodiazepine Receptor Binding Potential/Cerebral Blood Flow SPECT Imaging for Detecting Misery Perfusion in Patients With Unilateral Major Cerebral Artery Occlusive Diseases

The aim of the present study was to determine whether central benzodiazepine receptor binding potential (BRBP)/cerebral blood flow (CBF) or a combination of CBF and cerebrovascular reactivity (CVR) to acetazolamide on single-photon emission computed tomography (SPECT) more accurately detects misery perfusion, indicating elevation of absolute value of oxygen extraction fraction (OEF) on positron emission tomography (PET), in patients with unilateral major cerebral artery occlusive diseases. In 84 patients, OEF, CBF, CVR to acetazolamide, and BRBP were assessed using ¹⁵O-PET and N-isopropyl-p-[¹²³I]-iodoamphetamine and [¹²³I]-iomazenil SPECT, respectively. A region of interest was automatically placed in the middle cerebral artery territory using a 3-dimensional stereotactic region of interest template. Sensitivity, specificity, and positive and negative predictive values for the affected side-to-contralateral side asymmetry on SPECT-BRBP/CBF to detect the abnormally elevated PET-OEF in the affected hemisphere were 100%, 86.4%, 66.7%, and 100%, respectively. Area under the receiver operating characteristic curve in detecting the abnormally elevated PET-OEF in the affected hemisphere did not differ between analysis of the combination of SPECT-CBF and SPECT-CVR in the affected hemisphere (0.89; 95% confidence interval, 0.80-0.94) and that of the affected side-to-contralateral side asymmetry on SPECT-BRBP/CBF (0.93; 95% confidence interval, 0.86-0.97). The combination of the 3 detected abnormally elevated PET-OEF with 97.0% specificity and 90.0% positive predictive value. The accuracy of central BRBP/CBF asymmetry on SPECT is equivalent to that of the combination of CBF and CVR to acetazolamide on SPECT for detecting misery perfusion in patients with unilateral major cerebral artery occlusive disease.

Comparison of early and late images on 123I-iomazenil SPECT with cerebral blood flow and oxygen extraction fraction images on PET in the cerebral cortex of patients with chronic unilateral major cerebral artery occlusive disease

The aim of the present study was to determine whether early and late/early images on 123I-iomazenil (IMZ) single-photon emission computed tomography (SPECT) correlate with cerebral blood flow (CBF) images and oxygen extraction fraction (OEF) images on PET, respectively, in the cerebral cortex of patients with chronic unilateral middle cerebral artery or internal carotid artery occlusive disease. In 20 normal individuals and in 68 patients, CBF and OEF were assessed using 15O-PET, and brain SPECT scans were initiated immediately after (early images) and 180 min after (late images) the administration of 123I-IMZ. A region of interest was automatically placed in the middle cerebral artery territory in both cerebral hemispheres using a three-dimensional stereotaxic region of interest template, and the ratio of the value in the affected side to that in the contralateral side was calculated in each image. Among patients, a significant positive correlation was observed between PET-CBF ratios and the SPECT-early IMZ ratios (r=0.797, P<0.0001) as well as between the PET-OEF ratios and the SPECT-late/early IMZ ratios (r=0.679, P<0.0001). When an abnormally elevated PET-OEF ratio was defined as a value greater than the mean+2 SD obtained in normal participants, the SPECT-late/early IMZ ratios yielded 100% sensitivity and 93% specificity, with 76% positive-predictive and 100% negative-predictive values for detecting abnormally elevated PET-OEF ratios. Early and late/early images on 123I-IMZ SPECT correlate with CBF images and OEF images on PET, respectively, in the cerebral cortex of patients with chronic unilateral major cerebral artery occlusive disease.

