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SNMMI and EANM Guideline for Gastrointestinal Bleeding Draft V2.0 1

The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and 1 professional organization founded in 1954 to promote the science, technology, and practical application of 2 nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional nonprofit 3 medical association that facilitates communication worldwide between individuals pursuing clinical and 4 research excellence in nuclear medicine. The EANM was founded in 1985. SNMMI and EANM members are 5 physicians, technologists, and scientists specializing in the research and practice of nuclear medicine. 6

The SNMMI and EANM will periodically define new guidelines for nuclear medicine practice to help 7 advance the science of nuclear medicine and to improve the quality of service to patients throughout the 8 world. Existing practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth 9 anniversary or sooner, if indicated. 10

Each practice guideline, representing a policy statement by the SNMMI/EANM, has undergone a 11 thorough consensus process in which it has been subjected to extensive review. The SNMMI and EANM 12 recognize that the safe and effective use of diagnostic nuclear medicine imaging requires specific training, 13 skills, and techniques, as described in each document. Reproduction or modification of the published practice 14 guideline by those entities not providing these services is not authorized. 15

Revised 2014 16 17 THE SNMMI and EANM PRACTICE GUIDELINE FOR 18 GASTROINTESTINAL BLEEDING SCINTIGRAPHY 2.0 19 20 Hung Q. Dam1, David C. Brandon2, Vesper V. Grantham3 Andrew J. Hilson4, Douglas M. 21 Howarth5, Alan H. Maurer6, Michael G. Stabin7, Mark Tulchinsky8, Harvey A. Ziessman9, and 22 Lionel S. Zuckier10. 23 24 1Christiana Care Health System, Newark, Delaware; 2Emory University, Atlanta, Georgia; 25 3University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; 4Royal Free 26 Hospital, London, England; 5Newcastle Nuclear Medicine, Warners Bay, Australia; 6Temple 27 University, Philadelphia, Pennsylvania; 7Vanderbilt University, Nashville, Tennessee; 8Penn 28 State Milton S. Hershey Medical Center, Hershey, Pennsylvania; 9Johns Hopkins University, 29 Baltimore, Maryland; and 10The Ottawa Hospital, Ottawa, Canada. 30

31 PREAMBLE 32

These guidelines are an educational tool designed to assist practitioners in providing 33 appropriate care for patients. They are not inflexible rules or requirements of practice and are not 34 intended, nor should they be used, to establish a legal standard of care. For these reasons and 35 those set forth below, both the SNMMI and the EANM caution against the use of these 36 guidelines in litigation in which the clinical decisions of a practitioner are called into question. 37

The ultimate judgment regarding the propriety of any specific procedure or course of 38 action must be made by the physician or medical physicist in light of all the circumstances 39 presented. Thus, there is no implication that an approach differing from the guidelines, standing 40 alone, is below the standard of care. To the contrary, a conscientious practitioner may 41 responsibly adopt a course of action different from that set forth in the guidelines when, in the 42 reasonable judgment of the practitioner, such course of action is indicated by the condition of the 43 patient, limitations of available resources, or advances in knowledge or technology subsequent to 44 publication of the guidelines. 45 46


The practice of medicine includes both the art and the science of the prevention, 47 diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions 48 make it impossible to always reach the most appropriate diagnosis or to predict with certainty a 49 particular response to treatment. Therefore, it should be recognized that adherence to these 50 guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be 51 expected is that the practitioner will follow a reasonable course of action based on current 52 knowledge, available resources, and the needs of the patient to deliver effective and safe medical 53 care. The sole purpose of these guidelines is to assist practitioners in achieving this objective. 54 55 I. INTRODUCTION 56

Gastrointestinal bleeding scintigraphy (GIBS) is a noninvasive study that is 57 performed in patients with suspected gastrointestinal (GI) bleeding to determine if the 58 bleeding is active, to localize the bleeding site, and to approximate the bleeding volume 59 for prognostic purposes. These characteristics can be challenging to identify but are 60 important for initiation of prompt and effective therapy. The clinical signs and symptoms 61 and laboratory indicators of GI hemorrhage are often unreliable and misleading regarding 62 the presence of active bleeding. There is frequently a marked lag between the onset of 63 bleeding and the clinical findings. Melena is a sequela of earlier bleeding that could have 64 stopped and blood may remain in the bowel for hours before being evacuated. 65 Orthostatic hypotension and tachycardia may be detected more acutely, but are 66 insensitive and nonspecific. Decrease in hematocrit and elevation in serum blood urea 67 nitrogen (BUN) generally lag behind a bleeding episode, which may have ended hours 68 earlier. 69

GIBS enables continuous monitoring of the entire GI tract for up to approximately 70 24 hours (1). The ability to perform continuous imaging increases the likelihood of 71 detection of intermittent bleeding over other techniques that are limited to only a single 72 time point or periodic sampling (2-6). Furthermore, GIBS is a procedure that does not 73 require any patient preparation, can be performed with standard nuclear medicine 74 instrumentation, and is well tolerated even in patients who are acutely ill. 75

