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Biomedical subjects

J L Tyler

Publications and source records attributed to J L Tyler.

At least 19 recordsLinked to original sources

Functional imaging of epileptic foci with PET and SPECT.

Functional imaging with PET and SPECT provides valuable information, helping lateralize and localize the site of an epileptogenic focus. SPECT imaging has been somewhat hampered by lower resolution than PET, and the lack of true "metabolic" radiopharmaceuticals, however SPECT perfusion studies may also help localize the seizure focus. At present, PET metabolic imaging with FDG is the most sensitive functional imaging modality for identifying epileptogenic foci. However with the current availability, lower cost and improved visualization, the diagnostic and prognostic efficacy of SPECT should increase.

Brain

Measurement of cerebral blood flow and volume with positron emission tomography during isoflurane administration in the hypocapnic baboon.

Using positron emission tomography, cerebral blood flow (CBF) and cerebral blood volume (CBV) were measured after the addition of isoflurane (1.3 vols %, end-tidal concentration) to neuroleptanesthesia (fentanyl/droperidol) in hypocapnic baboons. The study was designed to determine whether isoflurane, when administered during hypocapnia, acted as a cerebral vasodilator to increase either CBF or CBV. Mean arterial pressure was maintained within 10% of preisoflurane levels with an angiotensin infusion. In the first protocol (A), CBF and CBV were measured as close together in time as possible in order to detect divergent effects of isoflurane on these variables. When PaCO2 was reduced from 40 mmHg to 25 mmHg, CBF decreased from 44 +/- 4 to 31 +/- 4 ml.100 g-1.min-1 (P less than 0.05) and CBV decreased from 3.1 +/- 0.3 to 2.6 +/- 0.3 ml/100 g (P less than .05). Neither CBF nor CBV was significantly changed by the addition of isoflurane. In the second protocol (B), serial CBV scans were performed frequently during the addition of isoflurane in a fashion designed to detect transient changes in CBV at the time isoflurane was first added to the breathing circuit. Induction of hypocapnia again reduced CBV from 3.1 +/- .3 to 2.7 +/- .2 ml/100 g, (P less than .05) and addition of isoflurane did not change CBV. From these results the authors conclude that in the normal hypocapnic baboon the addition of 1.3% isoflurane does not significantly change cerebral blood flow or volume.

Animals

Hemodynamic and metabolic effects of extracranial carotid disease.

Cerebral blood flow (CBF), cerebral blood volume (CBV), the CBF/CBV ratio - an index of the hemodynamic reserve capacity - the rate of oxygen metabolism (CMRO2), and the fractional extraction of oxygen by the brain (OEF) were studied by positron emission tomography (PET) in the cortical territory of both internal carotid arteries in 15 cases of transiently symptomatic or progressive extracranial atherosclerotic carotid disease. None of the patients had a major stroke or had a significant neurological deficit except 1 whose damaged hemisphere is excluded from study. All were asymptomatic at the time of PET scanning. Values were obtained in the middle cerebral artery (MCA) distribution, and in the anterior and posterior borderzone regions. Eight cases had unilateral carotid stenosis of 80% or greater and 7 had unilateral or bilateral occlusion of the origin of the internal carotid artery. Results obtained in patients were compared using Student's t-test, to those obtained in neurologically normal, elderly volunteers. Patients with carotid stenosis had a significantly decreased CBF (p less than .025) and CBF/CBV ratio (p less than .025) selectively in the anterior borderzone regions. This was accompanied by a trend toward elevated OEF and declining CMRO2 values. Patients with carotid occlusion had significantly decreased CBF (p less than .005), decreased CBF/CBV ratio (p less than .005) and decreased CMRO2 (p less than .025) in the ipsilateral anterior borderzone and MCA territories. Similar changes were present in the opposite hemisphere of patients with bilateral carotid disease. These results indicate that carotid stenosis is associated with hypoperfusion and diminished hemodynamic reserve capacity in the anterior borderzone, and that carotid occlusion produces more widespread hypoperfusion and metabolic depression.

Aged

Myoclonus epilepsy and ragged-red fibres (MERRF). 1. A clinical, pathological, biochemical, magnetic resonance spectrographic and positron emission tomographic study.

