The Society of Nuclear Medicine

1SNM Practice Guideline for Lung Scintigraphy DRAFT V4.0 1 2

1 Society of Nuclear Medicine (SNM) is an international scientific and professional organization founded in 1954 2to promote the science, technology and practical application of nuclear medicine. Its 16,000 members are physicians, 3technologists and scientists specializing in the research and practice of nuclear medicine. In addition to publishing 4journals, newsletters and books, the Society also sponsors international meetings and workshops designed to increase 5the competencies of nuclear medicine practitioners and to promote new advances in the science of nuclear medicine. 6 The SNM will periodically define new procedure guidelines for nuclear medicine practice to help advance the 7science of nuclear medicine and to improve the quality of service to patients throughout the United States. Existing 8procedure guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if 9indicated. 10 Each procedure guideline, representing a policy statement by the Society, has undergone a thorough consensus 11process in which it has been subjected to extensive review, requiring the approval of the Committee on SNM 12Guidelines, Health Policy and Practice Commission, and SNM Board of Directors. The SNM recognizes that the safe 13and effective use of diagnostic nuclear medicine imaging requires specific training, skills, and techniques, as 14described in each document. Reproduction or modification of the published procedure guideline by those entities not 15providing these services is not authorized. 16 17 Revised 2011 18 19THE SNM PRACTICE GUIDELINE FOR LUNG SCINTIGRAPHY DRAFT V4.0 20 21 22PREAMBLE 23 24These guidelines are an educational tool designed to assist practitioners in providing appropriate nuclear medicine 25care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be 26used, to establish a legal standard of care. For these reasons and those set forth below, the Society of Nuclear 27Medicine cautions against the use of these guidelines in litigation in which the clinical decisions of a practitioner 28are called into question. 29 30The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by the 31physician or medical physicist in light of all the circumstances presented. Thus, an approach that differs from the 32guidelines, standing alone, does not necessarily imply that the approach was below the standard of care. To the 33contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the 34guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition 35of the patient, limitations of available resources, or advances in knowledge or technology subsequent to 36publication of the guidelines. 37 38The practice of medicine involves not only the science, but also the art of dealing with the prevention, diagnosis, 39alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to 40always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. 41Therefore, it should be recognized that adherence to these guidelines will not assure an accurate diagnosis or a 42successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action 43based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical 44care. The sole purpose of these guidelines is to assist practitioners in achieving this objective. 45 46 47I. INTRODUCTION 48 49 This guideline describes the technique of performing and interpreting ventilation and perfusion 50 scintigraphy. 51 52II. GOALS 3SNM Practice Guideline for Lung Scintigraphy DRAFT V4.0 2 4

53 54 The purpose of this guideline is to assist nuclear medicine practitioners in recommending, performing, 55 interpreting, and reporting the results of ventilation and perfusion lung scintigraphy. 56 57III. DEFINITIONS 58 59 A. Lung Scintigraphy 60 61 A diagnostic imaging procedure that utilizes ventilation scintigraphy, perfusion scintigraphy or 62 both to evaluate cardiovascular and pulmonary disorders. 63 64 B. Aerosol Ventilation Scintigraphy 65 66 A diagnostic imaging test that records the bronchopulmonary distribution of an inhaled 67 radioactive aerosol within the lungs. 68 69 C. Gas Ventilation Scintigraphy 70 71 A diagnostic imaging test that records the pulmonary distribution of a radioactive gas during 72 breathing. 73 74 D. Pulmonary Perfusion Scintigraphy 75 76 A diagnostic imaging test that records the distribution of pulmonary arterial blood flow. 77 78 E. Radiographic Pulmonary Evaluation 79 80 Chest radiograph or CT used to evaluate pulmonary parenchyma. 81 82IV. COMMON CLINICAL INDICATIONS 83 84 Indications for Lung Scintigraphy include, but are not limited to: 85 86 A. The most common clinical indication for lung scintigraphy is to determine the likelihood of 87 pulmonary embolism. 88 89 B. Less common clinical indications are: 90 91 1. Document the degree of resolution of pulmonary embolism. 92 93 2. Quantify differential pulmonary function before pulmonary surgery for lung cancer (1-3). 94 95 3. Evaluate lung transplants (4-5). 96 97 4. Evaluate congenital heart or lung disease such as cardiac shunts, pulmonary arterial 98 stenoses, and arteriovenous fistulae and their treatment (6). 99 100 5. Confirm the presence of bronchopleural fistula (7-8). 101 102 6. Evaluate chronic pulmonary parenchymal disorders such as cystic fibrosis (9-10). 103 5SNM Practice Guideline for Lung Scintigraphy DRAFT V4.0 3 6

104 7. Evaluate the cause of pulmonary hypertension (11). 105 106V. QUALIFICATIONS AND RESPONSIBILITIES OF PERSONNEL 107 108 Refer to Section V of the SNM Procedure Guideline for General Imaging 109 110VI. PROCEDURE/SPECIFICATIONS OF THE EXAMINATION 111 112 A. Nuclear Medicine study request 113 114 1. In women of childbearing age, pregnancy and lactation status should be noted and the 115 procedure performed in a manner to minimize radiation exposure. 116 117 2. The referring physician’s estimate of the prior probability of pulmonary embolism may 118 be helpful. Use of validated tools such as the Wells (12) score is preferred. 119 120 3. Results of D-dimer test, if obtained. 121 122 4. History of prior deep venous thrombosis or pulmonary embolism should be elicited. 123 124 5. Review of prior lung scintigraphy. Defects from prior pulmonary emboli do not always 125 resolve completely. 126 127 6. Pertinent chest radiographic findings include, but are not limited to: a) consolidation; b) 128 atelectasis; c) effusions; d) masses; e) cardiomegaly; and f) decreased pulmonary 129 vasculature. The chest radiograph may be normal in patients with pulmonary embolism. 130 131 7. Treatment with anticoagulant or thrombolytic therapy should be noted. 132 133 8. Results of tests for deep venous thrombosis, e.g. compression ultrasonography, should be 134 noted. 135 136 B. Patient Preparation and Precautions 137 138 1. A standard chest radiograph in both posterior-anterior and lateral projections is preferred. 139 A CT scan can substitute for the chest radiograph. A portable anterior-posterior chest 140 radiograph is acceptable only if the patient cannot tolerate a routine chest radiographic 141 examination. In patients who have no changes in signs or symptoms, a chest radiograph 142 within a few days may be adequate. 143 144 2. A CT scan can substitute for the chest radiography. 7SNM Practice Guideline for Lung Scintigraphy DRAFT V4.0 4 8

