# Hepatobiliary Scintigraphy (HIDA Scan)

## Overview

Hepatobiliary iminodiacetic acid (HIDA) scintigraphy evaluates hepatocyte function, bile duct patency, gallbladder function, and bile flow dynamics. IDA agents are taken up by hepatocytes and excreted into the biliary system, mimicking the metabolic pathway of bilirubin. The primary indications include acute cholecystitis, bile leak detection, neonatal biliary atresia, chronic acalculous cholecystitis, and post-surgical biliary assessment.

## Radiopharmaceuticals

Tc-99m mebrofenin (Choletec) is the preferred agent because of its high hepatic extraction efficiency, which remains reliable even when bilirubin is elevated up to 20 to 30 mg/dL. Tc-99m disofenin (Hepatolite) is an alternative but becomes less effective when bilirubin exceeds 10 mg/dL. The dose is 5 to 10 mCi (185 to 370 MBq) administered intravenously. The mechanism involves uptake by hepatocytes via the organic anion transporter, followed by conjugation and excretion into the bile canaliculi.

## Technique

The patient should fast for 4 to 6 hours before the study to ensure optimal gallbladder filling. Prolonged fasting beyond 24 hours can cause a false positive result by preventing the chronically distended gallbladder from filling during the study. Dynamic anterior abdominal imaging is acquired at 1-minute frames for 60 minutes. The normal sequence shows liver visualization within 5 minutes, followed by intrahepatic bile ducts, then the common bile duct, and finally the gallbladder and duodenum, all within 30 to 60 minutes. If the gallbladder is not visualized at 60 minutes, the study is extended to 4 hours or morphine augmentation is performed.

<image>Normal hepatobiliary scintigraphy showing sequential visualization of the liver, intrahepatic bile ducts, common bile duct, gallbladder, and duodenum within 60 minutes</image>

## Acute Cholecystitis

### Pathophysiology

Acute cholecystitis results from cystic duct obstruction, usually by a gallstone, which prevents the gallbladder from filling with bile. Non-visualization of the gallbladder by 60 minutes (or 4 hours without morphine augmentation) is the hallmark scintigraphic finding.

### Diagnostic Criteria

A study is positive for acute cholecystitis when the gallbladder is not visualized at 60 minutes with morphine augmentation, or at 3 to 4 hours without morphine. A normal study shows gallbladder filling within 30 to 60 minutes. The sensitivity is 95 to 97% and the specificity is 90 to 95%, making HIDA scintigraphy the most accurate imaging modality for diagnosing acute cholecystitis.

### Morphine Augmentation

Morphine is administered when the gallbladder has not been seen at 60 minutes but the common bile duct and duodenum are visualized, confirming hepatocyte function and bile excretion are intact. The dose is 0.04 mg/kg intravenously. Morphine causes contraction of the sphincter of Oddi, which increases biliary pressure and forces bile into the gallbladder if the cystic duct is patent. Imaging continues for an additional 30 minutes after morphine administration. Persistent non-visualization after morphine is positive for acute cholecystitis. Contraindications include morphine allergy, acute pancreatitis, and risk of respiratory depression.

### Ancillary Findings in Acute Cholecystitis

The rim sign, also called pericholecystic hepatic activity, is increased tracer activity in the liver adjacent to the gallbladder fossa. It indicates severe inflammation or gangrenous cholecystitis and is associated with complications such as perforation and abscess. The rim sign has high specificity for acute cholecystitis and should be communicated urgently. Delayed bile duct visualization may suggest distal common bile duct obstruction. Absent bowel activity suggests complete biliary obstruction rather than isolated cystic duct obstruction.

<image>Acute cholecystitis on HIDA scan: non-visualization of the gallbladder at 60 minutes with morphine augmentation, positive rim sign indicating severe inflammation, and normal CBD and duodenal activity</image>

## False Positives (Non-Visualization Without Acute Cholecystitis)

Prolonged fasting beyond 24 hours can cause the chronically distended gallbladder to fail to fill during the study. This is addressed by pre-treatment with sincalide (CCK) at 0.02 mcg/kg intravenously over 15 minutes, administered 30 minutes before tracer injection, to contract the gallbladder and empty it. Total parenteral nutrition causes chronic gallbladder non-contraction and can produce the same false positive result. Chronic cholecystitis with cystic duct fibrosis may prevent filling. Severe hepatocellular disease impairs tracer extraction and excretion. A post-prandial state from a recent meal causes gallbladder contraction, and the cystic duct may be functionally closed.

| Finding | Interpretation | Sensitivity/Specificity | Action |
|---|---|---|---|
| GB non-visualization (with morphine) | Acute cholecystitis | 95–97% / 90–95% | Surgical consultation |
| GB visualization | Excludes acute cholecystitis | High NPV | Look for alternative diagnosis |
| Rim sign (pericholecystic activity) | Gangrenous/complicated cholecystitis | High specificity | Urgent surgical referral |
| GBEF <35% (60-min CCK infusion) | Gallbladder dyskinesia | Variable | Consider cholecystectomy |
| Tracer outside biliary/bowel | Bile leak | High sensitivity | Surgical/IR intervention |
| No bowel activity at 4 h | Complete biliary obstruction | High | Evaluate for CBD stone/mass |

## False Negatives (Gallbladder Visualization Despite Acute Cholecystitis)

Acalculous cholecystitis, in which no stone is obstructing the cystic duct, can allow tracer entry into the gallbladder. Partial cystic duct obstruction may permit some tracer entry. These scenarios are rare, and the sensitivity of HIDA for acute cholecystitis remains very high at 95 to 97%.

