`International Journal of Molecular ImagingVolume 2011 (2011), Article ID 682949, 7 pageshttp://dx.doi.org/10.1155/2011/682949`
Review Article

## Ventilation/Perfusion SPECT for Diagnosis of Pulmonary Embolism and Other Diseases

Department of Clinical Physiology, Lund University, 22185 Lund, Sweden

Received 5 October 2010; Accepted 10 November 2010

Academic Editor: Leonard M. Freeman

Copyright © 2011 Marika Bajc and Björn Jonson. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### Abstract

has the potential to become a first hand tool for diagnosis of pulmonary embolism based on standardized technology and new holistic interpretation criteria. Pretest probability helps clinicians choose the most appropriate objective test for diagnosis or exclusion of PE. Interpretation should also take into account all ventilation and perfusion patterns allowing diagnosis of other cardiopulmonary diseases than PE. In such contexts, has excellent sensitivity and specificity. Nondiagnostic reports are ≤3%. has no contraindication; it is noninvasive and has very low radiation exposure. Moreover, acquisition time for is only 20 minutes. It allows quantification of PE extension which has an impact on individual treatment. It is uniquely useful for followup and research.

#### 1. Introduction

Prior to the development of CT angiography, planar ventilation/perfusion scans were the primary noninvasive method for diagnosis of pulmonary embolism (PE). However, the technique suffered disrepute since the PIOPED I study showed that 65% of scans were nondiagnostic [1]. As will be reviewed below, results from later studies based upon modern imaging techniques and new holistic principles (combining clinical information, pretest probability, results of chest radiograph, and patterns typical of PE or other diseases) reduce the number of nondiagnostic findings to 3% or less, while sensitivity and specificity are excellent [2, 3].

Since the early 1980s, the advantage of tomography over planar imaging for PE detection was indicated [4]. Since then, numerous studies have shown such advantages of ventilation/perfusion single photon emission computed tomography () over alternative techniques, which indicated that lung scintigraphy is again appreciated as a first line method for diagnosis of PE.

An important issue is to estimate the clinical probability for PE before performing imaging tests as is elaborated upon in the European Guidelines for Lung Scintigraphy [2] and by Mamlouk et al. [5]. The object of this paper is to show the advantages of in accordance with the European Guidelines for [2, 3]. It will be emphasized that gives diagnostic information in other conditions such as pneumonia, COPD, and left heart failure. The presentation will focus on basic requirements on diagnostic methods for PE:(1)fast procedure, (2)low radiation dose,(3)no contraindications,(4)high diagnostic accuracy and few nondiagnostic reports,(5)utility for selection of treatment strategy,(6)suitability for followup and research.

#### 2. Agents Used for Imaging of Ventilation

Gases are distributed strictly according to regional ventilation. The only gas that is useful for is krypton, . Its short half life (13 s) implies that it disappears from the alveoli by decay rather than by exhalation. After some minutes of test gas breathing, when the alveolar concentration has approached a steady state reflecting alveolar ventilation, is performed. The rubidium generator that delivers has a half life of 4.6 h. Limited availability and high costs prevent a general use of .

Inhalation of a radio-aerosol is used in nearly all centers for ventilation scintigraphy. Aerosol particles are liquid or solid. Particles larger than 2 μm are deposited in large airways (hot spots). Smaller particles are deposited by sedimentation and diffusion in small airways and alveoli. Particles smaller than 1 μm are mainly deposited in alveoli by diffusion. Aerosol deposition is modified by flow pattern. High flow rates at forced breathing patterns and turbulent flow enhance particle deposition in airways and augment tendencies to hot spots in ventilation images, particularly in Chronic Obstructive Pulmonary Disease (COPD).

The mass median aerodynamic diameter, MMAD, reflects radioactivity carried by each liquid particle. Half of the radioactivity resides in particles smaller than MMAD and 50% in larger ones. It is often recommended that the maximum droplet size inhaled by the patient should not exceed 2 μm. Because of the complex physics behind aerosol deposition pattern, the performance of a nebuliser must be clinically tested.

Diethylenetriaminepentaacetic acid labelled with technetium, -DTPA, is in general use for ventilation scintigraphy with liquid aerosols. The size of the water solvable molecule is 492 Dalton [6]. Therefore, -DTPA diffuses through the alveolocapillary membrane to the blood. In a healthy patient, clearance of -DTPA occurs with a half life of about 70 minutes. Increased clearance, leading to a shorter half life is observed with alveolar inflammation of any kind, such as alveolitis of allergic or toxic nature and even in smokers [79].

