Effective penetration of the lung periphery using radioactive aerosols: concise communication

Radioactive microspheres could offer several advantages over gases in the investigation of pulmonary ventilation. Monodisperse microspheres of human serum albumin have been produced using a spinning-disc generator, and kits were prepared for subsequent labelling with technetium-99m. The average labeling efficiency was 88% and unlabeled Tc-99m was removed before aerosol delivery. A simple system was constructed to nebulize and deliver dry monodisperse microspheres. The ventilation images obtained were compared quantitatively with the corresponding krypton-81m images, subdividing the lung regions into inner, central, and peripheral zones. No significant difference was found in the proportions of the total counts for any lung region. There was good agreement between the distributions of microspheres obtained on separate days (r = 0.97, p less than 0.0001), An "aerosol penetration index" was defined as the ratio of the peripheral to the inner counts for the microspheres normalized by the corresponding ratio for krypton-81m. The mean value of this index for 16 normal subjects was 0.98 +/- 0.23 (s.d.), indicating that the microspheres had achieved penetration of the lung periphery. For patients with chronic obstructive lung disease, more localized defects were observed with the microspheres than with krypton-81m. The mean penetration index for this group was only 0.69 +/- 0.21 (s.d.). This was significantly different from the value for normal subjects (p less than 0.002).     

Mismatch between 99mTc-DTPA aerosol and 81mKr lung ventilation scintigraphy: a pitfall of radionuclide imaging

Pulmonary ventilation and perfusion scintigraphies were performed using 99mTc-MAA, 81mKr, and 99mTc-DTPA aerosol in a patient with asthma. Lung perfusion scintigraphy and 99mTc-DTPA aerosol scintigraphy showed multiple matching defects, however, 81mKr ventilation scintigraphy showed mismatch with lung perfusion scintigraphy. A pitfall of this examination was discussed.     

Regional comparison of technetium-99m DTPA aerosol and radioactive gas ventilation (xenon and krypton) studies in patients with suspected pulmonary embolism

The regional distribution of [99mTc]DTPA aerosol was compared with that of 133Xe (n = 30) and krypton (n = 24) in a group of patients with suspected pulmonary embolism. All patients had an aerosol study using a recently available commercial generator system, a ventilation study with one of the gases, and perfusion imaging. Regional information was assessed visually on xenon, krypton, and aerosol studies independently by considering each lung as three equal-sized zones. In addition, gas ventilation findings peripheral to regions of aerosol turbulence ("hot spots") were evaluated. Only 64% of the zones were in complete agreement on xenon and aerosol. Most of the discordance between xenon and aerosol was accounted for by minor degrees of 133Xe washout retention in zones that appeared normal in the aerosol study. An agreement rate of 85% was noted between 81mKr and aerosol regionally. The regions of discordance between aerosol and gas studies, however, usually were associated with unimpressive perfusion defects that did not change the scintigraphic probability for pulmonary embolism in any patient. Regarding zones of aerosol hyperdeposition, 76% had associated washout abnormalities on xenon; however, there was no correlation between the presence of these abnormalities or perfusion abnormalities. The results confirm the high sensitivity of 133Xe washout imaging, but suggest that radioaerosol imaging will detect most parenchymal abnormalities associated with perfusion defects of significance.     

Krypton-81m and 5-micron radioaerosol images in asymptomatic asthma: a blind marking assessment

Gamma camera images recorded during tidal breathing of krypton-81m (81mKr) and after slow inhalation of 99mTc-labelled monodisperse 5-micron polystyrene particles were assessed by three independent observers. Results from 20 symptom-free asthmatic subjects, all with a forced expiratory volume in 1 s (FEV1) at least equal to 75% of the predicted value, were compared with those from 16 healthy non-smoking volunteers. Blind marking scores for the 81mKr images of the asthmatic subjects related significantly to small airways function. Radioaerosol abnormalities in the asthmatic subjects included excessive deposition of the radioaerosol in the central airways and related significantly to small airways function. Radioaerosol imaging performed better than 81mKr imaging at differentiating asthmatic from normal subjects. Radioaerosol abnormalities in patients with poor small airways function probably reflect (1) uneven distribution of ventilation to different regions of the lung periphery and (2) changed patterns of airflow in the bronchial tree. Image abnormalities detected in routine clinical ventilation imaging - with 81mKr or radioaerosol - may sometimes be caused by small airways dysfunction even when the patient's FEV1 is normal.     

