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Contents

  1. 18.1 Salivary Gland Scintigraphy (Tc-99m Pertechnetate)
  2. 18.2 Oesophageal Transit Scintigraphy
  3. 18.3 Gastro-oesophageal Reflux Scintigraphy
  4. 18.4 Gastric Emptying Scintigraphy (Solid and Liquid)
  5. 18.5 Meckel's Diverticulum Scintigraphy
  6. 18.6 GI Bleeding Scintigraphy (Tc-99m Labelled Red Blood Cells)
  7. 18.7 Hepatobiliary Scintigraphy (Tc-99m HIDA/DISIDA)
  8. 18.8 Liver-Spleen Scintigraphy (Tc-99m Sulphur Colloid)
  9. 18.9 Hepatic Haemangioma with Tc-99m Labelled Red Blood Cells
  10. 18.10 C-14 Urea Breath Test (H. pylori)
  11. Key Points for the Board
  12. Current guidelines on this chapter's topics
← Back‹ Chapter 17Chapter 19 ›

Chapter 18Clinical applicationsLast reviewed: 14 Nov 2026 · What's new

Gastrointestinal System

Report template: Gastrointestinal bleeding scintigraphy (Tc-99m RBC) · Hepatobiliary scintigraphy (Tc-99m mebrofenin / disofenin)

This chapter's English text is a draft translation (prepared with Claude and checked against a terminology glossary and automatic checks); specialist review is in progress. Please report errors with the feedback button.

Solve questions (26) →
Contents
  1. 18.1 Salivary Gland Scintigraphy (Tc-99m Pertechnetate)
  2. 18.2 Oesophageal Transit Scintigraphy
  3. 18.3 Gastro-oesophageal Reflux Scintigraphy
  4. 18.4 Gastric Emptying Scintigraphy (Solid and Liquid)
  5. 18.5 Meckel's Diverticulum Scintigraphy
  6. 18.6 GI Bleeding Scintigraphy (Tc-99m Labelled Red Blood Cells)
  7. 18.7 Hepatobiliary Scintigraphy (Tc-99m HIDA/DISIDA)
  8. 18.8 Liver-Spleen Scintigraphy (Tc-99m Sulphur Colloid)
  9. 18.9 Hepatic Haemangioma with Tc-99m Labelled Red Blood Cells
  10. 18.10 C-14 Urea Breath Test (H. pylori)
  11. Key Points for the Board
  12. Current guidelines on this chapter's topics
Learning objectives and modules4 modules · about 3 h

Learning objectives

After this chapter you will be able to:

  • Explain the technique and interpretation of salivary gland, oesophageal transit and gastro-oesophageal reflux scintigraphy.
  • Apply the standard protocol and normal values of gastric emptying scintigraphy.
  • Explain tracer selection, preparation and interpretation in Meckel's diverticulum and gastrointestinal bleeding scintigraphy.
  • Interpret hepatobiliary scintigraphy for acute cholecystitis, bile leak, biliary atresia and gallbladder ejection fraction; select pharmacological interventions.
  • State the principle and indications of liver–spleen scintigraphy, haemangioma imaging and the urea breath test.

Modules

The chapter is divided into study modules without changing the order of the text: read, watch the animations, then answer the questions linked to those headings.

  1. Module 118.1–18.4 Salivary Gland Scintigraphy (Tc-99m Pertechnetate) · Oesophageal Transit Scintigraphy · Gastro-oesophageal Reflux Scintigraphy · Gastric Emptying Scintigraphy (Solid and Liquid)1 h · 1 animation · 22 questionsAnswer the questions →
  2. Module 218.5–18.6 Meckel's Diverticulum Scintigraphy · GI Bleeding Scintigraphy (Tc-99m Labelled Red Blood Cells)40 min · 17 questionsAnswer the questions →
  3. Module 318.7 Hepatobiliary Scintigraphy (Tc-99m HIDA/DISIDA)45 min · 2 animations · 16 questionsAnswer the questions →
  4. Module 418.8–18.10 Liver-Spleen Scintigraphy (Tc-99m Sulphur Colloid) · Hepatic Haemangioma with Tc-99m Labelled Red Blood Cells · C-14 Urea Breath Test (H. pylori) · Key Points for the Board35 min · 12 questionsAnswer the questions →

Times are estimates: 130 words per minute, 3 min per animation, 1.5 min per question.

Tip cards (72) →

MOST FREQUENTLY ASKED IN THIS CHAPTER

✓
Agent: Tc-99m pertechnetate (taken up via NIS)
✓
Stimulation: Lemon juice (at 15-20 minutes)
✓
Sjögren syndrome: Reduced uptake + absent/reduced secretion
✓
Pertechnetate-avid tumour: Warthin tumour (hot nodule)
✓
Commonest salivary gland tumour: Pleomorphic adenoma → does not take up pertechnetate (cold)
✓
Agent: Tc-99m sulphur colloid (in liquid)
✓
Normal transit time: <15 seconds (classical); EANM upper limit ≤30 seconds

18.1 Salivary Gland Scintigraphy (Tc-99m Pertechnetate)4 questions

Basic Principles

The salivary glands (parotid, submandibular, sublingual) actively trap and secrete Tc-99m pertechnetate. This property is used to assess salivary gland function. Mechanism: because of its structural similarity to the iodide ion, pertechnetate is taken up by salivary ductal cells via the sodium-iodide symporter (NIS) and secreted into saliva.

