Hepatobiliary and Liver–Spleen Imaging

1. Anatomy in brief

• The liver bud arises from the foregut; its cranial part forms the liver, its caudal part the gallbladder and cystic duct.
• Physiological lobes: divided by Cantlie's line (gallbladder fossa to IVC), along the middle hepatic vein. The caudate and quadrate lobes are anatomically right but functionally left.
• Couinaud segments: hepatic veins divide the liver vertically, portal branches horizontally, giving eight segments (I–VIII).
• Caudate lobe (I): drains directly into the IVC, so it is often spared in Budd–Chiari syndrome and appears relatively 'hot' on colloid imaging.
• Gallbladder: 7–10 cm long, 40–50 mL; stores and concentrates bile between meals.

2. Liver–spleen colloid imaging

• ⁹⁹ᵐTc-sulfur colloid: particles of ~0.1–1 µm are phagocytosed by reticuloendothelial cells. Most go to the liver (Kupffer cells), the rest to spleen and bone marrow.
• Colloid shift: in diffuse liver disease or portal hypertension, relatively more tracer goes to spleen and marrow.
• Most focal lesions, benign or malignant, are photopenic because they lack Kupffer cells.
• Historical: ¹⁹⁸Au colloid (411 keV γ, T½ 2.7 days, β⁻ dose) is obsolete.

3. Other liver agents

• ⁹⁹ᵐTc-labelled RBCs (haemangioma): normal arterial flow, reduced activity on early blood-pool images, then increased activity on 1–2 h delayed images, equal to cardiac blood pool. Large haemangiomas may have cold areas from thrombosis or fibrosis. SPECT improves detection.
• ⁹⁹ᵐTc-MAA hepatic-artery perfusion: particles of 10–90 µm lodge in arterioles on first pass. Used before radioembolisation to show tumour and extrahepatic perfusion and to measure lung shunting. A lung shunt above 20% contraindicates resin microspheres; the lung dose is kept below 30 Gy (50 Gy cumulative).
• ¹¹¹In-pentetreotide: somatostatin-receptor imaging of neuroendocrine liver metastases (111 MBq planar, 222 MBq SPECT); now largely replaced by ⁶⁸Ga-DOTA-peptide PET.
• ⁶⁷Ga citrate and labelled leukocytes: historical use for tumour and abscess; FDG PET/CT has largely replaced them.

4. Hepatobiliary scintigraphy (HIDA)

The tracers

• ⁹⁹ᵐTc-iminodiacetic acid (IDA) derivatives, originally lidocaine analogues; the ring substitutions change their kinetics.
• Mebrofenin (bromo-trimethyl IDA): hepatic extraction ~98%; the most resistant to displacement by high bilirubin.
• Disofenin (di-isopropyl IDA): hepatic extraction ~89%.
• They are transported bound to albumin, taken up by hepatocytes through organic-anion pathways (competing with bilirubin) and excreted into bile without conjugation.

Preparation and protocol

Reading the study

• Flow: spleen and kidneys appear first; the liver appears later because most of its supply is portal. Increased flow to the gallbladder fossa can accompany severe acute cholecystitis.
• Hepatocyte function: judged by how fast the cardiac blood pool clears (normally within minutes).
• Gallbladder: normally fills within 60 min; filling beyond 60 min is delayed.
• Ducts and bowel: ducts and small bowel should be seen within 60 min. Scintigraphy shows whether ducts drain, not whether they are dilated.

5. Clinical uses

Acute cholecystitis

• Usually caused by a stone obstructing the cystic duct.
• Non-filling at 60 min is abnormal but not yet diagnostic. Persistent non-visualisation at 3–4 h, or 30 min after morphine, is diagnostic (calculous and acalculous).
• Morphine augmentation: 0.04 mg/kg (or 2 mg) IV over 2–3 min contracts the sphincter of Oddi, raises duct pressure and fills the gallbladder if the cystic duct is patent; image a further 30–60 min.
• Accuracy: sensitivity 96% and specificity 90% in a meta-analysis of 57 studies, higher sensitivity than ultrasound (81%).
• Rim sign: increased pericholecystic hepatic activity, a marker of severe inflammation (gangrene, perforation risk). Cystic-duct sign: a small focus of dilated cystic duct mistaken for the gallbladder.

