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Biomedical subjects

C G Rhodes

Publications and source records attributed to C G Rhodes.

At least 73 records · Page 4Linked to original sources

Positron emission tomography in venous ulceration and liposclerosis: study of regional tissue function.

Oxygen-15 administered by continuous inhalation and emission computed tomography were used to study regional tissue oxygen utilisation and blood flow in the limbs of 11 patients with venous ulceration and five patients with liposclerosis due to venous insufficiency. The results showed increased blood flow and appreciably reduced fractional oxygen extraction in the diseased tissues. These findings indicated a local, functional shunting of blood through the abnormal microcirculation of the skin and subcutaneous tissues. This may be an important factor in the aetiology of the skin changes seen in patients with calf muscle pump failure.

Humans↗

In vivo disturbance of the oxidative metabolism of glucose in human cerebral gliomas.

Abnormalities in the oxidative metabolism of glucose in human cerebral gliomas have been studied in seven patients using positron emission tomography. Measurements of regional cerebral blood flow and oxygen consumption were obtained using the oxygen-15 steady-state inhalation technique. Values of regional cerebral glucose consumption were obtained using fluorine 18-labeled 2-fluoro-2-deoxy-D-glucose and a simplification of the method of Sokoloff. Functional values were obtained for regions of tumor and brain tissue in the middle cerebral artery territory of the contralateral cortex. Values of regional glucose consumption were calculated for both regions using a value of the lumped constant quoted for normal brain tissue (0.42). Tumor regional cerebral blood flow was comparable to that in the contralateral cortex, whereas regional cerebral oxygen consumption was depressed. This depression resulted in low tumor values of the fractional oxygen extraction ratio (0.21 +/- 0.07), indicating that oxygen supply exceeded the metabolic demand. In contrast, tumor regional cerebral glucose consumption was not depressed and regional glucose extraction ratios were similar for tumor and brain tissue. The metabolic uncoupling between regional oxygen consumption and regional glucose consumption (CMRO2/CMRGlu = 0.24 +/- 0.07 ml of oxygen per milligram of glucose) is indicative of increased aerobic glycolysis.

Adult↗

Disturbance of oxidative metabolism of glucose in recent human cerebral infarcts.

Eight patients with recent cerebral hemispheric infarction were studied with positron emission tomography and the oxygen-15 steady-state inhalation and [18F]deoxyglucose techniques to obtain values of regional cerebral blood flow, oxygen consumption, and glucose metabolism. The Sokoloff equation, used to calculate glucose metabolism, was simplified to exclude the exponential terms containing the rate constants. A value of the lumped constant quoted for normal brain (0.42) was used for infarcted regions and contralateral hemisphere. Mean regional cerebral blood flow, oxygen consumption, and glucose metabolism were all significantly depressed within the infarcts compared with the mirror regions in the contralateral cerebral hemisphere. The mean fractional extraction of oxygen was low, indicating an adequate supply of oxygen for residual oxidative metabolism. Regional oxygen consumption and glucose metabolism were significantly correlated within the infarcts, but with a relationship of 2 moles of oxygen per mole of glucose--one-third that in the contralateral hemisphere and in normal brain. Although these results suggest that the metabolizing tissue of a recent cerebral infarct utilizes aerobic glycolysis, caution about the validity of this pathophysiological observation is dictated by limitations in current positron emission tomographic tracer methodology.

Adult↗

Correction for the presence of intravascular oxygen-15 in the steady-state technique for measuring regional oxygen extraction ratio in the brain: 2. Results in normal subjects and brain tumour and stroke patients.

Values of regional cerebral oxygen extraction ratio and oxygen utilisation obtained with the oxygen-15 steady-state inhalation technique have been found to be overestimated due to the signal from intravascular oxygen-15. A previously described method to correct for this intravascular component has been applied to a series of studies on normal subjects, and on brain tumour and stroke patients. With this correction the regional cerebral oxygen extraction ratio in normals becomes comparable to the global values previously reported with arteriovenous sampling techniques. Within the lesions of brain tumour and stroke patients, the corrections have been found to be variable and often substantial. It is concluded that failure to apply this correction may result in major errors in the values for regional oxygen extraction ratio and oxygen utilisation. This is especially true when the regional blood flow and oxygen extraction ratio of a tissue is low and regional blood volume is high.

