Regional cerebral blood flow measured by the gamma camera after direct injection of 133Xe into the distal stump of the occluded middle cerebral artery.

Regional cerebral blood flow (rCBF) was measured after intracarotid injection of 133Xe concurrently with measurements of local cerebral blood flow (LCBF) after injection of 133Xe directly into the distal stump of the occluded middle cerebral artery (MCA) by the use of the gamma camera after producing experimental ischemia in baboons by occluding the MCA. Regional MCA stump pressure (rMCAP) was also measured. Regions of ischemia assessed by intracarotid injection of 133Xe correlated well with the territory of infarct defined by injection of 133Xe into the distal MCA stump. Flow values in ischemic regions obtained by direct injection of 133Xe into the MCA were 15% to 20% lower than those obtained by intracarotid injection of 133Xe. Possible explanations for these differences are discussed. During induced hypertension autoregulation in ischemic areas was abolished and paradoxical responses of LCBF and rMCAP to changes in arterial carbon dioxide tension (PaCO2) were confirmed.     

Evaluation of cerebral vasomotor reactivity by various vasodilating stimuli: comparison of CO2 to acetazolamide.

To evaluate the role of different vasomotor stimuli for the measurement of cerebrovascular vasomotor reactivity (VMR), 47 patients (i.e., 93 hemispheres) with various degrees of internal carotid artery (ICA) occlusive disease were studied. Patients were divided into clinical [asymptomatic, transient ischemic attack (TIA) or completed stroke] as well as angiological subgroups. Low-grade or high-grade unilateral ICA lesions were compared to bilateral ICA occlusive disease. Relative flow velocity changes within the middle cerebral artery were measured by means of transcranial Doppler during hyper- and hypocapnia (VMRTOT), during hypercapnia alone (VMRCO2), and after injection of 1 g acetazolamide (VMRACE). VMR was expressed as the percentage change in flow velocity after stimulus application as compared with flow velocity at rest. There was a close and statistically highly significant correlation of CO2-induced with acetazolamide-induced VMR (r = 0.69 in VMRTOT versus VMRACE and 0.79 in VMRCO2 versus VMRACE; P less than 0.0001; linear regression), indicating a strong similarity of the vasodilatative effects of CO2 and acetazolamide on cerebral arteries. Both stimulation techniques highly significantly differentiated between asymptomatic patients and those with TIA or completed stroke. Angiological subgroups were separated best by the acetazolamide test. Reclassification of patients into angiological subgroups by linear discriminant analysis was equally good with all three methods. We conclude that both acetazolamide- and CO2-induced stimulation of the cerebral vasomotors are valid techniques to measure reduction in perfusion reserve due to extracranial cerebrovascular occlusive disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of cerebrovascular reserve in unilateral middle cerebral artery stenosis using perfusion CT and CO2 inhalation tests

Purpose/Aim of the study: Cerebrovascular reactivity (CVR) is an important marker for assessing cerebrovascular disease. This study assessed the CVR by perfusion computed tomography (CT) and CO₂ inhalation tests in patients with unilateral middle cerebral artery (MCA) stenosis disease. Materials and Methods: Thirty-one patients with unilateral MCA stenosis disease diagnosed by digital subtraction angiography were studied. Patients were divided into two groups according to the degree of stenosis: severe and moderate. The regional cerebral blood flow (CBF) before and after CO₂ inhalation was determined by perfusion CT. Regional CVR values were obtained by the following formula: increase (%) = (post-CBF) ? (pre-CBF)/(pre-CBF) × 100%. Results: No significant differences in the mean CBF in the MCA stenosis region were found between the affected and contralateral sides before the CO₂ inhalation test; after the test, CBF was more significantly decreased on the affected side than on the contralateral side. The changes in CBF on the affected side were categorized into three types: increased CBF (17 cases), decreased CBF (12 cases) and no change in CBF (2 cases). The rate of CVR impairment among severe stenosis patients (13/19) was higher than that among moderate stenosis patients (3/12). CVR was significantly correlated with the degree of stenosis (r = 0.423, P = 0.018). Conclusion: CVR impairment was found in approximately half of patients with unilateral MCA stenosis. Along with an increase in the degree of stenosis, patients with unilateral MCA stenosis were more likely to exhibit CVR impairment. It is important to assess the CVR in patients with unilateral MCA stenosis, especially those with severe stenosis.     

