Indications for lung scintigraphy.

Respiration 32: 46-61 (1975)

Indications for Lung Scintigraphy Vincent Lopez-M ajano Nuclear Medicine Service, Jackson Park Hospital, and Medical Service, Chicago Medical School. Chicago, III.

Abstract. Perfusion and ventilation lung scintigraphy Key Words Lung scanning arc indicated: (I ) for evaluating regional perfusion and ventilation, (2) for establishing a ratio between ventila Preoperative lung studies Pulmonary chest surgery tion and perfusion in different areas of the lung, (3) Pulmonary thromboembolism when chest surgery is planned (especially for mapping Pulmonary embolism out the extent o f resection), (4) when surgery o f the upper abdomen is to be performed, and (5) when global func tion studies are compromised. Regional ventilation and perfusion studies are invaluable in the diagnosis of pulmonary thromboembolism in which a perfusion defect is accompanied by well-preserved ventilation in the underperfused area. Regional function tests are indicated for evaluating the distribu tion of ventilation and pulmonary circulation in practically any chronic pulmonary disease, especially when global function studies, such as spirometry, show significant decreases.

Received: December 19, 1973; accepted: January 7, 1974.

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The functioning of different organs should be evaluated preoperatively. This may render a diagnosis of associated diseases that should be treated in order to prevent complication. The lung has to be evaluated with global function studies such as spirometry, diffusion capacity, and blood gases. Another type of studies, regional lung function, is indicated when there are abnormalities in the global function tests or when chest surgery is planned. The appearance of the chest radiograph is caused by the contrast between tissues of different radiopacity due to their diverse densities. Therefore, since the air under the bronchi is of the same density as the air inside the alveoli, the condition of the bronchi cannot be ascertained by radiography but must be studied by bronchography.

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Fig. I. a This chesi radiography shows increased radiolucency in the left lung, b The vascular markings in the left lung are markedly attenuated except in the upper fourth o f the left lung. This tomographic section was obtained at a hilar level, c This lung scintigram was obtained with a rectilinear scintigraph after injection of 250 /tCi of 131I which labeled albumin macroaggregalcs. There is only radioactivity, pulmonary arterial blood flow, in the upper fourth of the left lung.


Lopez-M ajano

Lopez-M ajano

In the chest radiograph, there is a central radiopaque shadow caused by the blood in the cardiac cavity, the heart muscle, and the blood in the great vessels; the markings irradiating from the hilum are caused by the density of the blood in the pulmonary vessels. These vascular markings are clearer in tomography, especially if taken at the level of the hilum. An area of increased radiolucency appears when the vascular markings are not present (fig. la, b). The pulmonary circulation in its arterial phase can be visualized by scintigraphy which images the radioactivity in the lungs (fig. lc) caused by the intravenous injection of particles larger than the capillaries and labeled with a radionuclide of energy that can be adequately detected externally [1,2], The information provided by the lung scintigram is not anatomic in nature such as the one obtained by pulmonary arteriography; however, it indicates the areas of decreased pulmonary arterial blood flow [3] and provides infor mation that can be quantitated. This type of objective information is very important for diagnostic purposes and for the management of the patient’s condition [4], Other methods (table I), either direct or indirect, can be used to obtain information about the condition of the pulmonary vasculature [5]. Differen tial and lobar spirometry are indirect methods for studying the pulmonary circulation in each lung or lobe by measuring oxygen consumption in those areas. The regional distribution of the pulmonary circulation can be studied by direct methods. The most widely used o f these methods are (1) flow velo city probe, (2) pulmonary arteriography, (3) ventilatory lung scintigraphy, and (4) perfusion lung scintigraphy. Flow velocity probe. This method measures flow and pressure in the pul monary artery and can therefore be used to calculate the resistance. Pulmonary arteriography. This method visualizes the pulmonary vessels and permits the study of the three circulatory phases; arterial, capillary, and venous. The interpretation of this type of data is very subjective because it cannot be quantitated. Radioactive gases of adequate energy for external detection can be used to study the pulmonary circulation. The gases more commonly used can be seen in table II. When inhaled, the radioactivity from the wash-in of the gas offers a study of ventilation, while the radioactivity from the wash-out offers a study of the pulmonary circulation [6]. 1:i3Xe is used widely (5-10 mCi, equilibrated in saline, and injected intravenously or inhaled) because its physical character istics can be adequately detected with the scintillation camera or external counters. The first appearance of radioactivity, when injected intravenously,