Technegas is an aerosol of extremely small carbon particles, 0.005–0.2 μm, generated in a high temperature furnace [1012]. The small particle size implies that they are distributed in the lungs almost like a gas and are deposited in alveoli by diffusion [13, 14]. Technegas provides images which are equivalent to those with [1418].

Recently, a head to head study of deposition patterns using Technegas and -DTPA performed in a group of patients routinely admitted for and in a group of patients with known COPD was published [19]. Technegas reduced problems of central airway deposition and peripheral hotspots. Unevenness of radiotracer deposition and degree of central deposition were less with Technegas, particularly in the obstructive patients, Figure 1. In some patients, mismatched perfusion defects were only identified using Technegas because the marked peripheral unevenness of -DTPA obscured mismatch and thereafter PE might have been overlooked in COPD patients using -DTPA. In a few patients, -DTPA yielded images of poor quality. It was concluded that Technegas is the superior radio-aerosol, particularly in patients with obstructive lung disease. Another advantage of using Technegas is that a few breaths are sufficient to achieve an adequate amount of activity in the lungs.

Figure 1: Frontal slices in patient with COPD. Ventilation study with DTPA and technegas with corresponding perfusion images.

#### 3. Agent Used for Imaging of Perfusion

For perfusion scintigraphy, radio-labelled MAA, sized 15–100 μm, is injected intravenously. This causes microembolization of pulmonary capillaries and precapillary arterioles, reflecting regional perfusion if at least 60 000 particles are injected [20]. Routinely, about 400 000 particles are injected. As there are over 280 billion pulmonary capillaries and 300 million precapillary arterioles, only a small fraction of the pulmonary bed will be obstructed. Fewer particles might be used in patients with known pulmonary hypertension or after single lung transplantation.

#### 4. How to Perform

##### 4.1. Image Acquisition

Using a dual head camera, Palmer et al. developed a fast and efficient clinical method for [21]. The total acquisition time is only 20 minutes. A new algorithm allows calculation of the quotient between ventilation and perfusion and presentation of images for easier diagnosis and quantification of PE extension.

The ventilation study starts with inhalation of 25–30 MBq -DTPA or Technegas. Immediately after ventilation SPECT, a dose of 100–120 MBq MAA is given intravenously for perfusion imaging. During the examination, the supine patient carefully maintains the position between ventilation and perfusion acquisitions. Immobilization for only 20 minutes is usually well tolerated by patients. Examination in the supine position is comfortable even for most of critically ill patients. It is also more convenient for the staff.

When clearance measurements are required, -DTPA may be used. Clearance is then calculated from initial and final anteroposterior SPECT projections [21].

##### 4.2. Radiation Exposure

The doses of 30 MBq and 120 MBq for ventilation and perfusion, respectively, allow excellent quality at an effective radiation dose of 1.8 mSv [22].

##### 4.3. Reconstruction and Calculation of Images

Iterative reconstruction is performed using ordered subset expectation maximization (OSEM), for example, with 8 subsets and 2 iterations. In processing the images, the ventilation background was subtracted from the perfusion tomograms and a normalized V/P image set calculated, . The algorithms for were developed by Palmer et al. and further amended by Bajc et al. [21, 23]. The main consideration in the creation of   images was to scale smoothened ventilation and perfusion data sets to display in a fixed linear scale allowing separation of normal regions from those with mismatch (Figure 2).

Figure 2: Frontal slices in patient with massive PE. Absent perfusion in the right lung and sub-segmental defects in the left are clearly delineated in images.
##### 4.4. Presentation of

The basic format for presentation is displayed slices in frontal, sagittal, and transversal projections, available on any modern system. The slices must be accurately aligned so that ventilation and perfusion slices match each other and can be correctly compared. It is of value to achieve this acquisition in one session with maintained body position. This is also a prerequisite for the calculation of images, which greatly facilitates identification and quantification of PE.

Volume rendered images, such as “Maximum Intensity Projection”, are available with almost all SPECT systems, allowing rotating 3D views. Such displays might be useful, particularly for quantification and followup of PE patients [24].

