International Journal of Cardiovascular Sciences. 2019;32(3)302-309 302 GUIDELINE Guideline for Ventilation / Perfusion Scintigraphy Marcel Yanagihara Rigolon,1 Claudio Tinoco Mesquita,2 Bárbara Juarez Amorim1 Universidade Estadual de Campinas (Unicamp),1 Campinas, SP - Brazil Universidade Federal Fluminense,2 Rio de Janeiro, RJ - Brazil Abstract and may follow some specific recommendations, as in the case of patients with allergy to iodinated contrast or renal failure, in which scintigraphy should be preferred.2 This paper is about the Guideline for Ventilation / Perfusion Scintigraphy. It has been developed by the Brazilian Society of Nuclear Medicine to be a best practices guide used in Nuclear Medicine. Its function is to be an educational tool to help the Nuclear Medicine Services in Brazil to guarantee a quality care to the patients. If adequately used and interpreted, ventilation / perfusion scintigraphy is an important tool for the detection of regional abnormality of pulmonary perfusion and ventilation, allowing for the accurate diagnosis of pulmonary embolism with low radiation exposure and minimum risks of complications. Introduction Objectives This guideline presents the best practices for carrying out and interpreting Ventilation / Perfusion Scintigraphy. The purpose of this guideline is to provide practical guidance on the indication, performance and interpretation of the results of Ventilation / Perfusion Scintigraphy. The main indication for Ventilation / Perfusion Scintigraphy is the detection of acute pulmonary thromboembolism (PE). It is characterized by acute obstruction of a pulmonary artery, or one of its sub- branches, caused by venous thrombus. The typical picture includes symptoms such as dyspnea without other cause, chest pain on inspiration and hemoptysis, accompanied by signs of low blood oxygen saturation and tachycardia. Loss of consciousness, hemodynamic instability and death may occur in more severe cases.1 General information about the exam It is an imaging diagnostic procedure that uses ventilation and perfusion scintigraphy to assess pulmonary diseases. Indications The main indications for ventilation / perfusion scintigraphy are listed on Table 1. The American College of Radiology (2011) guideline classifies Ventilation / Perfusion Scintigraphy as highly recommended, combined with CT pulmonary angiography (CTPA). Both studies are highly accurate in the diagnosis of acute PE and the choice for one or the other will depend on the availability of each service Relative contraindication Pregnancy and breastfeeding. One should weight the cost/benefit and, if the procedure has to be performed, it should be done in such a way that exposure to radiation be minimized and, whenever possible, it would be preferable to carry out only the perfusion phase. It is worth noting that, in pregnant women with suspected pulmonary embolism and normal chest X-ray, the American Thoracic Society and the Society of Thoracic Radiology Clinical Practice recommend the use of Keywords Pulmonary Embolism/complications; Pulmonary Embolism/diagnostic imaging; Ventilation-Perfusion Ratio; Pulmonary Artery/pathology; Radionuclide Imaging/methods. Mailing Address: Marcel Yanagihara Rigolon Rua Gilberto Pattaro, 150, casa 61. Postal Code: 13084-375, Residencial Burato, Campinas, SP - Brazil. E-mail: email@example.com, firstname.lastname@example.org Manuscript received February 20, 2018; revised manuscript May 28, 2018; accepted June 07, 2018. DOI: 1 0.5935/2359-4802.201 801 03
Rigolon et al. Int J Cardiovasc Sci. 2019;32(3)302-309 303 Guideline Guideline for lung scintigraphy Table 1 - Indications for ventilation / perfusion scintigraphy Table 2 - Modified Wells Score Modified wells criteria Points 1. Diagnosis of acute pulmonary thromboembolism; Clinical symptoms of DVT 3 2. Diagnosis of chronic pulmonary thromboembolism; PE is more likely than other diagnoses 3 3. Assesment of the rate of resolution of PE (compared to previous study); HR > 100 bpm 1.5 Prior DVT/PE 1.5 4. Assessment and quantification of right to left shunt; Hemoptysis 1 5. Differential quantification of pulmonary function before pulmonary resection; Malignancy 1 6. Lung transplant evaluation; Clinical probability: High > 6; Intermediate: 2 - 6; Low < 2. 