A simple radioaerosol generator and delivery system for pulmonary ventilation studies

Details of a simple radioaerosol generator and delivery system are presented. Aerosol streams of 99mTc-DTPA solution of different distributions were produced. The most useful distribution had an activity median aerodynamic diameter (AMAD) of 0.9 micron with a geometric standard deviation of 1.5. This distribution also had more than 96% of aerosol particles with aerodynamic diameter less than 2 micron. The system has been used for patient lung ventilation studies. The aerosol breathing-in period to achieve a satisfactory count rate was 1.8 +/- 0.38 min. The radioaerosol images were excellent and comparable to those obtained with 81mKr gas.     

Can dynamic krypton-81m imaging separate regional ventilation and volume?

This study explores the assumption that 81mKr static images represent regional ventilation. Dynamic acquisition of 81mKr ventilation images permits creation of time-activity curves and the possible separation of the confounding influences of ventilation and volume. By using a two-compartment gas mixing lung phantom, the results demonstrate that both total and tidal 81mKr are closely related to regional ventilation. In 61 children and 15 adult volunteers, there was good agreement between fractional ventilation assessed by total and tidal 81mKr. The dynamic steady-state ventilation image can be analyzed to separate tidally exchanged and resident 81mKr. This may allow regional ventilation to be distinguished from regional volume.     

Lung ventilation studies with technetium-99m Pseudogas

Technetium-99m Pseudogas is an ultrafine near monodisperse aerosol of 0.12-microgram diam particle size. This report describes initial clinical experiences with 27 patients referred for investigation of suspected pulmonary embolism, and in whom Pseudogas ventilation images were compared with a high quality commercial aerosol. An additional group of ten patients with severe COPD was examined in a comparative trial of Pseudogas with 81mKr. Pseudogas was better than a conventional aerosol in reaching a diagnosis of pulmonary embolism using a simple blinded comparison with coded images. In addition, bronchial deposition was minimal unless COPD was severe. Moderately well patients had no difficulty inhaling the necessary activity in one or two breaths, and even severely ill and frail aged persons could accomplish the passive breathing maneuver in less than a minute. Clearance of Pseudogas was directly to the systemic circulation with a half-time of 10 min in normal subjects extending up to 100 min in patients with airways disease.     

Regional pulmonary distribution of krypton-81m gas delivered by different breathing systems

Regional pulmonary distribution of 81mKr gas delivered by three breathing systems was determined. Data from 18 patients were analyzed. Posterior images were obtained using each breathing system in turn. Distribution of Kr gas was determined in terms of penetration and zonal indices. For penetration indices each lung was divided into a central, intermediate, and peripheral region and these indices, defined as the ratio of counts/cell in the intermediate or the peripheral region over those in the central region, were calculated. For the zonal indices each lung was divided equally into upper and lower zones and the percentage ratio of the counts in each zone to the total counts in both lungs was calculated. For all patients, in addition, the size, height, and width of each lung were determined from computer images. These parameters were compared between the breathing systems using a paired t-test. It was found that there were no statistical differences among the three breathing systems, either in the regional pulmonary distribution of the 81mKr gas or in the overall shapes of the lungs.     

The distribution of lung damage in children with cystic fibrosis and its relationship to colonisation with Pseudomonas aeruginosa

Ventilation-perfusion lung scans were performed with 81mKr inhalation and 99mTc-albumin injection in 33 children with cystic fibrosis. It was found that both ventilation and perfusion scans yielded more information than radiographs of the chest in assessing lung damage. Using a scoring system, it was demonstrated by statistical methods that in the worst affected patients the disease was worse in the upper zones of the lungs, which changes were not detectable on chest radiographs. Pseudomonas was present in the sputum of these patients.     

Evaluation of the accuracy of steady-state krypton-81m method for calculating right ventricular ejection fraction

The accuracy of a steady-state 81mKr method for calculating the right ventricular ejection fraction (RVEF) has been examined in this study. Causes of errors using this method and their effects on the calculated RVEF were evaluated. The results suggested that mixing in the right ventricle during continuous infusion of 81mKr was homogenous, allowing for the calculation of ejection fraction using the count rate ratio. Lung activity was quite important and could not be neglected in computing RVEF, but the use of [99mTc]MAA lung perfusion scanning seemed to allow a correct subtraction of this background activity. The delineation of right ventricular regions of interest (ROIs) was complicated by the translation movements of the right ventricle during heart contraction. These ROIs should be drawn carefully on the count density distribution images and data shown by parametric images; such as first and second harmonic phase, amplitude images, and composite stroke volume image should be considered. Furthermore, this study demonstrates the superiority of the 81mKr technique compared with 99mTc methods for computing RVEF. In conclusion, even if the true accuracy of the 81mKr method for calculating RVEF cannot be proven due to the lack of reference methods, strong, suggestive evidence that the technique should be accurate is shown here.     

