(I) Page 16-21 Evaluation of SPECT Lung (148-153)


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(I) Page 16-21 Evaluation of SPECT Lung (148-153)

  1. 1. 148 World Journal of Nuclear Medicine, Volume 8, Number 3, July 2009 Evaluation of SPECT Lung Perfusion Scintigraphy in Patients with Suspected Pulmonary Embolism. 1 1 1 1 2 3 1 4 Goco GFL , Ote ELP , Ortiz AO , Torres MT , Vizcarra RP , Nolido RAB , Magboo VPC , Watanabe N 1 Department of Nuclear Medicine, St. Luke's Medical Center, Quezon City, Philippines 2 Institute of Radiology, St. Luke's Medical Center, Quezon City, Philippines 3 Institute of Pulmonary Medicine, St. Luke's Medical Center, Quezon City, Philippines 4 Nuclear Medicine Section, Division of Human Health, International Atomic Energy Agency, Vienna, Austria Correspondence: Gerard F. L. Goco, MD Department of Nuclear Medicine, St. Luke's Medical Center, 279 E. Rodriguez Sr., Blvd. Quezon City, Philippines 1102 Email: glgoco@yahoo.com Abstract Keywords: lung perfusion scan, SPECT, pulmonary embolism WorldJNucl Med2009;8:148-153 Imaging studies are essential to arrive at an accurate diagnosis of pulmonary embolism (PE). Computed tomography pulmonary angiogram (CTPA) is increasingly becoming the diagnostic tool of choice while the lung perfusion-ventilation scan (VQ) is the standard nuclear medicine procedure for PE. Single photon emission computed tomography (SPECT) lung perfusion scan can be an alternative since it has lower radiation exposure to the patient compared to CTPA and is a shorter procedure compared to the VQ scan. This study aims to determine if SPECT lung perfusion scan interpreted using the PISA- PED criteria yields the same results as a pre-test clinical score (Wells score), a VQ scan and CTPA. This is a prospective study wherein thirteen patients were clinically evaluated using the Wells score before they underwent VQ scanning, SPECTperfusion scan and CTPA. The agreement between the results of the SPECT scan and the Wells score, the VQ scans, and CTPA were determined using Kappa statistics. There is poor agreement between the SPECT and the Wells score. Agreement between SPECT and VQ scan is significant (p=0.000). Agreement between SPECT and CTPA is likewise significant (p=0.002). We conclude that SPECT perfusion scan is a viable alternative to the VQ scans and CTPA. It can also be used for correlation with the Wellsscore. Introduction Pulmonary embolism, an occlusive condition of the pulmonary arteries commonly resulting from deep venous thrombosis, is a potentially fatal disease if undiagnosed and untreated early. The clinical manifestations of pulmonary embolism (PE), which are used to make pre-test predictions of PE, are nonspecific, making imaging studies essential to arriveatanaccuratediagnosis(1,2). Conventional pulmonary angiography is considered the gold standard by which other imaging modalities have been compared. It is, however, a costly and invasive procedure with morbidity rates reported to be around 2 – 5 % (3). Non- invasive imaging tests for PE include the computed tomography pulmonary angiography and lung perfusion- ventilation scintigraphy. Computed tomography pulmonary angiography (CTPA) has increasingly become an important diagnostic modality for PE in recent years. It is a highly sensitive and specific test with a short acquisition time that is necessary for patients in respiratory distress (4,5). Lung perfusion-ventilation scintigraphy (VQ scan), on the other hand, has seen a decline in its role in diagnosing PE despite its high sensitivity.The two main drawbacks forVQ scans have been the length of time required for imaging and the interpretation of the images, which can be inconclusive. VQ scans are composed of two separate procedures: a lung perfusion scan and a lung ventilation scan, each of which uses different types of radiotracers (6). Imaging time is longer than the CTPA. Together, perfusion and ventilation scans can take up to one hour to complete. VQ scans are traditionally interpreted using the modified PIOPED criteria, a diagnostic criteria based on the results of the Prospective Investigation of Pulmonary Embolism Diagnosis (7-9). While the criteria accurately identify normal patients and those highly probable of having PE, a significant number of patients fall under the low probability and intermediate probability scans. The low and intermediate criteria, however, can be of little use to clinicians and may require patients to undergo further testing(10,11). A more simplified approach is to use the lung perfusion scan alone to detect wedge-shaped segmental defects, areas with decreased or absent tracer flow that are hallmarks of vascular occlusion (12). Ventilation scans are disregarded while the perfusion images are interpreted using the criteria proposed by the investigators of the Prospective Investigative Study of Acute Pulmonary Embolism Diagnosis (PISA-PED) (13). Sensitivity in detecting these In vivo Diagnostics