The reactivity of canine cerebral arteries to O2 and CO2 in vitro.

The responses of canine middle cerebral arteries to changes in pCO2 and pO2 were tested in vitro. It was found that there was no response to changes in pCO2 from 38.1 mm. Hg to 26.6 mm. Hg, but there was some constriction of the vessels with lowering of the pCO2 below 26.6 mm. Hg and there was minimal dilatation of the vessels when the pCO2 was increased from 38.1 mm. Hg to 87.2 mm. Hg. There was no response to changes in pO2 from more than 55 mm. Hg to 59.6 mm. Hg, but when pO2 was lowered below 50 mm. Hg there was a sudden, massive constriction of the arteries tested. It is postulated that this constriction is due to build-up of a substance (substances) during a period of hypoxia (pO2 less than 50 mm. Hg). The significance of the results obtained are discussed.     

Role of impaired CO2 reactivity in the diagnosis of cerebral low flow infarcts.

Previous studies on CO2 reactivity in cerebral low flow infarcts (LFIs) included patients with lesions in the frontoparasagittal area, supraganglionic white matter, and temporoparieto-occipital zone. Supraganglionic white matter LFIs are, however, difficult to separate from non-low flow induced infarcts of the lacunar type, and temporoparieto-occipital LFIs from infarcts in the territory of the inferior stem of the middle cerebral artery. The CO2 reactivity of the middle cerebral artery was studied in 56 patients with high grade stenoses and occlusions of the internal carotid artery and LFIs (n = 9) in the frontoparasagittal border zone, territorial infarcts (n = 26), no infarcts (n = 21), and normal subjects (n = 25) by means of transcranial Doppler sonography. The aim was to investigate whether patients with LFIs have significantly lower CO2 reactivity than patients with territorial infarcts, no infarcts, and normal subjects. Patients with LFIs had the most severely reduced CO2 reactivity on the symptomatic side and CO2 reactivity was significantly lower than on the asymptomatic side. It was also lower than in patients with unilateral and bilateral internal carotid artery obstructions and territorial infarcts, asymptomatic patients, and healthy volunteers. It is concluded that LFIs are associated with significantly reduced CO2 reactivity.     

Regional cerebral blood flow measured by 133Xe inhalation in tracheostomized and laryngectomized men and women.

The question of contamination of cerebral clearance curves utilized for measuring regional cerebral blood flow by radioactivity derived from the nasopharyngeal air passages following inhalation of 133Xe was tested in patients with chronic tracheostomy. The peak counts for head curves were 5--9% higher when 133Xe was inhaled via a face mask than when inhaled via the tracheal stoma. Calculated flow values using standard recommended start-fit-times were not significantly different between these two different methods. Present results indicate that neither overestimation of fast flow values due to contamination from rapid 133Xe washout recorded from the air passages nor the underestimation of slow flow due to contamination from 133Xe trapped in the air sinuses produced significant measurement errors. However, if earlier start-fit-times were used, flow values were artificially high, particularly for brain stem/cerebellar probes because of an initial rapid decline in the head desaturation curves due to an arterial peak believed to be derived from the basilar artery.     

Measurement of cerebral blood flow by intravenous xenon-133 technique and a mobile system. Reproducibility using the Obrist model compared to total curve analysis

The recent development of a mobile 10 detector unit, using i.v. Xenon-133 technique, has made it possible to perform repeated bedside measurements of cerebral blood flow (CBF). Test-retest studies were carried out in 38 atherosclerotic subjects, in order to evaluate the reproducibility of CBF level and side-to-side asymmetry. Data were analysed according to the Obrist model and the results compared with those obtained using a model correcting for the air passage artifact. Reproducibility was of the same order of magnitude as reported using stationary equipment. The side-to-side CBF asymmetry was considerably more reproducible than CBF level. Using a single detector instead of five regional values averaged as the hemispheric flow increased standard deviation of CBF level by 10-20%, while the variation in asymmetry was doubled. In optimal measuring conditions the two models revealed no significant differences, but in low flow situations the artifact model yielded significantly more stable results. The present apparatus, equipped with 3-5 detectors covering each hemisphere, offers the opportunity of performing serial CBF measurements in situations not otherwise feasible.     

