The document summarizes nuclear medicine techniques for evaluating various biliary tract disorders. Cholescintigraphy using radiotracers can help diagnose acute cholecystitis, functional gallbladder disorders, and gallstone ileus. It evaluates gallbladder ejection fraction to identify sphincter of Oddi dysfunction and determine surgical candidacy for patients with functional gallbladder disorders. Biliary leaks after surgery are also detectable on hepatobiliary scans.

1. Nuclear Medicine in
Biliary Tract Disorders:
An Evidence Based
Approach
Ramin Sadeghi, MD
Nuclear Medicine Research Center, Mashhad University of Medical
Sciences, Mashhad, Iran

2. Acute Cholecystitis
 A syndrome of right upper quadrant pain, fever, and leukocytosis associated
with gallbladder inflammation that is usually related to gallstone disease
 PATHOGENESIS —
 Occurs in the setting of cystic duct obstruction
 Clinical Presentation:
 Prolonged (more than four to six hours), steady, severe right upper quadrant or
epigastric pain, fever, abdominal guarding, a positive Murphy's sign, and
leukocytosis

4. Cholescintigraphy in acute cholecystitis
 Indicated if the diagnosis remains uncertain following ultrasonography
 Conditions that can cause false positive results despite a non-obstructed cystic
duct include:
 Severe liver disease, which may lead to abnormal uptake and excretion of the tracer.
 Fasting patients receiving total parenteral nutrition, in whom the gallbladder is already
maximally full due to prolonged lack of stimulation.
 Morphin augmentation or delayed imaging can overcome this problem
 Biliary sphincterotomy, which may result in low resistance to bile flow, leading to
preferential excretion of the tracer into the duodenum without filling of the gallbladder.
 Hyperbilirubinemia, which may be associated with impaired hepatic clearance of
iminodiacetic acid compounds. Newer agents commonly used in cholescintigraphy
(diisopropyl and m-bromotrimethyl iminodiacetic acid) have generally overcome this
limitation

7. Acalculous cholecystitis
 Accounts for approximately 10 percent of all cases of acute cholecystitis and
is associated with high morbidity and mortality rates
 Typically seen in patients who are hospitalized and critically ill
 Acalculous cholecystitis should be considered in patients who are critically ill
or injured and have a clinical picture of sepsis or jaundice without a clear
source. It should also be considered in patients with postoperative jaundice.
 In stable patients in whom the diagnosis is unclear after ultrasonography, a
scan using technetium labeled hepatic iminodiacetic acid (HIDA) may be
useful

9. Functional gallbladder disorders in
adults
 Biliary pain resulting from a primary gallbladder motility disturbance in the
absence of gallstones, sludge, microlithiasis, or microcrystal disease.
 Should be considered in patients with typical biliary-type pain who have had
other causes for the pain excluded.
 The prevalence of functional gallbladder disorder among patients with biliary-
type pain and a normal transabdominal gallbladder ultrasound is up to 8
percent in men and 21 percent in women

10. Clinical manifestation
 Present with biliary-type pain, also known as biliary colic.
 Their liver and pancreas blood tests are normal, no gallstones or gallbladder
sludge are seen on imaging, and upper endoscopic examinations are normal.
 Biliary colic is usually constant and not colicky.
 Intense discomfort located in the right upper quadrant or epigastrium that may radiate
to the back (particularly the right shoulder blade).
 The pain is often associated with diaphoresis, nausea, and vomiting.
 The pain plateaus in less than an hour, ranging from moderate to excruciating in severity.
Once it has plateaued, the pain typically lasts at least 30 minutes and then slowly
subsides over several hours, with the entire attack usually lasting less than six hours.
 Develops one to two hours after ingestion of a fatty meal,
 An association with meals is not universal, and in a significant proportion of patients the
pain is nocturnal, with a peak occurrence around midnight
 After an attack, the physical examination is usually normal

