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Biomedical subjects

S O Valind

Publications and source records attributed to S O Valind.

16 recordsLinked to original sources

Combined fluorine-18-FDG and carbon-11-methionine PET for diagnosis of tumors in lung and mediastinum.

UNLABELLED: We evaluated the value of PET using 18F-fluorodeoxyglucose (FDG) and 11C-methionine, individually or in combination, to distinguish malignant from benign tumors and to identify or exclude mediastinal metastases. METHODS: Seventeen patients with a tumor in the lung or mediastinum were evaluated with 18F-FDG and 11C-methionine PET. For morphological comparison, we used CT, and all findings were confirmed by histology of surgical resection specimens (n = 16) or by cytology (n = 1). RESULTS: All tumors were visualized equally well with both tracers, and there were no false-positive results. In 2 patients with a malignant tumor, coexisting pneumonia was correctly diagnosed as an inflammatory lesion because of its wedge-like shape. PET correctly excluded hilar invasion and mediastinal lymph node metastases in 10 of 14 patients with primary lung tumor. PET identified mediastinal metastases in 4 of 4 patients. CT failed to detect mediastinal tumor spread in 2 patients and gave a false-positive reading in 2 others. Significantly higher uptake (SUV) and transport rate (slope) values were obtained from malignant than benign lesions with both tracers. No major differences were seen in either the levels of significance or accuracy when the two tracers were compared. Slope values did not add further information to what was obtained with SUV. Density correction of SUV and slope values, to avoid the influence of surrounding air as well as tumor heterogeneity, increased these differences somewhat. Both tracers distinguished malignant from benign lesions with a 93% sensitivity and an accuracy of 89%-95%, but sensitivity improved to 100% when values from both tracers were combined. CONCLUSION: Fluorine-18-FDG and 11C-methionine PET visualized all tumors equally well and detected mediastinal spread better than CT. For differentiation purposes, the problems of false-positive and false-negative PET findings could not be safely overcome in a limited number of cases either by the use of both tracers, by the additional use of slope values or by lesion density correction.

Aged↗

Fluorine-18 deoxyglucose uptake in sarcoidosis measured with positron emission tomography.

Regional pulmonary glucose metabolism (MRglu; mumol h-1 g-1), extravascular lung density (D(EV); g cm-3) and vascular volume (VB; ml cm-3) were measured in a single midthoracic transaxial slice (approximately 2 cm thick) using position emission tomography (PET) in seven patients with histologically proven sarcoidosis. The measurements were repeated 1-7 months later after steroid therapy (in two cases, no treatment) in order to assess MRglu as an index of inflammation and relate it to routine pulmonary function tests, chest radiography and serum angiotensin converting enzyme (SACE) levels. MRglu was computed from serial lung scans and peripheral venous blood samples for 60 min following an i.v. injection of 18F-2-fluoro-2-deoxy-D-glucose (18FDG). Both MRglu (which was increased in six of seven patients) and elevated SACE levels returned to normal in those patients treated with high-dose steroids. Regional vascular volume was normal in six of seven cases and did not change significantly with therapy. The high tissue density measured in all patients decreased significantly in two of three patients treated with 40 mg prednisolone daily. The abnormal MRglu observed in active sarcoidosis becomes normal pari passu with SACE levels during high-dose steroid therapy. We conclude that MRglu measured with 18FDG and PET may reflect "disease activity" in sarcoidosis in quantitative terms (per gram lung tissue) and in respect of disease distribution.

Adult↗

Relationships between regional ventilation and vascular and extravascular volume in supine humans.