GI bleeding may be classified as upper GI bleeding (above the ampulla of Vater 76 and within reach of esophagogastroduodenoscopy (EGD)), mid GI bleeding (small bowel 77 from the ampulla of Vater to the terminal ileum and can be evaluated by capsule 78 endoscopy or double-balloon enteroscopy), or lower GI bleeding located in the colon 79 which can be evaluated by colonoscopy (7). Common causes of upper GI bleeding 80 include esophageal varices, gastric and duodenal ulcers, gastritis, esophagitis, Mallory-81 Weiss tears, and neoplasms. The most common causes of mid GI bleeding are 82 angiodysplasia, neoplasms, Crohn’s disease, diverticula, and Meckel’s diverticulum. 83 Common causes of lower GI hemorrhage include angiodysplasia, diverticulosis, benign 84 and malignant bowel neoplasms, adenomatous polyps, inflammatory bowel disease, and 85 infectious bowel disease. 86

While this guideline is focused on the use of 99mTechnetium-labeled autologous 87 red blood cells (99mTc-RBCs) for detection of sites of GI bleeding, the methods described 88 in this guideline may be applicable to localizing occult bleeding elsewhere in the body. 89 90

II. GOALS 91


The purpose of this guideline is to assist nuclear medicine practitioners in 92 recommending, performing, interpreting, and reporting the results of GIBS in adults and 93 children. The goals of GIBS are to determine whether the patient is actively bleeding, to 94 localize the bleeding bowel segment, and to estimate the rate of blood loss, which allows 95 for treatment planning and risk stratification. 96

97 III. DEFINITIONS 98

GIBS is a diagnostic radionuclide imaging study performed with 99mTc-RBCs that 99 detects active bleeding into the GI lumen. GI bleeding can be classified as: 1) occult GI 100 bleeding that is detected only on guaiac fecal occult blood testing and 2) overt GI 101 bleeding with clinical signs and symptoms of GI bleeding such as melena or 102 hematochezia. Obscure GI bleeding is defined as persistent or recurrent GI bleeding 103 from an unknown source despite an exhaustive work-up including EGD, colonoscopy, 104 and/or other initial studies and can be either overt or occult in nature (8). 105

106 IV. COMMON CLINICAL INDICATIONS 107

Common indications for gastrointestinal bleeding scintigraphy include but are not 108 limited to: 109 110 A. Identification of an active GI bleeding site in patients with overt GI bleeding. GIBS 111

should not be performed in patients with chronic occult GI bleeding because the 112 guaiac fecal occult blood test may detect bleeding at rates well below those necessary 113 to be identified on GIBS. 114

B. GIBS is indicated primarily for overt mid or lower GI bleeding, specifically for cases 115 where an upper GI bleed has been excluded by nasogastric lavage (9). In this 116 scenario, GIBS can be used as an early diagnostic study for GI bleeding especially for 117 hospitalized patients or patients in the emergency department (9-11). GIBS can be 118 beneficial when other studies require lengthy patient preparation or are 119 contraindicated and particularly after hours when other studies may not be readily 120 available. Although GIBS can also identify overt upper GI bleeding, nasogastric 121 lavage is usually the first procedure performed to confirm upper GI bleeding followed 122 by EGD to identify and treat suspected overt upper GI bleeding. 123

C. Help identify the source of obscure overt GI bleeding. Two guidelines have removed 124 GIBS from the diagnostic algorithm for obscure overt GI bleeding (12-13). However, 125 most studies have shown that GIBS is useful in assisting to localize the obscure overt 126 bleeding site in these patients (14-21). 127

D. Risk-stratification of patients with GI bleeding. (22-28) 128 E. Directing timely diagnostic angiography and assisting in plans for surgical or other 129

interventional procedures. (6,29-34) 130 131 V. QUALIFICATIONS AND RESPONSIBILITIES OF PERSONNEL (in the United 132

States) 133 Refer to Section V of the SNMMI Procedure Guideline for General Imaging 6.0. 134


135 VI. PROCEDURE/SPECIFICATIONS OF THE EXAMINATION 136

A. Request 137 At the time of the request, it is important for the referring clinician to have a 138

management plan in place prior to GIBS. By coordinating clinical services (such as 139 interventional radiology, gastroenterology, and/or surgery) early, the patient can be 140 directed promptly to the next diagnostic and/or therapeutic procedure if GIBS is 141 positive (35). Any unnecessary delay increases the likelihood of negative 142 angiography as bleeding often stops spontaneously (33). 143

All pertinent clinical information should be reviewed before the study is started. 144 Information specifically related to GIBS may include: 145 1. Clinical signs of GI bleeding: 146

a. Frequency, volume, and character (hematochezia, melena, or 147 hematemesis) of bleeding 148

b. Current and recent hemoglobin, hematocrit, and BUN 149 c. Number of recent transfusions 150 d. Current blood pressure and heart rate 151 e. Presence of orthostatic vital signs 152

2. History of prior abdominal or pelvic surgeries 153 3. Diagnostic studies: 154

a. Nasogastric tube aspiration 155 b. EGD 156 c. Capsule endoscopy 157 d. Double-balloon enteroscopy 158 e. Sigmoidoscopy or colonoscopy 159 f. Prior GIBS 160 g. Angiography 161 h. CT enterography/angiography 162

