Basilar and middle cerebral artery reserve: a comparative study using transcranial Doppler and breath-holding techniques.

BACKGROUND AND PURPOSE: A 1997 report suggests that the posterior circulation of the normal brain has diminished vasoreactivity compared with the anterior circulation. To further study this, we quantified and compared the vasodilatory capacities of the middle cerebral (MCA) and basilar artery (BA) territories in response to changes in PaCO(2), as indices of respective cerebrovascular reserve (CVR). If posterior circulation CVR is indeed physiologically lower than that of the MCA, it might indicate a greater risk of low-flow ischemia distal to basilar obstructive cerebrovascular lesions and provide a rationale for earlier treatment of such lesions with interventional techniques. We also wished to establish normal baseline CVR values for the posterior circulation. METHODS: Twelve patients with signs and/or symptoms suggestive of posterior circulation disease but without flow-limiting obstructive changes and 11 normal controls were entered into the study. With the use of transcranial Doppler techniques, alterations in blood flow velocity in response to sequential breath-holding trials of varying duration were simultaneously monitored in both MCAs and the BA. CVR was measured as the percent velocity increase (during breath-holding) from resting baseline values. RESULTS: No significant differences were found in CVR between the MCA and BA territories in or between patients and controls. CONCLUSIONS: Our study suggests that the anterior and posterior circulations have similar reserve capacities in individuals without flow-limiting cerebrovascular obstructive lesions and that the BA territory, relative to the MCA territory, is not at increased risk for low-flow stroke on the basis of limited reserve potential.

Contrast-enhanced transcranial color-coded duplexsonography in stroke patients with limited bone windows.

BACKGROUND AND PURPOSE: Thickening of the temporal bone in stroke-age patients may obviate sonographic evaluation of the circle of Willis in 20% to 30% of patients. We assessed the diagnostic efficacy of contrast-enhanced transcranial color-coded duplexsonography (TCCD) for noninvasive evaluation of the circle of Willis in stroke patients with limited bone windows. METHODS: Of 171 consecutive patients who presented with ischemic symptoms in the middle cerebral artery (MCA) territory, 49 patients (32 female, 17 male; age range, 70.5+/-10.6 years) had no detectable colorflow signals from the circle of Willis by TCCD because of limited acoustic windows. These 49 patients received an IV injection of a sonographic contrast-enhancing agent, Levovist (Schering; Berlin, Germany), and were re-examined. Correlative imaging studies of the circle of Willis were obtained in 42 of 49 of these patients. RESULTS: In 38 of 49 patients, contrast-enhanced TCCD enabled full visualization of the circle of Willis bilaterally; in an additional five patients, contrast-enhanced TCCD revealed only the portion of the circle of Willis ipsilateral to the probe through one temporal bone. In six of these 43 patients, contrast-enhanced TCCD showed MCA stenosis and MCA occlusion in three; three of the six cases of MCA stenosis and all three cases of the MCA occlusion were found on the symptomatic side. In six of 49 patients, no colorflow signals were obtained after contrast enhancement. All contrast-enhanced TCCD findings were confirmed by CT angiography, transfemoral digital subtraction angiography, MR angiography, or a combination of all three correlative studies. Levovist produced no serious adverse events. CONCLUSION: In stroke-age patients with limited acoustic windows, contrast-enhancement with Levovist can markedly increase the sensitivity of TCCD and increase the detection of clinically relevant intracranial arterial disease.

Effects of tissue type plasminogen activator in embolic versus mechanical models of focal cerebral ischemia in rats.

Tissue type plasminogen activator (tPA) can be effective therapy for embolic stroke by restoring cerebral perfusion. However, a recent experimental study showed that tPA increased infarct size in a mouse model of transient focal ischemia, suggesting a possible adverse effect of tPA on ischemic tissue per se. In this report, the effects of tPA in two rat models of cerebral ischemia were compared. In experiment 1, rats were subjected to focal ischemia via injection of autologous clots into the middle cerebral artery territory. Two hours after clot injection, rats were treated with 10 mg/kg tPA or normal saline. Perfusion-sensitive computed tomography scanning showed that tPA restored cerebral perfusion in this thromboembolic model. Treatment with tPA significantly reduced ischemic lesion volumes measured at 24 hours by >60%. In experiment 2, three groups of rats were subjected to focal ischemia via a mechanical approach in which a silicon-coated filament was used intraluminally to occlude the origin of the middle cerebral artery. In two groups, the filament was withdrawn after 2 hours to allow for reperfusion, and then rats were randomly treated with 10 mg/kg tPA or normal saline. In the third group, rats were not treated and the filament was not withdrawn so that permanent focal ischemia was present. In this experiment, tPA did not significantly alter lesion volumes after 2 hours of transient focal ischemia. In contrast, permanent ischemia significantly increased lesion volumes by 55% compared with transient ischemia. These results indicate that in these rat models of focal cerebral ischemia, tPA did not have detectable negative effects. Other potentially negative effects of tPA may be dependent on choice of animal species and model systems.

