Kinetics of lung clearance of 99mTc-DTPA in smoking patients with sarcoidosis compared to healthy smokers.

Investigation of lung clearance of 99mTc-labelled diethylene triamine penta-acetic acid (DTPA) in smoking sarcoid patients has been impeded by difficulties to differ between pathology of clearance kinetics caused by sarcoidosis and by smoking. This study explores the kinetics of lung clearance of 99mTc-DTPA in 15 current smokers with intrathoracic sarcoidosis. The results are compared with findings from 16 healthy smokers. Measurements of lung clearance over 180 min, i.e. longer than usual, revealed in II of the sarcoid patients a bi-exponential lung clearance course, which is pathologic. All healthy smokers also showed a bi-exponential lung clearance. In the analysis of the bi-exponential curve an initial fast, and a slow clearance component could be separated. The smokers with sarcoidosis had a significantly higher elimination rate of the slow component than the healthy smokers. Thus, analysis of the late part of the lung clearance curve may be rewarding in smoking sarcoid patients. The study shows that lung clearance of 99mTc-DTPA may be a method useful also in smoking patients with sarcoidosis.

Effect of local cold provocation on systolic blood pressure and skin blood flow in the finger.

Demonstration of increased vascular cold reactivity in patients with Raynaud's syndrome is difficult. For medico-legal reasons, it is important to get objective measures of vasospasm in these patients. Evaluation of the degree of vasospasm also provides prognostic information which is useful for patient management. In this study, we compare two methods of arterial circulation measurement. The laser Doppler scanning is a new method, which uses the recently developed laser Doppler perfusion imaging (LDPI) instrument. The aim of the present study was to compare the effect on finger skin blood flow measured with LDPI with changes in finger systolic blood pressure during local cold provocation. The effect of such provocation, skin blood flow and systolic blood pressure, were studied in 15 healthy controls. Six patients with known traumatic vasospastic disease (TVD) were also tested with both methods. Finger skin blood flow was measured with LDPI on the distal phalanx of the index finger of the left hand, every minutes during 6 min of local heating at 40 degrees C followed by local cooling for 3 min at 15 degrees C and then for 3 min at 10 degrees C. Finger systolic blood pressure was measured with strain-gauge method before and after local cooling to 10 degrees C with a cuff perfused with water of desired temperature. The test was performed in the same finger within a week of the laser Doppler scanning. Local finger cooling to 15 degrees C and 10 degrees C caused a significant decrease in blood flow, most marked at 10 degrees C. There was, however, no correlation between the decrease in blood flow and blood pressure. In the TVD-patients decreases in skin blood flow were similar compared with the healthy controls. In contrast, the changes in systolic blood pressure, were outside normal range (systolic quotient <0.65) in five of the six patients (83%), and also in 11 of the 15 healthy controls (73%). In conclusion, there is no correlation between the decrease in finger skin blood flow and systolic blood pressure during local cold provocation. For diagnosis of traumatic vasospastic disease (TVD), local cold-induced changes in finger systolic blood pressure seems superior to changes in skin blood flow, but the ideal clinical method for demonstrating increased cold-induced vasospasm is, however, still lacking.

Alveolar albumin leakage during large tidal volume ventilation and surfactant dysfunction.

Detergent given as an aerosol and large tidal volume ventilation (LTVV) have been observed, by us, to promote lung injury by an additive effect on alveolocapillary barrier function. The surfactant system may be further damaged if protein leakage occurs into the alveoli. The aim was to study the effect of detergent and LTVV on the alveolar leakage of albumin and also the effect of detergent on surface activity of lung washings and lung tissue extracts. Technetium-99m-labelled human serum albumin was given intravenously. The alveolar leakage of albumin was measured after perturbing the surfactant system with the detergent dioctyl sodium sulfosuccinate either singly or in combination with LTVV. Four groups of rabbits were studied after 3 h of experimental ventilation. Surface tension measurements of tissue extracts, lung mechanics and gas exchange did not show any differences between groups. Wet lung weight and albumin leakage were significantly increased in the two groups subjected to LTVV compared with groups given normal tidal volume ventilation. Low doses of detergent did not affect surface activity of lung tissue extracts or alveolar leakage of albumin. LTVV increased alveolar leakage of albumin and produced oedema. No additive effect was seen when detergent and LTVV were combined.