Preoperative Central Benzodiazepine Receptor Binding Potential and Cerebral Blood Flow Images on SPECT Predict Development of New Cerebral Ischemic Events and Cerebral Hyperperfusion After Carotid Endarterectomy

Risk factors for cerebrovascular complications developing during or after carotid endarterectomy (CEA) include preoperative impairments in cerebral hemodynamics, as detected by the demonstration of decreased cerebrovascular reactivity (CVR) to acetazolamide on brain perfusion SPECT. Central benzodiazepine receptor binding potential (CBRBP) and cerebral blood flow (CBF) images on SPECT provide high sensitivity and high specificity for detecting misery perfusion in patients with chronic unilateral major cerebral artery occlusive disease. The aim of the present study was to determine whether preoperative CBRBP/CBF images on SPECT could identify patients at risk for new cerebral ischemic events, including neurologic deficits and cerebral ischemic lesions on diffusion-weighted MRI, or cerebral hyperperfusion after CEA and to compare the predictive accuracy of CBRBP/CBF with that of CVR to acetazolamide on SPECT. CBF, CVR, and CBRBP were assessed using N-isopropyl-p-(123)I-iodoamphetamine ((123)I-IMP) and (123)I-iomazenil SPECT before CEA in 112 patients with unilateral internal carotid artery stenosis (≥ 70%). CBF measurement using (123)I-IMP SPECT was also performed immediately and 3 d after CEA. A region of interest was automatically placed in the middle cerebral artery territory in both cerebral hemispheres using a 3-dimensional stereotactic region-of-interest template. Diffusion-weighted MRI was performed within 3 d before and 24 h after surgery. A preoperative increase in the affected side-to-contralateral side asymmetry on CBRBP/CBF value was the only significant independent predictor of postoperative new cerebral ischemic events (95% confidence intervals [CI], 1.145-1.608; P = 0.0004) or post-CEA hyperperfusion (95% CI, 1.244-2.252; P = 0.0007). There was no difference in the ability to predict post-CEA hyperperfusion when comparing the area under the receiver-operating-characteristic curve of the affected side-to-contralateral side asymmetry on CBRBP/CBF and that of the CVR in the affected hemisphere. However, the former value (0.924; 95% CI, 0.854-0.972) was significantly greater than the latter value (0.782; 95% CI, 0.697-0.852) for the prediction of new postoperative cerebral ischemic events (P < 0.05). Preoperative CBRBP/CBF images on SPECT can more accurately identify patients at risk for cerebrovascular complications occurring during or after CEA when compared with preoperative CVR to acetazolamide.

Central Benzodiazepine Receptor Binding Potential and CBF Images on SPECT Correlate with Oxygen Extraction Fraction Images on PET in the Cerebral Cortex with Unilateral Major Cerebral Artery Occlusive Disease

Oxygen extraction fraction (OEF) is a key predictor of stroke recurrence in patients with symptomatic major cerebral arterial occlusive disease. The purpose of the present study was to compare central benzodiazepine receptor binding potential (BRBP) and cerebral blood flow (CBF) images on SPECT with OEF images on PET in patients with chronic unilateral middle cerebral artery (MCA) or internal carotid artery (ICA) occlusive disease. OEF, CBF, and BRBP were assessed using (15)O PET and N-isopropyl-p-(123)I-iodoamphetamine and (123)I-iomazenil SPECT, respectively, in 20 healthy subjects and in 34 patients with unilateral MCA or ICA occlusive disease. All images were transformed into the standard brain size and shape by linear and nonlinear transformation using statistical parametric mapping for anatomic standardization. A region of interest (ROI) was automatically placed according to the arterial supply using a 3-dimensional stereotactic ROI template, and the ratio of the value in the affected side to that in the contralateral side was calculated in each image. Among patients with occlusive disease, a significant positive correlation was observed between PET OEF and SPECT BRBP/CBF ratios in 3 cerebral cortical regions (r = 0.851, P < 0.0001, for anterior cerebral artery [ACA] ROI; r = 0.807, P < 0.0001, for MCA ROI; and r = 0.774, P < 0.0001, for posterior cerebral artery [PCA] ROI), but there were no correlations between these 2 parameters in the basal ganglia or the cerebellum. When an abnormally elevated PET OEF ratio was defined as a value greater than the mean + 2 SDs obtained in healthy subjects, sensitivity and specificity were, respectively, 100% and 96% for the ACA ROI, 100% and 89% for the MCA ROI, and 100% and 93% for the PCA ROI for the SPECT BRBP/CBF ratio for detecting an abnormally elevated PET OEF ratio. BRBP/CBF images on SPECT correlate with OEF images on PET in a specific clinical setting-that is, in the cerebral cortex of patients with chronic unilateral MCA or ICA occlusive disease.