7. Assessment of the etiology of pulmonary hypertension; 8. Assessment of chronic parenchymal diseases. The patient should be instructed about the exam and how to adequately perform the aerosol ventilation procedure, if possible practicing before the exam starts. perfusion lung scintigraphy as the method of choice for the diagnosis of PE, because it has the advantage of less exposure of the mother to radiation.2 Radiotracers Ventilation: Tc-diethylenetriaminepentaacetic acid (DTPA) labeled with 99mTc, 99mTc labeled microcolloid or solid 99mTc-labeled carbon particles in argon carrier gas. The latter should be preferred, as far as available, because it has a more uniform distribution in the lungs with lower retention in the airways and bronchi.7 Exam duration About 1 hour in total (acquisition of ventilation and perfusion images). Preparation Perfusion: 99mTc macro aggregated albumin (99mTc- MAA). The patient must be capable of tolerating the dorsal decubitus position necessary to perform the images and be cooperative enough to carry out the preparation for inhalation, as described hereafter. The patient’s standard chest radiograph, preferably in both posterior–anterior and lateral projections, and recently acquired (within a few-day-period), should be reviewed. The authors indicate a maximum interval of 48 hours. A CT scan can substitute for the chest radiography. In the assessment of PE, the standard chest radiography must be the first exam used to exclude other pathologies.5 Marking and quality control Marking and quality must always be done according to manufacturer guidelines. However, pharmacopoeial criteria must be respected (pH between 5.0 - 6.0 and radiochemical purity ≥ 90%).4,5 Adult activity Ventilation: The usual dispensed activity of 99mTc DTPA or sulfur colloid is 900–1300 MBq (25–35 mCi) in the nebulizer, from which only approximately 20–40 MBq (0.5–1.0 mCi) will reach the lungs.8 Relevant information to perform the procedure The likelihood of the patient having pulmonary thromboembolism6 should be assessed (through D-dimer testing or using the modified Wells score [Table 2], for instance), as well as by assessing the patient’s medical history (history of deep venous thrombosis (DVP), previous PE, chest X-rays, use of anticoagulant or thrombolytic).4,5 Solid 99mTc-labeled carbon particles in argon carrier gas – the activity administered should be calculated according to the distributor manual. Since it is more difficult to achieve higher activity in the lungs with inhalation, it should always be performed first. It is essential that the perfusion activity should be
Int J Cardiovasc Sci. 2019;32(3)302-309 Rigolon et al. 304 Guideline Guideline for lung scintigraphy Precautions to be taken during tracer injection at least three times the counting rate of the ventilation activity to ensure that the image shows pulmonary perfusion, because both agents are labeled with 99mTc.4,5 Since the particles tend to decant, the syringe should be gently rotated prior to use. Blood should not be drawn back into the syringe to prevent MAA aggregation, because it can cause damage to the images. It is important that a single dose be administered over 30 seconds. The patient is oriented to inhale and breathe deeply during the tracer administration, facilitating its uniform distribution. Perfusion: 40–150 MBq (3–4 mCi); depending on the number of particles administered, this value could be higher), and should be in the range of 200,000–700,000 particles. The particles administered should be within a size range of 15 to 100 micrometers. In Brazil, currently available preparations have at least 90% of MAA particles between 10-100 micrometers in size.9 In certain clinical conditions, the number of particles must be reduced, such as pulmonary hypertension and presence of right to left shunting. In the case of right-to- left shunt investigation, the number of particles should be decreased to 100,000 - 150,000. Imaging acquisition Nowadays, there are 3 possibilities to acquire the images: planar imaging, SPECT imaging and SPECT/ CT imaging. Several studies have demonstrated that SPECT imaging yields a higher sensitivity compared to planar imaging. Major segmental defects and more periferal defects are detected by planar imaging. However, especially mesial defects and subsegmental defects are more easily detected by SPECT imaging. SPECT imaging can detect around 50% more defects compared to inhalation imaging. Despite this, the recent Apropriate Use Criteria published by the Society of Nuclear Medicine and Molecular Imaging (SNMMI) recommends that both types of imaging (planar or SPECT) are valid in the clinical practice.10,11 We recommend that SPECT imaging be performed whenever possible. Pregnant women: as mentioned before, it is preferable to perform only the perfusion analysis with 99mTc macroaggregated dose reduction (0.5 to 1 mCi).4,5 Pediatric dosage Ventilation: Minimum activity should be no less than 10 MBq (0.27 mCi) to allow for sufficient count statistics to achieve good quality images. Since approximately 10% is retained within the lungs, it is suggested to administer as much as 15 times the activity of the DTPA needed (4 mCi).3 SPECT/CT combines increased sensitivity of SPECT imaging with high specificity of CT imaging. Several studies have shown that SPECT/CT provides increased sensitivity, specificity and accuracy compared to planar imaging. The improved specificity of SPECT/CT may reduce the number of false-positive results by 50%. Some studies have even demonstrated that SPECT/CT can increase specificity of scintigraphy to almost 100%, and make the study more accurate than CTA.12-16 However, to our knowledge, there are no studies which assess the clinical impact on patient evolution when