Measurement of cerebral blood flow by intravenous Xenon-133 technique and a mobile system: Reproducibility using the Obrist model compared to total curve analysis

The recent development of a mobile 10 detector unit, using i.v. Xenon-133 technique, has made it possible to perform repeated bedside measurements of cerebral blood flow (CBF). Test-retest studies were carried out in 38 atherosclerotic subjects, in order to evaluate the reproducibility of CBF level and side-to-side asymmetry. Data were analysed according to the Obrist model and the results compared with those obtained using a model correcting for the air passage artifact. Reproducibility was of the same order of magnitude as reported using stationary equipment. The side-to-side CBF asymmetry was considerably more reproducible than CBF level. Using a single detector instead of five regional values averaged as the hemispheric flow increased standard deviation of CBF level by 10-20%, while the variation in asymmetry was doubled. In optimal measuring conditions the two models revealed no significant differences, but in low flow situations the artifact model yielded significantly more stable results. The present apparatus, equipped with 3-5 detectors covering each hemisphere, offers the opportunity of performing serial CBF measurements in situations not otherwise feasible.     

The effect of caffeine on dilated cerebral circulation and on diagnostic CO2 reactivity testing.

Reduction of cerebral blood flow by caffeine has been shown in multiple studies. However, the effect of this substance on pathologically dilated cerebral vessels is not clearly defined. The aim of this study was to investigate the effect of caffeine on an already dilated cerebral circulation and specify if these vessels are still able to constrict as a consequence of caffeine stimulation. A second aim of this study was to compare results of cerebral vasomotor CO(2) reactivity testing with and without caffeine ingestion. Seventeen healthy adult volunteers had vasomotor reactivity tested before and thirty minutes after ingestion of 300 mg of caffeine. Each vasomotor reactivity test consisted of velocity measurements from both middle cerebral arteries using transcranial Doppler ultrasound during normocapnia, hypercapnia, and hypocapnia. Hemodynamic data and end-tidal CO(2) (etCO(2)) concentration were also recorded. The vasomotor reactivity (VMR) and CO(2) reactivity were calculated from a measured data pool. At a level of etCO(2)=40 mmHg the resting velocity in the middle cerebral artery (V(MCA)) dropped from 70.7+/-22.8 cm/sec to 60.7 +/- 15.4 cm/sec 30 minutes after caffeine stimulation (14.1% decrease, p<0.001). During hypercapnia of etCO(2)=50 mmHg there was also a significant decline of V(MCA) from 103.1+/-25.4 to 91.4+/-21.8 cm/sec (11.3%, p<0.001). There was not a statistically significant reduction of V(MCA) during hypocapnia. Calculated VMR and CO(2) reactivity before and after caffeine intake were not statistically significant. The presented data demonstrate a significant decrease in cerebral blood flow velocities after caffeine ingestion both in a normal cerebrovascular bed and under conditions of peripheral cerebrovascular vasodilatation. These findings support the important role of caffeine in regulation of CBF under different pathological conditions. Despite significant reactive vasodilatation in the brain microcirculation, caffeine is still able to act as a competitive antagonist of CO(2) on cerebral microvessels. The fact that caffeine may decrease CBF despite significant pathological vasodilatation offers the possibility of therapeutic manipulation in patients with traumatic vasoparalysis. For routine clinical testing of CO(2) reactivity it is not necessary to insist on pre-test dietary restrictions.     

Comparison of cerebral vascular reactivity measures obtained using breath-holding and CO2 inhalation