Thirteen patients, including 6 from one family, with the syndrome of myoclonus epilepsy and ragged-red fibres (MERRF) were studied. There was considerable heterogeneity in the age of onset, severity and associated clinical features. Postmortem studies in 3 patients from the one family showed a particular system degeneration. In addition, the youngest and most severely affected family member showed the pathological changes of Leigh's syndrome. Cortical dysfunction is a prominent clinical feature in MERRF, but postmortem examination failed to reveal cortical abnormalities. Positron emission tomographic studies, however, showed decreased cortical metabolic rates for glucose and oxygen utilization, with normal cortical blood flow and cerebral pH. Analyses of kinetic rate constants for uptake and phosphorylation of the glucose analogue, fluorodeoxyglucose showed decreased hexokinase-mediated phosphorylation: normal K1 and k2 values but reduced k3. Phosphorus magnetic resonance spectroscopy studies suggested a normal cerebral intracellular pH. Biochemical studies on muscle homogenates in 6 patients showed partial deficiencies of the activities of certain mitochondrial enzymes in 4 cases, whereas in 2 patients no abnormality was found. Our data, combined with previous reports, show that MERRF is biochemically and genetically heterogeneous. Our experience, and analysis of the literature, suggests that many cases previously described as the Ramsay Hunt syndrome, as well as other hitherto unclassified system degenerations associated with myoclonus epilepsy, are examples of MERRF. These data permit the formulation of a hypothesis to explain the clinical, biochemical and genetic heterogeneity of MERRF, and its overlap with Leigh's syndrome. We suggest that different biochemical defects of the mitochondrial respiratory chain may cause similar cerebral metabolic effects, as measured by positron emission tomography, resulting in similar phenotypes. Reduced activity of one enzyme, however, may result in different phenotypes, depending on the severity of the defect and its tissue distribution. Moreover, the phenotypic expression of certain biochemical defects may be influenced by randomly occurring factors such as fever, which may increase metabolic demand and result in more deleterious cellular metabolic effects.

Adolescent

Hemodynamic and metabolic effects of cerebral arteriovenous malformations studied by positron emission tomography.

Seventeen patients with an intracranial arteriovenous malformation were studied with positron emission tomography. Cerebral blood flow, cerebral blood volume, oxygen extraction fraction, and glucose and oxygen metabolism were evaluated in both hemispheres, excluding the area of the malformation itself. Patients were divided into three groups according to the size of their malformation, and results obtained were compared with studies in healthy volunteers. The glucose metabolism was significantly (p less than 0.01) decreased in the ipsilateral hemisphere in all patients. The cerebral blood volume was significantly increased (p less than 0.001) ipsilaterally in the three groups, and contralaterally in patients with medium- and large-sized arteriovenous malformations. The cerebral blood volume to cerebral blood flow ration, an index of vascular mean transit time, was significantly increased (p less than 0.005) ipsilaterally in patients with medium- and large-sized malformations and contralaterally in patients with large ones. Cerebral blood flow, oxygen extraction fraction, and oxygen metabolism were within the normal range bilaterally in all three groups, but oxygen extraction fraction tended to be higher in patients with larger lesions. The lack of significant change in oxygen metabolism suggests that oxygen metabolism in cortical areas remote from the arteriovenous malformation has been maintained by compensatory hemodynamic mechanisms. These data reveal widespread metabolic and hemodynamic consequences of arteriovenous malformations and suggest that they are associated with impairment of glucose metabolism, both in ipsilateral regions remote from the lesion and in the contralateral hemisphere in patients with large lesions.

Adult

Stability of regional cerebral glucose metabolism in the normal brain measured by positron emission tomography.

Cerebral glucose utilization (LCMRGI) was measured using the [18F]fluorodeoxyglucose method with PET in two groups of ten healthy young volunteers, each scanned in a resting state under different methodological conditions. In addition, five subjects had a second scan within 48 hr. Mean hemispheric values averaged 45.8 +/- 3.3 mumol/100 g/min in the right cerebral hemisphere and 47.0 +/- 3.7 mumol/100 g/min in the left hemisphere. A four-way analysis of variance (group, sex, region, hemisphere) was carried out on the results using three different methods of data manipulation: (a) the raw values of glucose utilization, (b) LCMRGI values "normalized" by the mean hemispheric gray matter LCMRGI value, and (c) log transformed LCMRGI values. For all analysis techniques, significantly higher LCMRGI values were consistently seen in the left mid and posterior temporal area and caudate nucleus relative to the right, and in the right occipital region relative to the left. The coefficient of variation of intrasubject regional differences (9.9%) was significantly smaller than the coefficient of variation for regions between subjects (16.5%). No differences were noted between the sexes and no effect of repeat procedures was seen in subjects having multiple scans. In addition, inter-regional LCMRGI correlations were examined both in values from the 20 normal subjects, as well as in a set of hypothetical "abnormal" values. Results were compared with those reported from other PET centers; despite certain methodological differences, the intersubject and inter-regional variation of LCMRGI is fairly constant.