SPECT/CT is also used. Thus, the authors suggest that SPECT/CT imaging be performed whenever possible due to its higher accuracy, even though other studies are needed to confirm the impact on the clinical management of patients. Solid 99mTc-labeled carbon particles in argon carrier gas - the activity administered should be calculated according to the distributor manual. Perfusion: 1.11 MBq/kg (0.03 mCi/kg), with a minimum of 14.8 MBq/kg (0.4 mCi) if no 99mTc ventilation study is performed or 2.59 MBq/kg (0.07 mCi/kg) if a 99mTc ventilation study is performed. The number of particles depends on the age and weight, according with the table below: 1 5 10 15 Parameter Newborn year years years years Weight (kg) 3.5 12.1 20.3 33.5 55.0 Dosage (mCi) 0.2 0.5 1.0 1.5 2.5 Ventilation: Particles 10-50 50-150 200-300 200-300 200-700 Low energy high resolution collimator (LEHR), with an energy window of 20% centered at 140 keV. In case of pulmonary hypertension and cardiac shunt investigation, these values should be reduced, depending on the age and the weight of the patient. Planar imaging must be obtained in anterior, posterior, left and right anterior and posterior oblique views, in addition to lateral views.
Rigolon et al. Int J Cardiovasc Sci. 2019;32(3)302-309 305 Guideline Guideline for lung scintigraphy Perform differential analysis of lung function prior to surgical procedure: the ventilation phase should not be performed; only lung perfusion imaging should be performed, as described above. Counting recommendation:8 Posterior: 250,000 counts; Other projections: use same time as the posterior view. Assess lung transplantation: perfusion images and pulmonary ventilation. The following is a suggested protocol for image acquisition using SPECT/CT: LEHR (Low Energy High Resolution) collimator; Interpretation4,5 64x64 matrix; Acute PE Diagnosis: 64 views (with a dual-head camera, 32 views per head); The interpretation of ventilation/perfusion lung scans, both planar and SPECT/CT, is based on comparison. Thus, when there are ventilation-perfusion defects, a V/Q matched defect is characterized. When there is a defect in perfusion, but not in ventilation, it can be said that there was a mismatch defect. Thus, when there is a defect in ventilation, and there is not the same area in perfusion, we say that there was a reverse mismatch. 20 sec acquisition; Zoom 1.0 180 degrees (dual-head) or 360 degrees (single-head camera). For CT image acquisition: If the equipment allows it, the algorithm for dose reduction in CT (for example, CareDose, Auto mA); In the past, the PIOPED criteria were widely used. These are old criteria based on planar images. In addition, their classification as high, intermediate, and low probability does not meet clinical needs. It is also important to take into consideration the pretest clinical probability calculated using the modified Wells score (see below) and assess the laboratory tests. The observer’s experience will also be an important factor. Thus, we believe that the report must be as accurate as possible, providing a “yes or no” response for the presence of acute PE. Below are the criteria used by the EANM, which are similar to the ones we use in our clinical practice. 130 kV; 5 mm slice thickness; Pitch 1.8; 0.8 s rotation time; Number of images = 61 Perfusion: Low energy high resolution collimator (LEHR), with an energy window of 20% centered at 140 keV. The SNMMI has recently published an important document on appropriate use criteria for lung scintigraphy. The diagram below corresponds to the proposed investigation of pulmonary embolism in patients with low to moderate risk of PE (Wells Criteria: < 6). The presence of normal chest x-ray combined with increased D-Dimer values is associated with an accurate indication for ventilation/perfusion lung scintigraphy. In these patients the D-Dimer values are crucial to continue the investigation using imaging methods. Planar imaging must be obtained in anterior, posterior, left and right anterior and posterior oblique views, in addition to lateral views. Counting recommendation:8 500,000 to 750,000 counts per image. In the case of perfusion SPECT with low-dose CT, perform tomographic imaging (see the acquisition protocol recommended above). Thus, according to the SNMMI document, in patients with higher likelihood for PE (Wells Criteria: > 6), there is no clinical impact associated with the use of the D-Dimer assay for the diagnosis of PE (Figure 2). In these patients, imaging methods must be requested regardless of the D-Dimer values. In the same way, patients with normal chest x-ray are candidates for lung scintigraphy as diagnosis method of choice to CT pulmonary angiography. Lung scintigraphy will Acquisitions for other indications Shunt investigation: the inhalation phase isn't performed. Following the administration of technetium Tc 99m injection, a whole-body scan should be performed in the anterior and posterior views; a static head imaging may be performed to better assess the brain.
