CHAPTER 92
Nuclear medicine imaging

Mathurika Jeyasingam and Harvey A. Ziessman

The Johns Hopkins University, Baltimore, MD, USA

Nuclear medicine is based on physiology and function. Radiopharmaceuticals (radioactive drugs and molecules) are developed and utilized to detect disease and provide therapy.

Cholescintigraphy

Radionuclide hepatobiliary imaging (cholescintigraphy or HIDA) is a time‐proven diagnostic methodology with many indications including acute cholecystitis, chronic acalculous cholecystitis, biliary obstruction, hepatic dysfunction, biloma, bile leak, neonatal jaundice, and choledochal cyst, to name a few. HIDA stands for hepatic iminodiacetic acid. Two HIDA radiopharmaceuticals are approved by the Food and Drug administration (FDA) for clinical use in the United States: Tc‐99m disofenin (Hepatolite®) and Tc‐99m mebrofenin (Choletec®). Due to its greater liver excretion and rapid clearance Tc‐99m mebrofenin has increasingly become the agent of choice (Figure 92.1).

Acute cholecystitis is the most common indication for cholescintigraphy. It has a high accuracy for making the diagnosis, with sensitivity >95% and specificity >90%. Nonvisualization of the gallbladder after HIDA imaging is diagnostic. Delayed imaging at 3–4 h is required to confirm diagnosis. Alternatively, morphine sulfate 0.04 mg/kg infused over 30 min can confirm the diagnosis (Figure 92.2). Morphine sulfate contracts the sphincter of Oddi and increases intrabiliary pressure, resulting in preferential bile flow towards and through the cystic duct, if it is patent. With morphine, the study is completed in 90 min rather than the 3–4 h required with delayed imaging. Diagnostic accuracy is similar.

Chronic acalculous gallbladder disease (biliary dyskinesia) is a common indication for cholescintigraphy. After the gallbladder fills, sincalide (CCK) is infused for 60 min during imaging. Normal gallbladder contraction (gallbladder ejection fraction, GBEF) is greater than 38% (Figure 92.3). A diseased gallbladder does not contract well. A low GBEF is consistent with chronic acalculous disease (Figure 92.4). The only contraindication to sincalide administration is pregnancy and intestinal obstruction. Acute illnesses and various drugs can inhibit gallbladder contraction, e.g., calcium channel blockers, progesterone, octreotide, theophylline, benzodiazepine, and others. They should be withheld prior to the test. CCK cholescintigraphy is a confirmatory test, not a screening test. It should not be performed in a hospitalized sick patient but rather as an outpatient after other conditions have been otherwise investigated.

High‐grade biliary obstruction is often diagnosed during ultrasonography by detection of dilated biliary ducts. However, dilation may take 24–72 h to become apparent after an acute obstructive event. Cholescintigraphy can confirm the diagnosis immediately after onset because it demonstrates the underlying pathophysiology, obstruction to bile flow. The cholescintigraphic images of acute high‐grade biliary obstruction demonstrate good hepatic function (prompt hepatic extraction of tracer from blood) but no secretion into biliary ducts, i.e., a persistent hepatogram (Figure 92.5). The lack of bile secretion is caused by the high back‐pressure causing obstruction to flow. Further delayed imaging usually shows unchanged images. The accuracy of cholescintigraphy for the diagnosis of high‐grade obstruction is >97%.

Partial biliary obstruction typically presents with recurrent biliary colic‐like pain. The diagnosis can be challenging clinically and image‐wise. It is most commonly caused by biliary stones or stricture, rarely tumor. Cholescintigraphy typically shows good hepatic function, secretion into biliary ducts and gallbladder, but retention of HIDA radiotracer in the proximal biliary ducts and delayed transit from the common duct into the small intestines. The accuracy for diagnosis of partial biliary obstruction is reported to be good, with a sensitivity of 97% compared to 78% for sonography, with similar specificity (86%).

Spincter of Oddi dysfunction (SOD) presents post cholecystectomy as recurrent biliary colic‐like pain. It is another cause for partial biliary obstruction. To confirm the diagnosis, stones, tumor, and biliary stricture must be excluded as the cause. Cholescintigraphy can be a valuable method to screen patients for this entity. The HIDA study allows for physiological assessment of biliary duct drainage, which correlates well with the washout of contrast material from the biliary tract observed on endoscopic retrograde cholangiopancreatography (ERCP). Cholescintigraphy is routinely used at some biliary centers as a screening test, thus avoiding ERCP in patients with a negative study. The findings are delayed clearance from the common duct and delayed transit to the bowel. Quantification of cholescintigraphy for diagnosis of a partial biliary obstruction and sphincter of Oddi dysfunction can improve the accuracy over image analysis alone. Regions‐of‐interest are drawn around biliary ducts or hepatic hilum, time–activity curves generated, and quantitative parameters of bile clearance determined (Figure 92.6). Several methods have been described.

