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.     

Sensitivity of Kr-81m and Xe-127 in evaluating nonembolic pulmonary disease

The relative sensitivities of Kr-81m and Xe-127 in detecting lung ventilation defects was evaluated in 80 patients with nonembolic pulmonary diseases. Krypton-81m ventilation images (500,000 count) were interdigitated with Tc-99m MAA perfusion images; both were compared with Xe-127 images. The distributions of the two gases were also compared on the basis of point-by-point computer analyses. Xenon-127 was found to be more sensitive than Kr-81m in clinical evaluations of scintiphotos--although they were equivalent by computer analyses--in indicating regions of impaired ventilation in patients with obstructive airways disease.     

Indeterminate lung imaging. Can the number be reduced?

During a 2 1/2-year period, 1131 patients with suspected pulmonary embolism had ventilation-perfusion lung scans; 150 of these patients also underwent pulmonary angiography. In a retrospective study, these 150 patients were re-evaluated using the reference criteria of Biello and Alderson, with 62% read as indeterminate. Twenty patients who had chronic obstructive pulmonary disease with retention of Xe-133 in greater than 50% of the lung fields without corresponding radiographic abnormality were included. Ventilation/perfusion matches and mismatches could be correctly determined in 15 of these patients. These 15 of 20 studies could be correctly reclassified as low-probability, while the other five remained indeterminate. With increasing intervals between ventilation/perfusion lung imaging and the onset of symptoms, the percentage of patients with proven pulmonary emboli correctly diagnosed as high probability continuously decreased, and the percentage of studies read as indeterminate constantly increased. Serial chest radiographs suggested that the development of infiltrates in the region of the embolus convert high-probability ventilation/perfusion scans to indeterminate.     

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.     

Role of chest radiography in predicting the extent of airway disease in patients with suspected pulmonary embolism

An independent evaluation of the chest radiographs and ventilation-perfusion (VP) scintigrams of 119 patients (121 studies) was performed to assess the ability of radiographic findings to indicate the extent of ventilation abnormalities in patients suspected of having pulmonary embolism (PE). VP scans were obtained with krypton-81m in 72 cases and with xenon-133 in 49. All scintigrams showing ventilation abnormalities in greater than 50% of the lung were considered indeterminate for PE, owing to an increased likelihood of false-negative interpretations, as reported in previous studies. Indeterminate VP studies were found in all 21 patients who had radiographic findings of widespread obstructive pulmonary disease (OPD), in 35% with radiographic findings of focal OPD (P less than .001), and in only 18% with no OPD seen radiographically (P less than .001). VP scintigraphy is likely to be indeterminate for PE when widespread OPD is seen by chest radiography and ventilation imaging may not be warranted in these patients.     

Pulmonary ventilation and perfusion studies in lung cancer

In 46 patients with bronchogenic carcinoma, the diagnostic significance of pulmonary ventilation images by the continuous inhalation of Kr-81m gas, which has an extremely short half life, was studied in comparison with pulmonary perfusion images with Tc-99m MAA. The data were processed using digital analysis techniques. There were 15 cases with discrepancies between ventilation and perfusion. The V/Q ratios of the affected lung among the 43 patients showed values above 1.2 in nine cases and below 0.8 in six cases. The Kr-81m ventilation and Tc-99m perfusion images were compared before and after radiation therapy in eight patients. It was possible to assess the therapeutic effect on regional ventilation and regional perfusion, which could not be evaluated by chest x-ray alone, under the same conditions of normal breathing.     

