Seminars in Nuclear Medicine
Volume 42, Issue 1 , Pages 33-40, January 2012

Planar Scintigraphic Imaging of the Gastrointestinal Tract in Clinical Practice

  • Michael L. Middleton, MD

      Affiliations

    • Corresponding Author InformationAddress reprint requests to: Michael L. Middleton, MD, Scott & White Healthcare, Division of Nuclear Radiology & Advanced Molecular Imaging, 2401 S 31st Street, Temple, TX 76513
    • ,
  • Mark D. Strober, MD

Division of Nuclear Radiology & Advanced Molecular Imaging, Department of Radiology, Scott & White Healthcare System, Texas A&M Health Science Center, Temple, TX

Article Outline

In the last 30 years, nuclear medicine has paralleled other imaging fields with the development of 3-dimensional techniques, including single-photon emission computed tomography and positron emission tomography. However, conventional nuclear medicine planar scintigraphy remains a common procedure at most imaging centers. Gastrointestinal studies constitute a significant portion of these planar procedures. The most common gastrointestinal studies, including hepatobiliary, gastric emptying, and gastrointestinal bleeding evaluations, resemble their original protocol. However, serial improvements have optimized the diagnostic efficacy of these procedures. Conventional Technetium-99m sulfur colloid liver/spleen imaging and hepatic blood pool imaging with labeled red blood cells now mainly serve an adjunctive role in the evaluation of equivocal findings on computed tomography. Salivary gland imaging is a less commonly requested evaluation, but can be used to evaluate functional capacity in some disease entities.

 

Planar nuclear studies evaluating gastrointestinal (GI) tract function are routine daily occurrences in most nuclear medicine departments. These basic planar scans remain common procedures in nuclear medicine facilities that range from the most basically equipped to state-of-the-art centers that use single-photon emission computed tomography (SPECT) and positron emission tomography technologies. Planar GI studies account for approximately 5%-10% of nuclear imaging studies performed across the country. Hepatobiliary, GI bleeding, and gastric-emptying studies constitute the mainstay of these planar imaging modalities. Standardization of gastric-emptying and gallbladder functional studies has increased the acceptance of these procedures. However, planar nuclear evaluation can be used to assess the full extent of the alimentary tract. Nuclear evaluation of salivary gland and esophageal function are occasionally ordered to answer specific clinical questions. Scintigraphic localization of ectopic gastric mucosa remains a common study in the pediatric population. Hepatic morphologic and blood pool evaluation have adjunctive utility in the assessment of equivocal findings detected on anatomic imaging. The integral role of planar nuclear procedures in the evaluation of common clinical problems ensures that demand for these studies will continue into the future. The following article will touch upon the gamut of planar, GI nuclear modalities. Advances in the more common procedures will be discussed in-depth.

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Salivary Imaging 

The use of planar scintigraphy for the evaluation of the salivary glands has diminished during the last several decades. There are two essential indications for salivary imaging. The first is to provide functional information about excretion of the parotid and submandibular glands. The second indication is the characterization of salivary neoplasms, such as Warthin's tumor.1, 2

The most common agent used in salivary gland imaging is intravenous Technetium (Tc)99m pertechnetate. Salivary glands epithelial cells transport large monovalent ions, such as pertechnetate, and secrete them into saliva. Typically, planar imaging is performed to evaluate both glandular uptake and excretory function. After the administration of radiotracer, anterior images of the head are obtained before and after an excretory stimulus. Symmetry of pertechnetate uptake is assessed on the first phase. Washout after a lemon juice stimulus is subsequently evaluated. Because of the smaller size of the minor salivary glands, only the parotids and submandibular glands are typically evaluated. The sublingual glands are rarely included. An overall, diminished salivary excretory response is typical of some clinical syndromes that cause xerostomia, such as Sjögren's syndrome. Similarly, lack of excretion after stimulation can indicate salivary obstruction.1, 2, 3, 4