145 146 C. Radiopharmaceuticals 147 148 Physical Characteristics of Radionuclides Radionuclide T1/2 Photopeak (keV) Decay 99mTc 6 hour 140 IT 133Xe 5.2 days 81 Beta 81mKr 13 seconds 190 IT 149 IT = Isomeric Transition 150 151 1. Aerosols 152 153 a. 99mTc diethylenetriamine-pentaacetic acid (DTPA) is the preferred most 154 commonly used radiopharmaceutical. 99mTc sulfur colloid is another option and 155 has a slower clearance from the lungs. 156 157 b. The usual dispensed activity of 99mTc DTPA or sulfur colloid is 900–1300 MBq 158 (25–35 mCi) in the nebulizer, from which the patient receives approximately 20– 159 40 MBq (0.5–1.0 mCi) to the lungs. 160 161 c. 99mTc labeled ultrafine carbon suspension has more uniform distribution in the 162 lungs than 99mTc DTPA aerosol, but is currently not available in the United 163 States. 164 165 d. Aerosol imaging is usually performed before perfusion imaging because it is 166 more difficult to deliver a larger dose of the 99mTc aerosol than it is to deliver a 167 larger dose of 99mTc macroaggregated albumin (MAA). Because both agents are 168 labeled with 99mTc, it is extremely important that the count rate of the second 169 study is at least three to four times the count rate of the first study. 170 171 2. Krypton-81m 172 173 a. 81mKr is obtained from an 81 Rb/81mKr generator, but is currently not available in 174 the United States. 175 . 176 177 b. 81mKr is administered by continuous inhalation of approximately 40–400 MBq 178 (1–10 mCi). 179 180 3. Xenon-133 181 182 a. The usual administered activity is 200–750 MBq (5–20 mCi). The usual dose for 183 children is 10–12 MBq/kg (0.3 mCi/kg) with a minimum of 100–120 MBq (3 184 mCi). 185 186 b. 133Xe should be used in room that is at negative pressure with respect to the 187 surroundings.The imaging room should provide appropriate exhaust for 188 radioactive gas. Regulations for safe handling of radioactive gas should be 189 followed. 190 191 4. Perfusion 9SNM Practice Guideline for Lung Scintigraphy DRAFT V4.0 5 10

192 193 a. Before intravenous administration of the pulmonary perfusion 194 radiopharmaceutical, the patient should be instructed to cough and to take several 195 deep breaths. The patient should be in the supine position during injection, or in 196 the case of a patient with orthopnea, as close to supine as possible. 197 198 b. The radiopharmaceutical used for perfusion imaging is 99mTc macroaggregated 199 albumin (MAA). 200 201 c. The biological half-life of the MAAmacroaggregated albumin in the lungs varies 202 (usually 1.5 to 3 hr). 203 204 d. The usual adult administered activity is 40–150 MBq (1–4 mCi). The usual 205 pediatric administered activity is 1.11 MBq/kg (0.03 mCi/kg) with a minimum of 206 14.8 MBq/kg (0.4 mCi) if no 99mTc ventilation study is performed or 2.59 207 MBq/kg (0.07 mCi/kg) if a 99mTc ventilation study is performed (13). 208 209 e. The number of particles should be in the range of 200,000–700,000. For children, 210 the number of particles should be is a function of age (14). 211 212 f. Freshly prepared 99mTc MAA with reduced numbers of particles should be 213 considered for patients with pulmonary hypertension or right-to-left shunting, 214 and in infants and children. In adults, the number may be reduced to 100,000– 215 200,000 particles without altering the quality of the images for detection of 216 perfusion defects. Inhomogeneous distribution of activity may result from a 217 reduction of the number of particles below 100,000 in adults. 218 219 g. Labeled MAA particles will settle in the vial with time. Vials 220 should be agitated prior to withdrawing a dose, and the syringe should be 221 inverted prior to injection. 222 223 D. Protocol/Image Acquisition 224 225 1. Sequence of Imaging 226 227 a. A chest radiograph should be obtained and reviewed before lung scintigraphy. 228 229 b. Ventilation scintigraphy using 133Xe is usually performed before perfusion 230 scintigraphy. Alternately, perfusion scintigraphy can be performed first and 231 ventilation scintigraphy omitted if not needed. 232 233 c. The disadvantages of performing perfusion imaging before ventilation imaging 234 with 133Xe: 235 236 i. The perfusion image contributes background activity to the ventilation 237 image. 238 239 ii. A decision to perform or not to perform the ventilation study must be 240 made in a timely manner. 241 11SNM Practice Guideline for Lung Scintigraphy DRAFT V4.0 6 12