Int J Cardiovasc Sci. 2019;32(3)302-309 Rigolon et al. 306 Guideline Guideline for lung scintigraphy Figure 1 - Adapted from Waxman, et al. Appropriate Use Criteria for Ventilation–Perfusion Imaging in Pulmonary Embolism. be the imaging modality of choice for investigation of suspected PE in patients with allergy to iodine, renal failure and inadequate venous access, even with abnormal chest x-ray. Inconclusive study: Presence of multiple abnormalities identified in the images that do not correspond to any specific disease. There are some causes for false-positive results. The main cause is an old or chronic PE. At the end of a hospital stay in which the patient was diagnosed with PE, it is recommended to perform a Ventilation/Perfusion Scintigraphy for this study to serve as reference for future suspicion of a PE. That is because, in some patients, the defect observed in the perfusion image may not normalize and remain as a mismatch defect. Nevertheless, in the vast majority of cases in which acute PE does occur, or the scintigraphy normalizes after treatment, or an infarction occurs in the region of the PE, the defect is regarded as a matched ventilation-perfusion defect. Other reasons for false positive results are: certain rare cases of pulmonary and mediastinal tumors, vasculitis and arteriovenous malformations; however, these possibilities, in general, do not represent a diagnostic problem when the overall patient’s data is considered. Negative Acute PE: Normal perfusion pattern conforming to the anatomic boundaries of the lungs; Matched or reversed mismatch V/P defects of any size, shape, or number in the absence of mismatch; Mismatch that does not have a lobar, segmental or subsegmental pattern, such as a stripe sign (perfusion defect with a normal perfusion stripe sign interposed between the defect and the adjacent pleural surfaces). Positive Acute PE: V/P mismatch of at least one segment or two subsegments that conforms to the pulmonary vascular anatomy (peripheral wedge- shaped defects – pleural based defects, and that conforms to the pulmonary vascular anatomy).
