Lung Imaging with radioaerosols for the assessment of airway disease

Lung Imaging With Radioaerosois for the Assessment of Airway Disease Michael Hayes for George V. Taplin* Aerosol inhalation lung scans offer distinct advantages in the evaluation of airways and the qualitative distribution of ventilation. The sensitivity in detecting mild obstructive disease is similar to t h a t of xenon washout and both probably surpass standard pulmonary function tests that measure total rather than regional ventilation. Although imaging studies using krypton gas are ideal for assessment of rapidly ventilated space, krypton's short half-life precludes its usefulness for demonstrating air trapping. Neither ~33Xe nor slr"Kr gas demonstrates sites of

airway abnormality as aerosol does. Aerosols are ideal for the general nuclear medicine practice in community hospitals because of their convenience, cost effectiveness, and information yield. Current technique using same-day multiple-view aerosol scans after a preliminary perfusion scan, makes use of the most logical diagnostic scheme in the vast majority of patients with chest complaints, since a normal perfusion scan often eliminates the need for a ventilation scan.

BACKGROUND

METHOD

inhalation lung scanning was A EROSOL introduced independently by Pircher et al. 1 and Taplin and Poe 2 in 1965. The procedure was proposed as a means of estimating regional ventilation and localizing areas of airway narrowing. General acceptance of the method has been slow because of technical difficulties in obtaining high-quality scans and criticisms that ventilation could only be assessed with true gases. The main technical problem that discouraged many from continuing to utilize aerosol scans, after initial trials, was excessive deposition of activity within the posterior pharynx, large airways, and stomach. These artifacts made interpretation of parenchymal abnormalities difficult and were used as evidence against the procedure's potential to assess "ventilation." Recently, several investigators have made improvements in aerosol delivery systems. Pircher et al) added a heating chamber to reduce particle size by evaporation. Mullins and Hayes 4 employed baffles to remove large droplets by impaction. Wasnich 5 improved images with an ultra-high-frequency ultrasonic nebulizer. Using Verma's suggestion,6 Salk and Mullins v substituted an inexpensive plastic compressed-air nebulizer for the previously used ultrasonic model, and Hayes et al. 8 introduced a 3-liter reservoir bag into the delivery line to reduce mean particle size. The currently used system, as described in the Method section, has been used over a 4-yr period without significant modification in a large number of patients with highly satisfactory results. A comparison of scans before and after these technical advances is shown in Fig. 1. Seminars in Nuclear Medicine, Vol. X, No. 3 (July), 1980

Essential elements of a system for delivery of radioaerosol (as shown in Fig. 2) include a tank of dessicated compressed air or oxygen, an airflow regulator, a plastic mechanical nebulizer, disposable corrugated tubing, a reservoir settling bag, a one-way demand valve, a nonrebreathing positive closing valve, a mouthpiece, and plastic tubing leading through a bacterial filter to a 40-liter collection bag or to a vented hood. Both Tc colloid and Tc DTPA are available in commercial kit form and may be used as test agents. A small amount (2.5-3.5 ml) of high specific activity tracer containing 10-40 mCi of 99~"Tc is added to the nebulizer after the patient has completed a trial run using nonradioactive normal physiologic saline as a practice material. If preferred, ~3mln-albumin solution is also a satisfactory agent. Its principle advantage is that its higher physical peak energy allows aerosol imaging after 9*mTc MAA perfusion imaging. This indium method has been superceded at our hospitals by adjusting 99rnTc MAA perfusion dosages downward and inhalation doses upwards

*This article, although originally planned by Dr. Taplin, was completed after his death based on his writings, notes, and the coauthor's memory o f discussions with him on the role o f aerosol scanning. From the Department o f Nuclear Medicine, Memorial Hospital Medical Center o f Long Beach, and the Department o f Radiology, UCLA School o f Medicine, Los Angeles, Calif. Reprint requests should be addressed to Michael Hayes, M.D., 2801 Atlantic Avenue, Long Beach, Calif. 90801. 9 1980 by Grune & Stratton, Inc. 0001-2998/80/1003-0003501.00/0 243