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Indications for Lung Scintigraphy

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Table I. Methods used to study the pulmonary circulation I Indirect methods

II

Direct methods

pulse contour, good only in animals because data have been ob' tained only in normal arteries ballistocardiography Fick’s principle dilution methods dye dilution (Stewart-Hamilton) nitrous oxide differential spirometry, lobar spirometry non-radionuclidic cardiometry flowmeters (can be used only in animals) flow velocity probes radiographic chest radiography hilar tomography X-ray cardiometry angiocardiography (cine) arterial phase capillary phase venous phase radionuclidic inhaled or injected radioactive gases 133X e , 135X e , 1 27X e , 1 S N , 8 3 K r

intravenously injected particles macroaggregated. albumin microspheres, labeled with i3 ii, 09Tcm or 113 In stannous chloride labeled with 113In ferrous hydroxide labeled with 113In Microcirculation techniques

observation of blood cells behavior; injection of plastic, glass carbon particles plastic carbonized microspheres sephadex dextran

is caused by the pulmonary circulation while the wash-out measures the ventilation [6], The biological half-life of 133Xe is short - 3-8 min - and thus permits repeated studies. 127Xe, when available, will be a better gas for these studies since its energy (203 keV) is more adequate for imaging. Its biological halflife is the same as that of 133Xe, but its physical half-life is longer (36 days).


III

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Lopuz-M ajano Table II. Radioisotopes commonly used to study lung perfusion and ventilation

Radioisotope

I33Xe 127 Xe 1 13 1( 113m|n 90T c m

Half-life

Energy, MeV

Dose, mCi

physical

biological

beta

gamma

5.27 days 36.4 days 8.05 days 1.7 h 6h

3-8 min 3-8 min 6h 1.7 h 6h

0.346

0.080 0.203 0.364 0.392 0.140

0.806

2-10 2-10 0.2-0.4 2-6 2-6

The visual imaging of the radioactivity should be complemented by quantification o f the scintigrams. Comparison among predetermined regions of the lung should be made with ventilatory and pertusory data to establish a ventilation/perlusion ratio in the different areas of the lung [7J. The regional study of ventilation, bronchial patency, and mucociliary clearance can be studied with radioactive particles such as "T cm in the form of pertechnetate and 9yTcm-sulfur colloid. Other radioactive particles, such as the albumin macroaggregates and ferrous hydroxide particles [8], can also be used for these studies. The main requirement is that they should be used with an ultrasonic nebulizer to produce sufficiently small particles, less than 6 //m, which will be able to penetrate into the alveoli. Otherwise, they will remain in the large airways (fig. 2). The chest radiograph and the regional ventilation studies should first be compared to each other and then to the perfusion lung scintigram. Ventilatory lung scintigraphy. This method is indicated when the regional ventilation must be known. This is very important in preoperative studies, especially when the vital capacity is markedly decreased and, even more, when severe obstructive diesase is present. This method is also indicated to ascertain if the projected resection of lung parenchyma is contraindicated and to try to limit the extent o f resection to functionless areas. Regional ventilation studies are indicated in general surgery to ascertain the extent and degree of involvement of associated chronic obstructive lung disease and also to study the influence of treatment on the ventilation and pulmonary circulation [9]. Regional ventilation tests are also indicated in preoperative studies when other diseases, such as cystic fibrosis, are present. They are especially necessary for diagnosing the extent of disease in mild