  2. 2. wedge-shaped defects can be increased significantly if the perfusion scan images are acquired using singe photon emission computed tomography or SPECT instead of planarviews(14,15). We decided to undertake a prospective study wherein SPECT lung perfusion scans were compared with the pre- test probability of PE, VQ scans, and CTPA scans. The purpose was to determine if a SPECT lung perfusion scan alone would yield the same results. This could lead to the development of a simpler nuclear medicine imaging procedure that can be presented as a viable alternative to the currentVQ scansorCTPA. 78 consecutive patients suspected of having pulmonary embolism were screened at the Department of Nuclear Medicine, St. Luke's Medical Center between November 2004 and December 2007 as part of a multicenter study.The following patients were excluded: pregnant patients, children below 18 years, patients on anti-coagulants for more than three days, those with a life expectancy of less Materialsand Methods Variable No. of points Risk Factors Clinical signs and symptoms of deep venous thrombosis (DVT) 3.0 An alternative diagnosis deemed less likely than PE 3.0 Heart rate > 100 beats/min 1.5 Immobilization or surgery in the previous 4 week 1.5 Previous DVT or PE 1.5 Hemoptysis 1.0 Cancer (receiving treatment, treated in the past 6 mo, or palliative 1.0 care Clinical probability Low <2.0 Intermediate 2.0 – 6.0 High >6.0 Table 1. Wells criteria for predicting the probability of embolism PIOPED criteria for Interpretation of PISA-PED criteria for interpretation VQ scans of SPECT lung perfusion scans Normal / Very low probability (<10%) Normal scan Normal scan No perfusion defects Near-normal scan (minor matching patchy changes) Matching VQ defects in 2 or 3 zones of a lung Matching VQ defects in mid or upper zones with matching CXR changes Perfusion defects less extensive than CXR changes Non-segmental defects or stripe sign Low probability (10 – 20%) Near normal scan Matched VQ defect in one zone of a lung Impressions caused by enlarged heart, and normal CXR hila, or mediastinum seen on an Lower zone matching VQ defects of otherwise normal scan small or large size with matching CXR changes Intermediate probability (20% - 80%) Abnormal scan but not consistent with Single segment, or the equivalent, of VQ PE mismatch Perfusion defects other than wedge- Lower zone matching VQ defect of shaped moderate size with matching CXR changes Moderate size or large subsegmental perfusion defects associated with small pleural effusion High probability (>80%) Abnormal scan consistent with PE Two or more segments, of the equivalent, Single or multiple wedge-shaped of VQ mismatch perfusion defects Table 2. PIPOED and PISAPED criteria 149 World Journal of Nuclear Medicine, Volume 8, Number 3, July 2009 Goco GFL, Ote ELP, Ortiz AO, et al.
  3. 3. than six months, those known to be allergic to contrast material, renal failure patients, those unable to use the inhalation delivery system during the ventilation scan, and patients known to have primary pulmonary hypertension, acute myocardial infarction, and unstable angina.Atotal of 13subjectswereincluded. On arrival at the department, a clinical assessment was undertaken by a senior nuclear medicine resident involved in the study. Pertinent clinical history and physical examination findings were recorded. The pre-test probability of pulmonary embolism was determined for eachsubjectusingtheWellsscore(Table1)(2). Scintigraphic images were acquired in the supine position at 500,000 counts per view using an Infinia Hawkeye dual- head gamma camera (GE-Milwaukee,MN, USA) with low energy, high resolution collimators and a 128 x 128 matrix. The lung ventilation scintigraphy was performed on each patient after 1110 MBq (30 mCi) of Tc99m DTPA aerosol were delivered by inhalation using an Ultravent (Mallinkrodt, St Louis,MO, USA) delivery system. This was followed by lung perfusion scintigraphy using 185 MBq (5 mCi) of Tc99m MAA containing 150,000 to 200,000 particles. Anterior, posterior, lateral, anterior and posterior oblique views of the lungs were acquired. Additional tomographic (SPECT) perfusion images of the lungs were acquired using the following parameters: step 0 and shoot acquisition, 64 projections over 360 , pixel size lessthan3mm,Hannfilter,andcutoffat0.7. The VQ scans were interpreted by a board-certified nuclear medicine physician using the modified PIOPED criteria. Figure 1. Mismatched VQ scan consistent with pulmonary embolism. Anterior views of a lung showing multiple subsegmental defects in the perfusion scan (left) with normal corresponding ventilationscan(right). Figure 2. SPECT perfusion scans in the coronal (left) and transverse (right) views show wedge-shaped defects(arrows) thatareconsistentwithpulmonaryembolism. 150 World Journal of Nuclear Medicine, Volume 8, Number 3, July 2009 Goco GFL, Ote ELP, Ortiz AO, et al.