An independent evaluation of a new method for automated interpretation of lung scintigrams using artificial neural networks.

The purpose of this study was to evaluate a new automated method for the interpretation of lung perfusion scintigrams using patients from a hospital other than that where the method was developed, and then to compare the performance of the technique against that of experienced physicians. A total of 1,087 scintigrams from patients with suspected pulmonary embolism comprised the training group. The test group consisted of scintigrams from 140 patients collected in a hospital different to that from which the training group had been drawn. An artificial neural network was trained using 18 automatically obtained features from each set of perfusion scintigrams. The image processing techniques included alignment to templates, construction of quotient images based on the perfusion/template images, and finally calculation of features describing segmental perfusion defects in the quotient images. The templates represented lungs of normal size and shape without any pathological changes. The performance of the neural network was compared with that of three experienced physicians who read the same test scintigrams according to the modified PIOPED criteria using, in addition to perfusion images, ventilation images when available and chest radiographs for all patients. Performances were measured as area under the receiver operating characteristic curve. The performance of the neural network evaluated in the test group was 0.88 (95% confidence limits 0.81-0.94). The performance of the three experienced experts was in the range 0.87-0.93 when using the perfusion images, chest radiographs and ventilation images when available. Perfusion scintigrams can be interpreted regarding the diagnosis of pulmonary embolism by the use of an automated method also in a hospital other than that where it was developed. The performance of this method is similar to that of experienced physicians even though the physicians, in addition to perfusion images, also had access to ventilation images for most patients and chest radiographs for all patients. These results show the high potential for the method as a clinical decision support system.

One year follow-up of lung clearance of 99mTc-diethylene triamine penta-acetic acid and disease activity in sarcoidosis.

BACKGROUND AND AIM OF THE WORK: In interstitial lung disease lung clearance of 99mTc-diethylenetriaminepentaacetic acid (DTPA) reflects alterations in the alveolar capillary barrier. Our objective was to describe changes in lung clearance during one year in sarcoidosis, and to relate clearance to other data of lung function and disease activity. METHODS: Twenty-three newly diagnosed patients were studied with respect to lung DTPA clearance, spirometry, 67Ga scintigraphy and serum angiotensin converting enzyme (SACE). Lung mechanics and arterial PO2 at rest and exercise were studied in patients with radiological parenchymal changes. Six of these patients were prescribed peroral steroids. RESULTS: At inclusion lung DTPA clearance measured over 30 minutes was 53 +/- 16 minutes and at follow-up 59 +/- 20 minutes (p > 0.05). The number of pathological clearance curves at inclusion was 10 and at follow-up 6. In treated patients lung DTPA clearance improved as did lung 67Ga score and SACE. However, lung clearance did not correlate significantly with changes in lung function or other activity parameters. CONCLUSIONS: Lung DTPA clearance reflects lung function from an aspect different from that of other methods. It seems sensitive to pathology reversed by steroids and may, in some cases, help in the evaluation of disease activity.

Automated interpretation of ventilation-perfusion lung scintigrams for the diagnosis of pulmonary embolism using artificial neural networks.

The purpose of this study was to develop a completely automated method for the interpretation of ventilation-perfusion (V-P) lung scintigrams used in the diagnosis of pulmonary embolism. An artificial neural network was trained for the diagnosis of pulmonary embolism using 18 automatically obtained features from each set of V-P scintigrams. The techniques used to process the images included their alignment to templates, the construction of quotient images based on the ventilation and perfusion images, and the calculation of measures describing V-P mismatches in the quotient images. The templates represented lungs of normal size and shape without any pathological changes. Images that could not be properly aligned to the templates were detected and excluded automatically. After exclusion of those V-P scintigrams not properly aligned to the templates, 478 V-P scintigrams remained in a training group of consecutive patients with suspected pulmonary embolism, and a further 87 V-P scintigrams formed a separate test group comprising patients who had undergone pulmonary angiography. The performance of the neural network, measured as the area under the receiver operating characteristic curve, was 0.87 (95% confidence limits 0.82-0.92) in the training group and 0.79 (0.69-0.88) in the test group. It is concluded that a completely automated method can be used for the interpretation of V-P scintigrams. The performance of this method is similar to others previously presented, whereby features were extracted manually.