##### 4.5. Primary Validation of the Method

Using a porcine model based upon 201Tl-marked emboli as a “gold standard”, Bajc et al. validated the new method for diagnosis of PE and confirmed the superior value of tomography over planar imaging and improved interobserver agreement of defects on the subsegmental level [25]. In a following clinical head to head comparison between planar imaging and , it was shown that 53% more mismatch points were identified with compared to the planar technique [26]. Similar results have been found by others [27, 28]. SPECT eliminates superimposed structures, clarifying the segmental and sub-segmental nature of perfusion defect caused by PE.

#### 5. Interpretation with Emphasis on PE

Lung scintigraphy for diagnosis of PE and other diseases should routinely include ventilation and perfusion studies [21, 23, 25, 27, 29]. In PE, a perfusion defect is due to an embolus blocking blood flow. Because there is no corresponding blockage in the airway, ventilation remains normal causing a mismatch pattern. The distinction of whether a given perfusion defects is matched or mismatched is fundamental. The next step is to characterize the perfusion defects. Perfusion defects due to blockage of a pulmonary artery should reflect the branching of pulmonary circulation and its classical segmental anatomy. A segmental defect is wedge shaped and with its base on the pleura as will be illustrated (Figure 3).

Figure 3: Sagittal slice in patient with segmental PE. Perfusion defect in anterior segment initially, nicely delineated in image. After 3 days, resolution is observed.

The European guidelines [2, 3] advocate the new holistic interpretation and reporting of lung SPECT. Freeman et al. argued that “the expert’s successful interpretation of lung scans exceeds the best accuracy achievable by algorithms, which, by definition, are distillations of decision making into finite linear steps. The subjective of the whole is superior to any possible attempt to define its discrete parts” [30].

A holistic interpretation of images includes (1) clinical information and pretest probability for PE, (2) chest X-ray when available, (3) recognition of patterns typical for PE based upon segmental charts, and (4) recognition of patterns of other diseases than PE whenever possible [21, 23].

This is as important as the imaging technique. The clinician can only benefit from reports, which clearly express the presence or absence of PE. This goal was not reached with previous probabilistic reporting methods according to PIOPED or modified PIOPED, which defied how planar scans are reported [1, 31]. Large studies show that this is achievable if all patterns representing ventilation together with perfusion are considered [23, 3234]. Conclusive reports were given in 97 to 99% of studies.

Recommended criteria for reading with respect to acute PE described in the European Guidelines are as follows.

No PE is reported if there are any of the following features:(i)normal perfusion pattern conforming to the anatomic boundaries of the lungs, (ii)matched or reversed mismatch V/P defects of any size, shape, or number in the absence of mismatch, (iii)mismatch that does not have a lobar, segmental or subsegmental pattern.

PE is reported if there is(i)V/P mismatch of at least one segment or two subsegments that conforms to the pulmonary vascular anatomy.

Nondiagnostic for PE is reported if there are(i)multiple V/P abnormalities not typical of specific diseases.

In PE, it is fundamental that mismatched areas are conical with the base of the cone along the pleura and conform to known sub-segmental and segmental vascular anatomy. With such interpretation criteria, recent studies in over 3000 cases showed according to a recent review a negative predictive value of 97–99%, a sensitivity of 96–99%, and a specificity of 91–98% for PE [3]. The rate of nondiagnostic findings was 1–3% [23, 3234]. Using our technique, yields ventilation and perfusion images in exactly the same projections. This makes calculation of images possible and facilitates recognition of mismatch, particularly important in the middle lobe and lingula where mismatch may be overlooked if the lung is not accurately delineated by its ventilation images [35].

is the method of choice for quantification of the extent of embolism, because all emboli in the whole lung are recognised and it has greater sensitivity compared to MDCT [27, 32, 33]. The number of segments and sub-segments indicating for PE typical mismatch are counted and expressed in % of the total lung parenchyma [24]. A segmental reduction or a sub-segmental total deficiency of function is attributed 1 point, and a segmental total deficiency is attributed 2 points. Therefore, the 9 segments of each lung can be represented by the total of 18 points. Mismatch defects are expressed as mismatch points, which after division by 36 give the fraction of the lung that is embolized. The reduction in total overall lung function can be estimated by adding the number of regions with reduced ventilation and/or perfusion.

Patients with up 40% PE could be safely treated at home if ventilation abnormalities engaged not more that 20% of the lung. Since 2004, the University Hospital of Lund has safely treated about 60% of patients with PE at home (approximately 1500).