An evaluation of Technegas as a ventilation agent compared with krypton-81 m in the scintigraphic diagnosis of pulmonary embolism.

A ventilation agent that provides good quality lung images, which is cheap, easy to use and non-toxic, with a low radiation dose, has long been sought. Technegas, an ultrafine aerosol of technetium-99m-labelled carbon, was developed with these qualities in mind. We have studied Technegas in a clinical setting to evaluate some of these qualities. Twenty-five patients referred with a diagnosis of suspected pulmonary embolism were investigated during the same study using both krypton-81 m and Technegas as ventilation agents in conjunction with 99mTc-macroaggregated albumin as a perfusion agent. Technegas provided images which were of satisfactory quality. Images were obtained relatively easily and without discomfort to the patient, and Technegas has the advantage of always being available. A semi-quantitative regional assessment was employed which showed a good correlation (r = 0.499, P less than 0.001) between Technegas and krypton-81 m ventilation. We report on an effect not previously found to be significant, that is lung regions were better ventilated with Technegas than with krypton-81 m. This altered the diagnostic probability rating of pulmonary embolism in a number of patients (n = 3, 12%) compared with krypton-81 m. This effect was also noted in a further 8 patients (32%) without a change in the diagnostic probability. We offer possible explanations for this phenomenon.     

Semi-quantitative ventilation/perfusion scintigraphy and single-photon emission tomography for evaluation of lung volume reduction surgery candidates: description and prediction of clinical outcome.

Ventilation/perfusion scans with single-photon emission tomography (SPET) were reviewed to determine their usefulness in the evaluation of lung volume reduction surgery (LVRS) candidates, and as a predictor of outcome after surgery. Fifty consecutive planar ventilation (99mTc-DTPA aerosol) and perfusion (99mTc-MAA) scans with perfusion SPET of patients evaluated for LVRS were retrospectively reviewed. Technical quality and the severity and extent of radiotracer defects in the upper and lower halves of the lungs were scored from visual inspection of planar scans and SPET data separately. An emphysema index (EI) (extent x severity) for the upper and lower halves of the lung, and an EI ratio for upper to lower lung were calculated for both planar and SPET scans. The ratios were compared with post-LVRS outcomes, 3, 6 and 12 months after surgery. All perfusion and SPET images were technically adequate. Forty-six percent of ventilation scans were not technically adequate due to central airway tracer deposition. Severity, extent, EI scores and EI ratios between perfusion and SPET were in good agreement (r = 0.52-0.68). The mean perfusion EI ratio was significantly different between the 30 patients undergoing biapical LVRS and the 17 patients excluded from LVRS (3.3+/-1.8 versus 1.2+/-0.7; P<0.0001), in keeping with the anatomic distribution of emphysema by which patients were selected for surgery by computed tomography (CT). The perfusion EI ratio correlated moderately with the change in FEV1 at 3 months (r = 0.37, P = 0.04), 6 months (r = 0.36, P = 0.05), and 12 months (r = 0.42, P = 0.03), and the transition dyspnea index at 6 months (r = 0.48, P = 0.014) after LVRS. It is concluded that patients selected to undergo LVRS have more severe and extensive apical perfusion deficits than patients not selected for LVRS, based on CT determination. SPET after aerosol V/Q imaging does not add significantly to planar perfusion scans. Aerosol DTPA ventilation scans are not consistently useful. Perfusion lung scanning may be useful in selecting patients with successful outcomes after LVRS.     

Comparison of technetium-99mC and phytate aerosol in ventilation studies.

The image quality obtained with technetium-99mC aerosol (Technegas) was evaluated and compared with that obtained with 99mTc-phytate aerosol generated by a jet nebulizer. Fifty patients underwent ventilation scanning after inhalation of each aerosol (mean interval of 3 days). Four views (anterior, posterior, left and right posterior oblique) were recorded with 200 k precounts. Both sets of images were blindly compared for (i) qualitative evaluation of images, (ii) quantitation of penetration (PI) and heterogeneity (HI) indices and (iii) assessment of ventilation state. Peripheral penetration was the same in 64% of cases, greater with 99mTc-C in 27% and greater with 99mTc-phytate in 9%. The use of 99mTc-C led to fewer and less intense foci of bronchial or gastric activity. The differences for 99mTc-C and 99mTc-phytate, respectively, between mean PI (0.78 vs. 0.70) and HI (15 vs. 18) were not significant. Consideration of all the parameters indicates the overall superiority of 99mTc-C. The final interpretation of the lung ventilation scans was, however, similar with both tracers.     