Efficient lung scintigraphy.

Lung scintigraphy is a first-choice method to diagnose lung embolism. The clinical routine in most centres is a perfusion study complemented with a ventilation study when judged necessary. We describe a routine with ventilation scintigraphy preceding perfusion scintigraphy, which is completed within one hour. Furthermore, the data acquired allow the determination of lung clearance of the tracer 99mTc-DTPA (diethylene triamine penta-acetate) used for the ventilation scintigraphy. An aerosol generator charged once a day with 99mTc-DTPA solution is used for all inhalations during the day. Inhalation is monitored with a counter and interrupted when the count rate corresponds to about 20 MBq. The ventilation imaging starts and ends with posterior projections. This allows calculation of lung clearance of 99mTc-DTPA. Perfusion scintigraphy is performed in a standard fashion with 100 MBq of 99mTc-MAA (macro-aggregated albumin). The ventilation study was considered to give some diagnostic information in the majority of the patients. The clearance determination allows detection of inflammatory lung disease. The background activity caused by the ventilation study comprised only 13% of the activity in the perfusion scintigraphy and did not significantly interfere with interpretation of the perfusion scan. The cost for the investigation is low because of the rational system for aerosol administration and the short time for a complete study.

Pulmonary clearance of [99mTc]DTPA and [99mTc]albumin in smokers.

We measured the pulmonary clearance of [99mTc]DTPA and [99mTc]albumin for 3 h in 10 non-smokers and 10 healthy smokers. Seven of the non-smokers had a monoexponential clearance of [99mTc]DTPA with a mean half-life of 66 +/- 18 min. The other three had a biexponential clearance of [99mTc]DTPA with a fraction of radio-activity clearing rapidly (fF) of 14 +/- 4%. Eight smokers had biexponential clearance of [99mTc]DTPA. The half-life of the fast and slow clearance components was 12 +/- 5 and 62 +/- 11 min respectively. The fF was 56 +/- 25%. Two of the smokers showed a monoexponential clearance of [99mTc]DTPA with a half-life of 72 and 55 min. All non-smokers had monoexponential clearance curves for [99mTc]albumin, compared with seven smokers. The half-life was 279 +/- 43 min in non-smokers and 236 +/- 64 min in smokers. The difference in half-life was not significant. In three smokers, the clearance curves of [99mTc]albumin were significantly better described by a bi-exponential equation. The fF was 22 +/- 9%. The effects of smoking on the clearance of [99mTc] albumin appear to be qualitatively similar to those on the clearance of [99mTc]DTPA. Clearance of [99mTc]albumin seems less sensitive to the effects of smoking than clearance of [99mTc]DTPA.

Additive nature of distension and surfactant perturbation on alveolocapillary permeability.

The aim of this study was to determine whether the effects of alveolar distention and surfactant dysfunction on alveolocapillary barrier function are different and additive. Pulmonary clearance of aerosolized technetium-99m-labelled human serum albumin (99mTc-HSA) was used to characterize barrier function after perturbing the surfactant system with the detergent dioctyl sodium sulphosuccinate either singly or in combination with large tidal volume ventilation (LTVV). Clearance was measured for 3 h (Experimental ventilation) in four groups (n = 6 each) of rabbits: 1) Controls; 2) Detergent; 3) LTVV; and 4) Detergent + LTVV. Restoration of clearance (Recovery) was studied for 3 h under conventional ventilation. The half-life of clearance (t 1/2) decreased during LTVV (305 min) compared to 1,055 min in Controls. Detergent induced a biexponential clearance with slow (t 1/2S) and fast (t 1/2F) half-lives of 670 and 15.4 min, respectively. The fast fraction (fF) was 0.20. Clearance in the Detergent + LTVV group was also biexponential. The t 1/2F and fF were similar to the Detergent group. The t 1/2S was similar to the LTVV group. The fF in this group increased to 0.36 during Recovery (p < 0.01 versus Detergent group and p < 0.05 versus Experimental ventilation). The diverse kinetics of clearance during large tidal volume ventilation and surfactant dysfunction suggest the presence of different mechanisms affecting the barrier. The mechanisms have additive characteristics, which superimpose to produce lung injury.

Surfactant dysfunction makes lungs vulnerable to repetitive collapse and reexpansion.

