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Biomedical subjects

M E Raichle

Publications and source records attributed to M E Raichle.

At least 109 records · Page 6Linked to original sources
PubMed1987

Left globus pallidus abnormality in never-medicated patients with schizophrenia.

Schizophrenia is a severe psychiatric disorder characterized by onset in young adulthood, the occurrence of hallucinations and delusions, and the development of enduring psychosocial disability. The pathophysiology of this disorder remains unknown. Studies of cerebral blood flow and metabolism designed to identify brain abnormalities in schizophrenia have been limited by inadequate methods of anatomical localization and the possibility of persistent medication effects. We have now used positron emission tomography and a validated method of anatomical localization in an attempt to identify abnormalities of regional cerebral blood flow in newly diagnosed never-medicated patients with schizophrenia. An exploratory study of 5 patients and 10 normal control subjects identified abnormally high blood flow in the left globus pallidus of patients with schizophrenia. A replication study of 5 additional patients and 10 additional control subjects confirmed this finding. No other abnormalities were found.

Adolescent↗
PubMed1987

MPTP-induced up-regulation of in vivo dopaminergic radioligand-receptor binding in humans.

We measured in vivo dopaminergic receptor binding using positron emission tomography and 18F-spiperone in an untreated symptomatic subject with MPTP-induced parkinsonism. Our technique determines four variables related to entry of 18F-spiperone into brain tissue and subsequent binding to receptors: (1) the combined forward-rate constant k1' (equal to the product of the maximum number of available specific binding sites, Bmax, times the association rate constant [ka] of 18F-spiperone and receptor); (2) the binding site dissociation rate constant k-1; (3) the free fraction of radioligand not specifically bound in brain tissue, f2; and (4) the regional permeability-surface-area product (PS) of the blood-brain barrier for spiperone. PS and f2 in the patient were not different from that of 10 normal volunteers, whereas the combined forward-rate constant (left caudate: k1' = 67.6 sec-1, normal = 0.140 +/- 0.056) and the dissociation rate constant (left caudate: k-1 = 0.116 sec-1, normal = 0.000339 +/- 0.000149) were evaluated. These findings provide potential new insights not only into the pathophysiology of this disease but into the clinical importance of dopamine receptor function as well.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Mapping human somatosensory cortex with positron emission tomography.

Positron emission tomography measurements of regional cerebral blood flow were used to detect focal neuronal activation in the first somatosensory cortex (SI) of humans induced by cutaneous vibratory stimulation. Intravenously administered water labeled with oxygen-15 (H2(15)O) was used as a blood flow tracer to obtain five stimulated-state and two resting-state blood flow images in each of eight normal volunteers. Three cutaneous surfaces were tested: lips, fingers, and toes. Intense, highly focal SI responses were seen during all 39 stimulated-state trials. The SI responses from the three stimulation sites were anatomically distinct and formed a medial-to-lateral homonculus in every subject. Response magnitudes (increase in local blood flow) and response locales (expressed as proportionately measured bicommissural stereotaxic coordinates) were highly consistent among subjects and on repeated trials for each subject. These findings suggest that eliciting cerebral blood flow responses by cutaneous vibration provides a safe, rapid, and reproducible tool for locating and assessing the functional status of somatosensory cortex, and offers potential clinical and research utility. This study has established normative values for future applications of this experimental paradigm.

Brain Mapping↗
PubMed1987

The effect of hemodynamically significant carotid artery disease on the hemodynamic status of the cerebral circulation.

Although the presence of a hemodynamically significant carotid artery lesion is commonly used as an indicator of impaired cerebral circulation, the effect of such lesions on cerebral perfusion pressure and cerebral blood flow has never been determined accurately. We used positron emission tomography (PET) to study 19 patients with unilateral hemodynamically significant carotid artery disease (greater than 66% diameter reduction) and no evidence of cerebral infarction. According to PET measurements in the cerebral hemisphere distal to the lesion, 7 patients had normal cerebral hemodynamics, 8 had reduced perfusion pressure with normal blood flow, and 4 had reduced blood flow. Neither the percent stenosis nor the residual lumen diameter in the carotid artery was a reliable indicator of the hemodynamic status of the cerebral circulation. However, a significant relationship was found between the PET measurements of cerebral hemodynamics and the arteriographic circulation pattern (p = 0.006). The role of hemodynamic factors in the pathogenesis and treatment of cerebrovascular disease cannot be determined from the severity of carotid artery disease alone.

Aged↗
PubMed1987

Retinotopic organization of human visual cortex mapped with positron-emission tomography.

The retinotopic organization of primary visual cortex was mapped in normal human volunteers. Positron-emission tomographic measurements of regional cerebral blood flow were employed to detect focal functional brain activation. Oxygen-15-labeled water, delivered by intravenous bolus, was used as the blood flow tracer to allow multiple stimulated-state (n = 5) and control-state (n = 3) measurements to be acquired for each of 7 subjects. Responses were identified by applying a maximum-detection algorithm to subtraction-format images of the stimulus-induced change in cerebral blood flow. Response locales were described using a standardized system of stereotactic coordinates. Changes in stimulus location (macular, perimacular, peripheral, upper-field, lower-field) caused systematic, highly significant changes in response locale within visual cortex. Discrete extrastriate visual responses were also observed.