242 d. The advantages of performing perfusion imaging before ventilation imaging with 243 133Xe: 244 245 i. If the perfusion study is normal or matches the chest radiographic 246 findings, the ventilation study can be omitted. 247 248 ii. For single-projection ventilation studies, the projection that best shows 249 the defect can be obtained. 250 251 e. Because of the higher energy of the gamma emissions and the short half-life of 252 81mKr, images obtained with this gas can be alternated with those obtained with 253 99mTc MAA. 254 255 f. When 99mTc labeled aerosol imaging is performed before 99mTc MAA perfusion 256 imaging, smaller amounts (20-40 MBq [0.5-1.0 mCi]) of 99mTc labeled aerosol 257 should be administered to the lungs. 258 259 2. Processing 260 261 None. 262 263 3. Aerosol Ventilation Imaging 264 265 a. The aerosol is administered through a mouthpiece with the nose occluded while 266 the patient is tidal breathing. 267 268 b. An advantage of aerosol imaging is that images can be obtained in multiple 269 projections or with single-photon emission computed tomograph (SPECT) to 270 match those obtained for perfusion imaging. 271 272 c. It is preferable to have the patient inhale the aerosol in the upright position, but 273 the supine position can be used if necessary. 274 275 d. Aerosol ventilation imaging can be performed at the bedside. 276 277 e. A disadvantage of aerosol imaging is that aerosol deposition is altered by 278 turbulent flow, and central deposition can result in a suboptimal study. 279 280 f. SPECT can be used to obtain a three-dimensional evaluation of ventilation, and 281 is recommended by some investigators. 282 283 4. Xenon-133 Ventilation Imaging 284 285 a. An advantage of 133 Xe ventilation is that single-breath, wash-in and/or 286 equilibrium and washout images can be obtained, thus providing a more 287 complete characterization of ventilation and a more sensitive test for obstructive 288 airway disease. Physiologic information about ventilation can best be obtained 289 from 133Xe imaging. 290 291 b. The imaging room should provide appropriate exhaust for radioactive gas. 292 Regulations for safe handling of radioactive gas should be followed. 13SNM Practice Guideline for Lung Scintigraphy DRAFT V4.0 7 14

293 294 c. The patient is positioned upright in front of the scintillation camera. If necessary, 295 the patient can be positioned supine. 296 297 d. The projection that best shows the defect(s) on perfusion scintigraphy is used for 298 the ventilation scintigraphy if performed after perfusion scintigraphy. Otherwise, 299 the posterior projection is generally used. When possible, posterior oblique 300 images should be obtained during the washout phase (and during wash-in phase 301 if continuous imaging is performed during this phase). 302 303 e. If ventilation scintigraphy is performed after perfusion scintigraphy, a 99mTc 304 background image should be obtained using the 133Xe window. 305 306 f. A facemask or mouthpiece (with nose clip) should be connected via a bacterial 307 filter to the xenon delivery system. 308 309 g. Single-breath, equilibrium and washout images are obtained. 310 311 h. Equilibrium is obtained by breathing in a closed xenon delivery system for 3–4 312 minutes as tolerated by the patient. 313 314 5. Krypton-81m Imaging 315 316 a. The advantage of 81mKr is that images can be obtained in all views without 317 interference from prior perfusion imaging. Alternating 99mTc MAA and 81mKr 318 imaging allows ventilation and perfusion images to be obtained without patient 319 repositioning between paired 99mTc MAA and 81mKr views. 320 321 b. The patient breathes continuously from the 81Rb/81mKr generator. Due to the short 322 half-life of 81mKr, the distribution of radioactivity approximates regional minute 323 ventilation rate. 324 325 c. A collimator with low septal penetration at 190 keV should be used. 326 327 d. SPECT can be used to obtain a three-dimensional evaluation of ventilation. 328 329 e. A disadvantage of 81mKr is that the short half-life of the parent radionuclide, 81Rb 330 (4.57 h), decreases availability and increases cost of the generator. 331 332 6. Perfusion Imaging 333 334 a. After having the patient cough and take several deep breaths, 99mTc MAA is 335 injected slowly during 3–5 respiratory cycles with the patient in the supine 336 position. 337 338 b. A well-flushed indwelling line can be used if venous access is difficult. Do not 339 administer in the distal port of a Swan-Ganz catheter or any indwelling line or 340 port that contains a filter, e.g. chemotherapy line. 341 15SNM Practice Guideline for Lung Scintigraphy DRAFT V4.0 8 16

342 c. Imaging is preferably performed in the upright position to increase chest cavity 343 size and to minimize diaphragmatic motion. If necessary, images can be obtained 344 in the supine or decubitus position. 345 346 d. Planar images should be obtained in multiple projections including anterior, 347 posterior, both posterior oblique, both anterior oblique and both lateral 348 projections. Either the anterior oblique or the lateral projections can be omitted. It 349 may be possible to obtain only limited views in some patients. 350 351 e. SPECT can be used to obtain a three-dimensional evaluation of the perfusion, 352 and is recommended by some investigators. 353 354 f. Imaging of high blood flow systemic organs can be used to detect right-to-left 355 shunting. 356 357 g. Images of the brain may be obtained to distinguish right-to-left shunting from 358 systemic distribution of radiopharmaceutical components too small to be trapped 359 by capillaries. 360 361 7. SPECT/Low-dose CT (15, 16) 362 363 a. Lung scintigraphy for pulmonary embolism may be performed using 364 SPECT/low-dose CT. The low-dose CT portion of the study provides 365 information for attenuation, and also provided improved anatomic information 366 compared to a chest X-ray. 367 368 b. Ventilation imaging is practical using an agent that has a stable distribution, 99mTc 369 carbon micro-particles, 81mKr, or 99mTc aerosols. 370 371 c. The CT portion of the study should be performed as described in the Procedure 372 Guideline for SPECT/CT Imaging. 373 374 E. Interpretation 375 376 1. Several diagnostic criteria (summarized in the Table 1 below) have been described as an 377 aid in interpretation. 378 379 a. Modified PIOPED criteria: The modified PIOPED criteria were derived from a 380 retrospective analysis of the PIOPED database (17, 18). The criteria were 381 prospectively tested and shown to be more accurate than the original PIOPED 382 criteria (19). 383 384 b. Modified PIOPED II criteria: In an attempt to reduce the number of non- 385 diagnostic studies, the PIOPED II criteria were modified using fewer categories. 386 The performance of the modified PIOPED II criteria was evaluated on the 387 PIOPED II database (20). 388 389 c. Criteria using chest radiograph and perfusion scan: The modified PIOPED II and 390 PISAPED criteria not using the information from ventilation scintigraphy have 391 been shown to perform equivalently to those including ventilation scintigraphy 392 with fewer non-diagnostic studies (21). 17SNM Practice Guideline for Lung Scintigraphy DRAFT V4.0 9 18