4. Therapeutic interventions: 163 a. Endoscopic epinephrine injection, coagulation (by cautery, heater probe, 164

laser, or argon plasma coagulator) or mechanical therapy (clips, bands, 165 or detachable loops) 166

b. Angiographic embolization 167 c. Selective arterial infusion of vasoconstrictors such as vasopressin 168

5. Current medications 169 6. Factors that may decrease RBC radiolabeling efficiency (3,36-37) 170

a. Drug interactions: 171 i. Iodinated contrast 172

ii. Chemotherapy 173 iii. Digoxin 174 iv. Calcium channel blockers 175 v. Cyclosporin 176

vi. Metronidazole 177 vii. Ranitidine 178

viii. Propanolol 179 ix. Quinidine 180


x. Dipyridamole 181 xi. Heparin 182

b. Low hematocrit 183 c. Sickle-cell disease or thalassemia 184 d. Circulating antibodies from prior transfusion or transplantation 185

7. Oral contrast agents such as barium used for other GI imaging studies can cause 186 photopenic artifacts (38). However the presence of these agents is not an absolute 187 contraindication for GIBS (39). 188

189 B. Patient preparation and precautions 190

1. Patients with suspected GI bleeding who are considered hemodynamically 191 unstable should be monitored by a physician or nurse while in the nuclear 192 medicine department. 193

2. Reinjection of radiolabeled blood poses the risk of incorrect administration to the 194 wrong patient. Written policies must be in place with special safeguards 195 regarding the handling and administration of blood to eliminate any possibility of 196 administration to the wrong patient particularly when two or more red cell 197 labeling studies are performed simultaneously. Universal precautions must be 198 followed to avoid staff exposure to blood products. Refer to Section III.G of the 199 SNMMI Procedure Guideline for Use of Radiopharmaceuticals 4.0. 200

3. Fasting is not required for GIBS. However, fasting may be required for 201 subsequent procedures such as angiography or surgery. 202

4. Patients should be instructed to void immediately prior to imaging so they are 203 comfortable during a potentially long scan and to facilitate scan interpretation. 204 205

C. Radiopharmaceuticals 206 Historically, two radiopharmaceuticals have been used for GIBS: 99mTc-RBCs 207

and 99mTc-sulfur colloid. 99mTc-RBCs are the radiopharmaceutical of choice for 208 performing GIBS due to an intravascular half-life that allows continuous imaging of 209 the GI tract over many hours (40-43). In contrast, 99mTc-sulfur colloid is rarely used 210 because of its short residence time in the vascular compartment. 99mTc-sulfur colloid 211 is rapidly cleared from the blood by the reticuloendothelial system (liver, spleen, and 212 bone marrow) restricting scan times to only 20-30 minutes (41,44). In addition, 213 significant activity in the liver and spleen may mask the identification of a bleeding 214 site adjacent to these organs. The superior clinical utility of 99mTc-RBCs has been 215 demonstrated in comparison studies (40-42). 216

99mTc-RBCs can detect GI bleeding at a rate as low as 0.04 mL/min in 217 experimental animal models and 0.1 mL/min in clinical studies (28,45). High 218 efficiency of RBC labeling with minimal unbound 99mTc is critical to producing 219 optimal, artifact-free images. Three techniques are available to label RBCs: in vitro, 220 modified in vivo and in vivo methods. The in vitro method using a commercially 221 available kit yields the highest labeling efficiency (≥95%) and is the method of choice 222 (46-47). A further advantage of the in vitro method is that a sample can be evaluated 223 for radiolabeling efficiency with a centrifuge method as described in the 224 manufacturer’s package insert. Additionally, if radiolabeling is substandard due a 225 drug interaction, low hematocrit, or other factor (see Section VI.A.6 above), or to a 226


procedural deviation, a salvage technique may be attempted (48). This procedure 227 involves transferring the in vitro 99mTc-RBCs into a sterile 15 mL polypropylene 228 centrifuge tube and centrifuging at 400 g for 5 minutes. The supernatant is then 229 removed with a sterile pipette and the 99mTc-RBCs are resuspended in 2 mL of 0.9% 230 sodium chloride. If the radiochemical purity of the 99mTc-RBCs is subsequently more 231 than 95% and adequate radioactivity remains, the salvage is deemed successful. The 232 modified in vivo label (90% labeling efficiency) can serve as an alternative when the 233 in vitro method is not available (49-50). The in vivo method is not recommended due 234 to suboptimal labeling and a higher likelihood of free 99mTc-pertechnetate. However, 235 the in vivo method may be needed for patients who, due to religious convictions or 236 other reasons, will not accept injection of blood. 237

The recommended administered activity of 99mTc-RBCs is 555-1110 MBq (15-30 238 mCi) in adults. In children under 18 years old, the recommended administered 239 activity is based on the EANM Pediatric Dosage Card which uses a baseline activity 240 of 56 MBq (1.51 mCi) multiplied by a weight-based multiple (51-52). The resulting 241 minimum administered activity is 80 MBq (2.16 mCi) for a 3 kg patient and the 242 maximum administered activity is 784 MBq (21.19 mCi) for a 68 kg patient. 243