Adult↗
PubMed1986

Correction of positron emission tomography data for cerebral atrophy.

Because positron emission tomography (PET) provides measurements per unit volume of intracranial contents, these measurements may be affected by the inclusion of metabolically inactive CSF spaces in the volume in which they are made. Thus, PET measurements of CBF and metabolism may be artifactually lowered in normal aging and dementia, which are both associated with significant brain atrophy. We describe a method to correct global PET data, averaged over several tomographic slices, for cerebral atrophy by using measurements of CSF space volume obtained with quantitative x-ray computed tomography. The importance of making such a correction is demonstrated using PET measurements of CBF and oxygen metabolism obtained in normal young, normal elderly, and demented subjects.

Adult↗
PubMed1986

Strategies for in vivo measurement of receptor binding using positron emission tomography.

Dopaminergic ligands labeled with positron-emitting radionuclides have been synthesized for quantitative evaluation of dopaminergic binding in vivo. Two different methods, the explicit method and an operationally simplified ratio method, have been proposed for analysis of these positron emission tomographic (PET) data. The basis for both methods is the same three-compartment model. The two methods differ in the assumptions necessary for practical implementation. We have compared these two approaches using PET data obtained in our laboratory. Sequential scans and serial arterial blood samples from a baboon following intravenous injection of [18F]spiroperidol were collected. Application of the two methods to the same data yielded different values for corresponding parameters. Values calculated by the ratio method for the specific rate constant describing receptor binding varied depending upon the time after tracer injection, thus demonstrating an internal inconsistency in this approach. Tracer metabolism markedly affected the binding measurements calculated with either method and thus cannot be ignored. Our results indicate that the adoption of simplifying assumptions for operational convenience can lead to substantial errors and must be done with caution. Alternatively, we present simple new analytical solutions of the tracer conservation equations describing the complete, unsimplified three-compartment model that vastly reduce the computations necessary to implement the explicit method.

Animals↗
PubMed1986

Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects.

Coupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) was studied using multiple sequential administrations of 15O-labeled radiotracers (half-life, 123 sec) and positron emission tomography. In the resting state an excellent correlation (mean r, 0.87) between CBF and CMRO2 was found when paired measurements of CBF and CMRO2 from multiple (30-48) brain regions were tested in each of 33 normal subjects. Regional uncoupling of CBF and CMRO2 was found, however, during neuronal activation induced by somatosensory stimulation. Stimulus-induced focal augmentation of cerebral blood flow (29% mean) far exceeded the concomitant local increase in tissue metabolic rate (mean, 5%), when resting-state and stimulated-state measurements were obtained in each of 9 subjects. Stimulus duration had no significant effect on response magnitude or on the degree of CBF-CMRO2 uncoupling observed. Dynamic, physiological regulation of CBF by a mechanism (neuronal or biochemical) dependent on neuronal firing per se, but independent of the cerebral metabolic rate of oxygen, is hypothesized.

Adult↗
PubMed1986

The application of positron emission tomography to the study of panic disorder.

Positron emission tomography was used to study eight patients with panic disorder who were vulnerable to lactate-induced panic, eight patients with panic disorder who were not vulnerable to lactate-induced panic, and 25 normal control subjects. Patients who were vulnerable to lactate-induced panic had several abnormalities in the resting, nonpanic state: an abnormal hemispheric asymmetry of parahippocampal blood flow, blood volume, and oxygen metabolism; abnormally high whole brain metabolism; and abnormal susceptibility to episodic hyperventilation. A hypothetical model for the neurobiology of panic disorder, involving the abnormal parahippocampal region and its afferent and efferent connections, is proposed.

Adult↗
PubMed1985

Positron emission tomography in the asphyxiated term newborn: parasagittal impairment of cerebral blood flow.

Hypoxic-ischemic encephalopathy secondary to perinatal asphyxia in the term newborn is the most common recognized cause of the subsequent motor deficits often grouped under the rubric "cerebral palsy." In order to provide insight into the basic nature and pathogenesis of the brain injury in such infants, we studied regional cerebral blood flow (CBF) by positron emission tomography (PET) in 17 asphyxiated term infants during the acute period of illness. A consistent and apparently unifying abnormality was observed, namely, a relative decrease in CBF to parasagittal regions, generally symmetrical and more marked posteriorly than anteriorly. Thus, parasagittal values for CBF were generally 25 to 50% lower than those for the sylvian cortex; in the normal or near normal infant, parasagittal values are only approximately 10% lower than those for the sylvian cortex. (Additional normal findings for regional CBF were 50% higher flows to the cerebral cortex than to the cerebral white matter and flows to the basal ganglia and thalamus at least as high as those to the cerebral cortex). That the relative deficit in CBF to parasagittal regions reflects tissue injury was indicated by the close topographic correlation on technetium brain scans in 3 patients of increased tissue uptake of radionuclide and the CBF abnormality. Moreover, the single patient studied at postmortem examination exhibited parasagittal ischemic cerebral injury that correlated well with the PET abnormality of regional CBF. The topography of the PET abnormality, i.e., the cerebrovascular watershed regions, suggests that the brain injury is basically ischemic and that the pathogenesis relates to impaired cerebral perfusion, perhaps secondary to systemic hypotension occurring in association with the perinatal asphyxia. Experimental data support this formulation.