393 19SNM Practice Guideline for Lung Scintigraphy DRAFT V4.0 10 20

394 Table 1 395 Ventilation (V), Perfusion (Q), Radiographic (CXR) Interpretive Criteria for Pulmonary Embolism (PE) 396 PIOPED Modified PIOPED II Perfusion Only Modified Perfusion Only PISAPED PIOPED II High LR High LR PE Present PE Present >2 large mismatched (V:Q) ≥2 large mismatched (V:Q) ≥2 large mismatched ≥1 wedge-shaped Q defects segmental defects* segmental defects* (Q:CXR) segmental defects* Borderline High LR 2 large mismatched (V:Q) segmental defects* Intermediate LR Non-diagnostic Non-diagnostic Non-diagnostic 2 moderate or 1 large All other findings All other findings Cannot classify as PE-present mismatched (V:Q) defects* or PE-absent

Difficult to categorize as high or low Borderline Low LR 1 matched (V:Q) defect, CXR- Low LR Nonsegmental perfusion defects**

Q defect substantially < CXR defect

Matched (V:Q) defects, CXR-

Any number of small Q defects* Normal Very Low LR PE Absent PE Absent No Q defects***** Nonsegmental** Very low Probability Non-wedge-shaped Q defect

Q defect < CXR lesion Nonsegmental** Contour defect caused by Q defect < CXR lesion enlarged heart, mediastinum, 1-3 small segmental* defects or diaphragm 1-3 small segmental* defects Solitary matched ( V:Q:CXR) Near normal Q defect (≤ 1 segment) in mid Solitary matched (Q:CXR) or upper lung defect (≤ 1 segment) in mid Normal Q or upper lung Stripe sign*** Stripe sign*** Solitary large pleural effusion**** Solitary large pleural effusion**** ≥2 matched (V:Q) defects, regionally normal CXR Normal No Q defects***** 397 398LR = likelihood ratio 399* Or equivalent where a large segmental defect, >75% of a segment, equals 1 segmental equivalent; a moderate defect, 25-75% of a segment, equals 0.5 400segmental equivalents; a small defect, <25%, is not counted. 401** For example, prominent hilum, cardiomegaly, elevated diaphragm, linear atelectasis, or costophrenic angle effusion with no other perfusion defect in 402either lung and no other radiographic lesion. 403*** Peripheral perfusion in a defect (best seen on tangential view). 404**** Pleural effusion in at least 1/3 of the pleural cavity, with no other perfusion defect in either lung. 405***** Perfusion defects exactly match shape of CXR. 406 407 408 2. Gestalt interpretation: The experienced nuclear medicine physician may be able to 409 provide a more accurate interpretation of the ventilation-perfusion study than is provided 410 by the criteria alone; however, his/her opinion is usually informed by detailed knowledge 411 of the various lung image interpretive criteria given in E.1 (17). 21SNM Practice Guideline for Lung Scintigraphy DRAFT V4.0 11 22

412 413 3. Further Interpretive Considerations (22) 414 415 a. Ventilation-perfusion mismatch can result from any cause of pulmonary arterial 416 blood flow obstruction. Although there is a very long differential diagnosis for 417 ventilation-perfusion mismatch, there are few common causes: 1) acute 418 pulmonary embolism; 2) old pulmonary embolism; 3) obstruction of an artery by 419 tumor; and 4) radiation therapy. 420 421 b. On perfusion scintigraphy, extrapulmonary activity (which may be 422 seen at the edges of lung images in the thyroid or kidneys) may be either the 423 result of right-to-left shunting, free 99mTc pertechnetate, reduced 99mTc 424 compounds, or another recent nuclear medicine procedure. An image of the head 425 can be used to differentiate free 99mTc pertechnetate or reduced 99mTc compounds 426 from a right-to-left shunting. 427 428 c. The stripe sign (activity at the periphery of a perfusion defect) 429 lowers the likelihood that a perfusion defect is due to pulmonary embolism. 430 431 4. Interpretation of Right-to-Left Shunt Studies 432 433 a. Presence of a right-to-left shunt is identified by activity in systemic vascular 434 beds. 435 436 b. An image of the head provides the most accurate method to detect small shunts. 437 Activity due to shunting of 99mTc MAA particles will correspond to brain 438 perfusion while other activity will be seen in the scalp. 439 440 c. The fraction of right-to-left shunting can be approximated by comparing the 441 activity in the lungs to the activity in the rest of the body. 442 443 5. Interpretation of Preoperative Lung Scintigraphy 444 445 a. Each lung is generally divided into three equal rectangular regions-of-interest on 446 anterior and posterior views – top, middle, and bottom. 447 448 b. The activity in the 6 regions-of-interest is reported for perfusion or for both 449 ventilation and perfusion. 450 451 c. An anatomically based description of the perfusion should be provided. 452 453 d. Alternative methods of quantification with regions that correspond more closely 454 to pulmonary anatomy are preferred by some experts. 455 456 6. Interpretation of Post-transplant Lung Scintigraphy 457 458 a. In the immediate post-transplantation setting, perfusion imaging documents the 459 patency of the vascular anastomoses. 460 461 b. In single lung transplantation, the ratio of right-to-left lung perfusion and the 462 change in ratio correlates with rejection. 23SNM Practice Guideline for Lung Scintigraphy DRAFT V4.0 12 24