With the use of positron emission tomography, alveolar ventilation (VA), lung density, and pulmonary blood volume (VB) were measured regionally in eight nonsmokers in the supine posture and one nonsmoker in the prone posture during quiet breathing in a transaxial thoracic section at midheart level. Regional values of alveolar volume (VA) and extravascular tissue volume (VEV) were derived from the inherent relationships between different compartments in the lung. Ratios proportional to gas volume (VA/VEV) and ventilation (VA/VEV) per alveolar unit, respectively, were calculated. No differences between right and left lung were found. Variations in the vertical direction could explain approximately 65% of the total within-group variation in VA, VB, and ln (VA), whereas the corresponding value for horizontal variation was only 3-9% (right lung, supine subjects). Similar gravitational gradients were found in the single prone subject. There was a significant linear correlation between VA and ln (VA). When VA and VA are related to a given number of alveolar units (VEV), the data are consistent with a linear relationship between VA/VEV and VA/VEV, indicating that ventilation might be explained by the elastic properties of lung tissue according to Salazar and Knowles (J. Appl. Physiol. 19: 97-104, 1964). Regional VB was closely associated with the gradient of regional alveolar volume (VA/VEV) (by virtue of weight of blood and competition for space) and therefore, indirectly, closely associated with the vertical gradient of ventilation.

Adult↗

Interrelationships between regional blood flow, blood volume, and ventilation in supine humans.

Positron emission tomography was used to measure alveolar gas volume, pulmonary blood volume (VB), regional alveolar ventilation (VA), and the regional ventilation-to-perfusion ratio (VA/Q) in a transaxial slice at midheart level in eight supine subjects and one prone normal subject during quiet breathing. These relationships allow regional blood flow (Q) to be calculated as VA/(VA/Q). No significant differences between right and left lung were found. Within the volume studied, which excluded the peripheral 2 cm of the lung, there was an exponential increase in Q by 11%/cm from 1.2 ml.min-1.cm-3 in the upper (ventral) to 3.5 ml.min-1.cm-3 in the lower (dorsal) lung regions, explaining 61% of the total variation within groups, whereas the horizontal gradient only explained 7% (right lung; supine subjects). Similar gravitational gradients were found in the single prone subject. VA and Q were well matched except at the dorsal lung thoracic border where low values of VA/Q due to a reduction in ventilation were occasionally found even in these normal subjects. VB and Q were reasonably well matched, implying that variations in vascular transit time due to gravity are kept to a minimum. The coefficient of local variation of peripheral vascular transit times (VB/Q) (33%) was, therefore, less than would have been expected if VB and Q were uncorrelated (57%).

Adult↗

Error analysis of combined measurements of regional ventilation and V/Q ratio using positron emission tomography.

We measured the regional pulmonary ventilation/perfusion ratio with intravenous 13N in saline solution, using positron emission tomography, in eight normal healthy volunteers, 10 patients with asthma and 10 patients with chronic obstructive pulmonary disease. Regional pulmonary ventilation was also measured with 19Ne, and this information was used to (i) correct ventilation/perfusion ratios obtained with 13N in regions with impaired ventilation and (ii) calculate regional perfusion, Q. In this paper we analyse the errors inherent in these measurements. Dead space ventilation and focal inhomogeneities in ventilation and/or blood flow will affect the transport of both 19Ne and 13N, but in different ways. Combining the two methods, values of blood flow obtained tend to overestimate Q in normal supine subjects by some 6% in the non-dependent part of the lung and to underestimate Q by a similar amount in the dependent part. In patients with air flow obstruction, blood flow is underestimated in regions with low ventilation/perfusion ratios and overestimated in regions with high ventilation/perfusion ratios. In the groups of patients studied, errors may reach a level of 10-20%. The limitations of the method in regions with extensive gas flow and/or blood flow heterogeneities are discussed on a theoretical basis and in some extreme conditions blood flow may be overestimated by a factor of two to three.

Asthma↗

Regional structure-function correlations in chronic obstructive lung disease measured with positron emission tomography.

BACKGROUND: Positron emission tomography, performed with isotopes of very short half life, can be used to relate local lung tissue density to local ventilation and to the ventilation:perfusion ratio. This method has been used in 10 patients with severe chronic airflow obstruction and differing values for carbon monoxide transfer factor (TLCO) and transfer coefficient (KCO). METHODS: Ventilation (VA) and the ventilation:perfusion ratio (V/Q), lung density, and blood volume were measured regionally in a single transaxial section at mid-heart level with the patients in a supine position. Alveolar volume, extravascular tissue lung density, and perfusion (Q) were derived. Twenty five regions with abnormalities in the ventilation images were analysed. RESULTS: Tissue density showed a negative correlation with the ratio V/Q (r = 0.55) and a positive correlation with Q (r = 0.59) and blood volume (r = 0.65). In four patients with a low carbon monoxide transfer factor (TLCO) and transfer coefficient (KCO) < 50% predicted many regions with low VA had low tissue density and normal or high V/Q. On the other hand, in four patients with TLCO and KCO > 50% predicted many regions with low VA had normal or high tissue density and low values of V/Q. The other two patients had patterns between these two extremes. Individual ratios between mean values of tissue density and V/Q had a positive correlation with KCO (% pred; r = 0.79). CONCLUSIONS: These findings link structural differences with distinctive functional patterns; they reinforce the view that bronchial inflammation or oedema predominate in some patients with chronic airflow obstruction, whereas alveolar destruction is the major feature in others.