Feasibility of 62Cu-ATSM PET for evaluation of brain ischaemia and misery perfusion in patients with cerebrovascular disease

[(62)Cu]Diacetyl-bis(N (4)-methylthiosemicarbazone) ((62)Cu-ATSM) was used to evaluate brain haemodynamic impairment in patients with cerebrovascular disease (CVD) as a simplified evaluation method. The tracer distribution was compared with haemodynamic parameters obtained by (15)O positron emission tomography (PET). Ten patients with major cerebral arterial occlusive disease (aged 66 ± 7 years) underwent PET with (62)Cu-ATSM and (15)O tracers ((15)O-water, (15)O(2) and C(15)O). Seven healthy volunteers also underwent (62)Cu-ATSM PET as normal controls. After the injection of (62)Cu-ATSM, 20-min dynamic PET data acquisition was started. Early- and delayed-phase images of (62)Cu-ATSM were obtained by averaging the initial 3-min and the last 10-min frame data, which were used for perfusion and retention images. Cerebral blood flow (CBF), blood volume, metabolic rate of oxygen (CMRO(2)) and oxygen extraction fraction (OEF) were measured by (15)O-gas and water studies and compared with early- and delayed-phase (62)Cu-ATSM images and delayed to early (D/E) ratio. Regional values were compared after all parametric images were coregistered to individual MRI. The asymmetry index (AI) was also calculated for OEF and Cu-ATSM D/E ratio, and diagnostic ability for detecting misery perfusion was compared. In the affected hemisphere of the patients, the mean values of haemodynamic parameters were CBF = 33.8 ± 5.9 ml/100 g per min, CMRO(2) = 2.6 ± 0.3 ml/100 g per min and OEF = 48 ± 7%. Standardized uptake values (SUVs) for (62)Cu-ATSM in early and delayed phases were 2.00 ± 0.13 and 1.04 ± 0.09 in the ipsilateral hemisphere and 2.13 ± 0.14 and 1.04 ± 0.08 in the contralateral hemisphere, respectively. The early-phase (62)Cu-ATSM images corresponded well to CBF images, and the D/E ratio images were similar to OEF images. Regional values obtained from D/E ratio images were significantly correlated with regional OEF. AIs of OEF and D/E ratio showed a significant correlation and diagnostic ability of misery perfusion was slightly better in AI of D/E ratio than that of OEF. Dynamic PET acquisition with (62)Cu-ATSM provided information on CBF distribution and local elevation of OEF in patients with chronic CVD. The findings of the present study showed the feasibility of the noninvasive molecular imaging method for diagnosing misery perfusion with a single venous tracer injection.

Clinical implication and prognosis of normal baseline cerebral blood flow with impaired vascular reserve in patients with major cerebral artery occlusive disease

To investigate the prognosis of patients with cerebrovascular steno-occlusive disease who have preserved baseline cerebral blood flow (CBF) and reduced cerebral vasoreactivity (CVR), they were followed up after scans of positron emission tomography (PET). Fifty-seven patients with symptomatic unilateral major cerebral arterial occlusion or severe stenosis underwent O-15 gas and water PET scans to measure cerebral blood volume, metabolic rate of oxygen, oxygen extraction fraction (OEF), and CBF at the baseline and after acetazolamide administration. Thirty of them (mean age 60 +/- 10 years) had normal ipsilateral CBF, and were followed prospectively at least 30 months from the last ischemic event. They were medically treated for cerebral circulation and underlying diseases during follow-up periods. The primary endpoint was determined as stroke recurrence during the follow-up. Thirty patients were divided into two groups of reduced CVR (N = 16, 63 +/- 8 years) and normal CVR (N = 14, 56 +/- 10 years) on the basis of CVR values from healthy volunteers. None of them showed significant laterality in baseline CBF and OEF between the hemispheres although patients with reduced CVR showed a tendency of ipsilateral increases in OEF and CBV. Patients were followed up for 50.5 +/- 19.0 and 48.1 +/- 12.4 months in the reduced and normal CVR groups, respectively. Although one patient with reduced CVR died of heart disease, there was no incidence of ischemic events during follow-up periods for either group. In the present prospective study, patients with sufficient baseline CBF showed good prognosis and no difference in recurrent stroke risks even though they had poor CVR in the affected hemisphere, indicating that these patients can be treated by medication for cerebral circulation and baseline diseases if they have high risk factors for neurosurgical treatment.