Reexpansion of collapsed lung creates intrapulmonary shear forces. In an earlier study we showed that application of a negative end-expiratory airway pressure (NEEP) to normal rabbit lungs in vivo produced tidal collapse and reexpansion with transient changes in compliance and gas exchange but no histologic damage. In the present study we examined NEEP in a model of surfactant perturbation produced by an inhaled aerosol of 2% and 5% dioctyl sodium sulfosuccinate (DOSS). DOSS increased alveolocapillary permeability without affecting compliance or oxygenation. Repeated collapse and reexpansion (RECOREX), caused by NEEP for 3 h was compared with ventilation with positive-end expiratory pressure (PEEP). Groups ventilated with PEEP maintained normal lung mechanics and morphology even if pretreated with DOSS. NEEP disturbed lung mechanics and gas exchange with persistent dose-related histologic damage in animals pretreated with DOSS. Lungs subjected to NEEP without DOSS had normal morphology. We conclude that perturbation of the surfactant system makes lungs vulnerable to injury by RECOREX. The combination of DOSS and NEEP might lead to leakage of plasma proteins into alveoli, causing inactivation of surfactants and increased shear forces with resulting lung damage. Similar mechanisms may accelerate lung damage in the respiratory distress syndrome.

Respiratory mechanics in rabbits ventilated with different tidal volumes.

Respiratory mechanics was studied in 11 rabbits at tidal volumes (VT) of 6.7, 10, and 20 ml/kg. Flow interruptions were performed during the full respiratory cycle. The viscoelastic pressure (Pve) was measured as the dynamic elastic pressure (Pel(dyn)) after flow cessation minus the static elastic pressure (Pel(st)). Static elastic and viscoelastic parameters were determined with numerical technique. Static hysteresis was minimal even at large VT. The Pel(st)-V curve was linear at small VT and in 6 animals at moderate VT. In 5 animals at moderate VT and in all animals at large VT, a linear segment with constant compliance was followed by a segment with decreasing compliance. The Pve-V curve could be described with a linear model only at small VT. A non-linear model was needed at increased VT. Compliance increased with VT. Both static and viscoelastic behaviours were linear up to larger volume ranges at large VT compared to moderate VT.

Effect of detergent combined with large tidal volume ventilation on alveolocapillary permeability.

The combined effect of large tidal volume ventilation (LTVV) and detergent-induced surfactant dysfunction on the clearance kinetics of technetium-99m-labelled diethylene triamine pentaacetate was investigated. Four groups of rabbits (n = 6 in each) were studied: (1) controls, (2) detergent, (3) LTVV, and (4) detergent + LTVV. Clearance was measured for 3 h and the kinetics was analysed by fitting mono- and biexponential equations to the clearance curve and was expressed as a half-life (T 1/2). Pulmonary clearance of 99mTc-DTPA was monoexponential in control animals (T 1/2 = 194 min) and in animals ventilated with LTVV (T 1/2 = 43 min, P < 0.01 compared with controls). In contrast, clearance was biexponential after detergent administration with or without LTVV. T 1/2 values of the fast and slow compartments were 5.4 and 80 min, respectively, with the fast fraction comprising 81% of the radioactivity after detergent alone. When detergent was combined with LTVV, clearance was bicompartmental as with detergent alone, with the same size of the fast fraction. However, clearance from each of the slow (P < 0.01) and fast compartments (P < 0.05) increased significantly. Clearance from the slow compartment was thus similar to T 1/2 during LTVV alone. Large tidal volume ventilation induced a faster than normal clearance of a single compartment, whereas detergent induced kinetics that was distinctly bicompartmental. The mechanisms increasing permeability of the alveolocapillary barrier after detergent and during LTVV seem different and may be additive.

Healthy lungs tolerate repetitive collapse and reopening during short periods of mechanical ventilation.