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Fig. 1. Posterior view aerosol inhalation lung scans in the same normal 44-yr-old male volunteer, (Left) Example of false-positive excessive central deposition obtained with old-style equipment due to presence of large particles. (Right) Example of improved images obtained with aerosol administration system as described in the Method section.

so that aerosol scans may be performed with a 99mTc-labeled agent immediately after the perfusion scan, if desired. Administration Procedure The upright seated position is preferable during aerosol administration. Special care must be taken to insure that the mouthpiece is correctly placed with the flange between the lips and gums, and the patient instructed to keep the

Fig. 2. Diagram of currently used aerosol system. Dessicated compressed air or Oxygen powers mechanical nebulizer and aids in reduction of particle size through partial evaporation. Nebulizer allows use of small volume of high specific activity material. The reservoir-settling bag reduces mean particle size by sedimentation and impaction, while storing aerosol generated during patient exhalation.

tongue away from the mouthpiece opening. The patient who is unable to cooperate sufficiently may be studied in the supine position, utilizing a face mask that covers the mouth and is held in place by elastic straps. Dessicated oxygen may be substituted when indicated by the patient's condition. A minimal amount of central deposition may be unavoidable with supine administration, especially with uncooperative patients. Before administration of radioactivity, the patient is coached using normal saline to allay anxiety. This practice session may also reveal inoperative or misplaced valves in the system. The patient is assured that the procedure can be interrupted at anytime on a hand signal-administration is stopped by turning off the flow regulator and removing the mouthpiece and nose clip. Since the technical quality of a scan can be diminished by the rapid shallow respiration of an overly anxious patient, it is important to allow him to become familiar and comfortable with the apparatus. With a properly operating system, the patient will experience a mild resistance to breathing and the opening and closing of valves will be perceptible but not difficult. During radioaerosol delivery, a fine aerosol is produced from the test agent by compressed air or oxygen delivered at a rate of 8-10 liters/min. The patient is instructed to breathe at a normal rate and volume. The patient should be chaperoned through the entire administration and may require several reminders to breathe less rapidly or less deeply. Typical administration time is 2-4 rain. At the completion of the study, the patient is instructed to rinse his mouth and expectorate into a disposable container.

AEROSOL SCANNING IN AIRWAY DISEASE

Care of Equipment Following use, all contaminated components are placed as a unit behind a lead shield and allowed to decay. Later the non-rebreathing valve, accessory one-way demand valve, mouth piece, nose clip, and adaptors are washed, cold sterilized, and allowed to dry. The reservoir bag and disposable tubing are discarded. The nebulizer is rinsed several times with water, suctioned with a small-bore polyethylene tube, and placed in a drying box. The nebulizer is not contaminated by the patient's exhaled air and does not require cold sterilization or washing with detergents for cleaning. Before use, each nebulizer is tested for proper operation. Clogged, leaking, or poorly performing units are discarded. In practice, it is desirable to have several nebulizers of proven performance ready for use as needed. They may be used many times with proper care and storage. Before re-use, the valve leaflets should be freed up, as they occasionally stick shut during drying after being cleaned.

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and aerosol inhalation but awkward with xenon133. If the diagnostic scheme indicates possible same-day imaging of perfusion and ventilation, the recommended procedure is to perform the perfusion study first with a small dose, such as 500 #Ci of 99mTCMAA. Then, if one wishes to assess airway patency and ventilation, a relatively larger dose of a technetium-labeled aerosol agent is used to override the perfusion activity. Thirty milliCuries of 99mTc DTPA in 3 ml will result in approximately 10% or 3 mCi deposition in the lungs of the average patient. Thus, 80% or more of resultant lung activity will be from aerosol and less than 20% from the immediately preceding perfusion scan. "Fill in" of ventilation in areas of perfusion defect can be readily assessed. This easy technique has been in daily use at our institution for over 2 yr with gratifying results. Most of the cases illustrated in the remainder of this article were done with this "same-day" technique. RESULTS

Imaging

Normal Findings

Routine views of the lungs are obtained with a scintillation camera. Usually 300K count images can be obtained with less than 2 min/view. Although a large field camera is preferred, perfectly satisfactory results may be obtained with standard cameras utilizing divergent collimation. In addition to standard views, oblique views are obtained as indicated.