Radionuclide imaging of salivary masses can aid in the characterization of these neoplasms. Warthin's tumors of the salivary gland, which are benign, typically demonstrate increased uptake of radiotracer relative to surrounding salivary gland tissue. The persistence of radiotracer activity at the tumor site on the washout phase is also a characteristic of a Warthin's tumor. Localization of secretions within the tumor cystic spaces impedes excretion on a washout phase. Otherwise, most other salivary gland masses, including other benign salivary tumors, malignant tumors, and cysts, are scintigraphically nonfunctioning or “cold.”1, 2, 3

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Esophageal Reflux Imaging 

Esophageal transit and reflux imaging is a less commonly used planar nuclear medicine study, but has a unique role in evaluation of upper GI disorders. These examinations can be divided conceptually into esophageal transit time determination and esophageal reflux/retention evaluation.5, 6, 7

Although not standardized, esophageal transit imaging starts with the patient drinking a volume of water with a radiopharmaceutical, such as Tc-99m-diethylenetriamine pentaacetic acid (DTPA). The patient is instructed to swallow in a repetitive fashion. The transit time and/or retention in the esophagus is then assessed with supine or erect images. Regions of interest over the esophagus are then obtained. In general, normal esophageal transit is considered 6-15 seconds. There should be no significant retention of activity after 10 minutes. Although scintigraphy is more sensitive in detecting retention, videoflouroscopy is the imaging modality of choice for most esophageal disorders.5, 6, 7

Gastroesophageal reflux scintigraphy is more commonly performed in the pediatric population. Small amounts of Tc-99m sulfur colloid or Tc-99m DTPA are ingested in orange juice, milk, or formula. Imaging is again performed in the supine or erect position. Quantitative evaluation of reflux can be assessed graphically by the use of region of interest and time-activity curves. Abdominal binding has been performed to accentuate the reflux, but it is difficult to standardize. In normal patients, no reflux is confirmed scintigraphically.7, 8

In pediatric patients, a variation of this study is more commonly known as a “milk scan.” This study uses the child's most commonly taken liquid (milk, formula, juice). Tc-99m sulfur colloid in formula is preferred. Imaging is performed as soon as ingestion is completed. Rapid (15 s/frame) images are helpful to demonstrate reflux for up to 1 hour. Time-activity curves, with esophageal regions of interest, are obtained to graphically semiquantitate reflux. A common variation for the milk scan is to attempt to scintigraphically confirm pulmonary aspiration in pediatric patients with recurrent pulmonary infections. When this is suspected, delayed images of the thorax are obtained after a milk scan at 1, 4, and even 24 hours to detect radiotracer activity within the lungs. If present, then pulmonary aspiration is confirmed.5, 7

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Gastric-Emptying Studies 

Recent growth in the volume of gastric-emptying studies may be attributable to the increasing prevalence of diabetes with associated gastroparesis. A consensus protocol for this procedure in 2008 has served to standardize the procedure potentially increasing referring physician confidence.9, 10, 11 In our laboratory, gastric-emptying studies are the fastest-growing planar study in the last 5 years. The standardization of the technique includes a standard meal and imaging protocol with imaging time up to 4 hours. These factors have served to reduce the potential variability of results for individual patients.9

In the next issue of Seminars of Nuclear Medicine, this topic will be addressed in greater detail. Retention percentage of the initial total gastric activity is now reported in addition to gastric-emptying half-times. Graphically, the emptying-rates can be compared with the consensus, normal adult database. Retention percentages can be easily displayed at hourly time points. Greater than 10% retention at 4 hours is now considered an abnormal finding (Fig. 1). The new consensus protocol does require a longer time commitment for the patient (4 hours), but the amount of time under the camera is minimized compared with previous methods. Furthermore, the standardized gastric-emptying evaluation allows for comparison before and after therapeutic intervention. Comparison of studies between laboratories is now facilitated.9

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Hepatobiliary Imaging 

In the last decade, the advent of the laparoscopic cholecystectomy has altered the referral pattern of patients undergoing scintigraphic hepatobiliary evaluation. The traditional, acutely ill, inpatient with right upper quadrant discomfort has been largely supplanted with an outpatient population typically reporting chronic abdominal symptoms. Therefore, cholecystokinin augmented imaging with determination of gallbladder ejection fraction (GBEF) now represents the majority of hepatobiliary imaging studies in many nuclear clinics. As a result, the following discussion of hepatobiliary imaging will focus on an optimal determination of a GBEF value, which can best select those patients who may benefit from cholecystectomy.