Scintigraphic evaluation of pulmonary embolism

Pulmonary embolism (PE) is difficult to diagnose. The clinical signs and symptoms of the disorder are nonspecific, and the results of laboratory tests are undependable. Accordingly, imaging studies have played a major role in evaluation of patients with suspected PE. Chest radiography is an essential part of this imaging evaluation, but is neither sensitive nor specific, per se. The radiograph is used primarily to provide a regional comparison for ventilation-perfusion (V-P) scintigraphy. V-P scintigraphy typically is the pivotal noninvasive approach to diagnosis of PE. Multiview perfusion scintigraphy is a sensitive means for detecting the multiple, wedge-shaped defects characteristic of PE. The perfusion scan's inherent nonspecificity is improved by the ventilation study, which reveals abnormalities of ventilation that account for perfusion defects not caused by PE. Multi-view ventilation imaging with either the xenon gases, Kr-81m or radioaerosols is useful for comparison with perfusion scans. When performed properly and interpreted within the guidelines of current diagnostic schemes for scintigraphy, V-P studies provide approximately 90% reliability for the diagnosis of PE. When used alone or in conjunction with noninvasive studies of deep venous thrombosis, they provide an excellent basis for selection of certain patients for pulmonary angiography, and for other decisions about the clinical management of patients with suspected PE.

     

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.     

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.     

Idiopathic pulmonary fibrosis. A rare cause of scintigraphic ventilation-perfusion mismatch

A case of idiopathic pulmonary fibrosis with multiple areas of mismatch on ventilation-perfusion lung imaging in the absence of pulmonary embolism is presented. Idiopathic pulmonary fibrosis is one of the few nonembolic diseases producing a pulmonary ventilation-perfusion mismatch. In this condition, chest radiographs may not detect the full extent of disease, and xenon-133 ventilation imaging may be relatively insensitive to morbid changes in small airways. Thus, when examining patients with idiopathic pulmonary fibrosis, one should be aware that abnormal perfusion imaging patterns without matching ventilation abnormalities are not always due to embolism. In this setting, contrast pulmonary angiography is often needed for accurate differential diagnosis.     

Clinical experience with technetium-99m DTPA aerosol with perfusion scintigraphy in suspected pulmonary embolism

To evaluate the clinical value of radioaerosol imaging, 156 patients with suspected pulmonary embolism (PE) were studied. In 25 patients, a preperfusion xenon-133 (Xe-133) study was compared with a postperfusion study using Tc-99m DTPA aerosol. It was found that they were of equal value most of the time (56%), but that the aerosol study was more often helpful. Because of this, and the technical ease of using six standard views with radioaerosol, the series was completed using perfusion scintigraphy followed by radioaerosol images. In 19 patients the perfusion scintigraphy with Tc-99 macroaggregated albumin (Tc-99m MAA) was normal or nearly normal and no aerosol study was required. Tc-99m DTPA aerosol images were satisfactory when the count rate was at least twice and preferably three times that of the previous perfusion study. There were 17 studies (11%) classified as intermediate. There were 26 patients classified as high probability for PE, and angiographic or autopsy correlation was available in 14. All of the 14 proved to have PE. In the 113 patients classified as low probability, there were ten with angiographic or autopsy correlation. In the ten, there was one patient with a small pulmonary embolus found at autopsy. Clinical follow-up for over two months confirmed the absence of PE in the remainder of this group. Aerosol studies have proven technically easier to perform and a satisfactory substitute for xenon imaging in suspected PE.     

Scintigraphic evaluation of pulmonary embolism after total hip replacement, using a dry 99mTc-microaerosol for regional ventilation

A new 99mTc-microaerosol was used for ventilation scintigraphy in combination with perfusion scintigraphy for studying the incidence of pulmonary embolism (PE) from 189 consecutive investigations in patients undergoing total hip replacement. Diagnostic criteria are presented. Perfusion defects of triangular shape were significantly more frequent in combination with ventilation mismatch (PE) than with ventilation match (not PE) (P less than 0.001). Reevaluation of the scintigrams more than 2 months later gave identical results in more than 90% of patients and as regards the diagnosis of PE, in 93%. Attacks of sudden chest pain were more frequent in patients with pulmonary embolism (P less than 0.01), but measurement of arterial blood gases did not discriminate between patients with and without PE. The 99mTc-microaerosol provides a high resolution and images that are directly comparable to perfusion studies using the same, easily available isotope. In many aspects this new microaerosol seems to be superior to previously described radioaerosols and to 133Xe for ventilation studies.     

