No abstract

Active treatment of acute ischaemic stroke can only be successful as long as tissue in the area of ischaemic compromise is still viable. Therefore, the identification of the area of irreversible damage, and its distinction from the penumbral zone, may improve the estimation of the potential efficacy of various therapeutic strategies. Ten patients (seven male, three female, aged 52-75 years) with acute ischaemic stroke, in whom MRI delineated an infarct involving the cortex 3 weeks after the attack, were studied by [(11)C]flumazenil (FMZ) PET to assess their neuronal integrity, and regional cerebral blood flow (CBF) was measured by H(2)(15)O PET 2-12 h (median interval 6 h) after onset of symptoms. Cortical volumes of interest (3 mm radius) were placed on co-registered CBF, FMZ and on late MRI scans. Using initial CBF and FMZ binding data from volumes of interest finally located within or outside the cortical infarct, cumulative probability curves were computed to predict eventual infarction or non-infarction. Positive (at least 95% chance of infarct) and negative (at least 95% chance of non-infarct) prediction limits for CBF (4.8 and 14.1 ml/100 g/min, respectively) and for FMZ binding (3.4 and 5.5 times the mean of normal white matter, respectively) were determined to define the penumbral range. Using the lower FMZ binding threshold of 3.4 for irreversible tissue damage and the upper CBF value of 14.1 ml/ 100 g/min for the threshold of critical perfusion at or above which tissue will likely be preserved, various cortical subcompartments were identified: of the final cortical infarct (median size 25.7 cm(3)) a major portion comprising, on average, 55.1% showed FMZ binding critically decreased, thus predicting necrosis. In 20.5% of the final infarct, on average, CBF was in the penumbral range (<14.1 ml/100 g/min) and FMZ binding was above the critical threshold of irreversible damage. Only 12.9% of the final infarct exhibited neuronal integrity and CBF values above the penumbral range. Therefore, most of the final infarct is irreversibly damaged already at the time of the initial evaluation, when studied several hours after stroke onset. A much smaller portion is still viable but suffers from insufficient blood supply: this tissue may be salvaged by effective reperfusion. Only an even smaller compartment is viable and sufficiently perfused, but eventually becomes necrotic, mainly owing to delayed mechanisms, and may benefit from neuroprotective or other measures targeted at secondary damage. Therefore, early reperfusion is crucial in acute ischaemic stroke.

Thrombolytic therapy of acute ischemic stroke can be successful only as long as there is penumbral tissue perfused at rates between the thresholds of normal function and irreversible structural damage, respectively. To determine the proportion of tissue at risk of infarction, cerebral perfusion was studied in 12 patients with acute ischemic stroke who underwent treatment with systemic recombinant tissue plasminogen activator (0.9 mg/kg body weight according to National Institute of Neurological Disorders and Stroke protocol) within 3 hours of onset of symptoms, using [15O]-H2O positron emission tomography (PET) before or during, and repeatedly after thrombolysis. The size of the regions of critically hypoperfused gray matter were identified on the initial PET scans, and changes of perfusion in those areas were related to the clinical course (followed by the National Institutes of Health stroke scale) and to the volume of infarcted gray matter demarcated on magnetic resonance imaging 3 weeks after the stroke. Whereas the initial clinical score was unrelated to the size of the ischemic area, after 3 weeks there was a strong correlation between clinical deficit and volume size of infarcted gray matter (Spearman's rho, 0.96; P < 0.001). All patients with a severely hypoperfused (< 12 mL/100 g/min) gray matter region measuring less than 15 mL on first PET showed full morphologic and clinical recovery (n = 5), whereas those with ischemic areas larger than 20 mL developed infarction and experienced persistent neurologic deficits of varying degree. Infarct sizes, however, were smaller than expected from previous correlative PET and morphologic studies of patients with acute stroke: only 22.7% of the gray matter initially perfused at rates below the conventional threshold of critical ischemia became necrotic. Actually, the percentage of initially ischemic voxels that became reperfused at almost normal levels clearly predicted the degree of clinical improvement achieved within 3 weeks. These sequential blood flow PET studies demonstrate that critically hypoperfused tissue can be preserved by early reperfusion, perhaps related to thrombolytic therapy. The results correspond with experimental findings demonstrating the prevention of large infarcts by early reperfusion to misery perfused but viable tissue.