Determination of GBEF with pharmacologic intervention has been a work in progress during the last 4 decades. In previous work, investigators used oral contrast to opacify the gallbladder before cholecystokinin administration.12, 13 These investigators suggested that a radiographically determined GBEF of <20% coupled with reproduction of the patient's right upper pain indicated those cases likely to respond to cholecystectomy. The development of technetium-99m labeled hepatobiliary radiopharmaceuticals in conjunction with advancement of data processing gave rise to scintigraphic techniques with more accurate quantitation of the GBEF.14 Production of a reduced GBEF after cholecystokinin in normal subjects was a potential pitfall on these early studies. By using oral contrast, Dunn et al15 noted that some “control subjects” demonstrated an abnormal gallbladder response after a 30-second bolus injection of cholecystokinin. These reduced values in normal subjects have been attributed to gallbladder neck spasm in the setting of supraphysiologic serum levels of cholecystokinin.16 Subsequent iterations have used a 1- to 3-minute injection of cholecystokinin or the physiologically active, C-terminal octapeptide known as sincalide.17 However, validation of this method with controlled studies is nearly absent from the literature.

In the early 1990s, several investigators addressed the issue of variation of GBEF values in normal patients. Ziessman et al18 found that 6/23 normal volunteers receiving a 3-minute infusion of 0.02 μg/kg had GBEF below the widely accepted lower limit of normal of 35%. However, only 2 of 25 normal volunteers had a GBEF less than 35% with a 30-minute continuous infusion of the same dosage. Data from Fink-Bennett et al19 showed that the 3-minute infusion resulted in gallbladder ejections fractions of <35% in 16/25 normal volunteers.

The only controlled, randomized study to date investigated the ability of the GBEF obtained following a relatively long infusion time to predict the efficacy of cholecystectomy in symptomatic patients.20 The study contained both normal volunteer and patient arms. The authors used a 45-minute infusion of 20 ng/kg/h for 45 minutes. Patients with a GBEF <40% with this method were randomized cholecystectomy and observation arms. The normal volunteer arm of the study indicated that the maximal GBEF was obtained 15 minutes after the 45-minute infusion of sincalide. No symptoms were reported by these volunteers during the infusion. The lowest GBEF value among the volunteers was 46%. In the symptomatic patient arm of the study, 21 of 103 individuals had a GBEF of <40%. None of these patients reported abdominal discomfort during the infusion. Nearly all of these patients with a GBEF <40%, randomized to subsequent cholecystectomy, became asymptomatic. However, patients with a GBEF <40% by this method, who did not receive subsequent cholecystectomy, continued to report chronic abdominal discomfort over follow up period of several months. Pathologic evaluation of the resected gallbladders demonstrated evidence for chronic inflammation, gallbladder wall thickening, and cystic duct narrowing in most of the specimens.

In summary, these studies lead to several procedural conclusions. First, injections of sincalide over just several minutes can result in an unacceptable number of false-positive results. Slow, continuous infusions of sincalide are more reproducible and do not produce reduced values in normal adults. Finally, abdominal pain during the examination is not related to the presence of biliary pathology but is the result of the supraphysiologic sincalide levels attained from a relatively rapid injection.

A recent, multicenter trial builds on these data by investigating the variability of the GBEF in normal volunteers at 15-, 30-, and 60-minute infusion rates of 0.02 μg kg−1 sincalide.21 The coefficient of variation (CV; SD/mean) was measured for each of these methods. The CV for the 60-minute infusion was 19%, which is significantly lower than the CV for the 30-minute infusion of 35%. The CV for the 15-minute infusion was 52%. On the basis of these data, the authors suggested that the optimal study protocol uses the 60-minute infusion with the lower limit of normal set at a GBEF of 38%, which is at the fifth percentile.

The Society of Nuclear Medicine recently published a practice guideline for hepatobiliary scintigraphy.22 The “method of choice” is an infusion of 0.02 μg kg−1 of sincalide over 60 minutes. A normal GBEF is set at >38% by this method (Fig. 2).