#### 6. Diagnosis of Pulmonary Embolism

images allow clear identification of segmental and sub-segmental perfusion defects, as in Figure 2 from a woman with extensive PE.

Figure 3 shows a well-delineated segmental perfusion defect. Followup after three days showed an almost normal pattern, confirming the diagnosis of PE.

Importantly, mismatch findings without a segmental character do not indicate PE. Such findings are often observed in patients with heart failure, mediastinal adenopathy, postradiation therapy, and so forth.

##### 6.1. Indications for
###### 6.1.1. Diagnostic Accuracy and Methodological Considerations

The clinical value of has been confirmed in several studies [27, 29, 3234]. This has been highlighted by Stein et al. in a recent review [36]. is today the method recommended by the European Association of Nuclear Medicine for clinical diagnosis, followup, and research [2].

###### 6.1.2. Selection of Therapeutic Strategy

Management of PE was previously confined to in-hospital therapy, using thrombolysis or heparin injections followed by oral anticoagulants for extended periods of time.

allows objective quantification of PE. It has been shown that out-patient treatment is safe when based upon that quantifies PE extension and identifies V/P defects of other etiologies [24]. is accordingly a tool to guide the individual treatment.

###### 6.1.3. Followup

For followup, is the method recommended by the European Association of Nuclear medicine due to its high sensitivity, noninvasiveness, low radiation exposure, and absence of contraindications [2].

Clinical reasons for followup are(i)persistent V/P mismatches often occur after PE;(ii)PE may recur in identical locations;(iii)a prior study will help determine the age of a new defect;(iv)There is an impact on therapy decision.

Obviously, evaluation of different drugs and treatment strategies merits the use of because of its high sensitivity and quality with regards to quantification.

#### 7. Additional Findings

allows diagnosis of several other diseases which have different scintigraphic appearances to PE, as detailed below [2, 3, 37].

##### 7.1. Chronic Obstructive Pulmonary Disease (COPD)

In COPD matched areas with defects in ventilation and perfusion are observed. Ventilation defects are commonly more prominent than those of perfusion which leads to a pattern called reverse mismatch [19]. frequently provides the first indication of COPD. Notably, allows the diagnosis of PE even in the presence of COPD [32, 37], Figure 4.

Figure 4: Patient with COPD and extensive PE. On frontal slices, uneven ventilation with peripheral hot spots is observed, and perfusion images showed multiple perfusion defects, clearly delineated on VPquotient images.
##### 7.2. Heart Failure

In left heart failure, redistribution of perfusion towards upper lung regions is well recognised since long [38]. Ventilation is usually not affected to the same degree as perfusion, which leads to a mismatch pattern. Importantly, this pattern does not conform to segmental anatomy of pulmonary arteries and it is not of a segmental character. Among patients referred for suspected PE, redistribution of perfusion to upper ventral regions indicated heart failure in 15% of cases [39]. The positive predictive value of the referred pattern was 88%. Figure 5 shows before and after treatment for heart failure.

Figure 5: Patient with heart failure. Sagittal slice on the left panel shows redistribution of perfusion towards anterior region; ventilation is less affected causing mismatch of non-segmental character. Right panel shows control after 10 days of treatment with normalization of ventilation and perfusion distribution but with new ventilation and perfusion defect in upper lobe due to pneumonia.
##### 7.3. Pneumonia

Pneumonic regions lack ventilation while perfusion may partly be upheld. The most frequent finding is a matched defect [40]. In case of partly preserved perfusion, reversed mismatch is observed [40, 41]. Preserved perfusion along the pleural border leads to a “stripe sign” [42, 43]. frequently shows this sign because no overlaying structures obscure the images, Figure 6.

Figure 6: Patient with extensive pneumonia. Sagittal slices in a 79-year-old man who felt general illness, shivering, and low blood pressure. Chest X-ray was interpreted as pleural effusion. The ventilation study of the left lung showed almost absent ventilation, while perfusion was mainly preserved, and a stripe sign is observed. Diagnosis with was bilateral pneumonia, and this was confirmed later at autopsy.

The combination of PE and pneumonia is common [32]. Suspicion or knowledge that a patient has pneumonia does not contraindicate . On the contrary, may be life-saving in the most complex cases [44].

