THE FELLOWS’ CORNER
Nuclear medicine hepatobiliary imaging (cholescintigraphy) Multiple radiological (eg, CT, magnetic resonance imaging/MRCP) and endoscopic (eg, EUS, ERCP) techniques exist for anatomic hepatobiliary imaging. For the most part, these techniques provide detailed morphological characterization of hepatobiliary structures, but do not provide important physiological or functional information. Qualitative and quantitative hepatobiliary scintigraphy is a noninvasive imaging modality that can be used to diagnose different hepatobiliary pathologies, such as complete and partial biliary obstruction and calculous and acalculous cholecystitis. Gastroenterologists should be familiar with the physiology of this type of imaging and indications for cholescintigraphy. In this month’s edition of Fellows’ Corner, Dr. Kari Hopfer and Dr. Harvey Ziessman present a focused summary of the physiology and indications of nuclear hepatobiliary imaging. Mouen Khashab, MD Fellows’ Corner Editor Assistant Professor of Medicine Division of Gastroenterology and Hepatology Johns Hopkins Hospital Baltimore, Maryland, USA
tope emits gamma ray photons that are ideally suited for detection by nuclear medicine imaging cameras. It has a short physical half-life (6 hours), which minimizes patient radiation but necessitates imaging be completed within 24 hours of administration.
IMAGING BASICS Images are acquired using a specialized instrument, the gamma camera, that detects gamma rays or photons emitted by the radiotracer from within the patient rather than
Key Points ●
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Nuclear medicine imaging captures the function/physiology of a given system as opposed to most other imaging modalities that capture primarily anatomic structure/morphology. Abnormal function often precedes pathological anatomic changes. For example, in biliary obstruction, reduced bile flow may be seen with cholescintigraphy (hepatobiliary iminodiacetic acid [HIDA] scan) before ductal dilation on US. ●
RADIOPHARMACEUTICALS Nuclear medicine images are produced from radiation emissions originating from radiopharmaceutical that has been administered internally, often intravenously, sometimes orally, or into a body cavity, eg, peritoneum. Radiopharmaceuticals are composed of a radioactive atom attached, for example, to a subpharmacological dose of a chemical (sodium iodide), pharmaceutical (HIDA), or blood component (red blood cells). Technetium-99m is the most commonly used radiotracer. This man-made radionuclide or radioiso-
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Nuclear medicine hepatobiliary imaging (HIDA) is physiological/functional imaging compared with, for example, US and CT, which are primarily anatomic/morphological imaging. HIDA imaging is commonly used to diagnose acute cholecystitis manifested by nonfilling of the gallbladder. Biliary obstruction is a less common indication, but can be helpful when anatomic imaging is nondiagnostic or in patients with persistently dilated biliary ducts as the result of previous obstruction. HIDA imaging has an important role in the diagnosis of functional gallbladder disease (gallbladder dyskinesia, chronic acalculous gallbladder disease). A poor gallbladder ejection fraction can confirm the clinical diagnosis.
from an external beam radiation source as with radiographs, fluoroscopy, and CT. Gamma rays are physically identical to x-rays. The detected gamma photon emissions are used by the camera and its software to create images corresponding to the distribution of the radiotracer within the patient. Different acquisition techniques allow for different image presentation, eg, 2-dimensional dynamic images (1 minute each ⫻ 60), multiple views (anterior, latVolume 74, No. 2 : 2011 GASTROINTESTINAL ENDOSCOPY 375
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eral, posterior, oblique), or 3-dimensional cross-sectional images (single-photon emission CT).
CHOLESCINTIGRAPHY (HIDA) Technetium-99m–labeled HIDA radiopharmaceuticals used for hepatobiliary imaging (mebrofenin or disofenin) are extracted by hepatocytes and transported and secreted into the biliary system similar to bilirubin, although they are not conjugated. The HIDA tracer is subject to competitive inhibition in the presence of high serum bilirubin (⬎20-30 mg/dL). Hepatocellular dysfunction causes increased background activity and delayed and reduced hepatic uptake and clearance, which can interfere with diagnostic interpretation. The pattern of biliary flow is determined by duct patency, sphincter of Oddi tone, and intraluminal pressure. Approximately two thirds enters the gallbladder via the cystic duct with the remainder transiting the common bile duct and sphincter of Oddi into the second portion of the duodenum. All of this normally occurs within 1 hour after injection.