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Liver/Spleen Imaging 

Planar liver/spleen scintigraphic evaluation of hepatic morphology has been largely supplanted by computed tomography and ultrasound in recent years. There remains a small niche for the planar liver/spleen scan in the evaluation of diffuse hepatic disease. This study can also serve an adjunct role in the evaluation of some space-occupying abnormalities in unique clinical situations.23, 24 The use of this modality for evaluating diffuse hepatic disease is easily performed. Planar images are obtained in multiple positions (anterior, posterior, laterals, right anterior oblique, left anterior oblique, left posterior oblique, and right posterior oblique) after injection of Tc-99m sulfur colloid. Uptake by hepatic Kupffer cells and splenic phagocytic function is the mechanism for radiopharmaceutical localization.23 In cirrhosis, reduction in liver uptake is observed in conjunction with diffusely increased spleen and bone marrow activity. More uptake in the bone marrow correlates with severity of disease. This “colloid shift” is secondary to diminished phagocytic function by the diseased liver resulting in greater splenic and bone marrow uptake.23, 24, 25

Morphologically, the liver/spleen scan can help characterize only larger space occupying lesions (>2 cm for planar imaging), when used in conjunction with other anatomic imaging studies. The utility of this application has rapidly declined in the last 20 years. A concurrently acquired liver/spleen scan can be helpful for evaluating possible hemangioma if other anatomic studies are not available for direct correlation as discussed below.26

Several unique scenarios exist in which the liver/spleen scan has specific clinical utility. For example, sparing of the caudate lobe with diminished uptake in the right and left lobe of the liver is suggestive of Budd–Chiari syndrome (hepatic vein thrombosis).23 Otherwise, the differential for photopenic defects in the liver on a sulfur colloid scan is extensive and nonspecific.23, 24 With the advent of more sensitive and specific anatomic imaging methods, liver mass characterization with sulfur colloid planar scintigraphy has grown out of favor.

Spleen anatomic imaging can also be performed with Tc-99m sulfur colloid. This modality can be useful in confirming splenules or accessory splenic tissue. Although denatured Tc-99m red blood cells (RBC) imaging has also been used, it is more cumbersome to perform. Planar scintigraphy is limited to evaluating splenic findings, which are larger than the one cm resolution of this modality. SPECT or SPECT/CT should be used for smaller lesions.27

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Hepatic Blood Pool Scintigraphy 

Planar imaging to confirm hepatic hemangiomas is also a relatively infrequently performed study. With planar imaging, larger hemangiomas (>3 cm) can still be imaged with high sensitivity. Smaller hepatic lesions or more deep-seated lesions may require SPECT or magnetic resonance for more accurate confirmation.26

Most hepatic masses are detected serendipitously during anatomic work up of other clinical entities. These common benign entities are the second most common hepatic tumor.26, 28 The study relies on the tendency of hepatic hemangiomas to demonstrate increased venous blood pooling relative to surrounding hepatic parenchyma. RBC are labeled with Tc-99m by conventional RBC tagging, preferably with a commercial kit. After injection of Tc-99m RBC, immediate and delayed planar imaging in multiple projections are obtained (anterior, posterior, laterals, and oblique images). Classically, focally increased blood pool activity on delayed images suggests hemangioma with only rare exceptions.26, 28

Comparison of planar Tc-99m RBC blood pool images can be made to other anatomic imaging modalities, such as ultrasound, CT, or magnetic resonance. However, if correlative studies are not available, direct comparison with a planar Tc-99m sulfur colloid liver/spleen scan is an alternative. This approach only requires one visit by the patient. A liver/spleen colloid scan is acquired with a low dose of Tc-99m sulfur colloid. Subsequent images are obtained after labeling the blood pool with a greater dose of Tc-99m RBC. Although planar imaging is adequate for large lesions, SPECT imaging will likely be required for characterizing lesion <2 cm. Blood pool imaging can also help confirm larger splenic hemangiomas, which are less common.29

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GI Bleeding 

Acute lower GI bleeding is a common clinical problem increasing in frequency in the elderly patient population. Although most bleeding ultimately resolves spontaneously, a brisk bleed with hemodynamic instability is a potential life-threatening event. Localization of the bleeding site can be problematic, and a significant proportion of patients are discharged from the hospital without a definitive identification of the bleeding site.30, 31 Scintigraphic techniques employed in an expeditious manner can facilitate management of these patients.