  4. 4. Segmental mismatches (abnormal perfusion image but normal ventilation image) were considered highly probable forPE(Figure1). The same nuclear medicine physician evaluated the SPECT perfusion images using the PISA-PED criteria. A wedge- shaped defect was considered consistent with PE (Figure 2). A Brilliance 64-slice CT scanner (Philips) was used to perform CTPA on each patient after their scintigraphic studies.The field of view extended from the top of the aortic arch to the diaphragm. Images were acquired at 4 mm/sec with non-ionic contrast. The CTPA images were evaluated by a board certified CT radiologist.Astudy was considered positive for PE when a filling defect, representing a thrombus, is seen within the lumen of a pulmonary artery (Figure3). For purposes of analysis, the grade of near normal in PISA- PED corresponded to low probability in the PIOPED criteria while abnormal but not PE corresponded to intermediate probability in PIOPED (Table 2). In comparison with CTPA, only the abnormal SPECT scans consistent with PE correspond to the positive CTPA scans. The normal, near normal and abnormal scans not consistent with PE correspond to the negative CTPAscans. Measure of agreement between the SPECT perfusion scan results and the pre-test probability (Wells score), the VQ scan results, andCTPAresultsweredeterminedusingKappastatistics. There were 10 female and 3 male subjects included. Their ages ranged from 21 to 75 years with a mean age of 55 years. Inability to use the aerosol delivery system for the ventilation scan was the most common cause for exclusion Results Figure. 3. 64-slice CTPA showing a filling defect consistent with thrombus in the right pulmonary artery. Patient Age/Sex Wells' criteria VQ-PIOPED SPECT-PISAPED CTPA 1 23 / F Intermediate Normal Normal PE 2 75 / M Intermediate Intermediate PE PE 3 73 / F Intermediate High – PE PE PE 4 67 / F High High – PE PE PE 5 75 / F Intermediate Low Near normal No PE 6 21 / F Intermediate Low Near normal No PE 7 45 / F Intermediate Intermediate PE PE 8 47 / F Intermediate High – PE PE PE 9 69 / M Intermediate Low Near normal No PE 10 44 / F Intermediate Normal Normal No PE 11 61 / M Intermediate Normal Normal No PE 12 49 / F Intermediate Normal Normal No PE 13 63 / F Intermediate Intermediate Intermediate No PE Table 3. Results by patient. 151 World Journal of Nuclear Medicine, Volume 8, Number 3, July 2009 Goco GFL, Ote ELP, Ortiz AO, et al.
  5. 5. (34%) from the study. Using the Wells score, 12 subjects had an intermediate pre-test probability for PE and only one had a high pre-test probability for PE. Five SPECT perfusion scans were consistent with PE while only three VQ scans were highly probable for PE. CTPA detected pulmonary embolism in six subjects. A summary of the resultsforeachpatientisgiveninTable3. The Wells score and SPECT perfusion scan results only agreed in two patients (15%). The VQ and SPECT perfusion scans agreed in 11 patients (85%). CTPA and SPECT perfusion scans had the highest agreement (12/13 or 92%). Using Kappa statistics, there was significant agreement between the SPECTperfusion scan andVQ scan (p=0.000) and between the SPECT perfusion scan and CTPA (p=0.002). The agreement between the SPECT perfusion scan and Well's criteria did not show any statisticalsignificance. The comparisons being made in this study are aimed to determine if different methods would yield similar results. It is not our intention to come up with the ideal non-invasive diagnostic tool for pulmonary embolism since the accepted gold standard, pulmonary angiography, is not performed. If pulmonary angiography had been required for the subjects, enrolment would have been more difficult and could have led to significant referral bias with only patients highly probableofhavingPEbeingincluded. Anumber of papers have concluded that SPECT lung scans are similar or better than the conventional VQ scans in predicting pulmonary embolism. Collart et al (14) reported similar sensitivities between the two but higher specificity for SPECT perfusion scans. Corbus et al (15) and Bajc et al (16) both reported that SPECT scans are more sensitive and specific than planar VQ scans. Reinartz et al (17) reported a higher number of perfusion defects being detected by SPECT scans, an increase of 12.8% in the segmental level