Blood Volume↗

Regional extravascular lung density and fractional pulmonary blood volume in patients with chronic pulmonary venous hypertension.

Using a technique based on positron transmission and emission tomography, we measured regional extravascular lung density (lung tissue and interstitial water per unit thoracic volume) and fractional pulmonary blood volume (volume of blood per unit thoracic volume) in normal subjects and in patients with cardiomyopathy and chronic pulmonary venous hypertension. We found an increase in extravascular lung density in the patients. Extravascular density was increased in all parts of the lung studied, but higher values were seen in the dorsocaudal portion than in the ventrocaudal portion of the lung (average 151% and 130% of normal, respectively). Fractional blood volume was markedly reduced in the dorsocaudal part of the lung (mean 74% of normal). The increase in extravascular density probably reflects structural changes in the lung as well as accumulation of interstitial fluid. The distribution of extravascular density is consistent with previous radiological and morphological studies, and may reflect a higher tendency to oedema formation in the dependent parts of the lung. The measurements of fractional blood volume suggest that intrapulmonary blood volume is reduced in chronic pulmonary venous hypertension. This may reflect a decrease in the distensibility of the pulmonary vessels due to structural abnormalities, as well as functional changes in the pulmonary vasculature.

Adult↗

Measurement of pulmonary erythromycin concentration in patients with lobar pneumonia by means of positron tomography.

The concentration achieved in the infected tissue is of fundamental importance in the use of antibiotics. Erythromycin labelled with the positron-emitting nuclide carbon-11 and positron tomography were used to compare local concentrations of this antibiotic in the pneumonic and unaffected lungs of five patients with lobar pneumonia. The time course of uptake of erythromycin into the extravascular compartment (i.e., the intracellular, interstitial, and alveolar compartments) of the pneumonic lung was measured. The mean extravascular concentrations obtained during the first hour after an intravenous injection of 270 mg erythromycin lactobionate were similar in the pneumonic lung and the unaffected lung (5.5 +/- 2.2 and 6.6 +/- 2.2 micrograms/g, respectively). An effective concentration of erythromycin was reached in the pneumonic lung within 10 min of the injection and was maintained throughout the period of measurement (60 min).

Acute Disease↗

Measurement of lung water in dog lobes using inhaled C15O2 and injected H215O.

Indicator-dilution analysis was used in a recirculation-free isolated dog lobe preparation to compare an inhaled water tracer (C15O2) and an injected water tracer (H215O) with direct weighing as a measure of total lung water. Residue detection (counting over the lung) was compared with outflow detection (counting over the venous effluent). With outflow detection, inhaled C15O2 measured 74% and injected H215O 90% of the gravimetric lung water. In hemodynamic edema, the increase in lung water measured by residue detection of both tracers correlated well with increases in weight (r = 0.92, slope = 1.03). However, outflow detection of both tracers underestimated the lung water increase by 53% in edema (r = 0.88, slope = 0.47). Thus, in edema, equilibration of both tracers within the lung water volume is rapid, but clearance from the lung is delayed because slowly clearing water pools develop. The errors caused by inhomogeneity of perfusion distribution were investigated after pulmonary arterial injection of 34-, 50-, and 175-micrometers spheres. For the same lung weight, C15O2 transit was delayed and H215O transit accelerated greatly by the 175-micrometers spheres and slightly by the 50-micrometers spheres.

Animals↗

Measurement of CBF and CMRO2 using the continuous inhalation of C15O2 and 15O. Experimental validation using CO2 reactivity in the anaesthetised dog.