11. Rome III criteria
 To fulfill the Rome III criteria for biliary-type pain, patients need to have pain that:
 ●Is located in the epigastrium and/or right upper quadrant
 ●Is recurrent, but occurs at variable intervals (not daily)
 ●Lasts at least 30 minutes
 ●Builds up to a steady level
 ●Is severe enough to interrupt daily activities or lead to an emergency department visit
 ●Is not relieved by bowel movements, postural changes, or antacids
 Structural diseases that would explain the patient's symptoms are excluded, and that liver
enzymes, pancreatic enzymes, and bilirubin are normal.
 Criteria that support the diagnosis, but are not required, include:
 (a) pain that is associated with nausea and vomiting,
 (b) pain that radiates to the back and/or right subscapular region, and
 (c) pain that awakens the patient from sleep in the middle of the night.

12. Diagnosis
 Functional gallbladder disorder is a diagnosis of exclusion in a patient with
typical biliary-type pain.
 The first step in the evaluation of such patients is to exclude other causes for
the patient's pain.
 If no other causes are identified, patients should undergo cholecystokinin
(CCK)-stimulated cholescintigraphy to confirm the diagnosis

13. Cholescintigraphy
 Allows for
 calculation of the gallbladder ejection fraction (GBEF), which is low in patients
with functional gallbladder disorder (<40 percent)
 helps predict which patients are likely to respond to cholecystectomy.
 Should only be performed in patients with typical biliary symptoms.
 It should not be ordered for atypical symptoms such as bloating, fullness, or dyspeptic
symptoms, as these patients are unlikely to respond to surgery even in the presence of a
low GBEF

15. Method
 Following an overnight fast, radiotracer is given as an intravenous bolus.
 The radiolabeled tracer is excreted in the bile, and if the cystic duct is
patent, it will flow into the gallbladder.
 After 45 to 90 minutes, baseline radioactivity from the region of the
gallbladder is measured.
 30-60 min infusion of sincalide then another measurement of the gallbladder
 Alternatively fatty meal with 20 gr fat is used
 The potential disadvantage of the fatty meal stimulation is that the gallbladder
emptying has to be monitored for a minimum of 60 min following the meal because
of a longer latent period in comparison with CCK infusion

16. Fatty meals

17. The quantitative HIDA scan shows early filling of the gallbladder at 25
minutes. At 57 minutes, infusion of CCK was initiated (broad white
arrow). Mild reduction of gallbladder activity was demonstrated. The
ejection fraction was 30 percent (normal 40 percent or greater).

18. LAO view:
In the 60-min anterior view there is overlap of the gallbladder, common duct,
and duodenum.
The LAO view separates these structures and makes accurate calculation
possible.

19. This patient had chronic recurrent right upper quadrant pain with normal ultrasonography.
The 60-min study (not shown) was normal with visualization of the gallbladder
and normal biliary-to-bowel transit.
A: Sequential images every 5 min for 25 min after injection of CCK show no contraction
of the gallbladder.
B: Gallbladder time-activity curve from the patient in A. Abnormal gallbladder ejection
fraction is 160/0 (abnormal <35%).Surgery diagnosed chronic acalculus cholecystitis.

20. Pitfalls
 Multiple medications and medical conditions other than functional gallbladder
disorder are associated with decreased gallbladder emptying
 False-positive results can be seen with
 diabetes, celiac disease, obesity, cirrhosis,
 and several medications, including calcium channel blockers,
oral contraceptives/progesterone,histamine-2 receptor antagonists, opiates,
benzodiazepines, atropine, octreotide, and theophylline.

21. Patient selection for cholecystectomy
 Patients with functional gallbladder disorder are candidates for
cholecystectomy if they have typical biliary-type pain and a low GBEF (<40
percent).
 While studies suggest that such patients are likely to benefit from
cholecystectomy, most of the studies showing an association of a low GBEF
with improved outcomes are retrospective, and GBEF has not conclusively
been proven to be a reliable indicator of clinical outcome.
 However, while imperfect, it is the most studied predictor of whether a
patient will respond to cholecystectomy

