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Biomedical subjects

M E Raichle

Publications and source records attributed to M E Raichle.

At least 145 records · Page 8Linked to original sources
PubMed1984

Stimulus rate dependence of regional cerebral blood flow in human striate cortex, demonstrated by positron emission tomography.

The purpose of this investigation was to determine the relationship between the repetition rate of a simple sensory stimulus and regional cerebral blood flow (rCBF) in the human brain. Positron emission tomography (PET), using intravenously administered H2(15)O as the diffusible blood-flow tracer, was employed for all CBF measurements. The use of H2(15)O with PET allowed eight CBF measurements to be made in rapid sequence under multiple stimulation conditions without removing the subject from the tomograph, thus minimizing changes in base-line CBF and in head position due to longer intervals between scans. Nine normal volunteers each underwent a series of eight H2(15)O PET measurements of CBF. Initial and final scans were made during visual deprivation. The six intervening scans were made during visual activation with patterned-flash stimuli given in random order at 1.0-, 3.9-, 7.8-, 15.5-, 33.1-, and 61-Hz repetition rates. In each subject the region of greatest rCBF increase was determined. Within this region the rCBF was determined for every test condition and then expressed as the percentage change from the value of the initial unstimulated scan (rCBF% delta). Anatomical localization of the region of greatest rCBF response was performed employing bony landmarks from a lateral skull radiograph, a template of the cranium created from a transmission attenuation scan and a stereotaxic atlas. In every subject, striate cortex rCBF% delta varied systematically with stimulus rate. Between 0 and 7.8 Hz, rCBF% delta was a linear function of stimulus repetition rate. The rCBF response peaked at 7.8 Hz and then declined. The rCBF% delta during visual stimulation was significantly greater than that during visual deprivation for every stimulus rate except 1.0 Hz. The anatomical localization of the region of peak rCBF response was determined for every subject to be the mesial occipital lobes along the calcarine fissure, primary visual cortex. We conclude that stimulus rate is a significant determinant of rCBF response in the visual cortex. Investigators of brain responses to selective activation procedures should be aware of the potential effects of stimulus rate on rCBF and other measurements of cerebral metabolism. For cerebral responses to selective activation to be meaningfully interpreted, the stimulus repetition rate must be taken into consideration. Response amplitude may be maximized by proper rate selection or be undetectable due to selection of too high or too low a repetition rate. Stimulus rate must be controlled for when responses to unlike stimuli or performance tasks are compared or ambiguities will be present as to whether response differences are

Adult↗
PubMed1984

Extracranial-intracranial bypass surgery: hemodynamic and metabolic effects.

After superficial temporal artery-middle cerebral artery bypass, cerebral blood flow (CBF) in the operated hemisphere increased in 6 of 17 patients. Preoperatively, the symptomatic hemisphere showed lower CBF in all six, lower oxygen metabolism in five, higher blood volume in four, and higher oxygen extraction in two. With the postoperative increase in hemispheric CBF, there was a decrease in oxygen extraction, but no change in blood volume or oxygen metabolism. In these patients, chronic regional hypoperfusion followed major vascular occlusion. Compensatory responses included dilation of intraparenchymal vessels and increased transport of oxygen from blood to tissue. These changes were partially reversed by cerebral revascularization.

Adult↗
PubMed1984

Brain oxygen utilization measured with O-15 radiotracers and positron emission tomography.

We have developed, implemented, and validated a method for the measurement of the local cerebral metabolic rate for oxygen (CMRO2) with positron emission tomography (PET). We use data from a single inhalation of O-15-labeled CO for cerebral blood volume (CBV), an intravenous injection of [O-15]H2O for cerebral blood flow (CBF), and a single inhalation of [O-15]O2 for the final calculation of CMRO2 and the extraction of oxygen (E). The mathematical model used to analyze the data consists of two compartments and accounts for production and egress of water metabolism in the tissue, recirculating water of metabolism, and the arterial, venous, and capillary contents of [O-15]O2 in the brain. We validated our technique in baboons by comparing the PET-measured E with E measured using an intracarotid injection of [O-15]O2. The correlation between these two techniques was excellent. Mathematical simulations were done to examine the effect of errors in CBV, CBF, and recirculating water of metabolism on the measurement of E and CMRO2. The technique was implemented on five normal human subjects in whom the global CMRO2 was 2.93 +/- 0.37 (s.d.) ml/min X 100 g.