Stimulation of cerebral vasculature using hypercapnia has been widely used to study cerebral vascular reactivity (CVR), which can be expressed as the quantitative change in cerebral blood flow (CBF) per mm Hg change in end-tidal partial pressure of CO₂ (P_ETCO₂). We investigate whether different respiratory manipulations, with arterial spin labeling used to measure CBF, lead to consistent measures of CVR. The approaches included: (1) an automated system delivering variable concentrations of inspired CO₂ for prospective targeting of P_ETCO₂, (2) administration of a fixed concentration of CO₂ leading to subject-dependent changes in P_ETCO₂, (3) a breath-hold (BH) paradigm with physiologic modeling of CO₂ accumulation, and (4) a maneuver combining breath-hold and hyperventilation. When CVR was expressed as the percent change in CBF per mm Hg change in P_ETCO₂, methods 1 to 3 gave consistent results. The CVR values using method 4 were significantly lower. When CVR was expressed in terms of the absolute change in CBF (mL/100 g per minute per mm Hg), greater discrepancies became apparent: methods 2 and 3 gave lower absolute CVR values compared with method 1, and the value obtained with method 4 was dramatically lower. Our findings indicate that care must be taken to ensure that CVR is measured over the linear range of the CBF-CO₂ dose–response curve, avoiding hypocapnic conditions.     

A comparison of xenon-133 and xenon-127 for the determination of regional cerebral blood flow measured by dynamic SPECT.

Phantom studies and cerebral blood flow (CBF) measurements in 11 normal subjects at rest were performed by single photon emission tomography (SPECT) with Xe-133 (16 mm full-width at half-maximum [FWHM] collimation) and Xe-127 (16 mm, 12 mm, and 9 mm FWHM collimation). The phantom results clearly illustrated the feasibility of Xe-127 studies and the advantage of Xe-127 over Xe-133 for equivalent patient dose exposures. CBF values obtained with Xe-127 were comparable to those of Xe-133 for the 16 mm collimator, although higher flow values were found with the better resolution, probably because of reduced partial volume effects. The correlations between the various groups of examinations were high, except for the Xe-133 and Xe-127 16 mm collimator groups. Xe-127 allows a considerable increase in the resolution of the images, while exposing the patient to a lower radiation dose. Potential limitations because of higher energy penetrating photons from Xe-127 were not observed in this specially shielded equipment.     

Global ischemia in dogs: cerebrovascular CO2 reactivity and autoregulation.

One hypothesis on the pathogenesis of post-ischemic-anoxic encephalopathy is impaired cerebral perfusion or the no-reflow phenomenon. Therapies aimed at preventing the development of this phenomenon are increased cerebral perfusion pressure (CPP) and hyperventilation or hypercapnia. Using a dog model in which we have described the progressive development of post-ischemic (PI) cerebral hypoperfusion after 15 minutes of global ischemia induced by aortic and vena cavae clamping, our aims in this study were to determine during the PI cerebral hypoperfusion period: (1) cerebrovascular reactivity to CO2, and (2) cerebral blood (CBF) autoregulation. Post-ischemic cerebral hypoperfusion to about 50% of normal was not accompanied by raised intracranial pressure (ICP) but cerebrovascular CO2 reactivity was markedly attenuated while maintaining some kind of autoregulatory phenomenon. Cerebral uptake of oxygen was not significantly affected by changing PACO2 from 20 to 60 torr at constant CPP or by changing CPP from 64 to 104 torr at constant PaCO2. These results suggest that increasing both CPP and hypocapnia/hypercapnia would not significantly attenuate PI neurological deficit after global cerebral ischemia. However, in two dogs inadvertently hemodiluted in the PI period, increasing CPP from 50 to 200 torr increased CBF by 200%, suggesting that hemodilution plus increased CPP may be effective therapy for amelioration of post-ischemic-anoxic encephalopathy. The significance of our findings on cerebrovascular CO2 reactivity and autoregulation with respect to the mechanism of the no-reflow phenomenon is discussed.     

Comparison of Doppler velocimetry of the common carotid artery with cerebral blood flow measured by PET