Posterior perfusion, aerosol, krypton, and xenon scans in a 33-yr-old normal male volunteer are shown in Fig. 3. All images were taken

PERFUSION

AEROSOL

KRYPTON

XENON

Same-Day Inhalation Perfusion Scans The low physical energy and poor count rates obtained with xenon-133 make it necessary to perform examinations in a illogical sequence. Cost effectiveness is not optimal because many xenon inhalation scans are needlessly performed before normal perfusion scans. Furthermore, diagnostic sensitivity is not ideal since an area of perfusion defect may not be shown to good advantage on the usual posterior xenon ventilation view. In addition, small inhalation defects may be missed on xenon scans, causing falsepositive readings of ventilation/perfusion mismatch. The most logical sequence in the performance of lung scans is to do the perfusion scan first; if it is normal there is often no need to assess ventilation. This sequence is feasible with krypton-81 m

Fig. 3. Posterior comparison images taken in an upright position of a a3-yr-old normal male volunteer.

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after the injection or inhalation of an agent with the subject in an upright position. Aerosol and krypton inhalation images are nearly identical and are quite similar to perfusion images. The amount of radioactivity in any region is proportional to air flow and/or ventilation. Krypton images were made during continuous tidal breathing of gas. After reaching a steady state, the lung image represents distribution of air flow or relative ventilation. 9 The short 13-sec half-life of krypton-81 m precludes measurement of washout rates. Aerosol images obtained after 2 4 min of tidal volume breathing also register relative regional ventilation in the absence of airway obstruction. Neither krypton nor aerosol permit measurement of lung volumes or ventilation on a quantitative basis. In normal subjects, xenon single breath wash-in or rebreathing images have distribution patterns similar to krypton or aerosols. Although normal breath-holding (wash-in) xenon images are frequently found in mild or moderate obstructive airway disease, ~~washout images often indicate ventilatory impairment or peripheral obstruction as localized regions that retain gas longer than adjacent lung tissue. Furthermore, the duration of xenon retention in a given region is an index of the degree of airway obstruction.

Moderate Obstructive Airway Disease Comparative perfusion, aerosol, and xenon images of a patient with moderate obstructive airway disease are shown in Fig. 4. Aerosol images provide evidence of narrowing of large-, medium-, and small-sized airways (excessive aerosol deposition). Additionally, areas of poor aerosol penetration correspond to regions of reduced activity or poor ventilation in the gas inhalation images. Xenon breath-holding images show regional ventilatory abnormalities but fail to indicate sites of obstruction. All types of ventilation images show abnormalities more dramatically than would be suspected from minor perfusion image defects. Xenon breathholding or rebreathing images show fewer regions of poor ventilation than do either the krypton or aerosol images, probably because of the lower information density and relatively poor camera resolution due to xenon-133's low 80 KeV emission. As mentioned earlier, this may theoretically lead to false-positive impressions

HAYES FOR TAPLIN

PERFUSION

AEROSOL

HOLDING

WASHOUT

Z 0 Z uJ x

Fig. 4. Posterior perfusion, aerosol, and xenon scans in a 45-yr-old male with moderate chronic obstructive airway disease. Note that abnormalities are more striking in the aerosol than in the perfusion scan. There is some increased aerosol deposition in the large- and medium-sized airways.