Adult↗
PubMed1983

Comparison in animal models of 18F-spiroperidol and 18F-haloperidol: potential agents for imaging the dopamine receptor.

Fluorine-18-labeled haloperidol and spiroperidol have been prepared by an exchange reaction using the corresponding non-labeled compound or the nitro analog. Studies in rats have shown that the distribution of labeled spiroperidol has a high striatum to cerebellum ratio which is not observed with haloperidol. A ratio of 10.66 +/- 1.6 is obtained two hours after administration of the 18F-spiroperidol. When 18F-spiroperidol was administered to a baboon and tomographic images obtained, the dopamine receptor rich areas were clearly visualized two hours after administration.

Animals↗
PubMed1983

The pathophysiology of brain ischemia.

Brain ischemia due to a critical reduction in cerebral blood flow is a well recognized and common cause of irreversible brain damage. The observation that brain cells are more resistant to ischemia than was previously assumed on the basis of clinical experience has stimulated considerable investigative work designed to determine those factors responsible for irreversible ischemic cell damage. At this time, data from these investigations indicate that cellular acidosis and biochemical disturbances initiated by abnormal intracellular ion homeostasis may be especially important in determining the ultimate survival of nerve cells. This review examines the biochemical events initiated by ischemia and their potential role in determining the ultimate survival of brain cells.

Acid-Base Equilibrium↗
PubMed1983

Cerebellar blood flow and metabolism in cerebral hemisphere infarction.

Positron emission tomography was used to study the effect of supratentorial infarction on cerebellar metabolic rate for oxygen and cerebellar blood flow. In a control group of patients, the mean cerebellar metabolic rate for oxygen was 2.97 +/- 0.11 (standard error of the mean [SEM] ) ml-1 . min-1 . hg-1 and mean cerebellar blood flow was 41.1 +/- 1.5 ml . min-1 . hg-1. No significant right-left asymmetry in either cerebellar metabolic rate for oxygen or cerebellar blood flow was noted. Patients with frontal lobe infarction showed 16.8 +/- 1.8% (cerebellar metabolic rate for oxygen) and 19.6 +/- 2.1% (cerebellar blood flow) differences between cerebellar hemispheres, with the hemisphere contralateral to the cerebral infarction having the lower values. These differences were highly significant (p less than 0.001). In addition, cerebellar blood flow and cerebellar metabolic rate for oxygen were significantly decreased in the ipsilateral cerebellar hemisphere (metabolism: 2.13 +/- 0.19 ml . min-1 . hg-1; p less than 0.002; blood flow: 35.2 +/- 2.4 ml . min-1 . hg-1; p less than 0.05). Patients with parietooccipital infarction also showed a significant bilateral decrease in cerebellar metabolic rate for oxygen (2.43 +/- 0.11 ml . min-1 . hg-1) and cerebellar blood flow (34.6 +/- 2.5 ml . min-1 . hg-1) relative to control subjects, but no significant cerebellar asymmetry. Our findings demonstrate a general depression of cerebellar blood flow and metabolism from cerebral hemisphere infarction unrelated to the site of infarction as well as a specific depression occurring contralateral to infarction involving the frontal lobe. These are among the first quantitative data concerning regional cerebellar metabolic rates for oxygen and cerebellar blood flow in humans.

Adult↗
PubMed1983

Neurogenic control of blood-brain barrier permeability.

Evidence from several laboratories strongly suggests that brain capillaries play a dynamic role in the regulation of the internal environment of the brain and, further, that these activities are under neuroendocrine control. First, brain capillaries exhibit a number of anatomical and biochemical features unique to membranes known to regulate water and electrolyte permeability. These include tight junctions between endothelial cells, a high mitochondrial content and a unique compliment of intracellular enzymes. Second, brain capillaries appear to be functionally innervated by adrenergic neurons originating in brain. Finally, brain capillaries exhibit several functional characteristics of membranes that dynamically regulate water and electrolyte permeabilities. These include a restricted permeability to water, a prompt and reversible increase in water permeability to transient hyperosmolarity, a prompt and reversible decrease in permeability to increase perfusion pressure, a change in permeability associated with activation of the central as well as peripheral sympathetic nervous system, and an increase in permeability to centrally administered vasopressin as well as angiotensin II.