Improved cerebrovascular reactivity following low flow EC/IC bypass in patients with occlusive carotid disease

Patients with major cerebral artery occlusive disease can suffer cerebral hypoperfusion and be at an increased risk of future strokes. EC/IC bypass has been shown to reduce this risk. Patients with cerebral hypoperfusion, and who are at risk of haemodynamic ischaemia, can be identified by the use of xenon computerised tomography (XeCT) to demonstrate severe impairment of the cerebrovascular reserve (CVR). We report our series on the effect of low flow EC/IC bypass on CVR in patients with symptomatic cerebral haemodynamic ischaemia. Thirteen patients with clinical and radiological features of cerebral hypoperfusion were assessed with acetazolamide activated XeCT. Pre- and postoperative regional cerebral blood flow (rCBF) and CVR were assessed. The change in CVR from pre- to post surgery was calculated (%CVR). Values were compared using ANOVA and Student's paired t-test. Unless otherwise stated, values are given as mean ± standard error of the mean. Statistical significance was taken at p < 0.05.Pre-operative symptomatic hemisphere CBF was 38 ± 2 mls/100g/min compared to 40 ± 3.2 mls/100 g/min in the asymptomatic hemisphere, with the greatest difference observed in the MCA territory (38.6 ± 2 cf 45.4 ± 3.2 mls/100g/min). Baseline CBF was not significantly improved post EC/IC bypass. However CVR was significantly improved in the symptomatic hemisphere post-operatively (p = 0.015), with the greatest increase (28%) seen in the MCA territory (p = 0.0105). First, 85% of patients had either an improvement in symptoms or no further symptoms. There was a 93% graft patency and no operative mortality. Low flow EC/IC bypass can improve CVR in patients with symptomatic cerebral ischaemia in the presence of occlusive carotid disease. However, therapy must be individualised, with careful patient selection and minimal surgical morbidity.

Relationship Between Cerebral Circulatory Reserve and Oxygen Extraction Fraction in Patients With Major Cerebral Artery Occlusive Disease

The present study examined the relationship between circulatory and metabolic reserve in patients with hemodynamic impairment. Positron emission tomography was used to investigate 40 patients with major cerebral artery occlusive disease. The ratio of cerebral blood volume to cerebral blood flow (CBV/CBF) and vasoreactivity in response to hypercapnia (%CBF(hypercapnia)) and acetazolamide (ACZ) stress (%CBF(ACZ)) were measured to evaluate circulatory reserve. Oxygen extraction fraction (OEF) was measured to evaluate metabolic reserve. To detect relationships between circulation reserve and OEF, cerebral hemispheres were grouped into 5 or 6 stepwise groups based on reduction of circulation reserve. OEF was significantly elevated in hemispheres with CBV/CBF > or =0.11 minutes and in hemispheres with %CBF(hypercapnia) <0%. OEF was significantly increased according to %CBF(ACZ) in hemispheres with %CBF(ACZ) <15% and plateaued at levels below -15%. Metabolic reserve consumption began at CBV/CBF > or =0.11 minutes, CBF(hypercapnia) <0%, and CBF(ACZ) <15%.

Quantitative Assessment of Cerebral Hemodynamics Using Perfusion-Weighted MRI in Patients With Major Cerebral Artery Occlusive Disease