23. Non-surgical treatment of gallstone
disease
 The main treatment is UDC
 Patient selection
 Patients with severe medical problems who are at high risk for or refuse surgery
and who have mildly to moderately symptomatic gallstone disease.
 Mild to moderate symptoms includes
 Episodic biliary pain that occurs fewer than two to three times a month and can be
controlled with the use of oral analgesics
 and the absence of complications such as cholecystitis, cholangitis, pancreatitis, or
obstructive jaundice

24. Non-surgical treatment of gallstone
disease
 Patient selection
 CT scan
 Highly calcified stones and stones with dense surface calcification are unlikely to dissolve
and are more resistant to lithotripsy.
 Cholescintigraphy
 A functioning gallbladder is necessary to ensure that gallbladder debris is expelled and to
minimize stone recurrence.
 Normal Gallbladder EF should be discerned.
 Asymptomatic patients with incidentally found gallstones should not be treated.

25. Gallstone ileus
 Caused by impaction of a gallstone in the ileum after being passed through a
biliary-enteric fistula.
 Through a biliary enteric fistula, which complicates 2 to 3 percent of all cases
of cholelithiasis with associated episodes of cholecystitis.
 Sixty percent are cholecystoduodenal fistulas, but cholecystocolonic and
cholecystogastric fistulas can also result in gallstone ileus
 The classic clinical presentation of gallstone ileus is in an older woman with
episodic subacute obstruction.

26. Gallstone ileus
 CT Scan
 The imaging modality of choice
 ●Gallbladder wall thickening
 ●Pneumobilia (nonspecific)
 ●Intestinal obstruction
 ●Obstructing gallstones
 Plain abdominal radiography
 When CT is not available
 ●Signs of partial or complete intestinal obstruction.
 ●Pneumobilia.
 ●Visualization of the gallstone (less than 15 percent of gallstones are visible
 ●Change in position of a previously located stone.
 ●Two adjacent small bowel air-fluid levels in the right upper quadrant.

29. Gallstone ileus
 Other tests may be performed when CT scan and plain radiography of the
abdomen have been performed but are not diagnostic of gallstone ileus
 Cholescintigraphy
 Cholescintigraphic criteria of perforation (were detected in 50% cases)
 free spill,
 pericholecystic hepatic activity
 and scintigraphic gallstone Ileus sign

34. Post Cholecystectomy syndrome
 Postcholecystectomy syndrome (PCS) is a complex of heterogeneous symptoms,
including persistent abdominal pain and dyspepsia, that recur and persist after
cholecystectomy
 ●Biliary causes of PCS include:
 •Early PCS can be due to biliary injury, retained cystic duct, or common bile duct stones.
 •Late PCS can be due to recurrent CBD stones, bile duct strictures, an inflamed cystic
duct or gallbladder remnant, papillary stenosis, or biliary dyskinesia. ●Extrabiliary
causes of PCS include:
 Extra-biliary causes
 •Gastrointestinal causes such as irritable bowel syndrome, pancreatitis, pancreatic
tumors, pancreas divisum, hepatitis, peptic ulcer disease, mesenteric ischemia,
diverticulitis, or esophageal diseases
 •Extraintestinal causes such as intercostal neuritis, wound neuroma, coronary artery
disease, or psychosomatic disorders

35. Post Cholecystectomy syndrome
 Diagnosis of the underlying problem causing PCS usually requires imaging to
look for
 retained or recurrent stones
 or identify a bile duct leak, stricture, or transection.
 This can be accomplished in most cases with ultrasound and/or computed
tomography (CT) scanning followed by direct cholangiography or magnetic
resonance cholangiopancreatography (MRCP).