Animals↗
PubMed1983

Effect of tissue heterogeneity on the measurement of cerebral blood flow with the equilibrium C15O2 inhalation technique.

The equilibrium C15O2 inhalation method for measuring cerebral blood flow with positron emission tomography (PET) is based on a one-compartment model for which it is assumed that the local flow and partition coefficient are uniform in the tissue region in which flow is to be determined. However, because of the limited spatial resolution of PET, a region of interest will contain a mixture of gray and white matter. We used a computer simulation to examine the effect of this heterogeneity on flow measurement in both normal and pathological states. With gray and white matter flows of 0.80 and 0.20 ml/min/g, respectively, flow is underestimated by a maximum of 20% in a region that is 30% gray. Errors occur not only because of flow heterogeneity, but also because of heterogeneity of partition coefficient and the sensitivity of the method to errors in partition coefficient. Larger errors occur in the case of cerebral hyperemia, although the method becomes more accurate with ischemia. In the case of simulated brain tumor, the accuracy of flow determination varies considerably, depending on the flow and partition coefficient of the tumor and of the surrounding tissue. Finally, incremental changes in gray matter flow, as would occur with functional cortical activation, are not well reflected. Thus, the equilibrium C15O2 inhalation method is limited in its ability to accurately quantitate local cerebral blood flow in heterogeneous tissue regions.

Brain↗
PubMed1983

Brain blood flow measured with intravenous H2(15)O. I. Theory and error analysis.

The tissue autoradiographic method for the measurement of regional cerebral blood flow (rCBF) in animals was adapted for use with positron emission tomography (PET). Because of the limited spatial resolution of PET, a region of interest will contain a mix of gray and white matter, inhomogeneous in flow and in tracer partition coefficient (lambda). The resultant error in rCBF, however, is less than 4%. Although the tissue autoradiographic method requires a monotonically increasing input function to ensure a unique solution for flow, the PET adaptation does not, because of an additional integration in the operational equation. Simulation showed that the model is accurate in the presence of ischemia or hyperemia of the gray matter. Inaccuracy in timing of the arterial input function will result in large errors in rCBF measurement. Propagation of errors in measurement of tissue activity is largely independent of flow, reflecting the nearly linear flow compared with activity relationship.

Cerebrovascular Circulation↗
PubMed1983

Brain blood flow measured with intravenous H2(15)O. II. Implementation and validation.

We have adapted the well-known tissue autoradiographic technique for the measurement of regional cerebral blood flow (CBF), originally proposed by Kety and his colleagues, for the measurement of CBF in human subjects using positron emission tomography (PET) and intravenously administered oxygen-15-labeled water. This report describes the steps necessary for the implementation of this PET/autoradiographic technique. In order to establish the accuracy of the method, we measured CBF with intravenously administered oxygen-15-labeled water and PET in anesthetized adult baboons and compared the results with blood flow measured by a standard tracer technique that uses residue detection of a bolus of oxygen-15-labeled water injected into the internal carotid artery. The correlation between CBF measured with PET and the true CBF for the same cerebral hemisphere was excellent. Over a blood-flow range of 10-63 ml/(min X 100 g), CBF (PET) = 0.90 CBF(true) + 0.40 (n = 23, r = 0.96, p less than 0.001). When blood flow exceeds 65 ml/(min X 100 g) CBF was progressively underestimated due to the known limitation of brain permeability to water.

Adult↗
PubMed1983

Relationship between lipophilicity and brain extraction of C-11-labeled radiopharmaceuticals.

The brain extraction of fifteen C-11-labeled compounds during a single capillary transit was studied in adult baboons by external detection of these tracers after injection into the internal carotid artery. The log Poct (partition coefficient for octanol/water) values of these compounds range from --0.7 to greater than 4.0. A parabolic relationship was found between the log Poct value of the C-11-labeled compounds and the fraction of the radiopharmaceutical entering the brain. Compounds with log Poct values between 0.9 and 2.5 were found to pass freely across the blood-brain barrier at a cerebral blood flow of 100 ml X min-1 X hg-1. An apparently decreased extraction of very lipophilic compounds was shown to be related to binding of the tracer to blood components and macromolecules (red blood cells, albumin, etc.). These data suggest that a radiopharmaceutical designed to measure blood flow should have a log Poct value of between 0.9 and 2.5.