1 Not yet available.


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forms. In this manner the appropriate preoperative treatment will be estab lished and complications avoided. Perfusion lung scintigrams can be obtained as a result of intravenous injection of a radioactive gas (again with physical characteristics that are adequate for external detection) such as 133Xe or, even better, 127Xe. Radioactive particles such as the ones described in table I can be used successfully to map out the distribution of the pulmonary circulation. Their use is based on K ety ’s principle [10], The particles must meet certain re quirements: (1) ability to be metabolized [11. 12]; the time of metabolization should be long enough to permit external detection; (2) capability to be labeled with radionuclides of energy adequate for detection with the gamma camera and the rectilinear scanner; (3) ability to hold a strong bond with the radionuclide (thus avoiding the presence of free radionuclide in the blood); (4) freedom from toxicity, pyrogenicity, and bacterial contamination; (5) possibility of sterilization, and (6) adequate size: the particles should be larger than 12//m (the size of the capillaries), then the particles will remain in the pulmonary vessels and do not recirculate. All these requirements are met by several particles: ferrous hydroxide [12], stannous chloride [13], albumin microspheres [14], and, most widely used, albumin macroaggregates.


Fig. 2. Particles of 99mTc were inhaled. The large airways are visualized. The ventilation is represented by the radioactivity in the lungs.

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Lopez-M ajano Table HI. Comparison between gammagraphy and radiography

1 or dual crystal scanner

multiple crystal scanner

camera

simple

angiocardio graphy

cineangiocardiography

adequate

adequate

adequate

excellent

excellent

excellent

simple simple simple complicated objective and objectiveand objectiveand subjective subjective subjective subjective

complicated subjective

complicated subjective

Ease

yes

yes

yes

yes

no

no

Complication

none

none

none

none

yes

yes

Radiation exposure

slight

slight

slight

slight

slight

serious 20-40 min

Optical resolution Interpretation of the image

Time

15-30 min

5-15 min

1-5 min

2-6 sec

20-40 min

Information

dynamic

dynamic

dynamic

anatomic

anatomic and anatomic and slight slight func functional tional

Quantitation

possible

possible

possible

impossible

impossible

impossible

Mobility o f the machine around the patient

none

none

yes

yes

none

none

The latter have proven very safe and can be easily and strongly labeled with " T cm [15]. On the other hand, albumin microspheres, although they have some good characteristics, cannot be strongly labeled, and the labeling efficiency is only about 60% which requires successive wash-ups to eliminate free " T cm [16]. Perfusion lung scintigraphy is an easy and practically innocuous proce dure for the patient; only two fatal cases have been associated with it [17]. Because of the minimal amounts of iodide and albumin used (1-2 ng iodide and 0.2 mg albumin), this procedure can be used even with people who are allergic to these materials. Since the first application in human beings, pulmonary scintigraphy has been used to diagnose pulmonary thromboembolism by demonstrating areas of avascularity corresponding to the obstructed vessels [18]. This can be achieved by using radioisotopes of externally detectable gamma energy, such


Radiography

Gammagraphy

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as 113Inm with 0.393 MeV. 131I with 0.637 MeV, and "T cm with 0.140 MeV (table II). Detection of this radioactivity can be achieved by using a rectilinear scanner with one [19] or several [20] crystals or by using a gamma camera [21]. The gamma camera has the advantage of providing the image in a much shorter time (table III; 15-30 min in the rectilinear scanner with one crystal, 5-15 min with several crystals, 1-15 min in the gamma camera). The camera should be used with a pinhole or diverging collimator to get the image of both lungs. At least two views - anterior and posterior - should be taken since a deep avascularity might be overlooked if only one view is taken. Lateral views should also be taken if the patient’s condition permits. The procedure should be recorded on tape for quantification. To minimize the action of gravity [3, 22, 23], the patient should be in the supine position when the radioisotope is injected. The syringe containing the isotope should be shaken to avoid precipitation of the particles on the wall of the syringe (recognized in 1964) [24]. The injection should take about 1 min in order to insure good mixing of the radioisotope with the blood. The indications for perfusion lung scintigraphy are the same as those for angiocardiography, that is, when it is necessary to know the condition of the vascular bed of the lung [4, 25]. Lung scintigraphy is indicated (1) before chest surgery, to map out the area of resection, leaving, if possible, a well-ventilated and well-perfused lung parenchyma [26], and (2) after chest surgery, especially if the operation had the goal of removing the compression of normal parenchyma as, for example, in the case of bullous disease [27] (fig. 3). Lung scintigraphy is also used: (1) to ascertain the influence of ventilation on the pulmonary circula tion such as in the decreased areas of perfusion seen during bronchospasm [28]; (2) to determine the extent of damage to the pulmonary circulation caused by diseases such as tuberculosis, carcinoma, sarcoidosis, etc. [29], and (3) in pediatrics, to diagnose and manage hyaline membrane disease. Lung scintigraphy is very useful in the diagnosis of pulmonary thrombo embolism [30], a frequent complication of surgery (orthopedic surgery, for example) that interferes with proper ambulation, and is often associated with debilitating diseases. The diagnosis of this condition is difficult because, among other reasons, the symptoms may be very minimal and they can mimic practically any other cardiopulmonary disease, especially myocardial infarction. Not infrequently, patients with pulmonary thromboembolism have no symptomatology at all, and frequently they have tachycardia or sudden dyspnea. Therefore, the determination of bilirubin, serum lactic