Cerebrovascular reactivity (CVR) to acetazolamide is a key parameter in determining the severity of hemodynamic impairment in patients with major cerebral artery occlusive disease. Perfusion-weighted MRI (PW MRI) can measure the cerebral blood volume (CBV) as an indicator of hemodynamic impairment. CBV measured by PW MRI was compared with CVR measured by positron emission tomography (PET). Twelve normal subjects and 17 patients with major cerebral artery occlusive disease underwent PW MRI and PET. The images were coregistered with 3-dimensional spoiled gradient-recalled acquisition images. Quantitative PW MRI-CBV maps were generated using the indicator dilution method with arterial input function. One large cortical region of interest for each unilateral middle cerebral artery territory was determined on each image. PET-CVR was calculated by measuring cerebral blood flow before and after acetazolamide challenge. A significant negative correlation was observed between PW MRI-CBV and PET-CVR (r=-0.713; P<0.0001). PW MRI-CBV higher than the mean +2 SD obtained in normal subjects (15.2 mL/100 g) was defined as elevated and PET-CVR lower than the mean -2 SD obtained in normal subjects (15.1%) was defined as reduced. Assuming the PET-CVR as the true determinant of hemodynamic impairment, PW MRI-CBV provided 80.0% sensitivity and 91.7% specificity, with 80.0% positive predictive value for detecting patients with reduced CVR. The PW MRI-CBV method can simply and accurately identify patients with hemodynamic impairment without exposure to ionizing radiation.

Measurement of arterial part of vascular volume ( V0) for the evaluation of hemodynamic changes in cerebrovascular disease

Evaluation of critical hemodynamic deficiency is important for the treatment of patients with cerebrovascular disease (CVD). To investigate the hemodynamic status in the impaired cerebral circulation, changes in regional cerebral blood flow (rCBF) and blood volume induced by acetazolamide (ACZ) were measured in CVD. Twenty-five patients with unilateral major cerebral arterial occlusive disease underwent H 2 15O-PET scans at baseline and 10 min after ACZ injection to calculate rCBF and arterial-to-capillary blood volume ( V 0), as well as scans with the 15O gas steady-state method to evaluate cerebral hemodynamics. A new parameter of rCBF/ V 0 ratio, which was expected to disclose the arterial part of the perfusion pressure, was also compared. The rCBF and V 0 increased significantly after ACZ administration in the contralateral hemisphere of the patients. However, a subgroup of patients (group A) showed a significant reduction of rCBF increase in the ipsilateral hemisphere after the ACZ injection, although V 0 increased significantly. A parameter defined by the rCBF/ V 0 ratio decreased significantly in the ipsilateral hemisphere of group A after ACZ administration, whereas the ratio showed no change in the contralateral hemisphere or in the other subgroup (group B). The increase in rCBF after the ACZ challenge may not represent the vasodilatory capacity in patients with CVD, especially in the regions with a reduced rCBF response. The changes in the rCBF/ V 0 ratio after the ACZ challenge may represent an alteration in the arterial part of the cerebral perfusion pressure (CPP) that is expected to indicate a critical hemodynamic status in patients with CVD who have a reduced rCBF response.

Diffusion tensor imaging in patients with major cerebral artery occlusive disease.

Diffusion tensor (DT) imaging provides quantitative information about the magnitude and the directionality (anisotropy) of water diffusion in vivo and can detect pathologic changes in brain ischemia. This study tried to detect ischemic brain damage using DT imaging in patients with symptomatic chronic major cerebral artery occlusive disease. DT imaging was performed using a 3.0 Tesla magnetic resonance (MR) scanner in 50 patients with unilateral internal carotid artery or middle cerebral artery stenosis or occlusion, who had no obvious infarct lesions on conventional MR imaging. Thirty-three patients underwent DT imaging before and after vascular reconstruction surgery. Fractional anisotropy (FA) was calculated in the middle cerebral artery territory. Preoperative FA values in the ipsilateral side were significantly lower than those in the contralateral side. After surgery, the FA value was significantly increased. DT imaging may indicate ischemic brain damage, not visualized by conventional MR imaging, in patients with major cerebral artery occlusive disease.