Usefulness of ventilation and perfusion scans in patients with collagen-vascular diseases

We studied 32 patients with collagen-vascular diseases with Xe-133 ventilation scans (V) and Tc-99m MAA perfusion scans (Q). Five patients underwent sequential studies at intervals of more than 3 months. Mean transit time (MTT) was calculated from the Xe-133 wash-out curve. V, Q images and MTT were compared with chest X-ray films and the values of %DLco. Of 32 patients, 17 had no abnormal finding on the chest X-ray films. Of the 17 patients, however, V and/or Q abnormalities were found in 10 (59%), 14 patients (82%), respectively. Every patient with abnormal findings on the chest X-ray film showed both V and Q abnormalities. Overall, Q abnormality was more frequent and severer than V one. Of the 5 patients with the sequential studies, 3 showed prolongation of MTT in concordance with deterioration of pulmonary fibrosis. V and Q abnormalities were not necessarily relevant to %DLco. In conclusion, ventilation and perfusion studies are useful in assessing the regional pulmonary function in patients with collagen-vascular diseases.     

Kr-81m ventilation imaging: clinical utility in suspected pulmonary embolism

The results of Kr-81m/Tc-99m ventilation-perfusion (VP) lung scintigraphy were correlated with the results of pulmonary angiography for 74 patients suspected of having pulmonary embolism (PE). Among patients having a diagnostic scan, the sensitivity and specificity of scintigraphy were 91% and 94%, respectively. Also, 157 consecutive cases of Kr-81m/Tc-99m VP lung scintigraphy were reviewed, and the frequency of an indeterminate scan was found to be 22%. A similar frequency was found for VP scintigraphy with xenon-133. Of eight patients who had indeterminate scans due to the presence of a single VP mismatch, four were demonstrated to have PE by angiography. Kr-81m is an excellent agent for VP scanning in cases of suspected PE, offering accuracy in diagnosis as well as favorable physical properties.     

99mTc particle perfusion/99mTc aerosol ventilation imaging using a subtraction technique in suspected pulmonary embolism

It is generally acknowledged that ventilation-perfusion mismatch is diagnostic of pulmonary embolism. Lung ventilation imaging with radioactive gases is a good method for the detection of pulmonary embolism, but it is not in widespread use because of the limited availability of 81mKr gas and the poor physical properties of 133Xe. Aerosols have been proposed, instead of gases for use in lung ventilation imaging. As perfusion and ventilation distributions may change very rapidly, the two imaging procedures should be done in rapid succession. The cheapest way to perform the combined perfusion-ventilation (Q/V) imaging is to use 99mTc-labelled macroaggregates and aerosols. In our method the perfusion imaging was done first, immediately followed by the ventilation imaging with 99mTc-labelled aerosols. A computer program was used to subtract the contribution of the perfusion from the combined Q/V image so that the pure ventilation image alone was obtained. The method was tested in 41 patients with suspected pulmonary embolism.     

A comparison of the economics of xenon 127, xenon 133 and krypton 81m for routine ventilation imaging of the lungs

We have compared the cost of providing routine lung ventilation scintigraphy using 127Xe with other radioactive gases in 100 patients. The physical properties of 127Xe permit a logical imaging sequence where a ventilation study is only carried out if indicated by perfusion scintigraphy which is performed first. With 133Xe, all patients must be ventilated prospectively, or a preselection carried out based on radiographic appearances at the time of imaging. This results in a greater number of ventilation studies than with 127Xe. Despite the greater cost per study of 127Xe, the overall cost of providing a routine diagnostic service with this gas is no more than that of using 133Xe in selected patients. The cost of ventilating all patients prospectively with 133Xe is considerably greater than using 127Xe only when indicated by abnormal perfusion images. If ventilation imaging is to be available at all times, either isotope of xenon costs very much less than 81Krm. We conclude that 127Xe is the radiopharmaceutical of choice for routine lung ventilation scintigraphy.     