54

Lopez-M ajano

dehydrogenase, and serum glutamic oxaloacetic transaminase can help in the diagnosis. According to some authors [31; for other views, see 32], the elevation of the first two - while the third remains normal - is compatible with pulmonary thromboembolism. Electrocardiography is useful in the diagnosis of pulmonary thrombo embolism [33], M c G in n and W hite ’s studies [34] outlined the indicators: widening o f P wave, lowering of T in lead II, inversion of T in lead III, and right bundle branch block. But these alterations are also present in myocar dial infarction.


Fig. 3. a There is increased radiolucency in the upper half o f both lungs in this chest radiograph in a patient with bilateral bullous disease, b This lung scintigram obtained with the same technique as the one in figure lc shows lack o f perfusion in the upper halves of both lungs and homogenous distribution o f the pulmonary circulation in the lower half o f both lungs, which indicates that this lung parenchyma is only compressed and probably capable o f re-expansion, c, d The blebs were resected in the left hemisphere, and the chest radiograph (c) shows good expansion of this lung and good re-expansion o f the vascular bed (d). e . f After resection o f the blebs in the contralateral hemithorax, there is good ventilation and perfusion in the lungs as demonstrated by the chest radiograph (e) and the lung scintigram (f).


Indications for Lung Scintigraphy 55

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Lopez-M ajano

Fig. 4. a The chest radiograph is normal in a patient who had sudden dyspnea for 3-5 min and no other symptomatology. When the chest radiograph was taken the patient was asymptomatic, b This anterior lung scintigram is markedly abnormal. There are bilat eral decreases o f pulmonary arterial blood flow with bilateral crescent signs, c In this posterior scintigram it is possible to see that the extent of damage to the right vascular bed is larger than that found in the anterior lung scintigram, d, e There is normalization of pulmonary arterial blood flow in the anterior scintigram (d) and in the first scintigram (e). This is due to recanalization o f the pulmonary arterial tree.


At the onset of pulmonary thromboembolism, bronchoconstriction is frequently present; but once the acute episode of pulmonary thrombo embolism is over, the underlying pathophysiology is a well-ventilated and inadequately perfused zone in the lung or lungs [35], Thus, abnormalities in the pulmonary function may be present, such as an increase of the alveolararterial pressure gradient for CO 2. In spite of all these and other tests, the diagnosis of pulmonary thrombo embolism is not established as frequently as it should be. One of the reasons for this failure is that the physician is not aware that pulmonary thrombo embolism is possibly the underlying disease; when physicians are aware of

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this, the number of diagnoses, according to M orrell et al. [36], increases from 33 (0.18% of admissions) to 154 (0.66% of admissions). Pulmonary thromboembolism is a disease that obstructs the flow in the pulmonary arteries. Therefore, the only definite way to establish the diagno sis o f this disease process is to demonstrate the lesion in the pulmonary vasculature. This can be done with angiocardiography. But gammagraphy has advantages over angiocardiography: (1) simplicity, (2) possibility for quantification (thus reducing the observer variation error), and (3) ability to demonstrate the zones of avascularity (possible only by the visual image). In 72% of pulmonary thromboembolism cases, focal defects in perfusion are present, and in some of them a concave defect, or crescent sign, has been found [37]. Avascular zones have also been found in other cardiopulmonary diseases (tuberculosis, for example); but in tuberculosis and other pulmonary diseases, the avascular zones are accompanied by abnormalities in the chest radiograph. This is not the case with pulmonary thromboembolism. There fore, the combination o f a normal chest radiograph and a normal ventilation study with an abnormal perfusion lung gammagram is diagnostic of pulmo