The possible occurrence of lung damage if alveolar units are allowed to collapse and reopen breath by breath during mechanical ventilation with normal tidal volumes was investigated. Anaesthetised, paralysed, open chest rabbits were subjected to either intrathoracic negative (NEEP; n = 6) or positive (PEEP; n = 6) end-expiratory pressure during volume controlled mechanical ventilation. Both experimental settings were preceded by a 30 min control period and followed by a 30 min recovery period during which a PEEP of 0.2 kPa was maintained. Pao2 and pulmonary compliance deteriorated significantly in the NEEP group during the experimental period and compared to ventilation with PEEP. Partial restoration of lung mechanics and blood gases was achieved during the recovery period. After an alveolar recruitment manoeuvre, this recovery was complete. Lung clearance studied by depositing an aerosol of technetium-99m-labelled diethylenetriamine pentaacetate (99mTc-DTPA) in the alveoli, was significantly faster during ventilation with NEEP compared to the PEEP group (P = 0.0002) as well as the control period (P = 0.0029). It did not recover completely during the recovery period but remained significantly faster. Light microscopic histology was normal in both groups with no evidence of inflammation or epithelial disruption. We conclude that previously healthy rabbit lungs show only a transient disturbance of lung mechanics and blood gases with repetitive collapse and re-expansion. The integrity of the alveolar microstructure is preserved. The disturbance in the alveolo-capillary permeability persists and may indicate surfactant related alveolo-capillary barrier dysfunction.

Different kinetics of lung clearance of technetium-99m labelled diethylene triamine penta-acetic acid in patients with sarcoidosis and smokers.

The rate of clearance from the lungs of inhaled technetium-99m labelled diethylene triamine penta-acetic acid (99mTc-DTPA) is often increased in interstitial lung disease as well as in smoking. In smokers a bi-exponential clearance course of 99mTc-DTPA when measured over 3 h has previously been shown. This study was performed to compare the kinetics of clearance of 99mTc-DTPA, measured for 3 h, in sarcoid patients and healthy smokers. Forty-one never-smoking patients with sarcoidosis and radiological signs of intrathoracic disease were studied. The results were compared with those of 16 healthy current smokers and of 14 healthy never-smokers reported previously. A mono-exponential clearance equation described the clearance in 22 of the sarcoid patients and all normal never-smokers, but with a shorter average tracer half-life in the patients (P < 0.05). In 19 patients and all smokers a bi-exponential equation gave a significantly better curve fit. The rate of clearance of the slow component was higher in patients with sarcoidosis than in smokers (P < 0.05). The fraction of the tracer cleared by the fast clearance component was smaller in patients with sarcoidosis than in smokers (P < 0.01). Differences in kinetics of clearance of 99mTc-DTPA in sarcoidosis and smoking could thus be demonstrated, suggesting that the abnormal clearance is caused by diverging pathophysiological mechanisms.

Biphasic pulmonary clearance of 99mTc-DTPA in smokers.

We measured the pulmonary clearance of 99mTc-labelled diethylene triamine penta-acetate (99mTc-DTPA) for 3 h in 17 non-smokers and in 16 healthy smokers. We found the clearance of 99mTc-DTPA to be well described by a mono-exponential equation in 14 non-smokers, the half-life being 66 +/- 17 min (mean +/- SD). In all smokers, a bi-exponential equation yielded a significantly better curve fit. The half-life of the slow and fast clearance components was 83 +/- 19 and 13 +/- 4 min, respectively. The relative amount of radioactivity cleared by the fast component was 57 +/- 15% and correlated significantly with cumulated tobacco consumption (r = 0.58, P < 0.02) and forced expiratory volume in 1 s in percentage of predicted value (r = -0.60, P < 0.02). We conclude that smoking induces a rapidly clearing pool of 99mTc-DTPA in the lung, the size of which may be related to smoking habits.

Biexponential pulmonary clearance of 99mTc-DTPA induced by detergent aerosol.

We measured the pulmonary clearance of technetium-99m-labeled diethylenetriamine pentaacetatic acid (99mTc-DTPA) for 3 h after perturbation of the surfactant system by administration of the detergent dioctyl sodium sulfosuccinate in aerosol. Forty-two rabbits were anesthetized with pentobarbital sodium. Tracheostomies were performed, and the rabbits were mechanically ventilated. Increasing concentrations of detergent (0.125-2%) or vehicle were given for 5 min, and clearance measurements were performed immediately or 60 min after detergent administration. No animals developed respiratory distress. After vehicle, the clearance was monoexponential with a half-life of 153 min. Detergent induced a biexponential clearance with a rapidly clearing additional pool of radioactivity with a half-life of 5-15 min. The relative amount of radioactivity clearing rapidly increased with detergent concentration. The detergent effect was partly reversible. We conclude that detergent induces a biexponential clearance of 99mTc-DTPA by accelerating the transfer of tracer across the alveolocapillary barrier in a proportion of lung units in a dose-related manner.