Aged↗

Measurements of regional ventilation pulmonary gas volume: theory and error analysis with special reference to positron emission tomography.

The adaptation to PET of the steady-state technique for the measurement of alveolar ventilation, based on the short-lived radionuclide 19Ne (T1/2 = 17.4 sec), allows the steady-state lung model to be analyzed in a quantitative way under well-defined geometrical conditions. The regional gas volume is essential to this analysis, and regional measurements of the pulmonary gas volume based on transmission tomography are presented and validated in this paper. The accuracy of the steady-state method rests largely with the validity of the lung model applied to describe the transport of tracer in the lung. This study considers tracer transport and mixing within individual lung regions. Blood flow and the alveolar-to-capillary exchange of gases do not significantly affect the values obtained, not even in regions with highly abnormal ventilation/perfusion ratios. A nonuniform intra-regional gas flow distribution results in an underestimation of the regional ventilation, determined by the dispersion of the ventilatory turnover rates of alveolar gas within the region. In the normal lung this underestimation is negligible. In disease, a mixing within the resolution volume of units that are almost non-ventilated and units that perform normally may result in an underestimation of alveolar ventilation by up to 60%.

Humans↗

Quantification of regional V/Q ratios in humans by use of PET. I. Theory.

With positron emission tomography, quantitative measurements of regional alveolar and mixed venous concentrations of positron-emitting radioisotopes can be made within a transaxial section through the thorax. This allows the calculation of regional ventilation-to-perfusion (V/Q) ratios by use of established tracer dilution theory and the constant intravenous infusion of 13N. This paper considers the effect of the inspiration of dead-space gas on regional V/Q and investigates the relationship between the measured V/Q, physiological V/Q, and V/Q defined conventionally in terms of bulk gas flow (VA/Q). Ventilation has been described in terms of net gas transport, and the term effective ventilation has been introduced. A simple two-compartment model has been constructed to allow for the reinspiration of regional (or personal) and common dead-space gas. By use of this model, with parameters representative of normal lung the effective V/Q ratio for 13N [(VA/Q)eff(13N)] is shown to overestimate VA/Q by 18% when VA/Q = 0.1 but underestimate VA/Q by 68% when VA/Q = 10. For physiological gases, the model predicts that the behavior of O2 should be similar to that of 13N, so that, in terms of gas transport, V/Q ratios obtained using the infusion of 13N closely follow those for O2. Values of the effective V/Q ratio for CO2 [(VA/Q)eff(CO2)] lie approximately halfway between (VA/Q)eff(13N) and VA/Q. These results indicate that dead-space ventilation is far less a confounding issue when V/Q is considered in terms of net gas transport (VAeff), rather than bulk flow (VA).(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Quantification of regional V/Q ratios in humans by use of PET. II. Procedure and normal values.

Regional measurements of tissue isotope concentration, made using positron emission tomography (PET), allow tracer models to be used in a quantitative manner to provide topographic distributions of many structural and functional parameters, each derived for the same well-defined lung element. In this paper we describe a technique to measure regional ventilation-perfusion ratios (V/Q), in absolute units, by use of PET and the continuous intravenous infusion of an inert gas isotope, 13N, and report on measurements made in 12 normal subjects (4 smokers). Data were obtained from a single lung section (slice thickness, 1.7 cm full width at half-maximum response to a line source) at the level of the right ventricle in the supine posture during quiet breathing. For the 12 subjects, volume-weighted mean values of V/Q, averaged over individual right and left lung fields, ranged from 0.50 to 1.29. Analysis of these means showed no difference between lungs: right, 0.80 +/- 0.23 SD; left, 0.76 +/- 0.20 SD. Topographically, a systematic fall of V/Q in the ventrodorsal direction was observed in eight of the subjects (mean ventrodorsal difference 0.39, range 0.19-0.90), whereas two showed a clear increase toward dependent lung regions (range 0.16-0.26). Seven of the subjects with a falling ventrodorsal V/Q gradient also exhibited discrete regions of low V/Q at the dorsal lung border. We conclude that, in normal subjects, ventilation and perfusion are generally well matched in the supine posture, but isolated mismatching often occurs in dependent lung regions.