Lopez-M ajano

nary thromboembolism (fig. 4). Abrupt changes in avascular zones have also been demonstrated in pulmonary thromboembolism by several authors, among them W agner et al. [38], Similar changes are obtained by treating pulmonary thromboembolism with urokinase [39]. Pulmonary gammagraphy has been used to classify the disease according to the size of avascularity. a classification that is important in establishing the prognosis and the urgency of treatment. There is a good correlation between angiocardiography and pulmonary gammagraphy [40], A mador and Potchen [32] found that in some cases the pulmonary gammagram may show avascular zones - caused by pulmonary thromboembolism - better than angiocardiography. This is especially true when the emboli are multiple [41]. Table III is a comparison of gammagraphic and radiographic methods. The machine used for the detection of the radioactivity should depend on the patient’s condition; thus, the most appropriate one in the case of a patient with severe dyspnea and/or chest pain should be the camera because it takes less time to obtain the image (table III). In asthma and in chronic bronchitis, the chest radiograph may be normal, but avascular zones can be present if the abnormal lung scan is associated with a history of obstructive lung disease. In this case, spirometry should be employed to find out if the expiratory flow rate, the timed vital capacity, and/ or the maximal voluntary ventilation in chronic pulmonary thrombo embolism are reduced. These tests will be normal in pulmonary thrombo embolism, thus contrasting with the reduction in these parameters present in obstructive lung disease. The diffusion capacity is decreased in pulmonary thromboembolism, whether acute or chronic. Obviously, when there is a combination of both diseases, it is very difficult to establish the diagnosis. Another method used advantageously for the diagnosis of thrombo embolism, in contradistinction to other possible causes of decreased flow in the pulmonary circulation, is the use of l33Xe to study the patient's ventila tion. This will be normal in uncomplicated pulmonary thromboembolism although the perfusion lung scintigram will be abnormal [42], Lung scintigraphy is used also for research studies. This is possible be cause the method is valid [43. 44] and reproducible under the most stringent conditions [45], With lung scintigraphy it was possible to demonstrate that the respiratory gases regulate the pulmonary circulation [46] and that alveolar hypoxia de creases the pulmonary arterial blood flow in the hypoxic lung [47], This has been used in the clinic during cobalt radio therapy [48],


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References 1 T aplin , G. V.; D ore, E. K.; J ohnson, D. E., and K aplan , H.: Colloidal radio-albu min aggregates for organ scanning. Scientif. Exhib. IOth Ann. Meet. Soc. Nucl. Med., 1963. 2 W agner, H. N., jr.; Sabiston, D. C., jr.; M asahiro, I.; M c A fee, J. G.: M eyer, J. K., and Langan , J. K.: Regional pulmonary blood flow in man by radioisotope scanning. J. amer. med. Ass. 187: 601 (1964). 3 W agner, H. N., jr.; Sabiston, D. C.; M c A fee, J. G.; T ow , D. E., and Stern , M. S.: Diagnosis of massive pulmonary embolism in man by radioisotope scanning. New Engl. J. Med. 271: 377 (1969). 4 L opf.z -M ajano, V. and W agner, H. N ., jr.; Clinical application of lung scanning. Dis. Chest 54: 46(1968). 5 K ramer, K.; Lochner , W., and W etterer, E.: Methods o f measuring blood flow; in Handbook of physiology, sect. II, vol. 2. chap. 38, p. 1277 (Williams & Wilkins, Baltimore 1966). 6 Ball, W. G., jr.; Stewart , F. B.; N ewsham, L. G., and B ates, D. V.: Regional pulmonary function studied with Xenon133. J. clin. Invest. 41: 519 (1962). 7 W est, J. B. and D ollery, C. T. ; Distribution o f blood flow and ventilation perfusion ratio in the lung, measured with radioactive CO». J. appl. Physiol. 15: 405 (1969). 8 Lopez -M ajano, V.; W agner, H. N., jr.; Tow, D. E., and C hernick : Radioisotope scanning o f the lungs in pulmonary tuberculosis. J. amer. med. Ass. 194: 1053 (1965). 9 M ishkin , F. ; W agner, H. N., jr., and Tow, D. E. : Pulmonary blood flow distribution in asthma. J. amer. med. Ass. 203: 1019 (1968). 10 K ety, S. S.: Measurement of local blood flow by the exchange o f an inert diffusible substance: in Methods in medical records, p. 280 (Year Book, 1960).