ACUTE CHOLECYSTITIS The most common indication for HIDA imaging is acute cholecystitis. Because the initiating event is obstruction of the cystic duct, usually by a stone, the gallbladder does not fill during HIDA imaging; persistent nonfilling is diagnostic of acute cholecystitis and can be detected immediately after onset. US is important for the evaluation of hepatobiliary disease and can suggest acute cholecystitis; however, direct comparison studies have shown cholescintigraphy to have superior accuracy for acute cholecystitis. Many of the findings seen in acute cholecystitis with sonography are not specific, eg, pericholecystic fluid may be secondary to ascites, a thickened gallbladder wall occurs with chronic cholecystitis, gallstones are often asymptomatic, and the sonographic Murphy’s sign is observer dependent. Anatomic imaging is most sensitive in latestage cholecystitis and less sensitive for early-onset disease. Sonography can detect other intra-abdominal pathology related to the patient’s symptoms. If there is no filling of the gallbladder by 1 hour after HIDA infusion, patients either receive a low dose of morphine or delayed imaging to confirm the diagnosis. Morphine, 0.04 mg/kg, increases tone at the sphincter of Oddi, increasing intrabiliary duct pressure, thus causing preferential flow into the gallbladder if the cystic duct is patent. A patent gallbladder will be seen within 20 to 30 minutes after morphine administration. Alternatively, delayed images at 3 to 4 hours showing no gallbladder filling confirm the diagnosis if morphine is contraindicated or unavailable. Morphine is not administered if biliary obstruction has not been excluded, evidenced by good flow through biliary ducts into the small intestine. 376 GASTROINTESTINAL ENDOSCOPY Volume 74, No. 2 : 2011
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BILIARY OBSTRUCTION HIDA imaging can be valuable in selected cases in patients with suspected acute biliary duct obstruction. The diagnosis of biliary obstruction is usually made by detection of ductal dilation by sonography. However, it takes as long as 24 to 72 hours after the inciting event for dilation to occur. HIDA imaging can demonstrate the abnormal physiology of high-grade obstruction, ie, good uptake but no biliary excretion. A persistent hepatogram is seen on initial and delayed images with little or no evidence of bile entering the extrahepatic ductal system and no evidence of bile transit into the small bowel. These are the same HIDA findings seen with biliary atresia in children. In patients with suspected acute biliary obstruction who have dilated biliary ducts caused by previous obstruction, HIDA imaging can distinguish recurrent obstruction from persistently dilated nonobstructed biliary ducts by observing bile transit. HIDA imaging can be used to help distinguish biliary obstruction from hepatic dysfunction, although this becomes increasingly difficult the longer the dysfunction or obstruction exists. HIDA imaging can also diagnose a partial biliary obstruction. These patients often have recurrent biliary colic, normal liver function studies, and no biliary dilation on US or MRCP. Typical HIDA findings are delayed clearance of bile from biliary ducts and delayed entrance into the small intestine.
CHRONIC ACALCULOUS GALLBLADDER DISEASE The clinical diagnosis of chronic calculous cholecystitis is often confirmed by the presence of stones noted on anatomic imaging, eg, US. However, patients with suspected chronic acalculous cholecystitis (gallbladder dyskinesia, chronic acalculous or functional gallbladder disease) are more difficult to diagnose. Poor gallbladder contraction after cholecystokinin infusion, used in conjunction with HIDA imaging, can confirm the suspected clinical diagnosis. Sincalide is an analog of the c-terminal octapeptide of cholecystokinin, the physiologically active portion. After the gallbladder fills, sincalide is administered intravenously and imaging is continued. The amount of emptying is easily quantified as a gallbladder ejection fraction. Radioactivity in the gallbladder is proportional to its volume, making calculation straightforward, simple, and accurate. Over the years, many different infusion rates and doses of sincalide have been used at different imaging centers. Evidence suggests that rapid infusions, used more in the past, are not physiological and have considerable variability of response in normal subjects. This may explain the discrepancy in reported studies on the utility of sincalide cholescintigraphy to diagnose the disease. A large multicenter trial comparing different infusion methods was recently pubwww.giejournal.org
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Nuclear medicine hepatobiliary imaging
Figure 1. Morphine infusion demonstrates gallbladder filling and excludes acute cholecystitis.
lished. This led to consensus recommendations by a group of expert gastroenterologists, surgeons, and nuclear medicine physicians strongly suggesting a specific standardized methodology be used at all imaging centers. This 60-minute infusion method mimics the physiology of gallbladder contraction, allowing for more accurate and reproducible gallbladder ejection fraction calculation without the side effects of abdominal cramping seen with more rapid infusions. With this method, a calculated gallbladder ejection fraction of less than 38% is abnormal (Fig. 1).
Figure 2. High-grade biliary obstruction. Image acquired at 2 hours shows good liver uptake but no biliary excretion. This is unchanged from the 60-minute image.
iary diversion procedures, complications of liver transplantation, and confirmation of a choledochal cyst.
POSTCHOLECYSTECTOMY SYNDROME
SUMMARY
Nuclear hepatobiliary imaging can also be useful in patients with recurrent biliary symptoms after cholecystectomy. Biliary causes of the postcholecystectomy syndrome include cholelithiasis, inflammatory stricture, and sphincter of Oddi dysfunction. They all manifest on HIDA imaging as a partial biliary obstruction, eg, delayed clearance of the biliary ducts and delayed clearance into the small bowel. HIDA imaging can be used as a screening test before proceeding to more invasive procedures such as ERCP. Various quantitative HIDA techniques have been described as ancillary diagnostic methods to confirm the diagnosis. There is some controversy regarding the utility of these quantitative methods; however, they are routinely used at some referral centers (Fig. 2).
Nuclear hepatobiliary (HIDA) imaging (cholescintigraphy) is a valuable noninvasive functional imaging method that provides diagnostic information based on physiology rather than anatomy.
OTHER HIDA INDICATIONS HIDA imaging also has diagnostic utility in patients with suspected bile leak, seen most commonly after cholecystectomy or other biliary surgery. It can confirm the diagnosis of leak and give some assessment regarding the rate of leakage. There are many other indications for HIDA imaging, including biliary stent patency, evaluation of bil-
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DISCLOSURE The authors disclosed no financial relationships relevant to this publication. Kari Hopfer, DO Harvey Ziessman, MD Department of Radiology and Radiological Science Johns Hopkins University Baltimore, Maryland, USA Abbreviation: HIDA, hepatobiliary iminodiacetic acid.
SUGGESTED READING 1. DiBaise JK, Richmond BK, Ziessman HA, et al. Cholecystokinincholescintigraphy in adults: consensus recommendations of an interdisciplinary panel. Clin Gastroenterol Hepatol 2011;9:376-84. 2. Ziessman HA. Nuclear medicine hepatobiliary imaging. Clin Gastroenterol Hepatol 2010;8:111-6.
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