463 464 c. Analysis of regional changes in ventilation and perfusion may also be useful. 465 Development of matched ventilation perfusion abnormalities consistent with 466 obstructive lung disease often reflect rejection (bronchiolitis obliterans). 467 468 7. Sources of Error 469 470 a. Perfusion images can show “hot spots” in the lung if clotting of blood occurs in 471 the syringe during the injection, or if the injection is made through an indwelling 472 catheter that is not well flushed. 473 474 b. Ventilation scintigraphy is obtained at a different point in time than the perfusion 475 scintigraphy. In the intervening time, there can be changes in ventilation and 476 perfusion. Similarly, ventilation scintigraphy may be obtained with the patient in 477 an upright position and the radiopharmaceutical for perfusion scintigraphy 478 typically is injected with the patient in the supine position. These changes in 479 position may also affect the comparability of the two scintigrams. 480 481 c. Injection of 99mTc MAA through a central line can result in inadequate mixing of 482 activity in the pulmonary artery. This inadequate distribution of activity is 483 especially true if the activity is injected through a pulmonary artery line. 484 485 d. A decubitus or oblique patient position can markedly affect the distribution of 486 ventilation and perfusion. If the injection for perfusion scintigraphy or if 487 ventilation scintigraphy is performed in the decubitus or oblique position, 488 mismatched patterns can result. Accordingly, any nonstandard patient positioning 489 should be recorded and considered during subsequent interpretation. 490 491 e. Activity in the thyroid is often used as an indicator of free 99mTc pertechnetate in 492 the radiopharmaceutical preparation. However, the thyroid is also a high flow 493 organ and may be visualized in the case of a right-to-left shunt. 494 495 8. Issues Requiring Further Clarification 496 497 a. There is considerable literature on SPECT lung scintigraphy and there is 498 emerging literature on SPECT/low-dose CT lung scintigraphy (23). However, 499 there is currently no information about the comparison of these methods with 500 planar imaging in a multi-institutional setting (24). 501 502 b. The criteria for interpretation of SPECT and SPECT/low-dose CT need to be 503 established. 504 505 c. The utility of breathing maneuvers or gating in the context of SPECT and 506 SPECT/low-dose CT need to be established. 507 508 d. The radiation absorbed dose that provides adequate diagnostic information for 509 use in low-dose CT needs to be established. 510 511 e. The utility of adding ventilation imaging to anatomic and perfusion imaging 512 needs further study (21, 23). 513 25SNM Practice Guideline for Lung Scintigraphy DRAFT V4.0 13 26

514 F. Interventions 515 516 1. In patients with acute obstructive lung disease, the use of bronchodilator therapy before 517 lung scintigraphy may decrease ventilatory defects and improve the accuracy of the 518 study. Because perfusion defects often change as acute obstruction resolves, patients are 519 best imaged when bronchospasm has resolved. 520 521 2. In patients with congestive heart failure, improved specificity will be obtained if imaging 522 can be delayed until therapy for heart failure has been instituted. 523 524VII. DOCUMENTATION/REPORTING 525 526 A. Goals of a Nuclear Medicine Report 527 528 Refer to Section VII in the SNM Procedure Guideline for General Imaging 529 530 B. Direct Communication 531 532 Refer to Section VII of the SNM Procedure Guideline for General Imaging 533 534 C. Written Communication 535 536 Refer to Section VII of the SNM Procedure Guideline for General Imaging 537 D. Contents of the Nuclear Medicine Report 538 539 Refer to Section VII of the SNM Procedure Guideline for General Imaging 540 541 1. Study identification 542 543 2. Clinical Information 544 545 3. Procedure description 546 547 4. Description of findings 548 549 The report should include a description of the lung scintigraphy findings, diagnostic category 550 and an overall assessment of the likelihood of pulmonary embolism based on the 551 scintigraphic findings. Terms referring to test outcome, e.g. “likelihood ratio for pulmonary 552 embolism,” are preferred over terms referring to posterior probability, e.g. “probability of 553 pulmonary embolism.” 554 555 5. Impression 556 557 6. Comments 558 559 a. The report may include an assessment of the post-test probability of pulmonary 560 embolism based on the result of lung scintigraphy and an estimate of the prior 561 probability of disease (25, 26). 562 563 b. Many experts believe limiting reporting to three categories – pulmonary 564 embolism present, pulmonary embolism absent, and nondiagnostic (intermediate 27SNM Practice Guideline for Lung Scintigraphy DRAFT V4.0 14 28