15 Lopez -M ajano, V. y C olombetti, L.: Una nueva tecnica de marcar macroagregados de albumina con tecnecio 99m. Proc. Mexican Congr. Nuclear Med., Merida 1973. 16 Burdine, T. A. ; Sonnemaker, R. E. ; R yder, L. A., and S pjut , M. J. : Perfusion studies with technetium 99m human albumin microspheres (HAM). Radiology 95: 101 (1970). 17 D workin , H. J.; S mith, J. R., and Bull, F. E.: Reaction after administration of macroaggregaled albumin for a lung scan. New Engl. J. Med. 1966: 375. 18 W agner, H. N., jr.; S abiston, D. D., jr.; M c A fee, J. G.; Tow, D. E., and Stern , M. S.: Diagnosis of massive pulmonary embolism in man by radioisotope scanning. New Engl. J. Med. 271: 377 (1964).


11 Lopez -M ajano, V. y R hodes, B. A.: Particulas usadas en la gammagrafia pulmonar perfusoria. Rev. Biol. Med. Nucl. 2: 127 (1970). 12 Stern , H. S.; G oodwin , D. A.; W agner, H. N„ jr., and K ramer, H. H.: In n3m short-lived isotope for lung scanning. Nucleonics 24: 57 (1966). 13 A lvarez, J. C.; M oran, R. y A rriaga , C. S.: Un nuevo compuesto para estudios gammagraficos perfusorios con radioisotopos de vida corta. Memorias Sociedad Mexicana de Medicina Nuclear, Guadalajara 1967. 14 R hodes, B. A.; Z olle, L; Buchanan, Z. W., and W agner, H. N., jr.: Radioactive albumin microspheres for studies o f the pulmonary circulation. Radiology 92: 1453 (1969).

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19 M c A fee, J. G.; M ozley, J. M., et al.: Experiences in rectilineal scanning with large diameter Na 1 (Tl) crystals. J. nucl. Med. 8: 371 (1967). 20 H indell , R. and G ilson. A. J.: Multicrystal scanner is rapid and versa. Nucleonics 25: 52 (1967). 21 Q uinlan, M. F. and W agner, H. N., jr.: Lung imaging with the pinhole camera. J. nucl. Med. 9: 497 (1968). 22 L opez-M ajano, V.; L in , S. C., and Lee, J. K.: Perfusion and ventilation scintigrams with a gamma-camera. Scand. J. Resp. Dis. (accepted for publication). 23 J ones, R. H.; G oodrich , J. K., and Sabiston, D . C.: Radioactive lung scanning in the diagnosis and management o f pulmonary disorders. J. thorac. cardiovasc. Surg. 54: 520(1967). 24 T aplin , G. V.; J ohnson , D. E.; D ore, E. K., and K aplan, H. S.: Lung photoscans with macroaggregates of human scrum radioalbumin. Experimental bast's and initial clinical trials. Hlth Phys. 10: 1219(1964). 25 Q uinn , J. C.: The lung. The challenge of nuclear medicine. Amer. J. Roentgenol. 105: 121 (1969). 26 Lopez -M ajano, V. and H ooker, D. M .: Pulmonary function and lung resection. Respiration 28: 555 (1971). 27 Lopez-M ajano, V.; K ieffer, R. F.; M arine, D. N.; G arcia . D. A., and W agner, H. N., jr. : Pulmonary resection in bullous disease. Amer. Rev. resp. Dis. 99: 554(1969). 28 M ishkin , F.; W agner , H. N .,jr.,an d Tow, D. E.: Pulmonary blood flow distribution in asthma. J. amer. med. Ass. 203: 1019 (1968). 29 Burdine, J. A.; R yder, L. A.; Sonnemaker, R. E.; D eP uey, G., and C alderon, M.: " T cm-human albumin microspheres (HAM) for lung imaging. J. nucl. Med. 12: 127(1971).