244 D. Protocol/Image acquisition 245

1. Image acquisition 246 In the supine position, anterior images of the abdomen and pelvis are 247

acquired using a large field-of-view gamma camera. A low-energy high-248 resolution collimator is preferred although a low-energy general-purpose 249 collimator can be used. If the study must be performed at the bedside using a 250 small field-of-view portable camera, a diverging collimator (if available) may be 251 used to visualize the entire abdomen and pelvis, particularly in large patients. A 252 minimum image matrix of 128 x 128 is recommended. Any items on the patient 253 that may produce imaging artifacts should be removed or moved out of the field-254 of-view. Care should be taken to keep patients’ upper extremities from overlying 255 the abdomen and pelvis during imaging as they can obscure findings and their 256 movement can cause artifacts. 257

Following the injection of 99mTc-RBCs, rapid image acquisition at a rate 258 of 1 frame per 1-3 seconds for 60 seconds (nuclear angiography) can be 259 performed to visualize the distribution of vascular structures and may help 260 differentiate between blood pool activity and bleeding on later images. However, 261 these angiographic images seldom add to the overall study result and are 262 considered optional. 263

Immediately following the angiographic study, dynamic imaging should 264 be performed. Serial intermittent static images are not recommended. The 265 maximum recommended frame rate should not exceed 1 frame per 60 seconds. 266 As the frame rate becomes longer, the temporal resolution of the scan decreases, 267 possibly leading to inaccurate localization of the bleeding source. 268

Since intraluminal blood promotes rapid bowel peristalsis and movement 269 of blood antegrade and/or retrograde away from the bleeding site, faster frame 270 rates such as 1 frame per 10-20 seconds allow for higher temporal resolution to 271 better localize the GI bleeding site (53). On the other hand, a small volume of 272


intraluminal blood and/or slow GI bleeding may be more difficult to detect when 273 utilizing fast frame rates due to lower count densities (53). This shortcoming can 274 be compensated by reformatting the acquired study into longer frames (53-54). 275 Therefore, reformatting is recommended when using fast frame rates. However, 276 the optimal dynamic frame rate for GIBS has not been established since there are 277 no published clinical studies that have compared these various acquisition 278 techniques. 279

Acquiring the dynamic images in 10-15 minute sequences may facilitate 280 review of these images by the physician as one series can be reviewed while 281 subsequent sequences are still being acquired. 282

Since GI bleeding occurs intermittently, the patient should be imaged 283 continuously for as long as practical to identify the bleeding source (10,34,55-57). 284 Initial imaging for a minimum of 60 minutes is recommended if no GI bleeding is 285 detected (14,19,42,54,58). 286

Urine activity in a full bladder may obscure sigmoid or rectal bleeding on 287 a standard anterior view. Lateral, posterior, and/or subpubic views may help in 288 identifying activity in the rectum that would otherwise not be detected due to 289 bladder activity or soft-tissue attenuation. The entire abdomen and pelvis must be 290 examined before concluding that no GI bleeding is detected. When a dual-headed 291 camera is used, simultaneous imaging in the anterior and posterior views may 292 improve the sensitivity for detecting rectal bleeding. Furthermore, lateral views 293 are helpful in differentiating anterior vascular penile activity (which can move or 294 change in intensity during imaging) from bleeding in the more posteriorly located 295 rectosigmoid colon (35). 296

If the patient has a bowel movement during the scan, the stool should be 297 imaged to assess for radioactivity. The presence of radioactivity in the stool 298 would only confirm active GI bleeding and does not necessarily localize the 299 origin of the bleeding. If gastric activity is visualized, an anterior image of the 300 head and neck should be obtained to evaluate for possible thyroid and salivary 301 gland activity. Activity at these sites suggests the presence of free 99mTc-302 pertechnetate as the cause of the gastric activity rather than gastric bleeding. 303

If no bleeding site is identified on the initial images, delayed images can 304 be acquired by re-scanning the patient for up to 24 hours, especially if there is 305 clinical evidence of recurrent GI bleeding (see section F.2 below). All delayed 306 images should be acquired using the same dynamic method as the initial images. 307

308 2. Processing 309

If motion correction software is available, it can minimize the effects of 310 patient movement. 311

Computer subtraction of background activity of early images from later 312 frames in the imaging sequence has the following limitations: 313

1) The patient must remain still during the examination or motion 314 correction software must be applied and 315

2) The biodistribution of the 99mTc-RBCs should be similar between the 316 early frames and any image to be subtracted (53,59-63). Failure to 317 control these factors can cause false positive findings. 318


319 3. Interventions 320

Pharmacologic intervention is controversial and is not widely used. The 321 use of anticoagulants and/or thrombolytics, such as heparin and urokinase, has 322 been suggested as an adjunct to provoke bleeding (64-67). However, these 323 interventions have a significant risk of severe bleeding and should only be 324 considered for select patients with recurrent bleeding from an unknown site 325 despite a comprehensive work-up and should be performed under direct physician 326 supervision. Glucagon has also been suggested as an adjunct to GIBS because it 327 decreases intestinal peristalsis and increases vasodilatation. Small studies have 328 shown mixed results on its use (68-69). 329