Tc-99m-DTPA aerosol and radioactive gases compared as adjuncts to perfusion scintigraphy in patients with suspected pulmonary embolism

To evaluate the clinical utility of improved methods for radioaerosol inhalation imaging, we obtained preperfusion radioaerosol images in 107 patients (mean age = 62 years), who were referred for evaluation of suspected pulmonary embolism (PE). For each patient, we compared six-view aerosol images with accompanying perfusion scans and chest radiographs and with Xenon-133 (Xe-133) or Krypton-81m (Kr-81m) studies. Four observers at four different institutions independently evaluated aerosol-perfusion and gas-perfusion pairs, classifying the probability of PE as low, high, or indeterminate. The radioaerosol images were good to excellent in quality; excessive central deposition of activity was infrequent and did not interfere with image interpretation. The aerosol-perfusion studies showed 86% agreement with Xe-133 perfusion interpretations (n = 299) and 80% agreement with Kr-81m perfusion interpretations (n = 99). These rates of agreement were comparable with those of intraobserver agreement for gas-to-gas and aerosol-to-aerosol comparisons, and higher than interobserver agreement rates. In a limited number (n = 9) of angiographically documented cases, aerosol-perfusion and gas-perfusion studies provided accurate and equivalent diagnoses. The results suggest that radioaerosol inhalation studies, performed with improved nebulizers, are diagnostically equivalent to ventilation imaging as an adjunct to perfusion scintigraphy in evaluating patients with suspected PE.     

Assessment of SPECT ventilation-perfusion imaging in patients with lung cancer

Ventilation and perfusion SPECT images during tidal breathing were studied in 15 cases of lung cancer using 81mKr gas and 99mTc-microspheres. Furthermore, functional images of V/Q ratio and Q/V ratio were prepared, and their clinical significance is discussed with reference to general lung function. There was a decrease in %VC and %FEV 1.0 in 7 of 15 cases, and an increase of AaDo2 in the blood gas analysis in 12 of 15 cases. Both planar and SPECT images showed ventilation and perfusion abnormalities in all 15 cases. Of these, 12 patients showed matched ventilation and perfusion defects, 2 patients a dead-space effect and 1 patient a shunt effect. In comparing planar and SPECT images, depiction of ventilation and perfusion impairments were equally clear in 11 cases, but in 3, showing a lobar or segmental defect with a shunt effect, the SPECT images were superior. In a patient with markedly impaired function of the affected lung, the remaining function could not be depicted by SPECT. From the above, it seems that better information can be obtained for understanding the ventilation and perfusion states of lung cancer by adding the SPECT images to the planar image.     

Pulmonary perfusion and ventilation scintigraphies before and after cardiac catheterization in infants with congenital heart diseases

We performed 99mTc-MAA pulmonary perfusion scintigraphies before and after catheterization of 50 infants with congenital heart disease. 81mKr ventilation scintigraphies were also performed in 41 patients. Both right and left heart catheterization (23 patients) and right heart catheterization (27 patients) were performed by Seldinger's method. Pulmonary perfusion scintigraphies showed new perfusion defects in 6 patients (12%) following catheterization. Of six patients, three had ventilation defects. Clinical characteristics, duration of catheterization, hemodynamic variables were not significantly different between patients with and without lung perfusion defects. The lung perfusion defects seemed to be due to pulmonary embolism following cardiac catheterization.     

Lung scintigraphy clustering by texture analysis

The efficiency of texture analysis parameters, describing the organization of grey level variations of an image, was studied for lung scintigraphic data classification. Twenty one patients received a 99mTc-MAA perfusion scan and 81mKr and 127Xe ventilation scans. Scans were scaled to 64 grey levels and 100 k events for inter subject comparison. The texture index was the average of the absolute difference between a pixel and its neighbors. Energy, entropy, correlation, local homogeneity and inertia were computed using co-occurrence matrices. A principal component analysis was carried out on each parameter for each type of scan and the first principal components were selected as clustering indices. Validation was achieved by simulating 2 series of 20 increasingly heterogeneous perfusion and ventilation scans. For most of the texture parameters, one principal component could summarize the patients data since it corresponded to the relative variances of 67%-88% for perfusion scans, 53%-99% for 81mKr scans and 38%-97% for 127Xe scans. The simulated series demonstrated a linear relationship between the heterogeneity and the first principal component for texture index, energy, entropy and inertia. This was not the case for correlation and local homogeneity. We conclude that heterogeneity of lung scans may be quantified by texture analysis. The texture index is the easiest to compute and provides the most efficient results for clinical purpose.     