Summary: Various approaches estimating local cerebral glucose utilization by positron emission tomography of labeled deoxyglucose are compared. Autoradiographic methods that predict the glucose utilization rate from a single scan are unreliable in pathologic tissue because of abnormal values of the model rate constants. A normal ization procedure using the ratio of measured tissue ac tivity to activity calculated with standard rate constants is proposed to readjust the values of the rate constants. Reliable estimates of metabolic rates can be obtained from dynamic recordings of tracer uptake. In the graphic approach, metabolic rate can be derived from the slope of a segment of a transformed uptake curve, which be comes linear at 15-20 min after intravenous tracer injec tion, with an accuracy comparable with that in complete dynamic studies. However, by recording and analyzingOver the last few years, the 2-deoxyglucose (DG) method has become generally accepted and widely used for measuring in vivo the glucose consumption of various structural and functional components of the brain. Originally developed for autoradiographic animal studies using 2-deoxY-D- Abbreviations used: CT, computed tomography; DG, 2-de oxyglucose; DG-6-P, 2-deoxyglucose-6-phosphate; FOG, 2-fluoro-2-deoxy-n-glucose; PET, positron emission tomography. 115full-length uptake curves, in addition to metabolic rate, the model rate constants can be determined regionally. The physiological significance of those parameters is demonstrated in crossed cerebellar deactivation in 30 pa tients with supratentorial infarcts. Mild hypometabolism both within the ischemic lesion and in the morphologi cally intact cerebellum is accompanied by a reduction of the phosphorylation rate only. Severe metabolic depres sion, by contrast, affects both cerebellar transport and phosphorylation processes, whereas in the cerebrum, only the rate constant kl is significantly correlated with the degree of metabolic disturbance.

Background and Purpose-Central benzodiazepine receptor ligands, such as [11 C]flumazenil (FMZ), are markers of neuronal integrity and therefore might be useful in the differentiation of functionally and morphologically damaged tissue early in ischemic stroke. We sought to assess the value of a benzodiazepine receptor ligand for the early identification of irreversible ischemic damage to cortical areas that cannot benefit from reperfusion. Methods-Eleven patients (7 male, 4 female, aged 52 to 75 years) with acute, hemispheric ischemic stroke were treated with alteplase (recombinant tissue plasminogen activator; 0.9 mg/kg according to National Institute of Neurological Disorders and Stroke protocol) within 3 hours of onset of symptoms. At the beginning of thrombolysis, cortical cerebral blood flow ([ 15 O]H 2 O) and FMZ binding were assessed by positron emission tomography (PET). Those early PET findings were related to the change in neurological deficit (National Institutes of Health Stroke Scale) and to the extent of cortical damage on MRI or CT 3 weeks after the stroke. Results-Hypoperfusion was observed in all cases, and in 8 patients the values were below critical thresholds estimated at 12 mL/100 g per minute, comprising 1 to 174 cm 3 of cortical tissue. Substantial reperfusion was seen in most of these regions 24 hours after thrombolysis. In 4 cases, distinct areas of decreased FMZ binding were detected. Those patients suffered permanent lesions in cortical areas corresponding to their FMZ defects (112 versus 146, 3 versus 3, 2 versus 1, and 128 versus 136 cm 3 ). In the other patients no morphological defects were detected on MRI or CT, although blood flow was critically decreased in areas ranging in size up to 78 cm 3 before thrombolysis. Conclusions-These findings suggest that imaging of benzodiazepine receptors by FMZ PET distinguishes between irreversibly damaged and viable penumbra tissue early after acute stroke. (Stroke. 2000;31:366-369.)

Ictal and interictal epileptic activity was recorded for the first time by multichannel magnetoencephalography (MEG) in three patients with partial epilepsy. Pre- and intra-operative localization of the epileptogenic region was compared. The interictal epileptic activity was localized at the same region of the temporal or frontal lobe as the ictal activity. Main zones of ictal activity were shown to evolve from the tissue at the centers of interictal activity. Pre- and intra-operative electrocorticography (ECoG) as well as postoperative outcome confirmed localization in the temporal and frontal lobe. Results also correlated with findings from scalp EEG, interictal and ictal single photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance imaging (MRI). Combined multichannel MEG/EEG recording permitted dipole localization of interictal and ictal activity.

No abstract

Regional cerebral blood flow (rCBF) of the left hemisphere was measured in 12 healthy young men at rest and during physical work on a bicycle ergometer in the supine position at work-load levels of 25 W or 100 W using the intravenous 133Xe method. Regional mean cerebral blood flow, regional gray-matter flow, and relative gray-matter weight was determined for six regions of interest. Arterial blood pressure, pulse frequency and expiratory CO2 concentration were recorded. Cerebral blood flow in all regions was significantly (P less than 0.001) higher during exercise than at rest. The increase in the 100 W group (24.7%) was significantly (P less than 0.05) greater than in the 25 W group (13.5%), but resting blood flow levels and alveolar CO2 concentrations were also different in both groups. Mean arterial blood pressure, pulse frequency and alveolar CO2 concentrations, but not arterial pCO2, were significantly higher during exercise and there was a faster washout of whole-body xenon. The CBF increase was interpreted as a combined effect of elevated systemic blood pressure and functionally activated brain metabolism. There was no evidence of impaired cerebral autoregulation.