36. Cytic Duct Remnant

37. Biliary injuries following biliary tract
surgery
 After an uncomplicated elective laparoscopic cholecystectomy, patients can
drink clear liquids once awake from anesthesia and their diet can be
advanced as tolerated
 US is the first imaging method to be done
 If necessary, better definition can be obtained by computed tomography (CT)
scan

41. Biliary leak
 After the demonstration of fluid in the peritoneum, we obtain a hepatobiliary
imino-diacetic acid scan (HIDA) scan to delineate leakage of radiotracer into
the peritoneal cavity and confirm that the fluid is bile.
 Biliary scintigraphy cannot anatomically localize the site of injury but is
diagnostic of an ongoing bile leak in virtually all patients
 Delayed imaging is mandatory if the early ones are negative

45. Patient with low GBEF who after
cholecystectomy had biliary leak

47. Bile leak
 If the HIDA scan confirms an active bile leak, determination of the site of the
leak is usually made by endoscopic retrograde cholangiopancreatography or
MRCP

50. Management of the bile leak
 Management is highly dependent of the type of leak
 In Type C and D injuries, a repeat HIDA scan is performed two to four weeks
after stent insertion. If there is no leak, the stent can be removed
endoscopically at repeat ERCP

52. Sphincter of Oddi dysfunction (SOD)
 The term sphincter of Oddi dysfunction encompasses both
 Sphincter of Oddi stenosis
 Sphincter of Oddi dyskinesia.
 SOD has been associated with two clinical syndromes:
 biliary pain
 Idiopathic recurrent acute pancreatitis
 two or more attacks of well documented acute pancreatitis of unclear cause despite an
exhaustive work-up (laboratory and noninvasive imaging) with complete resolution of
clinical and laboratory findings between attacks.

54. SOD
 Biliary SOD is most commonly recognized in patients who have undergone
cholecystectomy (hence the name postcholecystectomy syndrome).
 may be related to unmasking of pre-existing SOD due to removal of the gallbladder,
which may have served as a reservoir to accommodate increased pressure in the
biliary system occurring during sphincter spasm

55. Rome III criteria
 To fulfill the Rome III criteria for biliary-type pain, patients need to have pain that:
 ●Is located in the epigastrium and/or right upper quadrant
 ●Is recurrent, but occurs at variable intervals (not daily)
 ●Lasts at least 30 minutes
 ●Builds up to a steady level
 ●Is severe enough to interrupt daily activities or lead to an emergency department visit
 ●Is not relieved by bowel movements, postural changes, or antacids
 Structural diseases that would explain the patient's symptoms are excluded
 Criteria that support the diagnosis, but are not required, include:
 (a) pain that is associated with nausea and vomiting,
 (b) pain that radiates to the back and/or right subscapular region, and
 (c) pain that awakens the patient from sleep in the middle of the night.

56. SOD
ROME III Criteria
 Functional gallbladder disorder —
 ●Criteria for functional gallbladder and sphincter of Oddi disorders are fulfilled
 ●Gallbladder is present
 ●Normal liver enzymes, conjugated bilirubin, and amylase/lipase
 Functional biliary sphincter of Oddi disorder —
 ●Criteria for functional gallbladder and sphincter of Oddi disorder are fulfilled
 ●Normal amylase/lipase
 Supportive criteria include elevated serum aminotransferases, alkaline phosphatase, or
conjugated bilirubin (>twice the upper limit of normal) temporally related to at least two pain
episodes and a dilated common bile duct (>8 mm).
 Functional pancreatic sphincter of Oddi disorder —
 ●Criteria for functional gallbladder and sphincter of Oddi disorder are fulfilled
 ●Elevated amylase/lipase

57. Classification of SOL
Revised ROME III Milwaukee Biliary Group
classification
 ●Type I patients present with biliary-type pain, abnormal aminotransferases,
bilirubin or alkaline phosphatase (>2 times normal values) documented on two
or more occasions, and a dilated bile duct (>8 mm on ultrasound).
 Approximately 65 to 95 percent of these patients have manometric evidence of
biliary SOD.
 ●Type II patients present with biliary-type pain and one of the previously
mentioned laboratory or imaging abnormalities.
 Approximately 50 to 63 percent of these patients have manometric evidence of
biliary SOD.
 ●Type III patients complain only of recurrent biliary-type pain and have none
of the previously mentioned laboratory or imaging criteria.
 Approximately 12 to 59 percent of these patients have manometric evidence of
biliary SOD.