Bilateral basal Xe-133 retention and ventilation/perfusion patterns in mild and subclinical congestive heart failure

The Xe-133 ventilation pattern in congestive heart failure (CHF) was assessed using 24 inpatient ventilation/perfusion studies performed to rule out pulmonary embolism. Patients with histories of CHF, myocardial infarction (MI), and cardiomyopathy were included in the study. Frank pulmonary edema, pulmonary embolism, and other known lung diseases such as chronic obstructive lung disease, tumor, and pneumonia were excluded. Fifteen of the 24 patients had abnormal ventilation scans. Twelve of the 15 showed bilateral basal Xe-133 retention on washout; the remaining 3 showed diffuse, posterior regional retention. On perfusion scans, 14 of the 15 abnormal ventilation patients showed evidence of CHF such as inverted perfusion gradient, enlarged cardiac silhouette, or patchy perfusion, and all of them had a history of CHF or cardiac disease. Nine of the 24 patients had normal ventilation scans, including normal washout patterns. Seven of the nine had normal perfusion (p less than 0.01). Four of the nine normal ventilation patients had a history of cardiac disease or CHF but no recent acute MI. Bilateral basal regional Xe-133 retention, coupled with perfusion scan evidence of CHF such as inverted perfusion gradient, enlarged cardiac silhouette, and patchy perfusion pattern, appears to be a sensitive and characteristic ventilation/perfusion finding in mild or subclinical CHF.     

Ventilation-perfusion scintigraphy in suspected pulmonary embolism: correlation with pulmonary angiography and refinement of criteria for interpretation

Retrospective analysis of 139 ventilation-perfusion (V/Q) lung scans obtained for suspected pulmonary embolism (PE) was undertaken, using the Biello criteria for interpretation. All scans were correlated with chest radiographs obtained within 24 hours and with pulmonary angiograms obtained within 72 hours of the V/Q study. The prevalence of PE in the high-, intermediate-, and low-probability groups was 89.5%, 49.3%, and 3.6%, respectively. Using minor modifications of these criteria, V/Q scans interpreted as high or low probability had a sensitivity of 97.1%, specificity of 94.3%, and accuracy of 95.7%. Perfusion defects corresponding to radiographic abnormalities that were present for at least 10 days were less likely to be associated with PE. Separate analysis of 27 perfusion-only lung scans that met all other criteria for inclusion in the study confirmed the nonspecificity of perfusion-only lung imaging and indicated the need for ventilation imaging with Tc-99m-DTPA aerosol or Kr-81m gas for portable studies.     

Symmetrical perfusion defects without pulmonary embolism

We report two patients with ventilation-perfusion (V-P) images that demonstrate large symmetric perfusion defects with normal chest radiographs and ventilation images who did not have pulmonary embolism (PE) by angiography. This experience suggests that patients with symmetrical V-P mismatches should not be assumed to have PE. The need for pulmonary angiography in such patients should be carefully considered.This work was supported in part by National Institutes of Health SCOR in Thrombosis HL 14147     

Compression of the Right Pulmonary Artery by a Massive Descending Aortic Aneurysm Causing Bilateral Perfusion Defects on Pulmonary Scintigraphy

A 67-year-old woman, who presented with a 2 month history of dyspnea, had a ventilation and perfusion lung scan that showed absent perfusion of the entire right lung with normal ventilation, as well as a rounded matched defect in the left lower lung adjacent to midline, suspicious for an aortic aneurysm or dissection. CT pulmonary angiography revealed a massive descending aortic aneurysm compressing the right pulmonary artery as well as the left lung parenchyma, accounting for the bilateral perfusion scan defects. We present the Xe-133 ventilation, Tc-99m MAA perfusion and CT pulmonary angiography imaging findings of this rare case.