330 E. Interpretation 331

Accurate interpretation of GIBS requires knowledge of normal and abnormal 332 anatomic variations in the abdomen and pelvis. Comparison with anatomic imaging 333 studies (CT, MRI, or radiographs) of the abdomen and pelvis is useful in establishing 334 GI tract and vascular anatomy. Review of the dynamic images in cinematic display is 335 essential to detect subtle GI bleeding and avoid inaccurate localization of the bleeding 336 site (1-2,54,70-71). Proper adjustment of grayscale levels on the interpreting 337 physician’s computer display also facilitates the detection of subtle abnormalities. 338

99mTc-RBCs are rapidly distributed within the vascular space including the 339 heart, liver, spleen, and great vessels. Some excreted radioactivity may be seen in the 340 urinary tract due to small amounts of free 99mTc-pertechnetate and other 99mTc 341 moieties even when in vitro labeling is used (72). The initial angiographic phase 342 images rarely reveal the site of rapid GI bleeding that may be difficult to localize on 343 the subsequent dynamic images or a vascular blush in neoplasms, arteriovenous 344 malformations, or angiodysplasia (54,73-74). 345

The key diagnostic criteria for scintigraphic GI bleeding are: 1) appearance 346 of activity outside the expected anatomical blood pool structures, 2) changing 347 intensity of the activity on consecutive images, and 3) movement of the activity in a 348 pattern consistent with bowel. All three of the above criteria must be satisfied to 349 diagnose a site of active GI bleeding. 350

Small bowel bleeding usually can be distinguished from large bowel bleeding 351 by its rapid curvilinear movement and usual central location in the abdomen or pelvis. 352 In comparison, large bowel bleeding has a more linear pattern and typically occurs in 353 the periphery of the abdomen or pelvis. Large bowel bleeding can also be visualized 354 as an S-shaped pattern in the central pelvis conforming to the distribution of the 355 rectosigmoid colon. The origin of the site of GI bleed should be reported as the 356 location of the initial site of detected activity rather than the most intense, largest, or 357 most proximal site of activity. 358

GIBS may be used to estimate the severity of the bleeding. Factors 359 associated with a low bleeding rate include: visualization of blood after 1 h, activity 360 less intense than that in the liver, and shorter bleeding durations (28). Higher 361 bleeding rates are associated with early appearance of blood in the bowel, intense 362 activity equal to or greater than that in the liver and longer duration of bleeding (28). 363

364


F. Sources of error 365 1. Image acquisition should continue for sufficient time after abnormal focal red cell 366

activity is initially detected to confidently identify the bleeding site. Accurate 367 localization of the bleeding site is dependent upon identification of the initial 368 location of extravasated blood and movement of blood from that site within the 369 bowel lumen. Increased imaging time may be particularly needed to differentiate 370 a small bowel bleed from a large bowel bleed. Single photon emission computed 371 tomography/computed tomography (SPECT/CT) may be also helpful in this 372 context (75). 373 374

2. Delayed imaging after a period of non-imaging can be problematic since 375 bowel activity seen immediately on the first frame of delayed images merely 376 indicates that bleeding originating elsewhere in the GI tract has occurred during 377 the interim and should not be misinterpreted as the bleeding site. Therefore, the 378 location of delayed bowel activity should only be reported as the bleeding site 379 when an actual episode of RBC extravasation on dynamic imaging is observed. 380 Digital subtraction may be helpful for identification of the actual site of active 381 bleeding when delayed images have been obtained (see Section D2 above). 382 The benefits of delayed imaging, including its effect on patient management 383 such as transfusion requirements, referrals to angiography and/or surgery, and 384 clinical outcomes, are controversial (76-77). Many investigators have shown that 385 delayed images are not as accurate in localizing the site of GI bleeding compared 386 to early imaging (30,34,58,76,78-79). Some authors advocate imaging patients 387 for as long as possible during the initial phase rather than performing routine 388 delayed imaging at arbitrary time intervals hours after injection (10,56). Other 389 investigators have demonstrated usefulness of delayed imaging in detecting a site 390 of intermittent GI bleeding not seen on the initial phase (1,40,55,57,62,80-82). 391 Therefore, delayed imaging is considered optional. 392 393

3. Interpretative pitfalls include: 394 a. Free 99mTc-pertechnetate: 395

i. Free 99mTc-pertechnetate can be visualized in the upper GI tract 396 secondary to swallowed salivary gland activity and/or excreted 397 gastric mucosal activity. Since free 99mTc-pertechnetate can move 398 from the stomach into the small bowel over time, it can be 399 mistaken for upper GI bleeding. 400

ii. Urinary tract activity may be seen in the abdomen or pelvis. 401 iii. Images of the neck to detect thyroid and salivary gland activity can 402

confirm the presence of free 99mTc-pertechnetate as a source of 403 artifact. 404

b. The following causes of increased RBC activity can confound 405 interpretation: 406

i. Reproductive system: 407 1. Penile blood pool can be mistaken for rectal bleeding (83). 408