58. SOD
Diagnostic workup
 Only patients fulfilling the Rome III criteria should undergo invasive
evaluation for SOD
 Liver tests (transaminases, alkaline phosphatase, bilirubin) and pancreatic enzymes
(amylase, lipase) should be checked,
 Structural abnormalities need to be excluded.
 Transabdominal ultrasound is typically the initial imaging study
 Alternate imaging techniques, such as magnetic resonance cholangiopancreatography
(MRCP), may be required for evaluation of the pancreatic duct.

59. SOD
Diagnostic workup
 Type I SOD
 Do not require additional testing and can be referred directly for ERCP with
endoscopic sphincterotomy
 Type II SOD
 Should undergo SOM to confirm the diagnosis and to select patients likely to
respond to treatment.
 Alternatively hepatobiliary scintigraphy (in patients whose gallbladder is intact) or
a fatty meal ultrasound study (in patients with or without a gallbladder)

60. SOD
Diagnostic workup

61. SOD
Quantitative cholescintigraphy
 Hepatobiliary scintigraphy using technetium-99m labeled dyes can provide a
standardized, semiquantitative assessment of delayed biliary drainage in
patients whose gallbladder is absent
 Criteria used for diagnosis
 the time to peak
 the half time of excretion
 the duodenal appearance time (DAT)
 the hilum to duodenum transit time (HDTT)
 Some studies used CCK but many used simple cholescintigraphy

62. SOD
Cholescintigraphy

63. SOL
Cholescintigraphy indices

64. SOL
Cholescintigraphy indices

66. SOD
CCK augmented scintigraphy: Sostre score with 5 as
cutoff

67. SOD
CCK augmented scintigraphy: Sostre score
with 5 as cutoff

68. SOD
Manometry
 Recommended for Type II SOD as manometry results correlates with
sphincterotomy
 For Type I and III is not recommended generally
 Results of Manometry
 Patients with SOD have been divided into two groups based upon manometric
findings:
 ●Patients with structural alterations of the sphincter of Oddi (stenosis)
 elevated basal sphincter of Oddi pressure (>40 mmHg)
 ●Patients with functional abnormalities (dyskinesia)
 elevated basal sphincter of Oddi pressure (>40 mmHg) which disappears upon amyl nitrite
or glucagone infusion

69. SOD
Performance of Cholescintigraphy as
compared to manometry

70. SOD
Performance of other non-invasive tests

76. Bile Reflux

77. Biliary cysts
 Biliary cysts are cystic dilations that may occur singly or in multiples
throughout the biliary tree.
 They were originally termed choledochal cysts due to their involvement of
the extrahepatic bile duct.

78. Classification of cysts

79. Biliary cysts
Presentation
 The majority of patients with biliary cysts will present before the age of 10 years
 The classic presentation includes the triad of abdominal pain, jaundice, and a
palpable mass
 Patients may also present with signs and symptoms related to complications
associated with biliary cysts, including pancreatitis, cholangitis, and obstructive
jaundice.
 Serum liver tests are often normal in patients with biliary cysts.
 Biliary cysts are associated with an increased risk of cancer, particularly
cholangiocarcinoma
 Cancer is more common in patients who are older and in those with type I and IV cysts.
 patients with type I or IV cysts have the cysts completely removed with Roux-en-Y
hepaticojejunostomy.

80. Diagnostic approach
 Cysts are often first suspected based on the findings from transabdominal
ultrasonography or computed tomography (CT) in a patient being evaluated
for abdominal pain, jaundice, or an abdominal mass.
 If a cyst is suspected based on an ultrasound, cross-sectional imaging with CT
or MRI with magnetic resonance cholangiopancreatography (MRCP) is typically
the next step in diagnosis.