Adult

Effect of generalized spike-and-wave discharge on glucose metabolism measured by positron emission tomography.

Positron emission tomography was used to study the cerebral metabolic rate for glucose (CMRGlc) in 7 adult patients with generalized spike-and-wave activity in the electroencephalogram. No consistent changes were seen in the CMRGlc. There was a slight trend toward an increased CMRGlc in 2 patients with primary generalized epilepsy, while in the 5 other patients with minor deviations from this condition or with secondary generalized epilepsy, the CMRGlc was unaffected by spike-and-wave activity or was below the normal range. Neither the amount of spike-and-wave activity in the EEG nor the presence of clinically evident absence seizures appeared to influence the CMRGlc. Therefore, we conclude that neuronal activity underlying spike-and-wave discharge does not seem to require increased glucose utilization.

Adolescent

Borderzone ischemia.

Positron emission tomography was used to measure cerebral perfusion and metabolism in 7 patients with severe carotid stenosis. None of the patients had sustained a major stroke, and all had a normal neurological examination except 1 patient with a mild neurological deficit from a capsular lacuna. Cerebral blood flow (CBF), cerebral blood volume, the cerebral blood flow/cerebral blood volume ratio, oxygen metabolism, and the fractional extraction of oxygen by the brain were measured in the cerebral cortex of both hemispheres in the anterior and middle cerebral artery distributions, in the borderzone regions between the anterior and middle cerebral arteries (anterior borderzone), and between the middle cerebral and posterior cerebral arteries (posterior borderzone). Results obtained in patients were compared, using Student's t test, to those obtained in 6 neurologically normal, elderly volunteers. Cerebral blood flow and the cerebral blood flow/cerebral blood volume ratio were both significantly decreased (p less than 0.025 and p less than 0.05, respectively) in the anterior borderzone ipsilateral to the carotid stenosis. In the same region there was a tendency toward a rising fractional extraction of oxygen with the oxygen metabolism maintained in the low-normal range. Cerebral blood flow was also significantly decreased (p less than 0.05) in the contralateral anterior borderzone. Hemodynamic and metabolic variables in other vascular territories were not significantly different from values obtained in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Stereotaxic biopsy and positron emission tomography correlation of cerebral gliomas.

Computer-directed stereotaxis was used to obtain tissue diagnosis in two cases of cerebral glioma, one low grade, and the other high grade. Both lesions had a similar computed tomographic appearance. Positron emission tomography was performed in each case using [18F]fluorodeoxyglucose. A correlation was made in each case between the metabolic activity of the tumor as measured by positron emission tomography, the radiographic appearance, and the tumor histology.

Adult

Estimation of cerebral oxygen utilization rate by single-bolus 15O2 inhalation and dynamic positron emission tomography.

This study shows that regional CMRO2 can be estimated by means of nonlinear regression using dynamic positron emission tomographic data acquired during 1 min following single-bolus inhalation of 15O2. The feasibility of simultaneous estimation of CBF, cerebral blood volume (CBV), oxygen extraction ratio (OER), and CMRO2 was assessed by simulations using the model of Mintun et al. Four oxygen metabolic measurements, each consisting of a CBF, CBV, and 15O2 bolus study, were carried out on three volunteers. Regional values for CBF, CBV, OER, and CMRO2 were derived in two ways: from the fits of the time-activity curves of the dynamic 15O2 bolus study alone [CMRO2(fit)] and from the three separate studies [CMRO2 (control)]. For the 56 regions of interest analyzed, using a fit interval of 60 s, CMRO2(fit) was 93.4 +/- 7.8% of CMRO2(control) (mean +/- SD) with a correlation coefficient of r = 0.95. CMRO2(control) ranged from 87 to 290 mumol/min/100 g. Individual simultaneous estimates of CBF, CBV, and OER were not reliable. Finally, we found that the validity of the model was limited in practice to the first minute after tracer inhalation.

Administration, Inhalation

Cerebral blood volume is increased in dogs during administration of nitrous oxide or isoflurane.