of ventilation/perfusion mismatch. Cyclotronproduced xenon-127, with its 200 KeV gamma photon emission, would solve this problem, but has not been commercially available on a large scale. Aerosol or krypton scans with their better statistics, improved camera resolution, and multiple views are more likely to show small ventilation defects than xenon-133 studies. In Fig. 4, xenon-133 washout images show evidence of gas trapping in both apical regions. The xenon washout study is a sensitive indicator of peripheral airway obstruction or regionally impaired ventilation. A case study such as the one shown in Fig. 4 illustrates the value of controlled aerosol size. There is minimal deposition in the pharynx and trachea, which in the past has made interpretation difficult. In this case, the aerosol study not only indicates impaired ventilation in the right apical region, as do the gas studies, but also reveals evidence of partial obstruction of the major and medium-sized airways. This is shown by increased deposition resulting from turbulent air flow, as well as absence of penetration to numerous peripheral regions of the lungs that indicate small airway obstruction. In the past, aerosol scans have not been considered reliable

AEROSOL SCANNING IN AIRWAY DISEASE

247

for estimating ventilatory function mainly because of excessive particle retention in normal airways. With current technical advances, over 70% of the deposited activity is within lung parenchyma rather than ciliated airways, as evidenced by 24-hr retention studies. In obstructive lung disease, aerosol droplets smaller than 2.0 um are deposited in central airways in increasing amounts in proportion to the severity of airway obstruction. H In mild obstructive airway disease, such as early bronchitis or mild asthma, aerosol patterns show increased central deposition and nearnormal peripheral penetration. Perfusion patterns are almost always normal.

of the right lung periphery and lesser but similar abnormalities in the left lung. Such ventilation/perfusion findings are characteristic of severe obstructive airway disease and correlate well with an FEV1 equal to 45% of the predicted value. Angiographic findings were negative for pulmonary embolism, which was the original indication for performing the study. Alpharantitrypsin deficiency patients characteristically show reduced aerosol penetration to both lower lung fields associated with matched perfusion impairment. In these cases, xenon wash-in and washout images are both abnormal, since the small amount of gas that enters the lower lung fields is trapped for long periods, indicating severe impairment of ventilation.

Severe Obstructive Airway Disease Bronchial Asthma

In more severe obstructive pulmonary disease, the pattern is different, showing gross central deposition plus areas of poor or nearly absent aerosol penetration to the lung periphery) 2 Even in this type of patient with distinctly abnormal pulmonary function tests, discrete perfusion defects occur in only about 50% of patients. Typical findings of severe obstruction airway disease in a 55-yr-old man with a 50 pack/yr history of smoking are shown in Fig. 5. Perfusion images indicate reduction of blood flow to the right lung, especially peripherally. Aerosol images show increased deposition in the large central bronchi and reduced penetration to much

Patients with stable asthma show abnormal aerosol patterns characterized by excessive central deposition apparently related to large airway constriction. ~3 This pattern can be changed toward normal by administration of suitable bronchodilators. In some instances, inhalation images can become entirely normal within 30 rain. These rapidly changing aerosol image patterns provide strong evidence that aerosols can reveal sites of airway obstruction in bronchial asthma, and then demonstrate normal ventilation distribution following treatment, as shown in Fig. 6. ANTERIOR

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Fig. 5. Scans of a 55-yr-old patient w i t h severe obstructive airway disease showing increased aerosol deposition in the large central airways and poor penetration to the periphery.

POSTERIOR

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HAYES FOR TAPLIN

BEFORE

AFTER

Fig. 6. Posterior aerosol scans in a patient w i t h acute bronchial asthma before (using SS'Tc) and after (using 11~"1n) administration of bronchodilator. Note improved peripheral deposition and clearing of abnormal central deposition posttreatment.

Chronic Bronchitis The typical aerosol pattern in chronic bronchitis may show slightly increased large airway deposition, but the most striking feature is numerous punctate regions of hyperdeposition (hotl spots) in medium and small airways throughout the lung parenchyma, as shown in Fig: 7. Such images are found in cigarette smokers with heavy pack/year histories as well as atopic individuals with bronchitis and asthma. These images probably indicate partial airway obstruction and are likely produced by the same

mechanism involved in bronchial asthma. They may be improved by bronchodilator drugs and inhalation therapy.