Humans↗

Measurement of oxygen and carbon dioxide partial pressures in synovial fluid after tonometry.

A commercially available gas analyser was used to measure tension of oxygen (PO2) and carbon dioxide (PCO2) in synovial fluid samples after tonometry. Measured values of PCO2 were close to the expected (median difference 0.2 kPa, range -0.4 to 0.4) within the analysed concentration range of 4-10 kPa. No consistent difference between measured and expected values of PO2 were found for oxygen in the range 3-11 kPa (median difference 0.1 kPa, range -0.3 to 1.2). For oxygen tensions below 3 kPa, however, the measured values invariably overestimated the actual PO2, the errors ranging from 0.3 to 1.9 kPa, median 1.1. The importance of proper handling of samples was investigated and storage for 1 h at 0 degrees C in plastic syringes resulted in elevation of the PO2 levels measured (range of elevation 0.2 to 3.6 kPa, median 1.15), whilst no significant differences were found when stored in glass syringes. Within the limits stated, commercially available gas analysers may thus be used to investigate these parameters related to local tissue metabolism in effusive joint conditions.

Carbon Dioxide↗

Measures of the inflammatory response in cryptogenic fibrosing alveolitis.

Cryptogenic fibrosing alveolitis (CFA) is characterized by interstitial fibrosis and parenchymal inflammation. Eleven patients with CFA (10 proved by lung biopsy) were followed over 2 yr using clinical symptoms, radiographic change, and pulmonary function tests to adjust their treatment. Lung lavage, positron camera (PET) measurements of regional extravascular lung density (Dev), pulmonary blood volume (Vb), and the metabolic rate for 18F-deoxyglucose (MRglc), clearance of 99mTc-diethylenetriaminepentacetate (99mTc-DTPA) aerosol, and lung uptake of 67Ga were measured initially and at the end of the first year to give a profile of the inflammatory response. Compared with normal subjects, there was an increased percentage of neutrophils and eosinophils in the lung lavage, increased Dev (p less than 0.002) with no significant difference in Vb, increased MRglc (p less than 0.02), 99mTc-DTPA clearance (p less than 0.002), and 67Ga uptake (p less than 0.02). The smallest increases in Dev were seen in the two patients with most destruction shown by lung biopsy. There were inverse correlations between Dev and both FVC and TLC, but a direct correlation between Vb and transfer factor. 99mTc-DTPA clearance changed concordantly with clinical status and radiographic and respiratory function changes during the first year. If glucose utilization (MRglc) remained in the normal range between the initial and first yearly assessment, the patient improved or remained stable during the second year as shown by clinical status and radiographic and respiratory function measurements. If it rose or remained high, the patient's condition deteriorated.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Contribution of the positron camera to studies of regional lung structure and function.

Positron emission tomography is a major technological advance in the characterisation of structure-function relationships within and between regions in normal and abnormal lungs (Hughes et al. 1985). The measurements are noninvasive and relatively exact since the geometric conditions are precisely defined. Regional expansion, flow (ventilation, perfusion), oxygen concentration (from VA/Q) and glucose metabolism can be measured in absolute terms per cubic centimetre of thorax or per gram of extravascular lung. Examples of structure-function relationships in normal subjects, emphysema, bronchitis and sarcoidosis are briefly presented.

Blood Glucose↗

Regional lung density and blood volume in nonsmoking and smoking subjects measured by PET.