Obtaining lateral images or changing position of the penis 409 can distinguish penile activity from rectal bleeding (35). 410


2. Variable uterine activity during the ovulatory cycle causes 411 fixed increased perfusion due to endometrial proliferation 412 (84). 413

3. Uterine leiomyoma may show transient, fixed activity due 414 to hypervascularity (85-86). 415

ii. Renal activity is usually fixed but can confuse interpretation when 416 the activity arises from an unexpected location such as: 417

1. Pelvic or ectopic kidney (87-88) 418 2. Horseshoe kidney (89) 419 3. Renal transplant 420

iii. Movement or pooling of urine activity can mimic GI bleeding 421 located in the following areas: 422

1. Ureter 423 2. Bladder or bladder diverticulum (3) 424 3. Urinary diversion surgery 425

iv. Vascular: 426 1. Abdominal aortic or iliac aneurysms present as static 427

activity. However, rupture can mimic GI bleeding (90-93). 428 2. Aortoduodenal fistula rupture (94). 429 3. Hemangiomas in the liver or small bowel (95-96). 430 4. Abdominal varices usually present as fixed activity. 431

However, they can rupture and cause bleeding (97-101). 432 5. Ovarian vein may appear as static, linear activity (102). 433

v. Splenic variants and pathology can cause fixed activity in the form 434 of accessory spleens and splenosis. They can mimic GI bleeding if 435 they rupture (103-105). 436

vi. Activity in the gallbladder in patients with renal failure or prior 437 transfusions from hepatobiliary excretion of radiolabeled heme. 438 Less commonly, gallbladder activity can be seen with hemobilia 439 (106-111). 440

vii. Bleeding from a pancreatic pseudocyst through the papilla of Vater 441 and into the duodenum (112). 442

viii. A catheter site can cause static activity in the abdominal wall 443 (113). 444

ix. Blush of activity in bowel due to hyperemia following surgical 445 resection or in Crohn’s disease (91). 446

x. Non-enteric bleeding activity can move and accumulate and 447 confuse interpretation including: 448

1. Intraperitoneal hemorrhage (114-115) 449 2. Mesenteric bleeding (116) 450 3. Soft tissue hematoma/hemorrhage (117-122) 451

xi. Both benign and malignant neoplasms and metastatic disease can 452 cause hyperemia and bleeding when ulcerated or necrotic (123-453 132). 454

xii. Retroperitoneal bleeding can show focal uptake that grows in 455 intensity, but is not expected to move in a luminal pattern (133). 456


457 G. Issues requiring further clarification 458

SPECT: Using planar technique, GIBS may only be able to approximate the site 459 of bleeding. The inherent 3D nature of SPECT with multi-plane reconstruction may yield 460 more accurate localization of a GI bleeding site. Comparison of SPECT results to 461 anatomic cross sectional imaging such as CT and MRI can also help to identify the 462 source of bleeding. 463

SPECT/CT: Software fused SPECT and CT images can be beneficial but are 464 limited due to potential interval change in bowel location between the two modalities 465 (134). The use of dedicated SPECT/CT hybrid cameras can help overcome these 466 shortcomings. Several early studies have suggested that SPECT/CT scanning is able to 467 better pinpoint the site of bleeding not well localized or equivocal on planar images or to 468 differentiate physiologic uptake from pathologic activity (135-137). In one study where 469 abnormal activity on standard planar scans were evaluated by SPECT/CT, 37% of these 470 patients required SPECT/CT to either precisely localize the site of GI bleeding or to 471 exclude GI bleeding (136). While these authors used a 30 minute acquisition for the 472 SPECT images, a shorter acquisition (approximately 15 minutes) may be adequate. 473

SPECT/CT can be particularly helpful in slow GI bleeding when one may have to 474 wait a long time to see the bowel activity conform into a more specific pattern (75). 475 SPECT/CT can also estimate the length of the GI tract leading to the bleeding site and 476 therefore help decide which endoscopic approach to utilize for further evaluation (75). 477 Furthermore, SPECT/CT helps clarify and avoid the pitfalls that can mimic GI bleeding 478 (35). Larger studies are needed to validate these results. No data exists on the use of 479 SPECT/CT when planar GIBS shows no evidence of GI bleeding. 480

481 VII. DOCUMENTATION/REPORTING 482

A. Goals of the report 483 Refer to Section VII.A of the SNMMI Procedure Guideline for General Imaging 6.0. 484

485 B. Direct communication 486

Refer to Section VII.B of the SNMMI Procedure Guideline for General Imaging 6.0. 487 488 C. Written Communication 489

Refer to Section VII.C of the SNMMI Procedure Guideline for General Imaging 6.0. 490 491

D. Contents of the report 492 1. Study identification 493 2. Patient demographics 494 3. Clinical information (indication for the study) 495 4. Comparison/correlative imaging data 496 5. Procedure description 497

a. Radiopharmaceutical, dose, and route of administration 498 b. Radiolabeling method for RBCs (in vitro, in vivo, or modified in vivo) 499 c. Duration of the acquisition, frame rate, projections acquired, and whether 500

delayed or special images were obtained 501 6. Study quality and limitations, if any 502