Experimental support for the steady state 15O inhalation technique, as used to measure cerebral blood flow (CBF) and oxygen utilisation (CMRO2), was obtained by describing the response of the cerebral vasculature to variations in arterial PCO2 in 6 anaesthetised dogs. Measurements were made using a positron emission tomography (ECAT II) and arterial blood sampling, during the sequential constant inhalation of C15O2 and 15O2. Values of CBF and CMRO2 were calculated for a mixture of white and grey matter, using the steady state tracer equations derived by Jones et al. (1976). The mean CMRO2 was 3.58 +/- 0.81 ml O2 . 100 ml-1 . min-1, whilst the mean CBF and OER (oxygen extraction ratio) values (for an arterial PCO2 of 40 mm Hg) were 39.9 ml . 100 ml-1 and 0.50 +/- 0.06, respectively. Arterial PCO2 was varied between 20 and 150 mm Hg. CBF was found to correlate closely with arterial PCO2, resulting in a mean slope (specific reactivity) of 1.52 +/- 0.38 ml . 10 ml-1. mm Hg-1. Pooling the flow data resulted in a linear relationship between CBF (% change) and arterial PCO2 in the range 20-70 mm Hg, with a slope (% reactivity) of 3.2% mm Hg-1 (2 P less than 0.001). The oxygen extraction ratio (OER) fell with increasing values of arterial PCO2 resulting in a stable CMRO2 throughout each study. There was no correlation between CMRO2 and artificially increased CBF. These results support and give confidence in the use of the 15O inhalation technique for measuring CBF, OER and CMRO2.

Animals↗

Quantitative measurement of regional extravascular lung density using positron emission and transmission tomography.

A technique has been developed to measure regional values of vascular and extravascular lung density using positron emission and transmission tomography. Quantitative values of lung density in a transaxial plane are obtained by recording transmission scans during the exposure of a ring source of positron emitting germanium/gallium-68, which encircles the subject in the plane of the scan. Values of blood density are obtained by scanning in the emission mode following the labeling of the subject's red blood cells with a quantity of C-carbon monoxide inhaled as a bolus. Subtraction of the normalised blood volume scan from the normalised lung density (transmission) scan provides regional values of extravascular lung density. The response of the transmission scan to changes in density was obtained by scanning different tissue equivalent materials in the density range 0.02 to 1.0 g cm-3. This resulted in a linear relationship between pixel counts and density. Density measurements made in vitro on simulated chest phantoms suggest that, at worst, random errors of 3.5% and systematic errors (due to the influence of the chest wall) of between 10 and 15% will be incurred when measurements are made in vivo on lungs of average normal density (0.3 g cm-3). The random error associated with the emission scan (arising from counting statistics alone) was found to be 1.2%. Measurements of lung density made on five normal subjects (supine) resulted in a mean density of 0.29 g cm-3 for a region in the lower (caudal) part of the lung, with a range of values between 0.26 and 0.32 g cm-3 from subject to subject. A pronounced anteroposterior gradient of both lung density and blood density was observed, while the gradient of extravascular lung density was quite small. The mean value of the ratio extravascular: vascular lung density for both caudal and cranial lung regions was 0.92 +/- 0.25.

Adult↗

CMRO2 and CBF by the oxygen-15 inhalation technique. Results in normal volunteers and cerebrovascular patients.

The oxygen-15 inhalation technique has been applied to the quantitation of regional CBF, CMRO2 and OER with positron emission tomography. The introduction of corrections for gamma-ray attenuation, and for recirculation, has allowed us to obtain values for CBF, CMRO2 and OER in close agreement with values obtained using other techniques. In 27 normal volunteers mean CMRO2 shows values ranging from 4.98 to 3.79 ml/100/min, depending on the region evaluated. Mean CBF values range from 55.3 to 38.8 ml/100ml/min. Mean OER is more constant, ranging from 0.56 to 0.49, with a mean of 0.53 +/- 0.04, thus reflecting the close matching between metabolism and blood supply. We have further identified corrections for cerebral blood volume, which is measurable, and for water partition coefficient, which remains uncertain. In preliminary studies these corrections decrease the OER over the physiological range of flow by 10%, with a 15% lower CMRO2. The reproducibility of the results and the effects of aging have been studied. A series of 27 studies on acute ischaemic CVD are reported. The course of the clinical condition has been correlated with the quantitation of oxygen utilization and blood flow performed at different intervals from the onset of symptoms.