565 likelihood ratio) – facilitates communication. Some believe more accurate 566 categorization provides more information to referring physicians (16). 567 568 c. The outcome of patients with low likelihood ratio lung scans is good (27, 28, 569 29). 570 571VIII. EQUIPMENT SPECIFICATION 572 573 A. Ventilation 574 1. A disposable nebulizer is needed for 99m Tc-labeled aerosol. 575 576 2. A xenon gas ventilation system should include capabilities for single breath, wash-in and/ 577 or equilibrium, and washout phases. A xenon trap should be available for exhausted gas. 578 579 3. An ultrafine dispersion of 99mTc labeled carbon produced using a commercial system is 580 not currently available in the United States. 581 582 2. A xenon gas ventilation system should include capabilities for single breath, wash-in and/ 583 or equilibrium, and washout phases. A xenon trap should be available for exhausted gas. 584 585 3. A disposable aerosolizer is needed for 99mTc DTPA aerosol. 586 587 B. Planar Imaging 588 589 Refer to Section IV.D1 of the SNM Procedure Guideline for General Imaging. 590 591 C. SPECT 592 593 Refer to Section IV.D2 of the SNM Procedure Guideline for General Imaging. 594 595 D. SPECT/CT 596 597 Refer to the SNM Procedure Guideline for SPECT/CT. 598 599IX. QUALITY CONTROL AND IMPROVEMENT, SAFETY, INFECTION CONTROL, AND 600 PATIENT EDUCATION CONCERNS 601 602 Refer also to Section IX of the SNM Procedure Guideline for General Imaging 603 604 Radiochemical purity and particle size determination of 99mTc MAA should be performed. Reconstituted 605 MAA should be stored in a refrigerator and be used before expiration. Dose reduction in pediatric 606 imaging is always desirable, as long as image quality is maintained (30). 29SNM Practice Guideline for Lung Scintigraphy DRAFT V4.0 15 30

607X. RADIATION SAFETY IN IMAGING 608 609 Radiation Dosimetry – Adults 610 Administered Organ Receiving the Activity Largest Radiation Dose Effective Dose5 Radiopharmaceutical MBq mGy/MBq mSv/MBq (mCi) (rad/mCi) (rem/mCi) 99mTc MAA1 40-150 0.067 0.011 Lung (1.1-4.1) (0.25) (0.041) 99mTc DTPA2 20-40 0.047 0.0061 Bladder (0.54-1.1) (0.17) (0.023) 133Xe3 200-750 0.0011 0.00071 Lung (5.4-20) (0.0041) (0.0026) 81mKr4 40-400 0.00021 0.000027 Lung (1.1-11) (0.00078) (0.0001) 6111 Data are from (31), page 224 6122 Data are from (31), page 218 6133 Data are from (31), page 345, rebreathing for 5 minutes 6144 Data are from (31), page 160 6155 Data are from (32) 616 Radiation Dosimetry in Children 617 (5 year old) 618 Administered Organ Receiving the Activity Largest Radiation Dose Effective Dose Radiopharmaceutical MBq/kg mGy/MBq mSv/MBq (mCi/kg) (rad/mCi) (rem/mCi) 99mTc MAA1 0.5-2 0.21 0.038 Lung (0.014-0.054) (0.78) (0.14) 99mTc DTPA2 0.4-0.6 0.12 0.020 Bladder (0.011-0.016) (0.44) (0.074) 133Xe3 10-12 0.0037 0.0027 Lung (0.27-0.32) (0.014) (0.010) 81mKr4 0.5-5 0.00068 0.000088 Lung (0.014-0.14) (0.0025) (0.00033) 6191 Data are from (31), page 224 6202 Data are from (31), page 218 6213 Data are from (31), page 345, rebreathing for 5 minutes 6224 Data are from (31), page 160 62399mTc MAA: Dose estimates to the fetus were provided by Russell et al. (33). No information about possible 31SNM Practice Guideline for Lung Scintigraphy DRAFT V4.0 16 32

624placental crossover of this compound was available for use in estimating fetal doses. 625 Fetal Dose Fetal Dose* Stage of Gestation mGy/MBq mGy (rad/mCi) (rad) Early 0.0028 0.11-0.42 (0.010) (0.011-0.042) 3 months 0.0040 0.16-0.60 (0.015) (0.016-0.060) 6 months 0.0050 0.20-0.75 (0.018) (0.020-0.075) 9 months 0.0040 0.16-0.60 (0.015) (0.016-0.060) 626* Maternal administered activity 40-150 MBq (1.1-1.4 mCi). 627 628 62999mTc DTPA aerosol: Dose estimates to the fetus were provided by Russell et al. (33). Information about possible 630placental crossover of this compound was available and was considered in estimates of fetal doses. 631 Fetal Dose Fetal Dose* Stage of Gestation mGy/MBq mGy (rad/mCi) (rad) Early 0.0058 0.12-0.23 (0.021) (0.012-0.023) 3 months 0.0043 0.086-0.17 (0.016) (0.0086-0.017) 6 months 0.0023 0.046-0.092 (0.0085) (0.0046-0.0092) 9 months 0.0030 0.060-0.12 (0.011) (0.0060-0.012) 632* Maternal administered activity 20-40 MBq (0.54-1.1 mCi). 633 634133Xe:Dose estimates to the fetus were provided by Russell et al. (33). No information about possible placental 635crossover of this compound was available for use in estimating fetal doses. 636 Fetal Dose Fetal Dose* Stage of Gestation mGy/MBq mGy (rad/mCi) (rad) Early 0.00025 0.050-0.19 (0.00092) (0.0050-0.019) 3 months 0.000029 0.0058-0.022 (0.00011) (0.00058-0.0022) 6 months 0.000021 0.0042-0.016 (0.000078) (0.00042-0.0016) 9 months 0.000016 0.0032-0.012 33SNM Practice Guideline for Lung Scintigraphy DRAFT V4.0 17 34