Comparison of technetium-99m aerosol and krypton-81m in ventilation studies for the diagnosis of pulmonary embolism

A new method of producing aerosols (technegas) in which 99Tcm is bound to carbon atoms (99Tcm-C) was evaluated by comparing 99Tcm-C images with those obtained with 81Krm in the same patients. Twenty-five patients with suspected pulmonary embolism (PE) were studied. Immediately after the last 99Tcm-C view, the patients remained in supine position and inhaled 81Krm at tidal volume. Immediately after the 81Krm ventilation views were recorded, 4-7 mCi of MAA were injected IV. The same four views (ant, lop, rop, post) were recorded after inhalation of 99Tcm-C and 81Krm (200 kcounts) and 99Tcm MAA injection (400 kcounts). The mean penetration index of 99Tcm-C (0.91) was lower than that of 81Krm (1.04) (P less than 0.03). The apex to base lung distribution of 99Tcm-C and 81Krm appeared to be similar. The mean heterogeneity of 99Tcm distribution was 23, greater than that of 81Krm (14) (P = 10(-4)). The 99Tcm-C ventilation image quality was considered very good for 16 patients and good for 6 others. Significant foci of high bronchial uptake were infrequent. Interpretation of the examinations performed after inhalation of 99Tcm-C and 81Krm was concordant in all cases. No patient had an 81Krm/99Tcm MAA examination suggestive of PE when 99Tcm-C/99Tcm MAA indicated a low probability of PE, and vice versa. 99Tcm-C aerosols enable good quality ventilation images to be obtained in nearly all cases. Thus 99Tcm-C aerosols could be used in preference to 81Krm in ventilation studies for the diagnosis of PE.     

The use of a computer in ventilation-perfusion scintigraphy with Tc-99m macroaggregates and Kr-81m, to obtain a physiological model

In this article we describe a computer program to demonstrate ventilation-perfusion relationships in the lungs, using 99mTc-MAA and 81mKr, with the patients sitting upright, the normal physiological situation. The ventilation and perfusion scans are performed simultaneously with both gamma camera and computer adjusted for dual isotope mode. Steady state images are acquired in the frontal, dorsal, and left and right posterior oblique positions. Additionally, in the dorsal and frontal projections, a sequence of 12 washout images (5 s) is registered, after closing the Krypton supply. After normalization and further computer processing, the following parameters are calculated in the frontal and dorsal projections, in the whole lung and in four horizontal subregions: washout values, ventilation-perfusion ratios, left to right ratios of ventilation and perfusion, and left to right ratios of the average pixel values for ventilation and perfusion. Results in a group of eight healthy volunteers are described and discussed.     

Coregistered ventilation and perfusion SPECT using krypton-81m and Tc-99m-labeled macroaggregated albumin with multislice CT utility for prediction of postoperative lung function in non-small cell lung cancer patients

RATIONALE AND OBJECTIVE: Co-registered SPECT and CT imaging (SPECT-CT) has potential for more precise evaluation of regional pulmonary function and may be useful for prediction of postoperative lung function in non-small cell lung cancer (NSCLC) patients. The purpose of the present study was to prospectively assess the capability of co-registered SPECT-CT using krypton-81m (Kr-81m) and technetium-99m-labeled macroaggregated albumin (Tc-99m MAA) for prediction of postoperative lung function of NSCLC patients compared with SPECT and planar imaging. MATERIALS AND METHODS: Sixty consecutive patients considered candidates for lung resection underwent 16-slice CT, ventilation and perfusion scintigraphy with SPECT examinations, and preoperative and postoperative measurement of FEV(1)%. In each subject, SPECT and CT data were automatically fused by using commercially available software. Each postoperative FEV(1)% value was predicted from uptakes of Kr-81m and Tc-99m MAA within total and resected lungs. Then, reproducibility coefficients and the limits of agreement between actual and each predicted postoperative lung function were statistically assessed. RESULTS: Reproducibility coefficients of SPECT-CT (Kr-81m: 5.1%, Tc-99m MAA: 5.2%) were smaller than those of SPECT and planar image using Kr-81m (SPECT: 7.4%, planar image: 12.1%) and using Tc-99m MAA (SPECT: 7.2%, planar image: 11.8%). The limits of agreement for SPECT-CT (Kr-81m: 3.3 +/- 10.5%, Tc-99m MAA: 5.4 +/- 11.0%) were also smaller than that of SPECT and planar image and small enough for clinical purposes. CONCLUSIONS: Co-registered SPECT-CT using Kr-81m and Tc-99m MAA was able to more reproducibly and accurately predict postoperative lung function compared with SPECT and planar imaging.