7. Description of findings 503 a. Describe the presence of any baseline vascular, GI tract or solid organ 504

variants 505 b. Characteristics of any abnormal activity: 506

i. Description of the time of onset in relation to injection 507 ii. Shape 508

iii. Intensity: activity in relationship to the background liver activity 509 iv. Extent: 510

1. Subjective volume: small, medium, or large amount of 511 bleeding 512

2. Focal or diffuse 513 v. Presence or absence of movement: 514

1. Stationary activity 515 2. Movement of activity in the GI tract: 516

a. Curvilinear (small bowel type) progression of 517 activity versus more linear (large bowel type) 518 movement 519

b. Rapid versus slow movement 520 c. Antegrade and/or retrograde movement 521

c. Location 522 i. Quadrant of the abdomen and pelvis 523

ii. Gastric 524 iii. Small bowel: duodenum, jejunum, or ileum. If SPECT/CT is used, 525

an attempt should be made to approximate the distance from the 526 ampulla of Vater to the bleeding site to help determine which 527 endoscopic technique can be utilized should gastroenterology is 528 consulted. The ampulla of Vater is located in the medial aspect of 529 the 2nd (descending) portion of the duodenum at the confluence of 530 the common bile duct and pancreatic duct. 531

iv. Large bowel: Cecum, ascending colon, hepatic flexure, transverse 532 colon, splenic flexure, descending colon, sigmoid colon, or rectum. 533

v. If the bleeding site cannot be definitively localized, then giving an 534 approximate site based on the imaging characteristics is 535 appropriate. 536

8. Impression 537 a. State whether the study was positive or negative for active GI bleeding. 538 b. For a positive scan, describe the originating site of GI bleeding whenever 539

possible. 540 541 VIII. EQUIPMENT SPECIFICATION 542

A large field-of-view gamma camera equipped with a low-energy high-resolution 543 collimator is preferred although a low-energy general-purpose collimator may also be 544 used. When the study must be performed at the bedside, a diverging collimator is useful 545 to visualize the maximum abdominal and pelvic areas. A SPECT or SPECT/CT camera 546 can be used to assist further localization of the GI bleeding site. Refer to SNMMI 547 Guideline for SPECT/CT Imaging 1.0. 548


549 IX. QUALITY CONTROL AND IMPROVEMENT, SAFETY, INFECTION 550

CONTROL, AND PATIENT EDUCATION CONCERNS 551 Refer to Section IX of the SNMMI Procedure Guideline for General Imaging 6.0. 552 553 X. RADIATION SAFETY IN IMAGING 554

Refer to Section X of the SNMMI Procedure Guideline for General Imaging 6.0. 555 Radiation dosimetry in adults, 5-yr old child and fetus are presented in Tables 1-3. 556

Administration of radiopharmaceuticals to pregnant, potentially pregnant, or 557 lactating patients is addressed in the SNMMI Procedure Guideline for General Imaging 558 6.0. ICRP publication 106, Appendix D, suggests that lactating patients who receive in 559 vivo 99mTc-RBCs require a 12 hour interruption of breast feeding. No cessation of breast 560 feeding is required for patients receiving in vitro 99mTc-RBCs. The physician must 561 consider the indication for the test, the potential benefit the information may provide, and 562 the potential radiation risk to the mother and fetus. 563

564 TABLE 1 565

Radiation Dosimetry: Adults* 566 567

Radiopharmaceutical Administered activity

MBq (mCi)

Organ receiving the largest radiation dose

mGy/MBq (rad/mCi)

Effective dose

mSv/MBq (rem/mCi))

99mTc-RBCs

555–1,100 IV (15–30)

0.023 heart

(0.085)

0.0070

(0.026)

* International Commission on Radiological Protection. Radiation Dose to Patients from 568 Radiopharmaceuticals. ICRP Publication 80. London, UK: ICRP; 1999. 569 570

TABLE 2 571 Radiation Dosimetry: Children* 572

(5 Years Old) 573 Radiopharmaceutical Administered

activity

MBq/kg (mCi/kg)

Organ receiving the largest radiation dose

mGy/MBq (rad/mCi)

Effective dose

mSv/MBq (rem/mCi))

99mTc-RBCs

11.39-26.67 IV

(0.31-0.72)

0.066 heart (0.24)

0.021

(0.078)

*International Commission on Radiological Protection. Radiation Dose to Patients from 574 Radiopharmaceuticals. ICRP Publication 80. London, UK: ICRP; 1999. 575 576

TABLE 3 577


Radiation Dosimetry: Dose Estimates to the Fetus* 578 579

99mTc-RBCs 580 581

Stage of Gestation

Fetal Dose

mGy/MBq (rad/mCi)

Early 0.0068 (0.025)

3 months 0.0047 (0.017)

6 months 0.0034 (0.013)

9 months 0.0028 (0.010)