Bronchiectasis and End-Stage Bronchiolitis In this problem, findings are similar to those of chronic bronchitis. Although diseased segments remain viable because of bronchial circulation, pulmonary arterial perfusion is minimal and ventilation poor. Failure of improvement following bronchodiANTERIOR

Z 0 00 m

u. tr UJ

a.

.J A

Fig. 7. Chronic bronchitis with mucous plugging of the bronchus to the superior segment of right lower lobe. Note that general ventilation can be assessed even w i t h severe bronchitic changes manifested by multiple small hot spots on aerosol scan. The defect in the superior portion of the right lower lobe closely matches perfusion defects.

tun 0 tlt" LLI <~

RT. LAT.

AEROSOL SCANNING IN AIRWAY DISEASE

249

AEROSOL

XENON

SCANS

BREATH-HOLDING

WASHOUT

Fig. 8. Lower lobe bullae. Aerosol inhalation shows diminished ventilation in the region of lower lobe bullae. Xenon washout scan shows gas trapping in the same regions.

lator treatment indicates the irreversible nature of the destructive process and suggests the need for possible surgical intervention. Medical treatment should probably be continued when such therapy is shown to relieve airway obstruction, as documented by improved aerosol scans. The Swyer-James syndrome of hyperlucent lung and unilateral bronchiectasis frequently goes unrecognized unless episodes of hemoptysis occur. In such cases, aerosol inhalation usually shows poor ventilation corresponding to perfusion deficit in the hyperlucent lungJ 4 Aerosol images may disclose additional abnormalities in the contralateral lung not visible by gas images, and thus gives the best correlation with the bronchogram.

PERFUSION

Bullous Emphysema Bullae are demonstrated as voids of activity on aerosol inhalation lung scans. It is not possible to demonstrate airway trapping by this technique as it is with xenon gas scan during the late washout phase (Fig. 8).

Treatment Planning When quantitation of ventilation is necessary in a surgical candidate for bullectomy, lobectomy, or pneumonectomy, gas scans are generally preferrable to aerosol. Ventilation partition calculations may not be accurate by the aerosol method because of superimposed "hot spots" related to bronchial disease. Figure 9 illustrates a case where right lung ventilation is apparently

AEROSOL

XENON

Fig. 9. Assessment of ventilation and perfusion distribution in a pre-op patient with lung carcinoma. Perfusion: L = 75%, R = 2 5 % . A e r o s o l i n h a l a t i o n : L ~ 74%, R = 2 6 % . X e n o n i n h a l a t i o n : L = 6 1 % . R = 3 9 % . See t e x t for discussion.

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HAYES FOR TAPLIN

ANTERIOR

RT. L A T .

Z

O 00 LL n"

uJ n

/

O

Fig. 10. Carcinoma of lung. Solid a r r o w shows area w h e r e both perfusion and v e n t i l a t i o n are absent due t o mechanical blockage of right middle lobe bronchus. Dotted a r r o w s show area w h e r e perfusion to the right apex is impaired because of vascular compression by a hUar node, while ventilation remains intact.

O nUJ
POSTERIOR

z O m

r LL

n-

UJ Q.

/

O Fig. 11. Composite showing usefulness of aerosol in diagnosing emboli even in the presence of irregular deposition of inhaled material. Aerosol inhalation scan shows preservation of ventilation to area of right middle lobe embolus in a 75-yr-old male w i t h moderate a i r w a y disease of predominantly bronchitic nature.

,,=,
RT L A T

AEROSOL SCANNING IN AIRWAY DISEASE

u n d e r e s t i m a t e d by aerosol scan b e c a u s e of increased aerosol within the large a i r w a y s on the left.

Carcinoma of Lung Both perfusion and aerosol inhalation scans a r e helpful in staging and t r e a t m e n t planning. Both perfusion a n d ventilation a r e absent within the t u m o r mass or consolidated p a r e n c h y m a distal to compression by the tumor. S t r i k i n g perfusion defects associated with n o r m a l ventilation usually indicate vascular compression by e n l a r g e d hilar nodes, which m a y not be a p p a r e n t by other diagnostic means. S u c h a case is illust r a t e d in Fig. 10. In early cases, the only finding m a y be a hot spot on an aerosol scan at the site of a bronchial ulceration.