81. Diagnostic approach
Role of Cholescintigraphy
 Types II and IVB cysts – If it is unclear whether the cyst communicates with
the biliary tree after cross-sectional imaging, confirmation may be obtained
by hepatobiliary scintigraphy

82. Biliary cyst
Hepatobiliary Scintigraphy
 the characteristic appearance is of an ovoid or spherical photon-deficient
area that shows progressive radiotracer accumulation on delayed imaging (>2
hours after injection), with persistent pooling of activity seen for up to 24
hours
 HIDA scanning may also be useful in cases of cyst rupture since excreted
contrast may be seen within the peritoneal cavity in these patients

83. An example of choledochal cyst in a 10 year
old boy with jaundice and suspicious type II
biliary cyst on CT

84. En example of choloedochal cyst rupture
A 2-year-old girl presented with jaundice of 2 weeks’
duration. Ultrasonography of the abdomen revealed ascites
and a dilated common bile duct suggestive of a choledochal
cyst.

85. Caroli’s disease and syndrome
 Caroli disease is a congenital disorder characterized by multifocal, segmental
dilatation of large intrahepatic bile ducts
 The condition is usually associated with renal cystic disease of varying severity.
Caroli initially described two variants, which has led to some confusion in
terminology.
 ●Caroli disease is the less common form and is characterized by bile ductular ectasia
without other apparent hepatic abnormalities.
 ●The more common variant is Caroli syndrome in which bile duct dilatation is associated
with congenital hepatic fibrosis.

86. Caroli’s disease and syndrome
 Hepatobiliary scintigraphy can be used to differentiate Caroli’s disease from
polycystic liver disease

87. A 28 year old man with portal
hypertension

88. A 28 year old man with portal
hypertension

89. A 15 year old boy with hepatomegaly

90. A 15 year old boy with hepatomegaly
suspicious of Caroli’s disease

91. Liver transplantation
Role of cholescintigraphy
 Early bile leaks
 In cases where a T-tube is in place, small anastomotic leaks can be diagnosed with
a T-tube cholangiogram and be managed by leaving the tube open without further
intervention.
 In patients without a T-tube, ERC is considered the gold standard diagnostic
method in detecting bile leaks.
 Hepatobiliary scintigraphy (HIDA) scanning, which has a sensitivity of
approximately 50 percent and a specificity of approximately 80 percent, can be
helpful in cases where there is a low suspicion for a bile leak
 Roux-en-Y choledochojejunostomy anastomotic leaks are less common.
 A suspected bile leak in such patients can be diagnosed with a HIDA scan if the patient
does not have a drainage catheter in place.
 ERC is often not feasible

93. Neonatal cholestasis
 Conjugated hyperbilirubinemia in a neonate is defined as a serum conjugated
bilirubin concentration greater than 1.0 mg/dL (17.1 micromol/L) if the total
serum bilirubin is <5.0 mg/dL (85.5 micromol/L) or greater than 20 percent of
the total serum bilirubin if the total serum bilirubin is
>5.0 mg/dL (85.5 micromol/L).
 An elevated conjugated bilirubin is an abnormal finding and requires
additional evaluation

96. Diagnostic work up
 Biliary atresia must be identified early and differentiated from other causes
of neonatal cholestasis because early surgical intervention (ie, before 2
months of age) results in a better outcome. Important steps in making this
diagnosis are ultrasonography and liver biopsy.
 Combination of physical exam, laboratory tests and imaging should be done
 Ultrasonography — As a general rule, abdominal ultrasonography commonly is used
as the initial test

97. Diagnostic workup
Cholescintigraphy
 The test depends upon adequate hepatocellular function and patency of the
biliary tract.
 However, nonvisualization of the gallbladder or lack of excretion can occur in
patients without biliary atresia
 Several methods can increase the accuracy
 Scintigraphy adds little to the routine evaluation of the cholestatic infant, but
may be of value in determining patency of the biliary tract, thereby excluding
biliary atresia.
 However, it should never be relied upon solely to make a diagnosis in neonatal
cholestasis

98. Diagnostic workup
 In the evaluation of an infant with cholestasis of unknown etiology,
ultrasonography of the liver is almost always included and liver biopsy is
usually indicated.
 Scintigraphy and duodenal aspirate are not routinely recommended but may
be useful in situations in which other tests are not readily available.

99. Methods to increase accuracy of
Scintigraphy

101. Two examples