Dodecafluoropentane ultrasonic contrast enhancement in carotid diagnosis: preliminary results.

To assess the efficacy in carotid diagnosis of an investigational dodecafluoropentane ultrasonic contrast enhancing agent, we compared B-mode, color flow, and duplex Doppler findings in 16 patients with common carotid artery bifurcation disease after dodecafluoropentane and saline injections. Dodecafluoropentane produced enhanced backscatter in all patients for 4 to 20 min (mean, 8.4+/-4.74 min) after intravenous injection. In six patients this enhancement improved the color flow and pulsed Doppler signal detection in areas of sonographic shadowing. The enhanced color flow information changed the diagnostic impression in one case. Dodecafluoropentane produced enhanced backscatter in the carotid artery in all patients, and for a mean duration longer than that reported for other agents. It has the potential to improve the efficacy of carotid ultrasonic evaluation.

Gadolinium-enhanced MR angiography of the carotid arteries.

To assess the efficacy of gadolinium (Gd)-enhanced magnetic resonance angiography (gdMRA) in overcoming signal dropout artifacts on conventional MRA (cMRA), the authors examined 13 patients with suspected neurovascular stenotic/occlusive lesions on MRA pre- and post-gadolinium enhancement. The sample consisted of 18 internal carotid artery (ICA) les ons (16 extracranial, 2 cranial). In 13 of 16 stenotic vessels, gdMRA better characterized the pathoanatomy of moderate to severe stenotic lesions, changing MRA diagnosis in 3 patients. In zero of three vessels with no flow enhancement by cMRA, the lumen remained nonvisualized on gdMRA. For an ICA lesion at the skull base, enhancement of surrounding normal structures limited the usefulness of the technique. The authors conclude that Gd MRA is a fast, accurate, and convenient noninvasive technique for documenting the morphology and severity of carotid stenotic disease, especially extracranially.

[Ultrasound contrast media for neurovascular applications]. / Ultraschall-Kontrastmittel für neurovaskuläre Anwendungen.

Ultrasound is widely used in the assessment of neurovascular diseases. In spite of its effectiveness there are considerable limitations such as low flow detection in carotid disease or limited bony windows in transcranial Doppler. One approach to overcome these limitations is the use of ultrasound contrast enhancing agents. The usefulness of ultrasound contrast enhancing agents Levovist, EchoGen and BY 963 in neurovascular applications has been evaluated. Contrast enhanced colourflow Doppler for the diagnosis of carotid disease has been investigated in three small trials and might be effective for improving the diagnostic yield in severe disease. Contrast enhanced transcranial colourflow Doppler has been relatively more widely explored also with promising results. Based on the combined findings out of these preliminary investigational trials, it appears to be reasonable to undertake larger trials for assessment of usefulness of ultrasound contrast agents for a variety of neurovascular applications.

Arteriovenous malformation hemodynamics: a transcranial Doppler study.

Congenital arteriovenous malformation (AVM) of the brain represents a defect in capillary development resulting in a high flow fistula between arterial and venous systems. In this study, AVM hemodynamics were related with clinical findings. Volume flow was calculated based on transcranial Doppler (TCD) and angiographic data. Forty patients admitted to the Massachusetts General Hospital for proton beam therapy (33 +/- 10 yr old; mean +/- SD) were studied. Four symptoms were considered: intracranial bleeding, progressive neurological deficit, seizures, and headache. Fourteen control subjects aged 30 +/- 7 years (mean +/- SD) were normal volunteers. Angiography with calibrated markers permitting magnification correction was available for all patients. Lateral and medial depth limits of the intracranial basal arteries in relation to the TCD temporal window were determined by TCD and angiogram with excellent correlation. Selected depth for data acquisition was determined independently in the angiogram and by TCD. The difference between the two techniques was less than 4 mm. Mean flow velocity, pulsatility index, and vessel diameter were studied. Flow volume was calculated from these data. Mean flow velocity, pulsatility index, vessel diameter, and flow volume were significantly different among AVM feeders, non-feeders, and control arteries. The non-feeding middle cerebral artery, anterior cerebral artery, and posterior cerebral artery flows were 254 +/- 13, 136 +/- 14, and 79 +/- 8 ml/min, respectively. Accordingly, the estimated cerebral flow volume was 938 ml/min. The feeding middle cerebral artery, anterior cerebral artery, and posterior cerebral artery flows were 552 +/- 47, 369 +/- 70, and 484 +/- 67 ml/min, respectively (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Dipole-tracing of abnormal slow brain potentials after cerebral stroke--EEG, PET, MRI correlations.

A patient with major neurological deficits 5 years after a left cerebral infarction underwent correlative EEG, MRI and PET studies of cerebral blood flow and oxygen metabolism. The EEG showed abnormal slow electroencephalographic activity in the frontopolar region. The intracranial location of the slow electrical activity was estimated, as an equivalent current dipole, by using a newly developed dipole tracing (DT) method. The DT analysis showed that the dipole equivalent of the slow wave is approximately located at the frontal part of the left cingulate gyrus, away from the margins of the infarction and enlarged left lateral ventricle demonstrated by MRI, and in a region with intact oxygen consumption rate. The genesis of the slow wave is discussed.