582 *from Russell JR, Stabin MG, Sparks RB, Watson E. Radiation absorbed dose to the 583 embryo/fetus from radiopharmaceuticals. Health Phys. Nov 1997;73(5):756-769. Note - dose 584 estimates for in-vivo or in-vitro labeling are only slightly different. The slightly higher values for 585 in-vitro labeling are presented here. 586 587 XI. ACKNOWLEDGEMENTS 588 589 The Committee on SNMMI Guidelines consists of the following individuals: Kevin J. Donohoe, 590 MD (Chair) (Beth Israel Deaconess Medical Center, Boston, MA); Sue Abreu, MD (Sue Abreu 591 Consulting, Nichols Hills, OK); Helena Balon, MD (Beaumont Health System, Royal Oak, MI); 592 Twyla Bartel, DO (UAMS, Little Rock, AR); Paul E. Christian, CNMT, BS, PET (Huntsman 593 Cancer Institute, University of Utah, Salt Lake City, UT); Dominique Delbeke, MD (Vanderbilt 594 University Medical Center, Nashville, TN); Vasken Dilsizian, MD (University of Maryland 595 Medical Center, Baltimore, MD); Kent Friedman, MD (NYU School of Medicine, New York, 596 NY); James R. Galt, PhD (Emory University Hospital, Atlanta, GA); Jay A. Harolds, MD 597 (OUHSC-Department of Radiological Science, Edmond, OK); Aaron Jessop, MD (UT MD 598 Anderson Cancer Center, Houston, TX); David H. Lewis, MD (Harborview Medical Center, 599 Seattle, WA); J. Anthony Parker, MD, PhD (Beth Israel Deaconess Medical Center, Boston, 600 MA); James A. Ponto, RPh, BCNP (University of Iowa, Iowa City, IA); Lynne T. Roy, CNMT 601 (Cedars/Sinai Medical Center, Los Angeles, CA); Heiko Schöder, MD (Memorial Sloan-602 Kettering Cancer Center, New York, NY); Barry L. Shulkin, MD, MBA (St. Jude Children’s 603 Research Hospital, Memphis, TN); Michael G. Stabin, PhD (Vanderbilt University, Nashville, 604 TN); Mark Tulchinsky, MD (Milton S. Hershey Med Center, Hershey, PA) 605 606 The EANM Board consists of the following individuals: Fred Verzijlbergen, MD, PhD (Erasmus 607 MC Central Location, Rotterdam, The Netherlands); Arturo Chiti, MD (Istituto Clinico 608 Humanitas, Rozzano Milan, Italy); Savvas Frangos, MD (Bank of Cyprus Oncology Center, 609 Strovolos, Nicosia, Cyprus); Jure Fettich, MD (University Medical Centre Ljubljana, Ljubljana, 610 Slovenia); Bernd J. Krause, MD, PhD, (Universitätsklinikum Rostock, Rostock, Germany); 611


Dominique Le Guludec, PhD (Hopital Bichat, Paris, France); and Wim Oyen, MD, PhD 612 (Radboud University Medical Centre, Nijmegen, The Netherlands). 613

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1071 131) Sanli Y, Adalet I, Turkmen C, Kapran Y, Berberoglu K, Cantez S. Primary 1072 lymphoma of the small bowel detected with red blood cell scintigraphy. Clin Nucl 1073 Med. 2005;30(7):490-1. 1074 1075 132) Sun SS, Hsieh JF, Tsai SC, Lee JK, Kao CH. Unexpected detection of colon 1076 lymphoma on a Tc-99m-labeled red blood cell abdominal scan. Clin Nucl Med. 1077 2000;25(12):1052-3. 1078 1079 133) Ring DH, Silverman ED. Scintigraphic detection of an occult bleed into a 1080 retroperitoneal mass using Tc-99m labeled red blood cells. Clin Nucl Med. 1997;22(11):765-7. 1081 1082 134) Yama N, Ezoe E, Kimura Y, et al. Localization of intestinal bleeding using a 1083 fusion of Tc-99m-labeled RBC SPECT and x-ray CT. Clin Nucl Med. 2005;30: 1084 488–489. 1085 1086 135) Schillaci O, Danieli R, Manni C, et al. Is SPECT/CT with a hybrid camera useful to 1087 improve scintigraphic imaging interpretation? Nucl Med Commun. 2004;25:705-710. 1088 1089 136) Schillaci O, Spanu A, Tagliabue L, et al. SPECT/CT with a hybrid imaging system in the 1090 study of lower gastrointestinal bleeding with technetium-99m red blood cells. Q J Nucl Med Mol 1091 Imaging. 2009;53(3):281-9. 1092 1093 137) Schillaci O, Filippi L, Danieli R, Simonetti G. Single-photon emission computed 1094 tomography/computed tomography in abdominal diseases. Semin Nucl Med. 1095 2007;37:48–61. 1096 1097 1098 XIII. APPROVAL 1099 1100 This practice guideline (Version 2.0) was approved by the Board of Directors of the 1101 SNMMI on Month, Day, 2014. Version 1.0 was approved on February 7, 1999. 1102 1103 1104 1105

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