Positron emission tomography was used to study the effects of nitrous oxide (N2O) and isoflurane on regional cerebral blood volume (rCBV) in dogs during normocapnia and hypocapnia. Regional cerebral blood volume was measured serially during the addition of 50% N2O to a background anesthetic of fentanyl in normocapnic (group 1) and hypocapnic (PaCO2 25 mmHg, group 2) dogs. In each group, after 15 min of N2O administration accompanied by rCBV measurement, elimination of N2O with 100% O2 was continued for 15 min. This was followed by introduction of 2% isoflurane (no N2O), again accompanied by serial measurements of rCBV. In the normocapnic animals, the addition of 50% N2O caused an 11% increase in rCBV (6.1 +/- 1.4 to 6.8 +/- 1.0 ml/100 g, P less than 0.02) while 2% isoflurane caused a 36% increase (6.1 +/- 1.3 to 8.0 +/- 1.7 ml/100 g, P less than 0.02). The initial induction of hypocapnia during infusion of fentanyl in group 2 animals was associated with a 17% decrease in rCBV. In the hypocapnic dogs, there was no change in rCBV when N2O was introduced; however, an increase of 15% occurred following the addition of isoflurane (3.9 +/- 0.6 to 4.5 +/- 0.7 ml/100 g, P less than 0.02). Isoflurane, even during hypocapnia, may increase cerebral blood volume which in some circumstances may lead to an increase in ICP.

Animals

Hemodynamic and metabolic effects of cerebral revascularization.

Pre- and postoperative positron emission tomography (PET) was performed in six patients undergoing extracranial to intracranial bypass procedures for the treatment of symptomatic extracranial carotid occlusion. The six patients were all men, aged 52 to 68 years. Their symptoms included transient ischemic attacks (five cases), amaurosis fugax (two cases), and completed stroke with good recovery (one case). Positron emission tomography was performed within 4 weeks prior to surgery and between 3 to 6 months postoperatively, using oxygen-15-labeled CO, O2, and CO2 and fluorine-18-labeled fluorodeoxyglucose. Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rates for oxygen and glucose (CMRO2 and CMRGlu), and the oxygen extraction fraction (OEF) were measured in both hemispheres. Preoperatively, compared to five elderly control subjects, patients had increased CBV, a decreased CBF/CBV ratio, and decreased CMRO2, indicating reduced cerebral perfusion pressure and depressed oxygen metabolism. The CBF was decreased in only one patient who had bilateral carotid occlusions; the OEF, CMRGlu, and CMRO2/CMRGlu and CMRGlu/CBF ratios were not significantly different from control measurements. All bypasses were patent and all patients were asymptomatic following surgery. Postoperative PET revealed decreased CBV and an increased CBF/CBV ratio, indicating improved hemodynamic function and oxygen hypometabolism. This was associated with increased CMRO2 in two patients in whom the postoperative OEF was also increased. The CMRGlu and CMRGlu/CBF ratio were increased in five patients. Changes in CBF and the CMRO2/CMRGlu ratio were variable. One patient with preoperative progressive mental deterioration, documented by serial neuropsychological testing and decreasing CBF and CMRO2, had improved postoperative CBF and CMRO2 concomitant with improved neuropsychological functioning. It is concluded that symptomatic carotid occlusion is associated with altered hemodynamic function and oxygen hypometabolism. Cerebral revascularization results in decreased CBV, indicating improved hemodynamic reserve, but does not consistently improve oxygen metabolism.

Aged

Radiation dose to upper airways from inhaled oxygen-15 carbon dioxide.

According to Powell et al., significant retention of 15O in the tracheal mucosa results in a radiation absorbed dose of 75 to 200 rad upon breathing of 15O-CO2 for one hour at 1 mCi/liter. Such a high dose would seriously compromise the 15O-CO2 inhalation method for positron emission tomographic (PET) measurement of cerebral blood flow (CBF). In order to verify these results, we have assayed 15O activity in the tracheal region of three volunteers by PET during inhalation of 15O-CO2 and 15O-O2. Using methods similar to those of the above authors for estimating absorbed dose in the tracheal mucosa, we have obtained a value of 14-38 rad, which is more in keeping with 3-5 rad found by Bigler et al. from direct assay of mucus and saliva. We conclude that the 15O-CO2 inhalation method is a safe and practical means of measuring CBF by PET.

Carbon Dioxide

Metabolic and hemodynamic evaluation of gliomas using positron emission tomography.