Reduced blood flow response to acetazolamide reflects pre-existing vasodilation and decreased oxygen metabolism in major cerebral arterial occlusive disease

A decrease in the cerebral blood flow (CBF) response to acetazolamide may indicate an increase in cerebral blood volume (CBV) caused by reduced perfusion pressure in patients with major cerebral artery steno-occlusive lesions. However, a decrease in cerebral metabolic rate of oxygen (CMRO(2)) caused by ischemic changes may also decrease the CBF response to acetazolamide by decreasing the production of carbon dioxide. The purpose of this study was to determine whether the values of CBV and CMRO(2) are independent predictors of the CBF response to acetazolamide in major cerebral arterial occlusive disease. We used positron emission tomography to study 30 patients with major cerebral artery steno-occlusive lesions. The CBF response to acetazolamide was assessed by measuring baseline CBF and CBF 10 min after an intravenous injection of 1 g of acetazolamide. Multivariate analysis was used to test the independent predictive value of the CBV and CMRO(2) at baseline with respect to the percent change in CBF during acetazolamide administration. Both increased CBV and decreased CMRO(2) were significant and independent predictors of the reduced CBF response to acetazolamide. CBV accounted for 25% of the variance in the absolute change in CBF during acetazolamide administration and 42% of the variance in the percent change in CBF, whereas CMRO(2) accounted for 19% and 4% of the variance, respectively. In patients with major cerebral arterial occlusive disease, a decrease in CMRO(2) may contribute to the reduced CBF response to acetazolamide, although an increase in CBV appears to be the major contributing factor.

Spontaneous improvement in reduced vasodilatory capacity in major cerebral arterial occlusive disease.

Reduced vasodilatory capacity resulting from occlusive lesions of the major cerebral arteries may return to normal without surgical revascularisation. We aimed to determine prospectively the frequency and predictors of recovery of impaired haemodynamics as demonstrated by acetazolamide (ACZ) reactivity on single-photon emission computed tomography (SPECT). Vasoreactivity was measured by (123)I-IMP SPECT with an ACZ challenge, in 37 medically treated patients with unilateral occlusive disease of the internal carotid or middle cerebral artery at an interval of 1-2 years. Each ACZ challenge test was analysed semiquantitatively by calculating the degree of increase in cerebral blood flow (CBF) asymmetry after ACZ administration (DeltaAI). Vasodilatory capacity was abnormal initially in 20 patients (65 %); eight of whom (40 %) exhibited spontaneous normalisation on follow-up. Although the baseline characteristics did not differ significantly between patients with or without increase in reactivity, logistic regression analysis revealed that the initial DeltaAI (P < 0.05) and the type of vascular lesion (stenosis or occlusion) (P < 0.05) correlated significantly with a return towards normal of reduced ACZ reactivity. Spontaneous improvement of impaired vasodilatory capacity may not be a rare phenomenon. We found that mild reduction in the initial ACZ reactivity and a stenosis, but not complete occlusion, were independent factors contributing to normalisation of impaired cerebral haemodynamics.

Cerebral blood-flow responses to induced hypotension and to CO2 inhalation in patients with major cerebral artery occlusive disease: a positron-emission tomography study.

Our aim was to study the relationship between cerebral blood flow (CBF) responses to induced hypotension and to CO2 inhalation in patients with occlusive disease of the carotid or middle cerebral arteries. In 13 patients (8 men, 5 women) aged 31-73 years (mean +/- 1 SD = 63.2 +/- 10.6), regional CBF values during the resting state (CBFrest), 7% CO2 inhalation (CBFhypercapnia), and hypotension induced by 10-20 microg/kg/min intravenous trimethaphan (CBFhypotension) were measured using positron-emission tomography (PET) with H2(15)O. The % CBF change during induced hypotension (% CBFhypotension) was defined as (CBFhypotension - CBFrest)/CBFrest multiplied by 100. The % CBF change during CO2 inhalation (% CBFhypercapnia) was defined as (CBFhypercapnia - CBFrest)/CBFrest/mm Hg arterial partial pressure of CO2 x 100. We defined symptomatic hemispheres as those with a stenotic or occlusive lesion with neurological symptoms or signs and asymptomatic hemispheres as those which had a similar lesion and/or were influenced by the collateral flow pattern without neurological symptoms. In the territory of the occlusive lesion, % CBFhypotension correlated significantly with % CBFhypercapnia (r = 0.793, P < 0.002) in the symptomatic hemispheres. In the brain regions in which trimethaphan did not induce a reduction in CBF. % CBFhypercapnia was 6.13 +/- 1.79. In those in which % CBFhypotension ranged from 0 to -5, from -5 to -10, and more than -10%, % CBFhypercapnia was 4.05 +/- 1.99, 3.21 +/- 1.17, and 1.73 +/- 1.61, respectively, with significant differences between each pair of groups. In the asymptomatic hemispheres, % CBFhypotension also correlated with % CBFhypercapnia (r = 0.979, P < 0.0001). Failure to maintain CBF during induced hypotension was associated with diminished cerebrovascular vasoreactivity to hypercapnia in patients with arterial disease. This may indicate that failure of autoregulation can be assessed by the CBF response to both induced hypotension and CO2 inhalation. From the technical point of view, estimation of the CO2 response may be useful for assessing failure of autoregulation.

