Tc-99m-Mebrofenin (HIDA)⁹⁹ᵐTc-mebrofenin / disofenin

Quick Answer

Hepatobiliary iminodiacetic-acid agents (HIDA; mebrofenin/disofenin) are taken up by hepatocytes and excreted into bile, imaging the biliary system dynamically. Main uses: acute cholecystitis (gallbladder non-visualization), bile leak, neonatal biliary atresia, and the gallbladder ejection fraction (GBEF) with CCK for suspected functional/chronic biliary disease. Gallbladder non-visualization at 60 minutes (persisting after morphine or delayed imaging) is the highest-yield finding.

Mechanism & Biodistribution

HIDA agents are taken up by hepatocytes (sharing organic-anion transport with bilirubin) and excreted via MRP2 into bile, so the study follows liver → bile ducts → gallbladder → bowel. Mebrofenin is preferred at higher bilirubin levels (better hepatic extraction). High serum bilirubin competes for uptake and degrades images.

Clinical Indications

• Acute cholecystitis — cystic-duct obstruction (gallbladder non-visualization).
• Bile leak localization (post-cholecystectomy, trauma, transplant).
• Neonatal biliary atresia vs neonatal hepatitis (with phenobarbital preparation).
• Chronic acalculous cholecystitis / biliary dyskinesia — GBEF after CCK.
• Sphincter-of-Oddi dysfunction and biliary-enteric anastomosis patency (selected).

Protocol Essentials

• Fast ~4 hours before the study — but not too long: prolonged fasting or TPN gives a full, non-contractile gallbladder and false non-visualization (pretreat with CCK to empty it first).
• Dynamic imaging of liver → ducts → gallbladder → bowel over ~60 min, with delayed images as needed.
• Morphine augmentation or delayed (3–4 h) imaging for non-visualization at 60 min.
• CCK (slow infusion) to measure GBEF; phenobarbital for 3–5 days before neonatal atresia imaging.

Interpretation — Acute Cholecystitis

Gallbladder non-visualization at 60 min with normal duct/bowel transit indicates cystic-duct obstruction = acute cholecystitis. Confirmation uses one of two maneuvers:

• Morphine contracts the sphincter of Oddi, raising ductal pressure to promote gallbladder filling — persistent non-visualization despite morphine strengthens the diagnosis.
• Delayed imaging (3–4 h) — filling by then suggests chronic rather than acute cholecystitis.

The "rim sign" (increased pericholecystic hepatic activity) suggests complicated/gangrenous cholecystitis.

Gallbladder Ejection Fraction (GBEF)

After the gallbladder fills, a CCK infusion stimulates contraction; GBEF = (pre − post) ÷ pre volume (counts) × 100. A low GBEF (commonly < 38%) with reproduced symptoms supports chronic acalculous cholecystitis / biliary dyskinesia. Standardize the CCK infusion (rapid infusion causes paradoxical low EF).

Neonatal Biliary Atresia

The key question is bile-duct patency. With phenobarbital preparation (enhances biliary excretion), any tracer in the bowel excludes biliary atresia (favoring neonatal hepatitis). No bowel activity even on delayed (24 h) images is consistent with atresia — a time-critical diagnosis (Kasai portoenterostomy window).

Reporting Checklist

• Time to gallbladder, duct, and bowel visualization; response to morphine/delayed imaging.
• GBEF with the CCK protocol used; symptom reproduction.
• For neonates, explicit statement of bowel activity present/absent (patency).
• Note bilirubin level and fasting/TPN status affecting the read.

Common Pitfalls

• High serum bilirubin reduces hepatic extraction/image quality (favor mebrofenin).
• Prolonged fasting/TPN → full non-contractile gallbladder → false non-visualization (pretreat with CCK); a recent meal contracts the gallbladder and can also prevent filling.
• Rapid CCK infusion → falsely low GBEF.
• Reading neonatal studies without phenobarbital prep (reduces sensitivity for excluding atresia).

Board Pearls

HIDA follows liver → ducts → gallbladder → bowel; gallbladder non-visualization at 60 min (persisting after morphine or delayed imaging) indicates cystic-duct obstruction = acute cholecystitis — the single highest-yield finding. Morphine promotes gallbladder filling (sphincter-of-Oddi contraction); CCK measures the GBEF for chronic acalculous disease.

Prolonged fasting or TPN produces a full, non-contractile gallbladder and false non-visualization — pretreat with CCK; high bilirubin degrades extraction (use mebrofenin). The rim sign flags complicated/gangrenous cholecystitis.

In neonatal biliary atresia, prepare with phenobarbital; any bowel activity excludes atresia (favoring neonatal hepatitis), while absent bowel activity at 24 h is consistent with atresia — a time-critical read for the Kasai window. A GBEF < ~38% with symptom reproduction supports biliary dyskinesia (standardize CCK to avoid a paradoxically low value).

Related Pages

• Related: Liver–spleen & hemangioma imaging (hepatobiliary chapter), esophageal/reflux/salivary studies.
• Pitfalls: Pearls, pitfalls & normal variants.

Figure / Diagram Suggestions

• A normal biliary transit sequence (liver → ducts → GB → bowel) with timing.
• An acute-cholecystitis decision flow (60 min non-vis → morphine/delayed → diagnosis; rim sign).
• GBEF calculation schematic (pre/post CCK counts).

Self-Check (Board-Style)