Robert H. Ackerman

Whole blood viscosity parameters and cerebral blood flow.

This report describes the statistical relationship of several whole blood viscosity parameters and cerebral blood flow (CBF) in 53 consecutive patients and normal controls. Significant correlations were present between CBF and serum fibrinogen (P = .05), hematocrit (P less than .05), and a relationship involving both fibrinogen and hematocrit (P less than .01). We conclude that heightened whole blood viscosity does correlate with decreased cerebral blood flow in the ranges measured in our patients, that both fibrinogen and hematocrit must be taken into consideration in viscosity determinations, and that changes in viscosity may have an important effect on CBF in regions of low flow.

Strategy for the Measurement of Regional Cerebral Blood Flow Using Short-Lived Tracers and Emission Tomography

This report describes a strategy for measurement of regional CBF that rigorously accounts for differing tracer partition coefficients and recirculation, and is convenient for use with positron emission tomography. Based on the Kety model, the measured tissue concentration can be expressed in terms of the arterial concentration, the rate constant K, and the blood flow f. The local partition coefficient may be computed as p = f/K. In our approach, maps of K and f are computed from two transverse section reconstructions. The reconstructions are based on weighted sums of projection data measured frequently during the observation period. Theoretical studies of noise propagation in the estimates of K and f were carried out as a function of tomographic count rate, total measurement time, and tracer half-life for varying input functions. These calculations predict that statistical errors in f of between 5 and 10% at a resolution of 1 cm full width at half maximum can be obtained with existing tomographs following i. v. injection. To compare theory and experiment, a series of flow studies were carried out in phantoms using a positron tomograph. These measurements demonstrate close agreement between computed flow and noise estimates and those measured in a controlled situation. This close agreement between theory and experiment as well as the low statistical errors observed suggest that this approach may be a useful tool in clinical investigation.

Cerebral blood flow and cerebrovascular CO2 reactivity in stroke‐age normal controls

We used the noninvasive 133-xenon inhalation technique to determine cerebral hemodynamics in 55 normal volunteers aged 18 to 88. Values for cerebral blood flow and cerebrovascular CO2 reactivity in fastclearing tissue (flow gray) and slow-clearing tissue (flow white) were examined as functions of age and in relation to hematocrit, blood pressure, and evidence of extracranial vascular disease. Flow gray declined linearly with age, but no corresponding change was found in flow white or in CO, reactivity. The data suggest that the progressive fall in flow gray is due to a physiologic aging process.

Estimation of the Local Statistical Noise in Emission Computed Tomography

A simple modification of the filtered backprojection algorithm is presented for the computation of the local statistical noise in emission computed tomography. The technique is general in that any distribution of radioactivity may be accommodated. When applied to positron emission tomography, it is shown that the effects of photon absorption, random coincidences, radioactive decay, and detector nonuniformity may be included. Calculations have shown the effects of resolution, object size, and photon absorption on the statistical noise of disk-shaped emitters. Comparison of calculation and experiment show close agreement both in magnitude and spatial variation. Measurements of the noise level in tomograms of the brain obtained during continuous inhalation of 150-CO2 demonstrate that estimates of radioactivity concentration with a precision of a few percent are readily attainable.

A perspective on noninvasive diagnosis of carotid disease.

Since C. Miller Fisher defined the clinical syndrome of carotid occlusive disease in 1951,’ physicians have sought methods of diagnosing common and internal carotid lesions without subjecting the patient to arteriography. A large number of noninvasive tests have been developed (tables 1 and 2,2-29), testifying to the difficulty in finding a fully satisfactory one and to the technologic advances that have multiplied the number of possible ways to monitor the anatomy and physiology of the carotid system. Some observers maintain a healthy skepticism about noninvasive diagnosis of carotid disease, claiming that the hemodynamic tests cannot tell us about atheromatous plaques and that the tests that provide anatomic information cannot resolve ulcerative lesions. Moreover, in 1979 we still do not fully understand the epidemiology of carotid disease, the pathophysiology of occlusive changes, the natural history. of carotid lesions, and the mechanism of ischemic insults distal to a diseased bifurcation. Therefore, we do not necessarily know which lesions are important for us to look for and act upon. Identification of asymptomatic lesions, for example, may lead to surgery that is not indicated. Other observers hisve become enthusiastic about the possibility of noninvasive diagnosis of carotid disease as a means of identifying a treatable cause of stroke and of learning about features of carotid lesions that may halve prognostic importance. At the Massachusetts General Hospital (MGH) we have, over the past 5 t o 6 years, developed a Carotid Evaluation Laboratory (CEL) and have worked with a variety of tests (table 3); therefore, we receive numerous inquiries about the direction of the field. Three common questions are asked: (1) “Can noninvasive diagnosis replace arteriography?” (2) “Is it any good?’ and (3) “Which is the best test?” The purpose of this editorial is to help put in perspective developments in noninvasive diagnosis of carotid disease. Briefly, noninvasive testing should not replace arteriography. It can be important in evaluating patients with suspected carotid lesions and in providing insights into the natural history and pathophysiology of carotid disease. No “best test” exists; rather, a battery of tests is most effective for noninvasive diagnosis of carotid disease. The instrumentation and techniques can be confusing. The same name may be applied to tests that monitor different functions (tables4 and 5 ) and the same physiologic event can be used to provide different types of information for several tests (table 6). We divide the techniques for noninvasive diagnosis into direct and indirect tests (table 2). The direct tests examine the anatomy and/or physiology of the carotid artery itself. The indirect tests examine for hemodynamic changes in distal beds such as the orbital and cerebral circulations. Because the ophthalmic is the first major branch of the internal carotid, obstructive lesions at the bifurcation will cause pressure and flow changes in the orbital branches of the ophthalmic and their periorbital distributions. The indirect tests that monitor the orbital bed are the most common noninvasive techniques in use today, especially periorbital directional Doppler ultrasonography (PDDU) and two types of oculoplethysmography (OPG). Ginsberg, Greenwood, and Goldberg compare and discuss PDDU and one type of OPG elsewhere in this journal.31 We have arbitrarily designated the OPG which determines systolic ophthalmic artery pressure (Gee method) as OPG-P, and the method monitoring the relative arrival time of the ocular pulse waves (Kartchner and McRae method) as OPG-F because the results are related to flow. Attempts are being made to incorporate both techniques in one instrument. The indirect tests require a hemodynamic change before they become positive and therefore