Acute lower GI bleeding was first scintigraphically investigated with Tc-99m sulfur colloid imaging in the late 1970s.32 Rapid clearance of radiocolloid by the reticuloendothelial system limited the sensitivity of this initial method. The use of Tc-99m labeled RBC represented a subsequent innovation extending potential detection of intermittent bleeding events from minutes to hours.33 The labeled red blood cell method remains the most sensitive means for detecting lower GI hemorrhage. Bleeding rates as low as 0.12 mL/min can be detected.34 Although the basic procedure is largely unchanged during the last several decades, incremental refinement during the last 10 years has significantly improved the technique.

Before the era of computer processing, the Tc-99m RBC, GI bleeding scans used a series of static image acquisitions accomplished at 5 to 10-minute intervals. Because approximately 3-5 mL of radiolabeled blood must be present to produce an interpretable signal on the nuclear scan,35 relatively prolonged imaging intervals could theoretically fail to detect intermittent bleeding events because of dilution of the extravasated radiolabeled blood within the GI tract. Also, a detected focal region of increased activity may incorrectly assign the location of the bleed, given the potential for both rapid anterograde and retrograde movement. Therefore, an uninterrupted or cinematic imaging technique can improve the sensitivity of this modality for accurate localization of an active bleeding site. O'Neill et al36 acquired serial 1-minute image sets, which resulted in detection of a bleeding site in 96% of the patients scanned. Of these patients, the scan result accurately predicted the surgically confirmed bleeding site in 88% of the patients with a positive scan. The authors stressed the importance of image analysis by dynamic playback review of the acquired data. Both the sensitivity and accuracy of this method was superior to results from prior series, which used a discontinuous method for image acquisition.36

Despite meticulous adherence to optimal study technique, many radionuclide GI bleeding evaluations will not indicate a bleeding site. These “negative” studies may have prognostic value in stratifying those patients who can be conservatively managed. Hammond et al37 surveyed the natural history of patients with negative bleeding scans who initially presented with GI hemorrhage. Their data suggest that this subgroup of patients rarely require surgery. Although 27% of these patients were found to rebleed with an average follow up of 43 months, only 7 of the 84 study patients had a bleeding episode within 30 days of the initial study. None of these 7 patients were inpatients at the time of subsequent bleeding.

Conversely, a markedly positive study may define a relative high risk population of lower GI bleed patients requiring more aggressive therapy. Smith et al38 stratified 62 consecutive rectal bleed patients into 5 risk categories on the basis of both scintigraphic intensity of detected activity and time to scintigraphic detection. The authors correlated these data to bleeding rates calculated by blood transfusion requirements over time. The results indicated that intensely increased activity seen within the first hour of imaging had the largest transfusion requirements, longest duration of active bleeding, highest bleeding rate, and required more aggressive therapy than the other groups. Those patients with only a minimal focus of delayed activity or no detectable activity through the duration of the study defined a subgroup of patients who had the lowest transfusion requirements and bleeding rates. None of the patients in these lowest risk groups was referred for angiography, and none required surgery.

Scintigraphic identification of a lower GI bleed selects patients who may require surgical intervention. However, is the bleeding site localization sufficiently accurate to proceed to surgery without confirmation by other modalities, including angiography or colonoscopy? A series of studies performed mainly in the 1980s, with the authors using numerous different acquisition protocols and interpretational criteria, cumulatively demonstrated an accuracy rate of 82%.39 More recent studies demonstrate a somewhat higher accuracy rate. Suzman et al40 retrospectively evaluated patients presenting with lower GI bleed evaluated with a GI bleeding scan. Scanning protocol allowed for up to 4 hours of continuous imaging. Results indicated, that of 50 cases requiring surgery, there was only 1 case in whom bleeding site misassignment could have resulted in a potential alteration of segmental colonic resection. An additional, retrospective analysis by Olds et al41 used more extensive criteria for assessing GI scan accuracy. Studies were considered accurate if the following conditions were met: (1) angiographic identification of bleed at the same site, (2) potential causative finding on endoscopy at the same site as indicated by the scan, and (3) no subsequent bleeding following surgical resection based on the GI scan localization. For the acquisition technique, they used a continuous 1-hour acquisition protocol. Results indicated that 5 of 49, or 10% of GI bleeding evaluations, misidentified the hemorrhage site. These more recent studies suggest that meticulous adherence to optimal acquisition protocol can limit bleeding site misidentification. However, given the tendency for extravasated blood to move from its origin, occasional site mislocalization is inevitable. The ultimate place of the GI bleeding scan in a diagnostic algorithm for acute lower GI bleed will most likely require larger, prospective studies across institutional lines.