(0.000059) (0.00032-0.0012) 637* Maternal administered activity 200-750 MBq (5.4-20 mCi). 638 63981mKr: No dose estimates to the fetus were provided by Russell et al. (33), but were estimated using kinetic data in 640ICRP 53. No information about possible placental crossover of this compound was available for use in estimating 641fetal doses. 642 Fetal Dose Fetal Dose* Stage of Gestation mGy/MBq mGy (rad/mCi) (rad) Early 1.8x10-7 7.2x10-6 - 7.2x10-5 (6.7x10-7) (7.2x10-5 - 7.2x10-6) 3 months 1.8x10-7 7.2x10-6 - 7.2x10-5 (6.7x10-7) (7.2x10-5 - 7.2x10-6) 6 months 2.8x10-7 1.1x10-5 - 1.1x10-4 (1.0x10-6) (1.1x10-6 - 1.1x10-5) 9 months 3.4x10-7 1.4x10-5 - 1.4x10-4 (1.3x10-6) (1.4x10-6 - 1.4x10-5) 643* Maternal administered activity 40-400 MBq (1.1-11 mCi). 644 645The Breastfeeding Patient 646 647ICRP Publication 106, Appendix D suggests a 12 hour interruption of breast feeding for subjects receiving 150 648MBq (4.1 mCi) 99mTc MAA; it does not provide a recommendation about interruption of breastfeeding for 99mTc 649DTPA aerosols (but suggests that no interruption is needed for 99mTc DTPA intravenously administered or 99mTc 650technegas); the authors recommend that no interruption is needed for breastfeeding patients administered 133Xe or 65181mKr. 652 653XI. ACKNOWLEDGEMENTS 654 655 Task Force Members (V4.0) 656 J. Anthony Parker, MD, PhD (Beth Israel Deaconess Medical Center, Boston, MA); R. Edward Coleman, 657 MD (Duke University Medical Center, Durham, NC); Erin Grady, MD (Loyola University Medical 658 Center, Maywood, IL);Henry D. Royal, MD (Mallinckrodt Institute of Radiology, St. Louis, MO); Barry 659 A. Siegel, MD (Mallinckrodt Institute of Radiology, St. Louis, MO); Michael G. Stabin, PhD (Vanderbilt 660 University, Nashville, TN); H. Dirk Sostman, MD (New York Hospital-Cornell Medical Center, New 661 York, NY); Andrew J. W. Hilson, MB, FRCP (Royal Free Hospital, London, England). 662 663 Committee on SNM Guidelines: 664 Kevin J. Donohoe, MD (Chair) (Beth Israel Deaconess Medical Center, Boston, MA); Dominique 665 Delbeke, MD (Vanderbilt University Medical Center, Nashville, TN); Sue Abreu, MD (Sue Abreu 666 Consulting, Nichols Hills, OK);Twyla Bartel, DO (UAMS, Little Rock, AR); Paul E. Christian, CNMT, 667 BS, PET (Huntsman Cancer Institute, University of Utah, Salt Lake City, UT); S. James Cullom, PhD 668 (Cardiovascular Imaging Technology, Kansas City, MO); Vasken Dilsizian, MD (University of Maryland 669 Medical Center, Baltimore, MD); Kent Friedman, MD (NYU School of Medicine, New York, NY); Jay 670 A. Harolds, MD (OUHSC-Department of Radiological Science, Edmond, OK); Aaron Jessop, MD 671 (Vanderbilt University Medical Center, Nashville, TN); J. Anthony Parker, MD, PhD (Beth Israel 672 Deaconess Medical Center, Boston, MA); Rebecca A. Sajdak, CNMT, FSNMTS (Loyola University 35SNM Practice Guideline for Lung Scintigraphy DRAFT V4.0 18 36

673 Medical Center, Maywood, IL); Heiko Schoder, MD (Memorial Sloan-Kettering Cancer Center, New 674 York, NY); Barry L. Shulkin, MD, MBA (St. Jude Children’s Research Hospital, Memphis, TN); Michael 675 G. Stabin, PhD (Vanderbilt University, Nashville, TN); Mark Tulchinsky, MD (Milton S. Hershey Med 676 Center, Hershey, PA); Jerold W. Wallis, MD (Mallinckrodt Institute of Radiology, St. Louis, MO) 677 678XII. BIBLIOGRAPHY/REFERENCES 679 680 1. Beckles M, Spiro S, Colis G, Rudd R. The physiologic evaluation of patients with lung cancer 681 being considered for resectional surgery. Chest. 2003; 123:105S-114S. 682 683 2. Reilly J. Evidence-based preoperative evaluation of cadidates for thoracotomy. Chest. 1999; 684 116:474S-476S. 685 686 3. Win T, Tasker A, Groves A, White C, Ritchie A, Wells F, Laroche C. Ventilation-perfusion 687 scintigraphy to predict postoperative pulmonary function in lung cancer patients undergoing 688 pneumonectomy. AJR 2006; 187:1260-1265. 689 690 4. Humplik Bl, Sandrock D, Aurisch R, Richter WS, Ewert R, Munz DL. Scintigraphic results in 691 patients with lung transplants: a prospective comparative study. Nuklearmedizin. 2005 Apr; 692 44(2):62-68. 693 694 5. Starobin D, Shitrit D, Steinmetz A, Fink G, Hardoff R, Kramer MR. Quantative lung 695 perfusion following single lung transplantation. Thorac Cardiovasc Surg. 2007 Feb;55(1):48-52. 696 697 6. Gates GF, Orme HW, Dore EK. Measurement of cardiac shunting with technetium-labeled 698 albumin aggregates. J Nucl Med 1971;12:746-749. 699 700 7. Hollett P, Wright E, Wesolowski C, Harris R. Aerosol ventilation scintigraphy in the 701 evaluation of bronchopleural fistula: a case report and literature review. Can J Surg. 1991 Oct; 702 34(5) 465-467. 703 704 8. Jacobson AF, Herzog SA. Open bronchial stump post-pneumonectomy: findings on xenon-133 705 ventilation imaging. J Nucl Med 1993 Mar;34(3):462-464. 706 707 9. Itti E, Fauroux B, Pigeot J, Isabey D,Clement A, Evangelista E, Harf A, Meignan M. 708 Quantitative lung perfusion scan as a predictor of aeroxol distribution heterogeneity and disease 709 severity in children with cystic fibrosis. Nucl Med Commun 2004 Jun; 25(6):563-569. 710 711 10. Stanchina ML, Tantisira KG, Aquino SL, Wain JC, Ginns LC. Association of lung perfusion 712 disparity and mortality in patients with cystic fibrosis awaiting lung transplantation. J Heart Lung 713 Transplant. 2002 Feb;21(2): 217-225. 714 715 11. Tunariu N, Gibbs JR, Win Z. Ventilation-perfusion scintigraphy is more sensitive than 716 multidetector CTPA in detecting chronic thromboembolic pulmonary disease as a treatable cause 717 of pulmonary hypertension. J Nucl Med. 2007;48:680–68 718 719 12. Wells PS, Anderson DR, Rodger M, Ginsberg JS, Kearon C, Gent M, Turpie AGG, Bormanis 720 J, Weitz H, Chamberlain M, Bowie D, Barnes D, Hirsh J: Derivation of a simple clinical model 721 to categorize patients probability of pulmonary embolism: Increasing the models utility with the 722 SimpliRED D-dimer. 2000; Thromb Haemost 2000; 83:416-420. 723 37SNM Practice Guideline for Lung Scintigraphy DRAFT V4.0 19 38