andanincreaseof82.6%inthesubsegmentallevel. As early as 1993, Eustace et al (18) already predicted that SPECT is likely to become the method of choice in nuclear medicine for evaluating patients with suspected PE. Our findings of statistically significant agreement between the conventionalVQ scans and the SPECTperfusion scans also show that SPECT perfusion scans may be sufficient to evaluate patients suspected with pulmonary embolism. Ventilation scans may be eliminated, which would reduce the time, by as much as 40 minutes, patients spend in the nuclear medicine department. This would be a welcome development for patients in respiratory distress. Our study also reflects the need to be able to diagnose PE using the perfusion scans alone. One-third of the patients screened were excluded due to their inability to properly use the ventilation system used to deliver the radiotracer into the airways. The advances in CT technology have allowed for excellent angiographic studies for the anatomic demonstration of a clot in the pulmonary arteries. The ability of multidetector CT to detect pulmonary embolism has been comparable to the conventional pulmonary angiography (19). When comparison is made between SPECTand CTPA, sensitivity has been reported to be higher with SPECTbut specificity is Discussion better with CTPA (5,17,20). Reinartz et al (17) reported sensitivity, specificity, and accuracy for SPECT scans at 97%, 91%, and 94%, respectively, compared to 86%, 98%, and93%forCTPA. These high levels of accuracy for CTPA, together with its otheradvantages,such as arapidimagingtimeandabilityto detect other concomitant pulmonary diseases, would have removed VQ scans from the diagnostic algorithm for PE had it not been for the nephrotoxicity of the contrast media used in CTPA and the significant radiation burden to the patient, especially women (21). The radiation dose from CTPA is a particular concern for young female patients, a significant segment of the population often evaluated for deep venous thrombosis and PE stemming from their oral contraceptive use. A 64-slice CTPA delivers an estimated radiation dose of 50 – 80 mSv to the breasts (22) compared to 0.28 – 0.9 mSv from a lung scintigraphy study (23). This wide difference in radiation dose between the two procedures makes CTPA a factor to consider in breast cancerriskforyoungwomen(22,24,25). Our study, showing a high degree of agreement between SPECT and CTPA, provides evidence that SPECT perfusion scan can be used instead of CTPAwhen there is a concernfortheradiationexposuretothepatient. The poor correlation between the SPECT perfusion scans and the Wells score is not surprising in our study.Astudy by McLean et al (26) also showed a poor correlation between the PISA-PED criteria used here and clinical classification. Clinical assessment alone has often been reported to be unreliable in PE and needs to be correlated with D-dimer tests or imaging studies (1,2,27,28). SPECT perfusion scan can also be used for correlation with the Wells score since its results agrees with VQ scans and CTPA, which are the more commonly used imaging procedures in the evaluation ofpatientssuspectedwithPE. SPECT perfusion scans interpreted using the PISA-PED criteria is a viable alternative to the VQ scan and CTPA. Wells scores needing correlation with imaging studies can becorrelatedwiththeSPECTperfusionscan. This study was supported by a research grant from the Research and Biotechnology Department of the St. Luke's Medical Center. The authors also wish to acknowledge the help of the residents and medical technologists of the Department of Nuclear Medicine, St. Luke's Medical Center. 1. Hoffman JM, Lee A, Grafton ST, Bellamy P, Hawkins RA, Webber M. Clinical signs and symptoms in pulmonary embolism: A reassessment. Clin Nucl Med 1994;19:803-808. 2. Wells PS,Anderson DR, Rodger M, et al. Derivation of a simple clinical model to categorize patients' probability of pulmonary embolism: increasing the model's utility with SimpliRED D-Dimer. Thromb Conclusion Acknowledgement References Goco GFL, Ote ELP, Ortiz AO, et al. 152 World Journal of Nuclear Medicine, Volume 8, Number 3, July 2009