Asphyxia Neonatorum↗
PubMed1985

Stimulus rate determines regional brain blood flow in striate cortex.

Intravenous bolus administration of oxygen 15-labeled water and positron emission tomography were used to measure changes in brain blood flow induced by two modes of photic stimuli over a wide range of repetition rates. These stimuli (patterned-flash and reversing checkerboard) were chosen in order to determine whether stimulus luminance or stimulus frequency was responsible for previously observed increases in blood flow in the striate cortex during photic stimulation. The response curves of blood flow change as a function of stimulus rate were nearly identical for both stimuli. These results suggest that elementary stimulus variables, such as repetition rate, can have a major effect on local cerebral responses, as measured with positron emission tomography and other radiotracer methods.

Female↗
PubMed1985

Tonotopic organization in human auditory cortex revealed by positron emission tomography.

Positron emission tomography (PET) was used to map alterations in local neuronal activity induced in human primary auditory cortex by pure-tone stimulation. Patterns of blood flow were observed in specific regions on the superior temporal plane showing systematic changes in activity depending on the frequency of a stimulating pure tone. The orientation of these regions agrees well with data for non-human primates.

Acoustic Stimulation↗
PubMed1985

Standardized mean regional method for calculating global positron emission tomographic measurements.

A new "mean regional" method for calculating global hemispheric values of blood flow, blood volume, and metabolism with positron emission tomography is presented. It is based on a standardized set of regions defined according to coordinates in a stereotactic atlas of the brain. Region locations in each individual scan were determined by a localization technique that is independent of the appearance of the physiological images. Measurements obtained with this mean regional method minimize contributions from nonbrain structures such as ventricles or venous sinuses and provide the necessary basis for comparisons among different subjects and laboratories.

Adult↗
PubMed1985

Cerebral blood flow and cerebral metabolic rate of oxygen requirements for cerebral function and viability in humans.

This study was undertaken to determine the minimum CBF and CMRO2 required by the human brain to maintain normal function and viability for more than a few hours. Positron emission tomography (PET) was used to perform regional measurements in 50 subjects with varying degrees of cerebral ischemia but no evidence of infarction. There were 24 normal subjects, 24 subjects with arteriographic evidence of vascular disease of the carotid system, and two subjects with reversible ischemic neurological deficits due to cerebral vasospasm. Minimum values found in the 48 subjects with normal neurological function were 19 ml/100 g-min for regional cerebral blood flow (rCBF) and 1.3 ml/100 g-min for regional cerebral metabolic rate of oxygen (rCMRO2). Minimum values for all 50 subjects with viable cerebral tissue were 15 ml/100 g-min for rCBF and 1.3 ml/100 g-min for rCMRO2. Comparison of these measurements with values from 20 areas of established cerebral infarction in 10 subjects demonstrated that 80% (16/20) of infarcted regions had rCMRO2 values below the lower normal limit of 1.3 ml/100 g-min. Measurements of rCBF, regional cerebral blood volume, and oxygen extraction fraction were less useful for distinguishing viable from infarcted tissue. These data indicate that quantitative regional measurements of rCMRO2 with PET accurately distinguish viable from nonviable cerebral tissue and may be useful in the prospective identification of patients with reversible ischemia.

Adult↗
PubMed1985

What is the correct value for the brain--blood partition coefficient for water?

A knowledge of the brain-blood partition coefficient (lambda) for water is usually required for the measurement of CBF with [15O]water. The currently accepted value for whole-brain lambda, 0.95-0.96 ml/g, calculated from brain and blood water content data, is incorrect because in the calculation, the blood water content was not adjusted for the density of blood. The correct value is 0.90 ml/g. Variations in brain or blood water content affect lambda. Thus, lambda changes during development of the brain and varies regionally in it, even among different gray matter structures, owing to variation in brain water content. In addition, lambda would be expected to vary with the hematocrit, owing to changes in blood water content. The impact of using an incorrect value for lambda will depend on the sensitivity of the CBF measurement technique used to errors in lambda.

Blood-Brain Barrier↗
PubMed1985

Functional mapping of the human cerebellum with positron emission tomography.

Alterations of local neuronal activity induced within the human cerebellum by tactile stimulation and voluntary movement were mapped with positron emission tomographic measurements of brain blood flow. Finger movements produced bilateral, parasagittal blood-flow increases in anterior, superior hemispheric cortex of the cerebellum. Responses to tactile finger stimulation were coextensive with responses to voluntary finger movements but were less intense. Saccadic eye movements produced midline blood-flow increases in the posterior vermis of the cerebellum. Positron emission tomography now permits investigation of functional-anatomical relations within the human cerebellum.

Brain Mapping↗