724 13. Gelfand M, Parisi M, Treves ST. Pediatric Radiopharmaceutical Administered Doses: 2010 725 North American Consensus Guidelines. J Nucl Med 2010; 52:318-322. 726 727 14. Treves, ST. Pediatric Nuclear Medicine, 3rd ed. New York, NY: Springer-Verlag; 2006. 728 729 15. Semin Nucl Med 2010; 40(6): 393-479. 730 731 16. Parker JA: Improving lung scintigraphy. J Nucl Med 2009; 50:1919-1920.

733 17. PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism: 734 Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA 735 1990; 263:2753–2759. 736 737 18. Gottschalk A, Sostman HD, Coleman RE, et al. Ventilation-perfusion scintigraphy in the 738 PIOPED study. Part II. Evaluation of the scintigraphic criteria and interpretations. J Nucl Med 739 1993; 34:1119–1126. 740 741 19. Sostman HD, Coleman RE, DeLong DM, et al. Evaluation of revised criteria for ventilation- 742 perfusion scintigraphy in patients with suspected pulmonary embolism. Radiology 1994; 743 193:103– 107. 744 745 20. Sostman HD, Stein PD, Gottschalk A et al: Acute pulmonary embolism: Sensitivity and 746 specificity of ventilation-perfusion scintigrapahy in PIOPED II study. Radiology 2008; 246: 941- 747 946. 748 749 21. Sostman HD, Miniati M, Gottschalk A et al: Sensitivity and specificity of perfusion 750 scintigraphy combined with chest radiography for acute pulmonary embolism in PIOPED II. J 751 Nucl Med 2008; 49: 1741-1748. 752 753 22. Freeman LM, Krynyckyi, B, Zuckier LS: Enhanced lung scan diagnosis of pulmonary 754 embolism with the use of ancillary scintigraphic findings and clinical correlation. Semin Nucl 755 Med 2001; 31: 143-157. 756 757 23. Gutte H, Mortensen J, Jensen CV et al: Detection of pulmonary embolism with combined 758 ventilation-perfusion SPECT and low-dose CT: Head-to-head comparison with multidetector CT 759 angiography. J Nucl Med 2009; 50: 1987-1992. 760 761 24. Stein PD, Freeman LM, Sostman HD et al: SPECT in acute pulmonary embolism. J Nucl Med 762 2009; 50: 1999-2007. 763 764 25. Wells PS, Ginsberg JS, Anderson DR et al: Use of a clinical model for safe management of 765 patients with suspected pulmonary embolism. Ann Intern Med 1998; 129: 997-1005. 766 767 26. British Thoracic Society guidelines for the management of suspected acute pulmonary 768 embolism. Thorax 2003; 58:470-484. 769 770 27. Lee ME, Biello DR, Kumar B, et al. “Low-probability” ventilation perfusion scintigrams: 771 clinical outcomes in 99 patients. Radiology 1985; 156:497– 500. 772 773 28. Smith R, Maher JM, Miller RI, et al. Clinical outcomes of patients with suspected pulmonary 774 embolism and low-probability aerosol-perfusion scintigrams. Radiology 1987; 164:731–733. 39SNM Practice Guideline for Lung Scintigraphy DRAFT V4.0 20 40

775 776 29. Kahn D, Bushnell DL, Dean R, et al. Clinical outcome of patients with a “low probability” of 777 pulmonary embolism on ventilation-perfusion lung scan. Arch Intern Med 1989; 149:377–379. 778 779 30. Gelfand M, Parisi M, Treves ST. Pediatric Radiopharmaceutical Administered Doses: 2010 780 North American Consensus Guidelines. J Nucl Med 2010; 52:318-322. 781 782 31. International Commission on Radiological Protection, ICRP Publication 53, Radiation Dose to 783 Patients from Radiopharmaceuticals. Ann. ICRP 18 (1-4), 1988. 784 785 32. International Commission on Radiological Protection. ICRP Publication 80, Radiation Dose to 786 Patients from Radiopharmaceuticals: Addendum 2 to ICRP Publication 53, Ann. ICRP 28(3), 787 1998. 788 789 33. Russell JR, Stabin MG, Sparks RB, Watson EE: Radiation Absorbed Dose to the 790 Embryo/Fetus from Radiopharmaceuticals. Health Phys 1997; 73:756-769. 791 792XIII. BOARD OF DIRECTORS APPROVAL DATES: 793 794 Version 1.0 January 14, 1996 795 796 Version 2.0 February 7, 1999 797 798 Version 3.0 February 7, 2004 799 800