Chronic cholecystitis and gallbladder ejection fraction

• Delayed filling (>60 min) is common, but filling may be normal.
• Standard GBEF protocol: after gallbladder filling, sincalide 0.02 µg/kg infused over 60 min; GBEF at 60 min. Normal ≥38% (interdisciplinary consensus).
• A low GBEF supports chronic cholecystitis or functional gallbladder disorder in the right clinical setting; a normal GBEF argues against it.

Biliary atresia

• Progressive fibro-obliterative cholangiopathy of infancy; Kasai portoenterostomy is most effective when done early (ideally within the first 60 days).
• A gallbladder on ultrasound does not exclude atresia.
• Protocol: phenobarbital 5 mg/kg/day for 3–5 days to stimulate bile flow; image to 24 h.
• Pattern: atresia — good early uptake but no bowel activity by 24 h; neonatal hepatitis — poor uptake but bowel activity usually appears. Pooled sensitivity 98.7%, specificity 70.4%.

Bile leak

• After cholecystectomy, trauma or biliary surgery. Ultrasound and CT show fluid; HIDA shows whether it is bile.
• A progressively enlarging collection in the gallbladder fossa or hepatic hilum, spreading over the liver dome, into the gutters or free in the abdomen. Image drains and collection bags; right lateral decubitus views help.

Biliary obstruction

• High-grade (recent) obstruction: good hepatocyte uptake with no excretion (persistent hepatogram), often before ducts dilate on ultrasound (which can take 24–72 h).
• Partial obstruction: prompt uptake and excretion but delayed ductal clearance, retained or increasing ductal activity and delayed biliary-to-bowel transit.
• Sphincter of Oddi dysfunction: after cholecystectomy, a partial obstruction at the sphincter without stone, stricture or tumour; scintigraphic scoring systems help select patients.
• Choledochal cyst: a non-obstructed cyst fills slowly and retains tracer; this confirms its connection to the biliary tree.
• Biliary-enteric anastomoses (e.g. Roux loop, Whipple): HIDA shows leak, patency and recurrent obstruction; bowel activity by 60 min supports patency.
• Other uses: biliary stent function, enterogastric bile reflux, focal nodular hyperplasia (normal or increased uptake with delayed clearance).

6. Spleen and red cells

• The spleen is seen with colloids, labelled red cells (including heat-damaged RBCs for splenic tissue), leukocytes and somatostatin-receptor tracers, but not with HIDA agents.
• ⁵¹Cr-labelled red cells: hexavalent ⁵¹Cr enters the cell, is reduced to trivalent chromium and binds haemoglobin; released chromium does not relabel other cells. Used for red-cell volume and survival (with organ counting), not imaging.

Summary

1. Fast 2–6 h; pretreat with sincalide after >24 h fasting; delay the study for ~4 half-lives of an opioid.
2. Gallbladder not seen at 3–4 h or 30 min after morphine = acute cholecystitis.
3. GBEF: 60-min sincalide infusion, normal ≥38%.
4. No bowel activity by 24 h after phenobarbital suggests biliary atresia.
5. HIDA identifies bile leaks and shows obstruction before duct dilatation.
6. Colloid, RBC and MAA studies answer different liver questions.

Test yourself

5 quick questions. Pick an answer to see the explanation.

References

1. Tulchinsky M, Ciak BW, Delbeke D, et al. SNM practice guideline for hepatobiliary scintigraphy 4.0. J Nucl Med Technol. 2010;38(4):210-8.
2. Ziessman HA, Tulchinsky M, Lavely WC, et al. Sincalide-stimulated cholescintigraphy: a multicenter investigation to determine optimal infusion methodology and gallbladder ejection fraction normal values. J Nucl Med. 2010;51(2):277-81.
3. DiBaise JK, Richmond BK, Ziessman HH, et al. Cholecystokinin-cholescintigraphy in adults: consensus recommendations of an interdisciplinary panel. Clin Gastroenterol Hepatol. 2011;9(5):376-84.
4. Kiewiet JJ, Leeuwenburgh MM, Bipat S, et al. A systematic review and meta-analysis of diagnostic performance of imaging in acute cholecystitis. Radiology. 2012;264(3):708-20.
5. Kianifar HR, Tehranian S, Shojaei P, et al. Accuracy of hepatobiliary scintigraphy for differentiation of neonatal hepatitis from biliary atresia: systematic review and meta-analysis of the literature. Pediatr Radiol. 2013;43(8):905-19.