Rigolon et al. Int J Cardiovasc Sci. 2019;32(3)302-309 307 Guideline Guideline for lung scintigraphy Figure 2 - Adapted from Waxman, et al. Appropriate Use Criteria for Ventilation-Perfusion Imaging in Pulmonary Embolism. instance, since the free Tc-99m pertechnetate would not be present in the brain. In cases in which the ventilation cannot be performed, only the perfusion phase may be performed, keeping good accuracy, with a sensitivity of 86% and a specificity of 93% compared to CTA;17 and 80% and 96%, respectively, when combined with the interpretation of the chest x-ray.18 The calculation of percentageshunts can be assessed using regions of interest (ROIs) drawn over the whole body and the lungs, in both anterior and posterior images, and through comparison of the radioactive activity in the lungs in relation to the whole body, resulting in a percentage number. Usually, it is considered as positive if the difference between the activity present in the lungs compared to the whole body is greater than 10%, following the formula:19 (total number of whole body counts, including the background – total counts in the lungs) / total number of whole body counts, including the background x 100 = percentage of R-L shunt. Attention should always be drawn to radiopharmaceutical quality Evaluation of right to left shunts: The presence of right to left shunts is detected through the presence of a tracer in extrapulmonary tissue, primarily in the brain. An image of the head complements the evaluation and helps detect small shunts. The presence of the radiopharmaceutical in the brain helps distinguish between a right-to-left shunt and free Tc-99m pertechnetate due to kit unlabelling, for
Int J Cardiovasc Sci. 2019;32(3)302-309 Rigolon et al. 308 Guideline Guideline for lung scintigraphy control to ensure that the labeling efficiency is greater than 90%. Due to the presence of free Tc-99m pertechnetate. It should be remembered that visual analysis is always paramount and the presence of tracer in the brain and in renal cortex should be verified. The acquisition of images with the patient in different positions (dorsal decubitus or supine position) may hinder the comparability of the studies. The unilateral absence of one of the lungs in the perfusion imaging, with normal ventilation, is not an indicative of PE. In these cases, the chest CT scan must be assessed in order to look for tumors, aortic aneurysm, vascular defects or other pathologies. Perform differential analysis of lung function prior to surgical procedure: The aim of this indication is to help predict the lung function reduction in the postoperative period following lung resection (e.g. lung cancer). This is particularly important in those patients who already have a reduced function in the preoperative period. The differential function is calculated by drawing ROIs on each lung in the anterior and posterior views. The lung can also be divided into three equal rectangular ROI: top, middle, and bottom. Alternatively, posterior oblique views can be used to assess lobar segmentation, assisting in cases of segmentectomy or lobectomy.20 Author contributions Conception and design of the research: Rigolon MY, Amorim BJ. Acquisition of data: Rigolon MY. Analysis and interpretation of the data: Rigolon MY, Mesquita CT, Amorim BJ. Writing of the manuscript: Rigolon MY. Critical revision of the manuscript for intellectual content: Mesquita CT, Amorim BJ. Supervision / as the major investigador: Amorim BJ. Postoperative evaluation of lung transplantation Potential Conflict of Interest Evaluate the feasibility of vascular anastomosis. It is also possible to assess rejection, when there are matched defects suggestive of obstructive lung disease or changes in the perfusion between both lungs (in the case of unilateral transplantation). No potential conflict of interest relevant to this article was reported. Sources of Funding There were no external funding sources for this study. Important observations There may be hot spots on perfusion images, in case blood coagulation occurs in the syringe during injection of the tracer, which may occur when blood is aspirated into the syringe during injection. Study Association This study is not associated with any thesis or dissertation work. References 1. National Heart, Lung, and Blood. U.S. Department of Health and Human Services - National Institutes of Health. 2011. [Cited in 2018 May 10]. Available from: https://www.nhibi.nih.gov Pulmonary imaging with ventilation/perfusion single photon emission tomography. Eur J Nucl Med Mol Imaging. 2009;36(8):1356-70. 5. Parker JA, Coleman RE, Grady E, Royal HD, Siegel BA, Stabin MG, et al. SNM practice guideline for lung scintigraphy 4.0. J Nucl Med Technol. 2012;40(1):57-65. 2. Leung AN, Bull TM, Jaeschke R, Lockwood CJ, Boiselle PM, Hurwitz LM,; ATS/STR Committee on Pulmonary Embolism in Pregnancy. American Thoracic Society documents: an official American Thoracic Society/Society of Thoracic Radiology Clinical Practice Guideline-- Evaluation of Suspected Pulmonary Embolism in Pregnancy. Radiology. 2012;262(2):635-46. 6. Wells PS, Anderson DR, Rodger M, Stiell I, Dreyer JF, Barnes D, 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 Inter Med. 2001;135(2):98-107. 3. Ciofetta G, Piepsz A, Roca I, Fisher S, Hahn K, Sixt R, et al. Guidelines for lung scintigraphy in children. Eur J Nucl Med Mol Imaging. 2007;34:1518-26. 7. Jögi J, Jonson B, Ekberg M, Bajc M. Ventilation-perfusion SPECT with 99mTc-DTPA versus Technegas: a head-to-head study in obstructive and nonobstructive disease. J Nucl Med. 2010;51(5):735-41. 4. Bajc M, Neilly JB, Miniati M, Schuemichen C, Meignan M, Jonson B, et al. EANM guidelines for ventilation/perfusion scintigraphy: Part 1.
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