Positron emission tomography (PET) was used on 16 patients with untreated cerebral gliomas to measure cerebral glucose and oxygen metabolism, oxygen extraction, blood flow, and blood volume. In addition, pH values were obtained for seven cases. Gliomas were later proven by biopsy; two patients had tumors with degrees of malignancy of grade II, two patients had grade III, and 12 patients had grade IV tumors. Compared with homologous gray matter regions in the opposite hemisphere, tumor tissue showed increased blood volume, but decreased oxygen extraction and oxygen metabolism. Compared with grade II tumors, grade IV tumors demonstrated higher blood volumes, but lower relative oxygen extraction and utilization. Tumor blood flow was variable, but was lower in the higher grade tumors. Rates of glucose utilization in tumor, calculated by using individually determined rate constants, were variable, and did not correlate with tumor size or tumor grade. Parietal tumors (n = 6) tended to have higher relative glucose utilization and blood flow, and lower relative oxygen extraction, when compared with frontal tumors (n = 4). Tumor pH differed significantly from the pH in contralateral brain (p less than 0.005); alkalotic pH values were consistently seen. These findings in and around cerebral gliomas studied before intervention differ from the results found in gliomas after exposure to radiation or chemotherapy.

Blood Volume

Superselective intracerebral chemotherapy of malignant tumours with BCNU. Neuroradiological considerations.

Early experience shows that: Superselective intra-arterial catheterization above the ophthalmic artery minimizes the orbital complications. Catheterization in a distal branch may lead to the non-infusion of a part of the tumor territory. A much higher concentration of the drug is achieved by superselective intra-arterial infusion than by intravenous injection. Longer infusions seem more efficacious than bolus injection. Early trapping of the drug appears to be essential for therapeutic efficacy.

Blood-Brain Barrier

Effects of rapid mannitol infusion on cerebral blood volume. A positron emission tomographic study in dogs and man.

Positron emission tomography was used to study the effect of a rapid infusion of mannitol on cerebral blood volume (CBV) in five dogs and in three human subjects. The ability of mannitol to reduce intracranial pressure (ICP) has always been attributed to its osmotic dehydrating effect. The effects of mannitol infusion include increased osmolality, total blood volume, central venous pressure (CVP), and cerebral blood flow, and decreased hematocrit, hemoglobin concentration, serum sodium level, and viscosity. Mannitol's ability to dilate the cerebral vasculature, either directly or indirectly, and thus to transiently increase ICP, is a subject of controversy. By in vivo labeling of red cells with carbon-11, the authors were able to demonstrate an early increase in CBV in dogs of 20%, 27%, and 23% (mean increase, p less than 0.05) at 1, 2, and 3 minutes, respectively, after an infusion of 20% mannitol (2 gm/kg over a 3-minute period). The animals' muscle blood volume increased by 27% (mean increase, p less than 0.05) 2 minutes after infusion. In the human subjects, lower doses and a longer duration of infusion (1 gm/kg over 4 minutes) resulted in an increase in CBV of 8%, 14% (p less than 0.05), and 10% at 1, 2, and 3 minutes, respectively, after infusion. In dogs, ICP increased by 4 mm Hg (mean increase, p less than 0.05) 1 minute after the infusion, before decreasing sharply. The ICP was not measured in the human subjects. Hematocrit, hemoglobin, sodium, potassium, osmolality, heart rate, mean arterial pressure (MAP), and CVP were measured serially. Results of these measurements, as well as the significant decrease in MAP that occurred after mannitol infusion, are discussed. This study demonstrated that rapid mannitol infusion increases CBV and ICP. The increase in muscle blood volume, in the presence of a decreased MAP and an adequate CVP, suggests that mannitol may have caused vasodilation in these experiments.

Adult

Pharmacokinetics of superselective intra-arterial and intravenous [11C]BCNU evaluated by PET.

The pharmacokinetics of i.v. and superselective intra-arterial carbon-11 1,3-bis-(2-chloroethyl)-1-nitrosourea ([11C]BCNU) were directly compared for the first time in ten patients with recurrent gliomas using positron emission tomography (PET). Intra-arterial administration of [11C]BCNU achieved concentrations of the drug in the tumor that averaged 50 times higher than with a comparable i.v. dose. These preliminary results suggest that the degree of early metabolic trapping of BCNU in tumor correlates with the clinical response to this chemotherapy.

Adult