Adult↗

The measurement of spleen perfusion in man: a non-invasive method using the ratio between Rubidium-81 and its decay product Krypton-81m.

A non-invasive method has been developed for measuring spleen perfusion in man. This involves recording the gamma-ray energy spectra over the spleen following the localisation of Rubidium-81 within the organ by injecting intravenously labelled heat denatured red cells. The spectra are analysed to provide the ratio of Rubidium-81 to its radioactive decay product Krypton-81 m. This ratio is dependent on the rate of perfusion through the organ. The difficulties encountered in applying this steady state method for monitoring tissue perfusion are illustrated and practical means for their solution presented. The results of applying this method to patients with various splenic disorders are presented and compared with those obtained by other workers using different monitoring techniques.

Humans↗

Detection of intrapulmonary hemorrhage with carbon monoxide uptake. Application in goodpasture's syndrome.

We devised a noninvasive measure of pulmonary hemorrhage of value in the management of Goodpasture's syndrome. We reasoned that alveolar uptake of inhaled carbon monoxide during breath holding would increase in the presence of extravascular blood, but clearance of its radioisotope (C15O) from a lung field would be delayed. Thus, the ratio of uptake to clearance would indicate lung hemorrhage. In 15 controls and six patients with renal failure without hemorrhage, this ratio ranged from 0.73 to 1.5. In eight patients with Goodpasture's syndrome the ratio ranged from 1.5 to 16.5, returning to normal between episodes of bleeding. Measurements of carbon monoxide uptake alone in 10 patients with Goodpasture's syndrome were at times well above that predicted for their hemoglobin level, whereas in renal failure with acute pulmonary edema increased carbon monoxide uptake was rarely found. Thus, monitoring of the single-breath carbon monoxide uptake alone can detect episodes of lung hemorrhage.

Adolescent↗

Distribution of extravascular fluid volumes in isolated perfused lungs measured with H215O.

The distributions per unit volume of extravascular water (EVLW), blood volume, and blood flow were measured in isolated perfused vertical dog lungs. A steady-state tracer technique was employed using oxygen-15, carbon-11, and nitrogen-13 isotopes and external scintillation counting of the 511-KeV annihilation radiation common to all three radionuclides. EVLW, and blood volume and flow increased from apex to base in all preparations, but the gradient of increasing flow exceeded that for blood and EVLW volumes. The regional distributions of EVLW and blood volume were almost identical. With increasing edema, lower-zone EVLW increased slightly relative to that in the upper zone. There was no change in the distribution of blood volume or flow until gross edema (100% wt gain) occurred when lower zone values were reduced. In four lungs the distribution of EVLW was compared with wet-to-dry ratios from lung biopsies taken immediately afterwards. Whereas the isotopically measured EVLW increased from apex to base, the wet-to-dry weight ratios remained essentially uniform. We concluded that isotopic methods measure only an "exchangeable" water pool whose volume is dependent on regional blood flow and capillary recruitment. Second, the isolated perfused lung can accommodate up to 60% wt gain without much change in the regional distribution of EVLW, volume, or flow.

Animals↗

Measurement of regional pulmonary oedema in man using radioactive water (H215O).

Regional extravascular lung water (rELW) has been measured in normal subjects and in patients with left heart diseases using a double-indicator dilution technique and external counting over the chest. Gamma-emitting radioisotopes were injected intravenously, 113Inm as a vascular non-duffusible indicator, and H215O as a freely diffusible indicator. Time activity curves were then recorded over the upper and lower zones of the lung in the supine position with external probes. rELW per unit of blood volume and rELW per unit of blood flow were increased in patients with raised left atrial pressure even in the presence of radiologically clear lung fields. There was a uniform distribution of these ratios between upper and lower zones in normals, whereas in patients rELW was preferentially distributed in the lower zones.

Blood Flow Velocity↗