Crossed cerebellar hypoperfusion indicates the degree of uncoupling between blood flow and metabolism in major cerebral arterial occlusion.

In patients who have major cerebral arterial occlusive disease with low perfusion, a decrease in cerebral metabolism may be reflected by a reduction in contralateral cerebellar blood flow (crossed cerebellar hypoperfusion). This study was done to investigate whether comparison of the extent of cerebral blood flow asymmetry and crossed cerebellar hypoperfusion could be used to estimate the degree of uncoupling of cerebral blood flow and metabolism on the basis of a single blood flow study. We used positron emission tomography before and after reconstructive vascular surgery to evaluate regional blood flow and oxygen metabolism in the cerebral and cerebellar cortexes of 11 patients with major cerebral arterial occlusive disease. Preoperatively these patients had cortical blood flow asymmetry in the middle cerebral artery territory. The degree of crossed cerebellar hypoperfusion had no relation to the extent of cerebral blood flow asymmetry but was significantly correlated with the extent of asymmetry in cerebral oxygen metabolism. The preoperative extent of asymmetry in the cerebral oxygen extraction fraction and the postoperative improvement of asymmetry in cerebral blood flow were correlated with the preoperative difference between the severity of cerebral blood flow asymmetry and crossed cerebellar hypoperfusion. The difference between the extent of cerebral blood flow asymmetry and crossed cerebellar hypoperfusion can be used to estimate the degree of uncoupling between blood flow and metabolism, which can in turn predict the postoperative improvement of cerebral blood flow asymmetry. We suggest that this approach may be a simple means of estimating the relative uncoupling between blood flow and metabolism from a single blood flow study in patients who have major cerebral arterial occlusive disease with low perfusion.

Acetazolamide reactivity on 123I-IMP single photon emission computed tomography in patients with major cerebral artery occlusive disease: correlation with positron emission tomography parameters.

Single photon emission computed tomography (SPECT) with acetazolamide challenge has increasingly been used for evaluating hemodynamic reserve in stroke patients. The accuracy of this test, however, has not been validated with positron emission tomography (PET). In 14 patients who had occlusive disease of the internal carotid artery or the trunk of the middle cerebral artery (MCA) with minimal or no infarction on computed tomography (CT) and magnetic resonance imaging (MRI), we compared acetazolamide reactivity on SPECT with N-isopropyl-p-[123I]-iodoamphetamine to hemodynamic parameters determined with gas inhalation labeled 15O steady-state PET studies. The asymmetry index (AI)--i.e., the percentage of the activity rate of the ischemic MCA territory versus the contralateral one, was determined by SPECT. Acetazolamide reactivity expressed as delta AI, or change in AI after acetazolamide challenge, was significantly lower in seven patients than -8.4%, the lower limit of the 95% confidence interval for the normal reactivity. Values of ipsilateral CBF, cerebral blood volume (CBV)/CBF, and oxygen extraction fraction (OEF) and contralateral OEF were significantly different between patients with normal and reduced acetazolamide reactivity. Values of delta AI were correlated with OEF (r = -0.87; p < 0.001) and CBV/CBF (r = -0.56; p < 0.05). All patients with OEF > 0.52, the mean + 2 SD calculated from five normal volunteers, also had reduced acetazolamide reactivity, while the patients with normal OEF values had normal reactivity. The present study has demonstrated that SPECT studies with an acetazolamide challenge can detect the Stage II hemodynamic failure.

Carbonic anhydrase: chemistry, physiology, and inhibition.

Carbonic anhydrase: chemistry, physiology, and inhibition.