Alcohols↗
PubMed1983

Positron emission tomography in the newborn: extensive impairment of regional cerebral blood flow with intraventricular hemorrhage and hemorrhagic intracerebral involvement.

Of all patients with intraventricular hemorrhage, those with hemorrhagic intracerebral involvement exhibit the highest rates of mortality and neurologic morbidity and, indeed, account for the vast majority of all neurologic impairment in infants with intraventricular hemorrhage. Insight into the basic nature of the critical cerebral involvement requires determination of regional cerebral blood flow, previously not possible. Positron emission tomography (PET) now provides the capability of measuring regional cerebral blood flow with high resolution and little risk. In this study, we utilized PET in six premature infants (920 to 1,200 g) with major intraventricular hemorrhage and hemorrhagic intracerebral involvement to measure regional cerebral blood flow during the acute period (5 to 17 days of age). Cerebral blood flow was determined after intravenous injection of H2O, labeled with the positron-emitting isotope, 15O (oxygen 15). Findings were similar and dramatic in all six infants. In the area of hemorrhagic intracerebral involvement, little or no cerebral blood flow was detected. However, in addition, surprisingly, a marked two- to fourfold reduction in cerebral blood flow was observed throughout the affected hemisphere, well posterior and lateral to the intracerebral hematoma, including cerebral white matter and, to a lesser extent, frontal, temporal, and parietal cortex. In the one infant studied a second time, ie, at 3 months of age, the extent and severity of the decreased cerebral blood flows in the affected hemisphere were similar to those observed on the study during the neonatal period. At the three autopsies, the affected left hemisphere showed extensive infarction, corroborating the PET scans. These observations, the first demonstration of the use of PET in the determination of regional cerebral blood flow in the newborn, show marked impairments in regional cerebral blood flow in the hemisphere containing an apparently restricted intracerebral hematoma, indicating that the hemorrhagic intracerebral involvement is only a component of a much larger lesion, ischemic in basic nature, ie, an infarction. This large ischemic lesion explains the poor neurologic outcome in infants with intraventricular hemorrhage and hemorrhagic intracerebral involvement.

Acute Disease↗
PubMed1982

Antidepressants alter cerebrovascular permeability and metabolic rate in primates.

External detection of the annihilation radiation produced by water labeled with oxygen-15 was used to measure cerebrovascular permeability and cerebral blood flow in six rhesus monkeys. Use of oxygen-15 also permitted assessment of cerebral metabolic rate in two of the monkeys. Amitriptyline produced a dose-dependent, reversible increase in permeability at plasma drug concentrations which are therapeutic for depressed patients. At the same concentrations the drug also produced a 20 to 30 percent reduction in cerebral metabolic rate. At higher doses normal autoregulation of cerebral blood flow was suspended, but responsivity to arterial carbon dioxide was normal.

Amitriptyline↗
PubMed1982

An intravenous technique for the measurement of cerebral vascular extraction fraction in the rat.

An intravenous injection method to measure cerebral vascular extraction fractions of highly diffusible substances in the rat is described. The brain extraction fractions of 3H-labeled water (Ew) and ethanol (Ee) were defined as the ratio of either of those tracers to the freely diffusible reference tracer, 14C-butanol, in the brain, divided by the ratio of the tracers available for the extraction during the time between simultaneous intravenous injection of the tracers and decapitation of the rat. Ew and Ee were measured in five regions of brain, including brainstem and cerebellum, under PaCO2 conditions ranging from 15 to 85 mm Hg. The extraction fractions for both test tracers were shown to vary with PaCO2-induced flow changes according to the equation, ln(1 - E) = -PS/F. When PS/F values calculated from regional measurements of Ew and Ee were plotted versus PaCO2, least squares regression equations of the plots could be used to compare permeabilities of both tracers at any given PaCO2 value. Ratios of the permeabilities of water and ethanol varied regionally but were relatively constant in a given region under different flow states. This intravenous injection method allows for accurate measurement of the extraction fractions of even highly diffusible tracers under varied flow conditions in all brain regions regardless of arterial blood supply.

Animals↗