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.

Temporary Neurological Deterioration after Extracranial-Intracranial Bypass

Five patients who experienced temporary neurological deterioration after extracranial to intracranial bypass procedures are reported in detail. These patients suffered transient ischemic attacks or more prolonged deficits usually of a different nature than the preoperative symptoms. All patients had a good outcome and the spells ceased; the neurological deficits improved within a maximum of 2 weeks. Obvious causes of deterioration such as intra- or extracerebral hematomas, occlusion of a previously stenotic vessel, or graft occlusion were ruled out by computed tomography and angiography in each case. Intraoperative causes of neurological deterioration such as anesthetic effect, hypotension, and temporary occlusion of the cortical vessel or sacrifice of its small branches were not likely to be the cause of the deficits because in each case, the patient awoke satisfactorily and deterioration occurred hours to days later. In each case, postoperative angiography showed good perfusion of at least one major division of the middle cerebral territory. Anticoagulation with heparin in three patients did not change the clinical course. In one patient who was not anticoagulated, embolism could have been responsible for a single prolonged ischemic event, but in the other patients thromboembolism does not seem likely to have been responsible for the deficits. The cause of the deterioration in these patients remains unexplained. We speculate that hyperperfusion of chronically ischemic brain tissue and shifts in the watershed region resulting from the new flow pattern after bypass grafting are two mechanisms that may have been of importance in the etiology of these deficits.

Computed tomography of cerebral infarction: Hemorrhagic, contrast enhancement, and time of appearance

Large confluent petechial hemorrhages and/or hemorrhage within infarct may be seen on CT scan. Small petechial hemorrhages are not resolved by current equipment and techniques. Elevation of absorption values of an infarct following contrast media primarily occurs in the first month after onset, and may be occasionally confused with a tumor. Sequential CT changes in infarcts correlate well with established pathologic changes. Cerebral infarction may be seen on CT scan in some cases as early as 24--48 hr after its onset.

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)

Interleukin-1 receptor antagonist gene polymorphisms in carotid atherosclerosis

Background and Purpose— Inflammation plays an important role in the development of atherosclerosis. The gene for the counterinflammatory cytokine interleukin–1 receptor antagonist (IL-1ra) is polymorphic, and high frequencies of allele 2 have been found to be associated with other inflammatory diseases. This study examined the association of allele and carrier frequencies of the IL-1ra gene with the presence of carotid atherosclerosis and plaque symptomaticity. Methods— A total of 328 subjects identified as having carotid atherosclerosis or no atherosclerosis (controls) participated. Blood was obtained for DNA determination. Results— Frequency of allele 2 was significantly greater in patients with atherosclerosis compared with nonatherosclerotic subjects. No difference was seen between symptomatic and asymptomatic atherosclerosis patients. Noncarriage of allele 2 was associated with reduced likelihood of atherosclerosis (odds ratio [OR], 0.44; 95% CI, 0.27 to 0.71). The homozygous carrier state for allele 2 was associated with greater likelihood of atherosclerosis (unadjusted OR, 7.30; 95% CI, 2.31 to 22.94; adjusted OR, 13.78; 95% CI, 1.94 to 97.9). A gene-dose effect was detected. Conclusions— These data suggest that allele 2 of the IL-1ra gene represents a susceptibility factor in the development of carotid atherosclerosis. Further investigation appears warranted.