  6. 6. Haemost2000;83:416-420. 3. Stein PD, Athanasoulis C, Alavi A, et al. Complications and validity of pulmonary angiography in acute pulmonary embolism. Circulation 1992; 85:462-468. 4. McEwan L, Gandhi M, Andersen J, Manthey K. Can CT pulmonary angiography replace ventilation- perfusion scans as a first line investigation for pulmonary emboli? Australas Radiol 1999; 43:311- 314. 5. Stone E, Roach P, Bernard E, et al. Use of computed tomography pulmonary angiography in the diagnosis of pulmonary embolism in patients with an intermediate probability ventilation/perfusion scan. InternMedJ 2003;33:74-78. 6. Sostman HD, Gottschalk A. Evaluation of patients with suspected venous thromboembolism. In:Sandler MP, Coleman RE, Patton JA, Wackers FJT, Gottschalk th A, editors. Diagnostic Nuclear Medicine. 4 ed. Philadelphia: Lippincott Williams and Wilkins Press; 2003p.345-366. 7. The PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism.JAMA1990;263:2753-2759. 8. Freitas FE, Sarosi MG, Nagle CC, Yeomans ME, FreitasAE, Juni JE. Modified PIOPED criteria used in clinicalpractice.J NuclMed1995;36:1573-1578. 9. Worsely DF, Alavi A. Comprehensive analysis of the results of the PIOPED study. J Nucl Med 1995; 36:2380-2387. 10. Hull RD, Raskob GE. Low-probability lung scan findings: a need for change. Ann Intern Med 1991; 114:142-143. 11. Dalen J. When can treatment be withheld in patients with suspected pulmonary embolism? Arch Intern Med1993;153:1415-1418. 12. Zeissman HA, O'Malley JP, Thrall JH. Nuclear rd medicine: the requisites in radiology. 3 ed. Philadelphia:ElsevierMosby Publishers;2006 13. The PISA-PED Investigators. Value of perfusion lung scan in the diagnosis of pulmonary embolism: results of the prospective investigative study of acute pulmonary embolism diagnosis (PisaPED).Am J Resp CriticalCareMed1996;154:1387-1393. 14. Collart JP, Roelants V, Vanpee D, et al. Is a lung perfusion scan obtained by using single photon emission computed tomography able to improve the radionuclide diagnosis of pulmonary embolism? Nucl MedCommun2002;23:1107-1113. 15. Corbus HF, Seitz JP, Larson RK, et al. Diagnostic usefulness of lung SPET in pulmonary thromboembolism: an outcome study. Nucl Med Commun1997;18:897-906. 16. Bajc M, Blitzen U, Ollson B, Perez de Sa V, Palmer J, Jonson B. Lung ventilation/perfusion SPECT in the artificially embolized pig. J Nucl Med 2002; 43:640- 647. 17. Reinartz P, Wildberger JE, Schaefer W, Nowak B, Mahnken AH, Buell U. Tomographic imaging in the diagnosis of pulmonary embolism: A comparison between VQ lung scintigraphy in SPECT technique and multislice spiral CT. J Nucl Med 2004;45:1501- 1508. 18. Eustace S, Phelan N, Dowsett DJ, Ennis JT. A comparison of SPECTand planar ventilation perfusion lungscanning.IrJ MedSci1993;162:82-85. 19. Baile EM, King GG, Muller NL et al. Spiral computed tomography is comparable to angiography for the diagnosis of pulmonary embolism. Am J Respir Crit CareMed2000;161:1010-1015. 20. Macdonald WB, Patrikeos AP, Thompson RI, Adler BD, van der Schaaf AA. Diagnosis of pulmonary embolism: ventilation perfusion scintigraphy versus helical computed tomography pulmonary angiography.AustralasRadiol2005;49:32-38. 21. StrashunAM.AreducedroleofV/Q scintigraphyin the diagnosis of acute pulmonary embolism. J Nucl Med 2007;4:272-284. 22. Einstein AJ, Henzlova MJ, Rajagopolan S. Estimating risk of cancer of cancer associated with radiation exposure from 64-slice computed tomography coronaryangiography.JAMA2007;298:317-323. 23. Radiation dose to patients from radiopharmaceuticals. Ann ICRP1998;28:1-126. 24. The International Commission on Radiological Protection. Managing patient dose in computed tomography: a report of the International Commission on Radiological Protection—ICRP publication 87. Ann ICRP2000;30:7-45. 25. Freeman LM. Don't bury the V/Q scan: It's as good as multidetector CT angiograms with a lot less radiation exposure.J NuclMed2008;49:5-8. 26. McLean RG, Carolan M, Bui C et al. Comparison of new clinical and scintigraphic algorithms for the diagnosis of pulmonary embolism. Brit J Radiol 2004; 77:372-376. 27. Wells PS, Ginsberg JS, Anderson DR et al. Use of a clinical model for safe management of patients with suspected pulmonary embolism. Ann Intern Med 1998;129:997-1005. 28. Wells PS, Anderson DR, Roger M et al. Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and D- dimer.Ann InternMed2001;135:98-107. 153 World Journal of Nuclear Medicine, Volume 8, Number 3, July 2009 Goco GFL, Ote ELP, Ortiz AO, et al.