Regional lung density (DL) and regional fractional pulmonary blood volume (VB) were measured quantitatively during tidal breathing in 30 healthy supine subjects (15 smokers and 15 nonsmokers) in a 1.7-cm-thick midthoracic cross section using positron emission tomography (PET) and 11CO (inhaled)-labeled erythrocytes. Regional alveolar volume (VA), extravascular lung density (DEV), and relative alveolar size (Valv = VA/DEV) were calculated. For the nonsmokers, mean values (+/- SD between subjects) for the right lung were as follows: DL, 0.28 +/- 0.03 g/cm3; DEV, 0.10 +/- 0.02 g/cm3; and Valv, 7.1 +/- 1.9 ml/g lung tissue. In the smoking subjects DEV (right plus left lung) was 16% higher. No significant difference in VB between smokers and nonsmokers was found. The differences in DEV and VB between right and left lung were not significant. Mean values (+/- SD) of the dorsal-to-ventral ratios calculated for the right lung in the nonsmokers were as follows: DL, 1.34 +/- 0.16; VA, 0.90 +/- 0.05; VB, 1.52 +/- 0.26; DEV, 1.10 +/- 0.17; and Valv, 0.85 +/- 0.19. Almost identical ratios were found in the smokers. The influence of overall thoracic expansion was investigated in one subject restudied during voluntary hyperinflation and during positive end-expiratory pressure.

Adult↗

Quantification of regional ventilation in humans using a short-lived radiotracer--theoretical evaluation of the steady-state model.

The accuracy of the steady-state measurement of ventilation by means of a short-lived insoluble inert gas tracer rests with the validity of the steady-state flow equation. This has previously been applied to the qualitative assessment of regional ventilation using krypton-81m, but may potentially be used for the calculation of regional alveolar ventilation per unit alveolar gas volume--(VA/VA)cal--from measurements of the alveolar concentration of the tracer. The steady-state alveolar tracer concentration was calculated for the course of a breathing cycle, using a lung model featuring airways dead space and tidal gas flow. The calculations were made by computer simulations of a lung, characterized by predefined values of parameters describing the lung structure and the mode of ventilation. In the normal lung of supine man at rest (specific alveolar ventilation, ranging from 1.0 to 3.5 min-1) the errors of (VA/VA)cal relative to the predefined true values range from an overestimation by some 3% in the low ventilation regions to an underestimation by 8% in the best ventilated regions. The errors mainly result from ventilation of the airways dead space, which will influence the distribution of tracer in the lung by the transfer of tracer between regions by way of the common dead space and by the decay of tracer during its transport through the bronchial tree.

Humans↗

Regional lung hematocrit in humans using positron emission tomography.

Regional lung hematocrit ratio (R) was measured in five normal subjects and five patients (2 with pneumonia, 2 with nephrotic syndrome with anemia, and 1 with pancreatitis) using positron emission tomography, a red cell marker 11CO, and a plasma marker [methyl-11C]albumin). The measurements were made in a transaxial thoracic section at midheart level with the subject in supine posture and with a spatial resolution of 1.7 cm. The normal regional hematocrit ratio (means +/- SE) calculated for the lung was 0.90 +/- 0.014, 0.94 +/- 0.023 for the thoracic wall, and 1.00 +/- 0.003 for the heart chambers. The regional lung hematocrit ratio in the patients ranged between 0.81 and 0.86. No correlation was found among the regional lung hematocrit ratio and regional blood volume, lung extravascular density, and the peripheral hematocrit (obtained from venous blood samples). To the extent that 70% of the pulmonary blood in the field of view is in larger vessels with normal hematocrit, the hematocrit in the capillary bed is approximately two-thirds that of the peripheral venous value. Blood volume measurements on the basis of single vascular tracers need to take account of these results.

Adult↗

Positron emission tomography in the lung.

Positron emission tomography using the ECAT II scanner to image and measure regional lung function is outlined. The combined use of transmission and emission imaging provides quantitative information about regional lung structure (density, extravascular density, and vascular volume) and function (ventilation, perfusion, ventilation-perfusion ratios, glucose metabolic rate). Clinical applications in asthma, chronic obstructive lung disease, pulmonary vascular disease, interstitial lung disease, and squamous cell carcinoma are presented. Future prospects for PET are discussed.

Densitometry↗