Evaluation of the 11CO2 positron emission tomographic method for measuring brain pH. II. Quantitative pH mapping in patients with ischemic cerebrovascular diseases.

A practical method has been developed that, using 11CO2 and positron emission tomography (PET), computes and maps (a) "effective pH" (pHt), a weighted average of intra- and extracellular pH, and (b) "clearance" (K1), product of blood flow and 11CO2 extraction. This method, together with measurements of cerebral blood flow (CBF) and oxygen extraction fraction (OEF), was applied to 12 patients with cerebral ischemia or stroke. The regional K1 was positively correlated with CBF (n = +0.78). The k1/CBF ratio, representing the extraction fraction ratio of 11CO2 to H2 15O, was negatively correlated with CBF (r = -0.54), suggesting that 11CO2 extraction decreases as flow increases. In five acute stroke patients within 2 days of onset, the injured cortex had lower CBF (20.6 ml/min/100 g), higher OEF (78.1%), and lower pHt (6.96) than the contralateral cortex (CBF = 41.4 ml/min/100 g, OEF = 53.3%, pHt = 7.00), suggesting intracellular acidosis with intact cell membranes. In three stroke patients 5-8 days after onset, the injured cortex had higher CBF (60.9 ml/min/100 g), lower OEF (32.0%), and higher pHt (7.12) than the contralateral cortex (CBF = 45.3 ml/min/100 g, OEF = 58.0%, pHt = 7.06), which suggested an increase in extracellular volume compartment reflecting loss of cell membrane integrity. This method provides information on the regional tissue acid-base status and cell membrane integrity, which may be prognostic of tissue viability.

The 15O steady-state method: correction for variation in arterial concentration.

One of the factors limiting the accuracy of the 15O steady-state method for the measurement of regional cerebral blood flow and oxygen metabolism is the requirement that a constant arterial blood concentration be maintained over long periods. A new method has been developed to correct for the variation of the arterial concentration in the C15O2 and 15O2 steady-state inhalation technique. The time course of the arterial activity is obtained by multiple sampling over the study period. The same 15O model as is used in the steady-state method is employed but is solved without assuming equilibrium. Look-up tables are generated to relate flow and oxygen extraction fraction to tissue activity, and from them the regional parameters are estimated. Theory and simulation studies suggest that substantial improvement in accuracy can be obtained with no increase in statistical error. The validity of the method was checked experimentally by making repeated measurements in the same subject after perturbing the gas delivery. The conventional steady-state method showed significantly larger deviations in repeat measurement than did the new method. Thus, it is concluded that the proposed method is superior.

Measurement of end-capillary PO2 with positron emission tomography.

The analysis of positron emission tomography measurements of oxygen metabolism has been extended to provide a quantitative estimate of end-capillary PO2. The principle of this extension rests on the idea that the oxygen extraction fraction can be used to calculate the end-capillary oxygen saturation of the blood. The relation between oxygen saturation and PO2 is obtained through the oxygen dissociation curve. Our studies show that in addition to the local oxygen extraction fraction, arterial PO2 and pH values are needed in the calculation, whereas fairly large variations in factors such as PCO2, hematocrit, hemoglobin, and plasma protein levels have little or no effect. Rough estimates of end-capillary PO2 can be made using standard O2 dissociation nomograms. Blood gas and acid-base properties of blood have been known for decades, making it possible to account accurately for individual differences that may be encountered when studying patients. Measurements in nine normal subjects yielded a mean end-capillary PO2 value of 31.2 mm Hg. The ability to make a quantitative visualization of altered patterns of end-capillary PO2 provides an additional dimension to the investigation of stroke disease and tumor metabolism.

Evaluation of the 11CO2 positron emission tomographic method for measuring brain pH. I. pH changes measured in states of altered PCO2.

The 11CO2 method for measuring local brain pH with positron emission tomography (PET) has been experimentally evaluated, testing the adequacy of the kinetic model and the ability of the method to measure changes in brain pH. Plasma and tissue time/activity curves measured during and following continuous inhalation of 11CO2 were fit with a kinetic model that includes effects of tissue pH, blood flow, and fixation of CO2 into compounds other than dissolved gas and bicarbonate ions. For each of ten dogs, brain pH was measured with PET at two values of PaCO2 (range 21-67 mm Hg). The kinetic model fit the data well during both inhalation and washout of the label, with residual root mean square (RMS) deviations of the model from the measurements consistent with the statistical quality of the PET data. Brain pH calculated from the PET data shows a linear variation with log(PaCO2). These results were in good agreement with previously reported measurements of brain pH, both in absolute value and in variation with PCO2. The interpretation of these pH values in normal and pathological states is discussed.