Pulmonary clearance of inhaled [99Tcm]DTPA: effects of ventilation pattern.

While a rise in lung volume is known to increase the pulmonary clearance of technetium-99m-labelled dietylene triamine pentaacetate ([99Tcm]DTPA), little interest has been focused on the effects of changes in ventilation frequency, tidal volume and airway pressure. We studied adult, anaesthetized and intubated rabbits during three ventilation patterns (VP) using pressure controlled ventilation (ServoVentilator 900C). VP was either deep slow (f = 20 min-1, tidal volume (VT) = 30 +/- 4 ml kg-1 and positive end-expiratory pressure (PEEP) = 0.2 kPa [VP 20/0.2, n = 8]) or rapid shallow (f = 80 min-1, VT = 11 +/- 2 ml kg-1 and PEEP = 0.2 or 0.4 kPa [VP 80/0.2, n = 6 and VP 80/0.4, n = 6]). The mean airway pressure was similar at VP 20/0.2 and VP 80/0.4. During administration of [99Tcm]DTPA aerosol all animals were ventilated under the same conditions (f = 40 min-1 and PEEP = 0.2 kPa). The pulmonary clearance rate expressed as the half-life time (T1/2) of [99Tcm]DTPA was at VP 80/0.2 = 113 +/- 31 min, at VP 80/0.4 = 70 +/- 24 min (P less than 0.01 compared to VP 80/0.2) and at VP 20/0.2 = 36 +/- 18 min (P less than 0.001 compared to VP 80/0.2 and P less than 0.01 compared to VP 80/0.4). We conclude that the pulmonary clearance of [99Tcm]DTPA increases (1) during rapid shallow ventilation when PEEP is increased from 0.2 to 0.4 kPa; (2) during deep slow ventilation relative to rapid shallow ventilation even when the mean airway pressure is similar.

Distribution of renal parenchymal damage on 99m-Tc DMSA scintigraphy in vesico-ureteric reflux.

During a 2 year period renal scintigraphy was performed in 64 children prior to surgery for vesico-ureteric reflux (VUR). In total 126 kidneys were examined. Renal scintigraphy was performed 3 hours after intravenous injection of 99m-technetium labelled dimercaptosuccinic acid (DMSA). The renal parenchyma was assessed as normal in 64 kidneys and abnormal in 62. Renal parenchymal damage was revealed in the upper pole in 42 cases, the middle lateral part in 27, the lower pole in 47 and the middle medial part in 25. The whole kidney was affected in 21 cases. Damage within one or two poles was present in 59 of the 62 kidneys with parenchymal damage. Renal scintigraphy is regarded a sensitive technique for detection of renal parenchymal damage. The DMSA scintigraphy can reveal even minor scars. It can be recommended as a routine investigation in evaluating children with VUR.

Myocardial scintigraphy with 201thallium in pediatric cardiology: a review of 52 cases.

We report our experience of myocardial scintigraphy with 201thallium (201Tl) in 52 children, aged 4 days to 18 years, in which 80 studies were made primarily to demonstrate or exclude impaired myocardial perfusion. For analysis, the patients were divided into the following eight groups: group I, coronary artery malformations (five patients); group II, Kawasaki's syndrome (six patients); group III, arterial switch operation (seven patients); group IV, dilated cardiomyopathy (18 patients); group V, hypertrophic cardiomyopathy (four patients); group VI, myocardial dysfunction after surgery for congenital heart disease (five patients); group VII, pulmonary atresia (three patients); and group VIII, miscellaneous (four patients). Myocardial scintigraphy was performed with a planar or tomographic technique at rest or after exercise (four patients). Isotope-uptake defects, indicating impaired myocardial perfusion, were present in 14 patients, including small infants. Defects were seen in all groups except those with hypertrophic cardiomyopathy and pulmonary atresia. The absence of such defects in several of the patients with Kawasaki's syndrome was particularly valuable as it made coronary angiography unnecessary. In the other groups of patients myocardial scintigraphy was a valuable adjunct to other investigations.