33 C aird, F. I. and Stanfield, C. A.: The electrocardiogram in asphixial and in embolic cor pulmonale. Brit. Heart J. 24: 313 (1962). 34 M c G inn , S. and W hite, P. D.: Acute cor pulmonale resulting from pulmonary embo lism; its clinical recognition. J. amer. med. Ass. 104: 1477 (1939). 35 Lopez -M ajano, V.: Diagnosis of pulmonary embolism. Respiration 30: 201 (1973). 36 M orrell, M. T .; T ruelore, S. C., and Barr , A.: Pulmonary embolism. Brit. med. J. ii: 830 (1963). 37 Poulouse, K.; R eba, R. C .a n d W agner, H. N., jr.: Characterization o f the shape and location of perfusion defects in certain pulmonary diseases. New Engl. J. Med. 279: 1020(1968). 38 W agner, H. N., jr.; H olmes. R. A.; Lopez-M ajano, V., and Tow, D. E.: The lung; in Principles o f nuclear medicine, p. 422 (Saunders, Philadelphia 1968). 39 Tow, D. E.; W agner, H. N., jr., and H olmes, R. A.: Urokinase in pulmonary embo lism. New Engl. J. Med. 277: 1161 (1967).


30 Lopez-M ajano, V.: Diagnostico dc la embolia pulmonar. Rev. Biol. Med. Nucl. /.• 34(1969). 31 Levine, M.; Israel, M. L., and F isher, G. R .: LDH and SCOT levels in pulmonary embolism. Biochem. Clin. 4: 243 (1964). 32 A mador, E. and P otchen, E. J. : Serum lactic dehydrogenase activity and radioactivity lung scanning in the diagnosis o f pulmonary embolism. Ann. intern. Med. 65: 1247 (1966).


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Request reprints from: Vincent L opf.z -M ajano, MD, Ph. D., Nuclear Medicine Service, Jackson Park Hospital, 7531 Stony Island, Chicago, IL 60649 (USA)


40 M aser, K. M .,; T isi, G. M .; R hodes, P. G .; G regg , R .; L ardis, G. A., and M iale, A .: Correlation of lung photoscans with pulmonary angiography in pulmonary embolism. Amcr. J. Cardiol. 18: 810(1966). 41 S pencer, R.; S eaton, A., and L ittle, W. A .. Lung scanning in pulmonary embolism. Brit. J. Radiol. 41: 885 (1968). 42 W agner, H. N .,jr.; Lopez-M ajano, V.; Langan , J. K..and Josm, R. C.: Radioactive xenon in the differential diagnosis o f pulmonary embolism. Radiology 91: 1168 (1968). 43 Lopez -M ajano, V.; C hernick , V.; W agner, H. N.,jr., and D utton , R. E.: Compari son of radioisotope scanning and differential oxygen uptake o f the lungs. Radiology 83: 697(1964). 44 Tow, D. E .; W agner, H. N., jr.; Lopez -M ajano, V., and S mith, E. M.: Validity of measuring regional pulmonary arterial blood flow with macroaggregates o f human serum albumin. Amer. J. Roentgenol. 46: 664 (1966). 45 Lopez-M ajano, V.; T w ining , R. H.; G oodwin , D. A., and W agner, H. N., jr.: Reproducibility of lung scans. Invest. Radiol. 2: 410 (1967). 46 Lopez-M ajano, V.: Regulation o f the pulmonary circulation. Proc. Int. Symp. Pulmonary Circulation (Karger, Basel 1970). 47 L opez-M ajano, V.; W agner, H. N., jr.; T w ining , R. H.; T ow , D. E., and C hernick , V.: Effect o f regional hypoxia on the distribution of pulmonary blood flow in man. Circulat. Res. 18: 166(1966). 48 Lopez -M ajano, V.: Study o f regional lung function with radionuclides. Respiration 29: 97 (1972).

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