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Ectopic Gastric Mucosa Imaging 

Occurring in 1%-3% of the population, Meckel's diverticulum is the most common congenital abnormality of the GI tract. This malformation results from an incomplete closure of the omphalomesenteric duct. The diverticulum is located at the antimesenteric aspect of the ileum approximately 50-100 cm from the ileocecal valve. A total of 15% of Meckel's diverticula contain ectopic, gastric mucosa, which can secrete gastric acid and pepsin. Painless GI bleeding is the most common presentation, especially in the pediatric population. Abdominal pain is more commonly seen in older children and adults.42, 43

Scintigraphic detection of ectopic gastric mucosa is predicated upon the tendency of gastric mucosa to sequester Tc-99m pertechnetate. This radiopharmaceutical is most likely taken up by the mucus secreting cells within the gastric mucosa.44, 45 The imaging protocol is straight forward. After a 6 to 12-hour period of fasting, the patient is injected with the Tc-99m pertechnetate and serial planar images are obtained for up to 1 hour. A positive study is based on the visualization of early focal activity within the abdomen typically in the right lower quadrant. Renal pelvic activity early and gastric secretions in proximal small bowel later in study can pose potential pitfalls. However, the renal activity tends to dissipate with time. Increased activity in the proximal small bowel is a function of gastric emptying and is not seen on the initial portion of the study. A post void images is helpful as rarely bladder activity can obscure focal activity attributable to Meckel's diverticulum.

False-positive studies have been attributed to numerous etiologies. Some of these are simply imaging pitfalls described in the previous paragraph attributable to physiological structures. However, GI duplications containing ectopic gastric mucosa will also visualize on Tc-99m pertechnetate imaging.46 Failure to visualize ectopic gastric mucosa is usually attributable to insufficient volume of tissue. One paper estimates that tissue volume must approach 1 square centimeter to be detected.47

The sensitivity of this technique is difficult to estimate given the absence of a comparative standard short of surgical confirmation. However, false negative rates have been estimated to range from 20% to 50%.44, 46 Therefore, several pharmacologic interventions have been used to enhance the detectability of ectopic gastric mucosa. The most common intervention has been the use of H-2 receptor antagonists, such as cimetidine and ranitidine. The initial evidence for the use of these agents was in a paper by Petrokubi in which two previously negative scans were converted to positive following pretreatment with cimetidine.47 Similar results have been subsequently reported by multiple other investigators.42, 48, 49 These H-2 blocking agents are thought to work by inhibiting secretion of the radiotracer from the gastric mucosa.49 In other less-common interventions, investigators have used pentagastrin50 and glucagon51 either individually or in combination to enhance ectopic gastric visualization.

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Conclusions 

Planar imaging of the GI system yields rapid assessment of physiological processes at relatively low cost. Therefore, these basic studies will be in demand in the foreseeable future. Some of the aforementioned planar imaging studies have not increased in popularity during the last decade, usually because of more suitable, alternative diagnostic methods. However, hepatobiliary, GI bleeding, and gastric-emptying evaluations have gained widespread acceptance in the last decade. Standardization of techniques, advances in digital imaging, and pharmacologic interventions have enhanced the clinical applications of these examinations. It is therefore likely that planar GI imaging will continue into the foreseeable future.

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PII: S0001-2998(11)00097-3

doi:10.1053/j.semnuclmed.2011.07.006

Seminars in Nuclear Medicine
Volume 42, Issue 1 , Pages 33-40, January 2012

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