## Chronic Acalculous Cholecystitis (Gallbladder Dyskinesia)

### CCK-Stimulated Gallbladder Ejection Fraction (GBEF)

The gallbladder ejection fraction is measured after sincalide (CCK-8 analog) infusion at 0.02 mcg/kg intravenously over 60 minutes. The standardized 60-minute infusion rate is critical for reproducible results. The GBEF is calculated from pre- and post-CCK gallbladder counts. A normal GBEF is 35 to 40% or greater, though exact thresholds vary by institution and infusion duration. A low GBEF below 35% suggests gallbladder dyskinesia and may predict symptom improvement after cholecystectomy.

### Controversy

The clinical significance of a low GBEF remains debated. Some studies show that cholecystectomy relieves biliary-type symptoms in 80 to 90% of patients with a low GBEF, while others show no difference in outcomes between surgery and conservative management. The sincalide infusion rate significantly affects results: rapid infusion over 3 minutes causes artificially low GBEF values because the gallbladder contracts against a supraphysiologic stimulus. Standardization to a 60-minute infusion is essential for accurate and reproducible results.

## Bile Leak Detection

### Post-Cholecystectomy Bile Leak

A bile leak appears as progressive accumulation of tracer outside the biliary system and bowel lumen. It is seen as a progressively enlarging area that fills with tracer, typically adjacent to the cystic duct stump, the surgical bed, or the subhepatic space. Delayed images at 1 to 4 hours best detect this complication. SPECT/CT improves localization of the leak site.

### Post-Liver Transplant Bile Leak

The appearance is similar to a post-cholecystectomy leak, but the leak may occur at the bile duct anastomosis. Serial imaging monitors for resolution or progression.

## Neonatal Biliary Atresia

### Clinical Context

HIDA scintigraphy is used to differentiate biliary atresia from neonatal hepatitis in infants presenting with conjugated hyperbilirubinemia. Biliary atresia requires early surgical intervention with the Kasai portoenterostomy procedure, and delay worsens outcomes. Ultrasound findings may be equivocal, showing an absent or small gallbladder or the triangular cord sign.

### HIDA Scan Protocol

The infant is pre-treated with phenobarbital at 5 mg/kg/day for 5 days to enhance hepatocyte excretory function. Tc-99m mebrofenin or disofenin is administered, and imaging is obtained at 4 hours and 24 hours.

### Interpretation

In biliary atresia, there is good hepatic uptake initially but complete absence of intestinal activity at 24 hours, reflecting total biliary obstruction. In neonatal hepatitis, intestinal activity is present, even if delayed, because the biliary system is patent despite hepatocellular dysfunction causing poor hepatic uptake. With phenobarbital pre-treatment, the sensitivity for biliary atresia is approximately 97%. Specificity is 80 to 85%, as neonatal hepatitis with severe cholestasis may mimic atresia by also showing no intestinal activity.

<image>Neonatal biliary atresia on HIDA scan: good hepatic uptake at 5 minutes but complete absence of intestinal activity at 24 hours despite phenobarbital pretreatment, versus neonatal hepatitis showing delayed but present intestinal activity</image>

## Bile Duct Obstruction

Bile duct obstruction produces delayed or absent visualization of the common bile duct and duodenum. There is good hepatic uptake with persistent hepatic activity because bile cannot be excreted. Causes include choledocholithiasis, pancreatic head mass, and stricture. The study may show the level of obstruction when proximal ducts are dilated and no activity passes distally.

## Clinical Pearls

Fasting duration matters. The ideal fasting period is 4 to 6 hours. Fasting longer than 24 hours causes false-positive gallbladder non-visualization.

Morphine augmentation shortens the study from 4 hours to approximately 90 minutes without sacrificing accuracy.

The rim sign is a red flag for gangrenous cholecystitis or impending perforation and should be communicated urgently.

For gallbladder ejection fraction measurement, sincalide infusion over 60 minutes is mandatory for accurate results. Rapid infusion produces unreliably low values.

In neonates, phenobarbital pre-treatment for 5 days is essential to maximize diagnostic accuracy for biliary atresia.

Mebrofenin is preferred over disofenin when bilirubin is elevated above 5 mg/dL.

In post-cholecystectomy patients with abdominal pain and suspected bile leak, HIDA scan is the test of choice.

## References

- SNMMI Procedure Standard for Hepatobiliary Scintigraphy.
- Defined Role of HIDA Scan in Acute Cholecystitis. *Seminars in Nuclear Medicine*, 2012.
- Ziessman, H. A. "Sincalide-Stimulated Cholescintigraphy: Standard of Practice." *Journal of Nuclear Medicine*, 2014.
- AAP Guidelines: Evaluation of Cholestatic Jaundice in Infants.