#### 8. Concluding Remarks

The qualities of rely upon adequate and standardized technology of combined ventilation and perfusion studies as well as new holistic interpretation criteria as discussed.

has excellent sensitivity and specificity. The rate of nondiagnostic reports is ≤3%. is noninvasive and can be performed in all patients. The radiation exposure is low. With efficient technique and effective organization, acquisition time is only 20 minutes. Furthermore, it allows quantification of PE that in some centres has impact on choice of treatment. is uniquely useful for followup and research. Its outstanding qualities merit consideration of its use as the primary diagnostic method for PE in all hospitals in which nuclear medicine is practiced. frequently gives diagnosis of both PE as well as comorbid conditions as COPD, left heart failure, and pneumonia.

#### References

1. C. E. Vreim, H. A. Saltzmann, and H. A. Saltzmann, “Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED),” Journal of the American Medical Association, vol. 263, no. 20, pp. 2753–2759, 1990.
2. M. Bajc, J. B. Neilly, M. Miniati, C. Schuemichen, M. Meignan, and B. Jonson, “EANM guidelines for ventilation/perfusion scintigraphy: part 2. Algorithms and clinical considerations for diagnosis of pulmonary emboli with $\text{V}/{\text{P}}_{\text{SPECT}}$ and MDCT,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 36, no. 9, pp. 1528–1538, 2009.
3. M. Bajc, J. B. Neilly, M. Miniati, C. Schuemichen, M. Meignan, and B. Jonson, “EANM guidelines for ventilation/perfusion scintigraphy: part 1. Pulmonary imaging with ventilation/perfusion single photon emission tomography,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 36, no. 8, pp. 1356–1370, 2009.
4. J. S. Magnussen, P. Chicco, and P. Chicco, “Single-photon emission tomography of a computerised model of pulmonary embolism,” European Journal of Nuclear Medicine, vol. 26, no. 11, pp. 1430–1438, 1999.
5. M. D. Mamlouk, E. vanSonnenberg, and E. vanSonnenberg, “Pulmonary embolism at CT angiography: implications for appropriateness, cost, and radiation exposure in 2003 patients,” Radiology, vol. 256, no. 2, pp. 625–632, 2010.
6. G. R. Mason, A. M. Peters, E. Bagdades, M. J. Myers, D. Snook, and J. M. B. Hughes, “Evaluation of pulmonary alveolar epithelial integrity by the detection of restriction to diffusion of hydrophilic solutes of different molecular sizes,” Clinical Science, vol. 100, no. 3, pp. 231–236, 2001.
7. C. Beadsmoore, H. K. Cheow, K. Szczepura, P. Ruparelia, and A. M. Peters, “Healthy passive cigarette smokers have increased pulmonary alveolar permeability,” Nuclear Medicine Communications, vol. 28, no. 2, pp. 75–77, 2007.
8. J. Rinderknecht, L. Shapiro, and M. Krauthammer, “Accelerated clearance of small solutes from the lungs in interstitial lung disease,” American Review of Respiratory Disease, vol. 121, no. 1, pp. 105–117, 1980.
9. D. B. Yeates and J. Mortensen, Eds., Textbook of Respiratory Medicine, vol. 1, WB Saunders, Philadelphia, Pa, USA, 3rd edition, 2000.
10. W. M. Burch, P. J. Sullivan, F. E. Lomas et al., “Lung ventilation studies with technetium-99m pseudogas,” Journal of Nuclear Medicine, vol. 27, no. 6, pp. 842–846, 1986.
11. M. Lemb, T. H. Oei, H. Eifert, and B. Gunther, “Technegas: a study of particle structure, size and distribution,” European Journal of Nuclear Medicine, vol. 20, no. 7, pp. 576–579, 1993.
12. T. J. Senden, K. H. Moock, J. F. Gerald, W. M. Burch, R. J. Browitt, C. D. Ling, and G. A. Heath, “The physical and chemical nature of technegas,” Journal of Nuclear Medicine, vol. 38, no. 8, pp. 1327–1333, 1997.