The cervical carotid Doppler velocity is determined by the cardiovascular function, hemodynamic characteristics of proximal vascular beds, the carotid artery, and the distal vascular beds, i.e., cerebral circulation. If the former three factors remain constant, cervical carotid Doppler velocimetry reflects the cerebral circulation. The purpose of this report is to study whether the cervical carotid Doppler velocimetry reflects cerebral circulation or not. Parameters measured by the common carotid Doppler velocimetry were compared with cerebral blood flow (CBF) in the internal carotid arterial distribution measured by positron emission tomography (PET) in 50 patients, aged from 33 to 72 years old (mean: 56.5 +/- 8.6). These subjects were 14 with cerebral infarction, 12 with no abnormality (normal volunteers), 5 with brain tumor, 2 with normal pressure hydrocephalus, 3 with spinocerebellar degeneration, and so on. CBF was measured by the 15O-gas steady state method or H2(15)O autoradiographic method using a HEADTOME III scanner. Subsequently, pulsed Doppler flow velocimetry of the common carotid artery was performed using a RT-3600 scanner which employed a 5-MHz transducer, and systolic velocity (SV), diastolic velocity (DV), mean velocity (MV), and pulsatility index (PI) were measured. Cerebral angiography was performed in every patient except for normal volunteers, and it demonstrated no evidence of stenoocclusive lesions in the cervical carotid artery. X-ray computed tomogram (CT) was also performed in all patients. We compared CBF in the internal carotid arterial distribution with SV, DV, MV, and PI.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia. Assessment with xenon 133 single-photon emission computed tomography and the Tower of London.

The "hypofrontality hypothesis" has been supported by many neuroimaging studies, but not all, perhaps because of heterogeneity of samples. The present study examined three different samples that permitted assessment of a variety of confounders, such as effects of long-term treatment, chronicity of illness, and presenting phenomenology: (1) 13 neuroleptic-naive schizophrenic patients, (2) 23 nonnaive schizophrenic patients who had been relatively chronically ill but were medication free for at least 3 weeks, and (3) 15 healthy normal volunteers. Regional cerebral blood flow was measured using single-photon emission computed tomography with xenon 133 as the tracer. The control condition consisted of looking at undulating colored shapes on a video monitor, while the experimental task was the Tower of London. We observed the Tower of London to be a relatively specific stimulant of the left mesial frontal cortex (probably including parts of the cingulate gyrus) in healthy normal volunteers. Both the neuroleptic-naive and the nonnaive patients lacked this area of activation, as well as a related one in the right parietal cortex (representing the circuitry specifically activated by the Tower of London). Decreased activation occurred only in the patients with high scores for negative symptoms. These results suggest that hypofrontality is related to negative symptoms and is not a long-term effect of neuroleptic treatment or of chronicity of illness.     

血清Lp-PLA2,IL-6水平与急性脑梗死患者rt-PA静脉溶栓治疗预后的相关性

目的 探讨血清脂蛋白磷脂酶A2(lipoprotein associated phospholipase A2,Lp-PLA2)、白细胞介素(Interleukin,IL)-6水平与急性脑梗死(Acute cerebral infarction,ACI)患者重组组织型纤溶酶原激活剂(Recombinant tissue plasminogen activator,rt-PA)静脉溶栓治疗预后的关系。方法 前瞻选择2017年5月-2020年5月医院217例行rt-PA静脉溶栓治疗的ACI患者作为研究对象,入院时检测血清Lp-PLA2、炎症因子[IL-6,IL-1β、肿瘤坏死因子α(Tumor necrosis factor-α,TNF-α)]水平,rt-PA静脉溶栓治疗后第90 d用改良Rankin评分(Modified Rankin scale,mRS)评估预后情况,对比不同预后患者基线资料与实验室指标水平,重点分析入院时血清Lp-PLA2,IL-6水平与ACI患者rt-PA静脉溶栓治疗预后的关系。结果 溶栓后第90 d 217例ACI患者中预后不良患者有68例,占31.34%; 预后不良组Lp-PLA2,IL-6,IL-1β,TNF-α水平均高于预后良好组(P<0.05); 组间其他基线资料比较均无明显差异(P>0.05); 经Logistic回归分析显示,Lp-PLA2,IL-6水平与ACI患者rt-PA静脉溶栓治疗预后不良有关,各指标过表达可能是ACI患者rt-PA静脉溶栓治疗预后不良的风险因子(OR>1,P<0.05); 绘制ROC显示,入院时血清Lp-PLA2,IL-6水平单独及联合预测ACI患者rt-PA静脉溶栓治疗预后不良的AUC分别为0.841、0.847、0.906,均有一定预测价值。结论 血清Lp-PLA2,IL-6表达水平与ACI患者rt-PA静脉溶栓治疗预后不良有关,早期监测血清Lp-PLA2,IL-6水平对ACI患者rt-PA静脉溶栓治疗预后情况具有一定预测价值。