Emboli Superimposed on Obstructive Airway Disease T h e most frequent cause of regional perfusion defects in cases o f suspected emboli is obstructive a i r w a y disease. ~5 G e n e r a l l y , m o d e r a t e to severe obstructive a i r w a y disease is required to produce alveolar hypoxia, reflex vasoconstriction, and ischemia. ~6 T h e perfusion scan is usually less a b n o r m a l than the aerosol or gas inhalation scan. Conversely, in the case of embolus, a i r w a y changes, if any, a r e usually relatively mild and transient. A l t h o u g h in the presence of obstructive a i r w a y disease it m a y not be possible to exclude small emboli with absolute certainty, in most cases, s e g m e n t a l or l a r g e r emboli m a y be detected or excluded. F i g u r e 11 illustrates a case where, d e s p i t e i r r e g u l a r aerosol d e p o s i t i o n because of bronchitic disease, a superimposed s e g m e n t a l perfusion defect was clearly demonstrated. REFERENCES

1. Pircher FJ, Temple JR, Kirsch WJ, et al: Distribution of pulmonary ventilation determined by radioisotope scanning. Am J Roentgenol 94:807-814, 1965

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2. Taplin GV, Poe ND: A dual lung scanning technic for evaluation of pulmonary function. Radiology 85:365-368, 1965 3. Pircher FJ, Lerner SR, Cooper PH, et al: Aerosol scans with particles in the submicronic range. J Nucl Med 12:385386, 1971 4. Mullins J, Hayes M: Improved technique for aerosol inhalation scanning. J Nucl Med 13:872, 1972 (abstr) 5. Wasnich RD: A high frequency ultrasonic nebulizer system for radioaerosol delivery. J Nucl Med 17:707-710, 1976 6. Verma RC, Rennett LR, Poe ND, et al: Aerosol inhalation lung scanning made easy. Scientific exhibit presented at 62nd Scientific Assembly of the Radiologic Society of North America, Chicago, 1976 7. Salk R, Mullins J: A simple, effective method for aerosol inhalation scanning. J Nucl Med Tech 4:94-95, 1976 8. Hayes M, Taplin GV, Chopra SK, et al: Improved radioaerosol administration system for routine inhalation lung imaging. Radiology 131:256-258, 1979 9. Goris ML, Daspit SG, Walter JR, et al: Application of ventilation lung imaging with S"krypton. Radiology 122:399-403, 1977 10. Ramanna L, Tashkin DP, Taplin GV, et al: Radioaerosol lung imaging in chronic obstructive pulmonary disease--Comparison with pulmonary function tests and roentgenography. Chest 68:634-640, 1975 11. Taplin GV, Chopra SK: Lung perfusion-inhalation scintigraphy in obstructive airway disease and pulmonary embolism. Radio Clin North Am 16:491-513, 1978 12. Taplin GV, Chopra SK: Inhalation lung imaging with radioactive aerosols and gases, in Guter M (ed): Progress in Nuclear Medicine, vol 5. Basel, S. Karger, 1978, pp 119143 13. Chopra SK, Taplin GV, Tashkin DP, et al: Imaging sites of airway obstruction and measuring functional response to bronchodilator therapy in asthma. J Nut} Med 18:606, 1977 (abstr) 14. O'Dell CW, Taylor A, Higgins CW, et al: Ventilationperfusion lung images in the Swyer-James syndrome. Radiology 121:423-426, 1976 15. Taplin GV, Chopra SK: Recent lung imaging studies, in: Medical Radionuclide Imaging, vol. 2. Vienna IAEASM-210/313, 1977, pp 303-330 16. lsawa T, Wasserman K, Taplin GV: Lung scintigraphy and pulmonary function studies in obstructive airway disease. Am Rev Resp Dis 102:161, 1970