13. T. Inoue, N. Watanabe, and N. Watanabe, “Clinical evaluation of lung scintigraphy with 99mTc-technegas,” Nippon Igaku Hoshasen Gakkai Zasshi, vol. 50, no. 12, pp. 1590–1600, 1990.
14. J. M. James, J. J. Lloyd, and J. J. Lloyd, “99Tcm-Technegas and krypton-81m ventilation scintigraphy: a comparison in known respiratory disease,” British Journal of Radiology, vol. 65, no. 780, pp. 1075–1082, 1992.
15. G. Cook and S. E. M. Clarke, “An evaluation of Technegas as a ventilation agent compared with krypton-81m in the scintigraphic diagnosis of pulmonary embolism,” European Journal of Nuclear Medicine, vol. 19, no. 9, pp. 770–774, 1992.
16. I. J. C. Hartmann, P. J. Hagen, M. P. M. Stokkel, O. S. Hoekstra, and M. H. Prins, “Technegas Versus ${}^{81\text{m}}\text{Kr}$ Ventilation–Perfusion Scintigraphy: A Comparative Study in Patients with Suspected Acute Pulmonary Embolism,” Journal of Nuclear Medicine, vol. 42, no. 3, pp. 393–400, 2001.
17. J. Magnant, L. Vecellio, and L. Vecellio, “Comparative analysis of different scintigraphic approaches to assess pulmonary ventilation,” Journal of Aerosol Medicine, vol. 19, no. 2, pp. 148–159, 2006.
18. P. Peltier, P. De Faucal, A. Chetanneau, and J. F. Chatal, “Comparison of technetium-99m aerosol and krypton-81m in ventilation studies for the diagnosis of pulmonary embolism,” Nuclear Medicine Communications, vol. 11, no. 9, pp. 631–638, 1990.
19. J. Jögi, B. Jonson, M. Ekberg, and M. Bajc, “Ventilation-perfusion SPECT with 99mTc-DTPA versus Technegas: a head-to-head study in obstructive and nonobstructive disease,” Journal of Nuclear Medicine, vol. 51, no. 5, pp. 735–741, 2010.
20. L. L. Heck and J. W. Duley, “Statistical considerations in lung imaging with 99mTc albumin particles,” Radiology, vol. 113, no. 3, pp. 675–679, 1974.
21. J. Palmer, U. Bitzén, B. Jonson, and M. Bajc, “Comprehensive ventilation/perfusion SPECT,” Journal of Nuclear Medicine, vol. 42, no. 8, pp. 1288–1294, 2001.
22. J. Valentin, “Radiation dose to patients from radiopharmaceuticals (Addendum 2 to ICRP publication 53),” Annals of the ICRP, vol. 28, no. 3, pp. 1–126, 1998.
23. M. Bajc, C.-G. Olsson, J. Palmer, and B. Jonson, “Quantitative ventilation/perfusion SPECT ($\text{QV}/{\text{P}}_{\text{SPECT}}$): a primary method for diagnosis of pulmonary embolism,” in Nuclear Medicine Annual, L. M. Freeman, Ed., pp. 173–186, Lippincott Williams & Wilkins, Philadelphia, Pa, USA, 2004.
24. C. G. Olsson, U. Bitzén, B. Olsson, P. Magnusson, M. S. Carlsson, B. Jonson, and M. Bajc, “Outpatient tinzaparin therapy in pulmonary embolism quantified with ventilation/perfusion scintigraphy,” Medical Science Monitor, vol. 12, no. 2, pp. PI9–PI13, 2006.
25. M. Bajc, U. Bitzén, B. Olsson, V. Perez de Sá, J. Palmer, and B. Jonson, “Lung ventilation/perfusion SPECT in the artificially embolized pig,” Journal of Nuclear Medicine, vol. 43, no. 5, pp. 640–647, 2002.
26. M. Bajc, C. G. Olsson, B. Olsson, J. Palmer, and B. Jonson, “Diagnostic evaluation of planar and tomographic ventilation/perfusion lung images in patients with suspected pulmonary emboli,” Clinical Physiology and Functional Imaging, vol. 24, no. 5, pp. 249–256, 2004.
27. P. Reinartz, J. E. Wildberger, W. Schaefer, B. Nowak, A. H. Mahnken, and U. Buell, “Tomographic imaging in the diagnosis of pulmonary embolism: a comparison between V/Q lung scintigraphy in SPECT technique and multislice spiral CT,” Journal of Nuclear Medicine, vol. 45, no. 9, pp. 1501–1508, 2004.