Photo depicts normal HIDA scan. — **Figure 92.1** Normal HIDA scan. Note initial good hepatic uptake and subsequent clearance into patent biliary ducts and gallbladder and transiting to the small bowel, all within 60 min.

Differentiation of chronic biliary obstruction from severe hepatic dysfunction. Both entities may show poor biliary clearance. Thus, differentiating high‐grade biliary obstruction from severe primary hepatic dysfunction can be challenging. However, cholescintigraphy is often able to accomplish this. High‐grade obstruction has the typical appearance of good hepatic uptake but no biliary clearance (see Figure 92.5). Delayed imaging for up to 24 h may be needed to see biliary clearance with hepatic dysfunction (Figure 92.7).

Biliary atresia presents in neonates as cholestatic jaundice. Progressive inflammatory sclerosis obliterates extrahepatic and intrahepatic biliary ducts. Early diagnosis must be made within the first 60 days of life to prevent irreversible liver failure. Treatment requires a palliative hepatoportoenterostomy (Kasai procedure), but ultimately liver transplantation. The differential diagnosis is neonatal hepatitis of various etiologies.

Patient preparation for biliary atresia cholescintigraphy requires 3–5 days of oral phenobarbital prior to the study to activate liver excretory enzymes and increase function and bile flow. Biliary atresia shows a picture of high‐grade biliary obstruction; that is, a persistent hepatogram and no biliary‐to‐bowel transit over 24 h (Figure 92.8). The negative predictive value of the study is very high, approaching 100%. The positive predictive value has been reported to be somewhat lower. False‐positive studies may occur in some patients due to severe neonatal hepatitis. Importantly, if the serum phenobarbital level is in the therapeutic range at the time of the study, the specificity has been found to be quite high, greater than 90%.

Bile leaks usually occur as a complication of recent cholecystectomy or biliary tract surgery. Leakage is seen on cholescintigraphy as progressively increasing radiotracer collection in the region of the gallbladder fossa or hepatic hilum, or more extensive transit into the subdiaphragmatic space, over the dome of the liver, into the colonic gutters, or spread diffusely as free bile throughout the abdomen (Figure 92.9). Peritoneal tubing, drains, and collection bags may show accumulation and sometimes be the only evidence of leak. Cholescintigraphy can differentiate slow from rapid leaks. Slow bile leaks often resolve spontaneously with conservative therapy, whereas more rapid leaks usually require intervention. Cholescintigraphy can determine whether the fluid collection is of biliary origin, rather than caused by ascites, infection, etc. It can also provide an estimate of the rate of leakage. Before percutaneous drainage of a biloma, cholescintigraphy can help ensure that biliary obstruction is not the underlying cause. With obstruction, bile leakage cannot be effectively treated by percutaneous drainage without addressing the underlying obstruction.

Photo depicts acute cholecystitis – imaging post morphine. — **Figure 92.2** Acute cholecystitis – imaging post morphine. Initial 60 min (not shown) revealed no gallbladder visualization. The images showed good hepatic uptake, biliary duct visualization, transit to the small bowel, but no gallbladder. The images shown here are for 30 min after morphine sulfate infusion. No gallbladder visualization occurred, although the cystic duct is seen on the later images. This study is consistent with cystic duct obstruction or acute cholecystitis.

Tc‐99m‐labeled red blood cells

Liver cavernous hemangiomas have long been diagnosed with Tc‐99m‐labeled RBCs. Although today, magnetic resonance imaging (MRI) is more commonly used for this purpose because of its superior anatomical resolution and high sensitivity for detecting small lesions and those adjacent to vascular structures, the specificity of MRI is less than Tc‐99m‐labeled RBCs. Some benign and malignant lesions have findings similar to hemangioma on MRI. Few false‐positive Tc‐99m RBC studies have ever been reported. With single photon emission computed tomography (SPECT), sensitivity approaches 100% for detection of hemangiomas greater than 1.4 cm in size. Sensitivity decreases for small hemangiomas, although hemangiomas as small as 0.5 cm may be detected. Hemangiomas show increased activity compared to normal liver (Figure 92.10). All other liver masses, benign and malignant, appear cold on Tc‐99m RBC imaging.

Tc‐99m sulfur colloid (SC) liver spleen imaging

Tc‐99m SC was routinely used for liver spleen imaging before the advent of CT to evaluate benign and malignant disease in the liver. Its role today is more limited, but it still provides valuable information in selected situations.