28. H. Gutte, J. Mortensen, C. V. Jensen, P. Von Der Recke, C. L. Petersen, U. S. Kristoffersen, and A. Kjaer, “Comparison of V/Q SPECT and planar V/Q lung scintigraphy in diagnosing acute pulmonary embolism,” Nuclear Medicine Communications, vol. 31, no. 1, pp. 82–86, 2010.
29. M. Lemb and H. Pohlabeln, “Pulmonary thromboembolism: a retrospective study on the examination of 991 patients by ventilation/perfusion SPECT using Technegas,” Nuklearmedizin, vol. 40, no. 6, pp. 179–186, 2001.
30. L. M. Freeman, B. Krynyckyi, and L. S. Zuckier, “Enhanced lung scan diagnosis of pulmonary embolism with the use of ancillary scintigraphic findings and clinical correlation,” Seminars in Nuclear Medicine, vol. 31, no. 2, pp. 143–157, 2001.
31. P. D. Stein, R. D. Hull, W. A. Ghali, K. C. Patel, R. E. Olson, F. A. Meyers, and N. K. Kalra, “Tracking the uptake of evidence: two decades of hospital practice trends for diagnosing deep vein thrombosis and pulmonary embolism,” Archives of Internal Medicine, vol. 163, no. 10, pp. 1213–1219, 2003.
32. M. Bajc, B. Olsson, J. Palmer, and B. Jonson, “Ventilation/Perfusion SPECT for diagnostics of pulmonary embolism in clinical practice,” Journal of Internal Medicine, vol. 264, no. 4, pp. 379–387, 2008.
33. H. Gutte, J. Mortensen, and J. Mortensen, “Detection of pulmonary embolism with combined ventilation-perfusion SPECT and low-dose CT: head-to-head comparison with multidetector CT angiography,” Journal of Nuclear Medicine, vol. 50, no. 12, pp. 1987–1992, 2009.
34. M. Leblanc, F. Leveillée, and E. Turcotte, “Prospective evaluation of the negative predictive value of V/Q SPECT using 99mTc-Technegas,” Nuclear Medicine Communications, vol. 28, no. 8, pp. 667–672, 2007.
35. M. A. Meignan, “Lung ventilation/perfusion SPECT: the right technique for hard times,” Journal of Nuclear Medicine, vol. 43, no. 5, pp. 648–651, 2002.
36. P. D. Stein, L. M. Freeman, and L. M. Freeman, “SPECT in acute pulmonary embolism,” Journal of Nuclear Medicine, vol. 50, no. 12, pp. 1999–2007, 2009.
37. M. Bajc and B. Jonson, “Lung,” in Clinical Nuclear Medicine, H. J. Biersack and L. Freeman, Eds., pp. 118–137, Springer, Berlin, Germany, 2007.
38. W. F. Friedman and E. Braunwald, “Alterations in regional pulmonary blood flow in mitral valve disease studied by radioisotope scanning. A simple nontraumatic technique for estimation of left atrial pressure,” Circulation, vol. 34, no. 3, pp. 363–376, 1966.
39. J. Jögi, J. Palmer, B. Jonson, and M. Bajc, “Heart failure diagnostics based on ventilation/perfusion single photon emission computed tomography pattern and quantitative perfusion gradients,” Nuclear Medicine Communications, vol. 29, no. 8, pp. 666–673, 2008.
40. D. J. Li, I. Stewart, K. A. Miles, and E. P. Wraight, “Scintigraphic appearances in patients with pulmonary infection and lung scintigrams of intermediate or low probability for pulmonary embolism,” Clinical Nuclear Medicine, vol. 19, no. 12, pp. 1091–1093, 1994.
41. P. Carvalho and J. P. Lavender, “The incidence and etiology of the ventilation/perfusion reverse mismatch defect,” Clinical Nuclear Medicine, vol. 14, no. 8, pp. 571–576, 1989.
42. H. D. Sostman and A. Gottschalk, “The stripe sign: a new sign for diagnosis of nonembolic defects on pulmonary perfusion scintigraphy,” Radiology, vol. 142, no. 3, pp. 737–741, 1982.
43. H. D. Sostman and A. Gottschalk, “Prospective validation of the stripe sign in ventilation-perfusion scintigraphy,” Radiology, vol. 184, no. 2, pp. 455–459, 1992.
44. C. G. Olsson, M. Bajc, B. Jonson, and U. Albrechtsson, “Value of ventilation/perfusion SPECT detecting extensive pulmonary embolism in a patient with pneumonia,” Thrombosis and Haemostasis, vol. 93, no. 5, pp. 993–994, 2005.