Indications

•
Assessment of Sjögren syndrome (the commonest indication)
•
Assessment of salivary gland function (before/after radiotherapy)
•
Aetiology of xerostomia (dry mouth)
•
Functional assessment of salivary gland masses
•
Warthin tumour and oncocytoma (pertechnetate-avid tumours)

Protocol

•
Radiopharmaceutical: Tc-99m pertechnetate, 5-10 mCi (185-370 MBq) IV
•
Imaging: Dynamic images (1 min/frame, 30 minutes)
•
Stimulation: Lemon juice is given at 15-20 minutes → stimulates salivary secretion
•
ROI analysis: ROIs over the parotid and submandibular glands → time-activity curve
•
EANM European Nuclear Medicine Guide: adult 37 MBq is recommended (the methods part of the same chapter gives 185-370 MBq; there is no EANM or SNMMI guideline for this study, so the method is validated locally); 13 µSv/MBq, i.e. ~0.5 mSv. Peak uptake without background correction is seen at ~30 minutes. Breastfeeding is interrupted for 12 hours (the test is postponed if possible)
•
In the salivary gland NIS has been shown to be present only in ductal cells; quantitative assessment is recommended
•
It is among the American-European Consensus Group classification criteria for Sjögren syndrome; it is also used to monitor salivary gland damage after RAI treatment
•
The test can only distinguish loss of parenchymal function from an outflow (obstruction) problem; it does not determine the cause of xerostomia
•
Preparation: fasting for at least 2 hours. Drugs affecting salivary secretion or uptake (such as anticholinergics, SSRIs, opioids) are stopped at least 5 biological half-lives before, unless a treatment effect is being measured, and thyroid-blocking agents such as iodine or perchlorate 48 hours before; no thyroid-blocking agent is given. Some conditions such as GER may influence the choice of sialogogue (EANM Technologists' Guide 2023; European Nuclear Medicine Guide)

Normal Findings

•
Uptake phase (0-15 min): Progressively increasing uptake in the glands
•
Normally the glands appear in the first minutes and activity in the oral cavity appears at ~10-15 minutes. Salivary gland uptake is equal to or greater than that of the thyroid; uptake markedly lower than the thyroid suggests parenchymal dysfunction
•
Secretion phase (after lemon juice): Rapid fall in glandular activity + increase in activity in the oral cavity
•
In normal glands activity falls by >50% after lemon juice
–
European NM Guide: ejection fraction about >55% for the parotid and >45% for the submandibular glands; parotid/thyroid uptake ratio 0.7-0.9, submandibular/thyroid 0.6-0.8. Normal values depend on the method and population
–
Pitfalls: the gland/thyroid ratio depends on thyroid function and regional iodine status and is not used in hypo- or hyperthyroidism. Head movement during acquisition impairs semi-quantitative and quantitative analysis. Contamination on the collimator surface degrades the image; the collimator is covered. The sublingual glands are usually not visible

Pathological Findings

Sjögren syndrome:

•
Uptake reduced or absent
•
Secretion after lemon juice markedly reduced or absent → flat curve
•
Bilateral and symmetric involvement
•
EANM: Conditions with bilaterally reduced uptake and a weak response to citric acid: RAI damage, connective tissue diseases, chemotherapy, advanced age, sarcoidosis, amyloidosis, diabetes, primary biliary cirrhosis, chronic pancreatitis, cystic fibrosis
•
Sialadenosis: Uptake is increased because secretion is reduced; secretion is abnormal (reduced)
•
Acute sialadenitis: Intense activity is seen in the flow phase; because the gland is swollen, subsequent accumulation and excretion are reduced
•
Abscess: Peripheral hyperaemia (rim) in the flow phase and a photopenic focus on delayed images. Cysts and tumours other than Warthin tumour and oncocytoma also produce cold defects

Warthin tumour:

•
Pertechnetate-avid salivary gland tumour (hot nodule)
•
Usually in the parotid, in men, may be bilateral
•
Oncocytoma also takes up pertechnetate but is much rarer
•
Another name for Warthin tumour is papillary cystadenoma lymphomatosum, and for oncocytoma oxyphilic adenoma. Because they have no ductal connections, they do not empty after lemon juice; as the normal gland empties, the focus becomes more conspicuous
BOARD TIP
▸
"Pertechnetate-avid salivary gland tumour?"

→ Warthin tumour (and oncocytoma).

▸
"Scintigraphic finding in Sjögren syndrome?"

→ Reduced uptake + absent/reduced secretion after lemon juice.

▸
"Why is pertechnetate taken up by the salivary gland?"

→ Via NIS (sodium-iodide symporter).

Pleomorphic adenoma (mixed tumour):

•
The commonest salivary gland tumour, but it does NOT take up pertechnetate → cold nodule
•
Important in the differential diagnosis from Warthin tumour
BOARD TIP
▸
"Commonest salivary gland tumour?"

→ Pleomorphic adenoma → does not take up pertechnetate (cold).

▸
"Pertechnetate-avid tumour?"

→ Warthin tumour → hot nodule. This distinction is frequently asked in board exams!

A Tc-99m pertechnetate time-activity curves lemon juice >50% fall (secretion) uptake phase reduced uptake, no response → flat curve Normal parotid Oral cavity Sjögren (bilateral) 0 5 10 15 20 25 30 Time (min) Gland activity B Parotid masses (anterior, schematic) hot nodule Warthin tumour (and oncocytoma) pertechnetate AVID cold nodule Pleomorphic adenoma (commonest tumour) pertechnetate NON-AVID parotid lateral, submandibular below; thyroid also avid

Figure 18.1: Normal and Sjögren time-activity curves on salivary gland scintigraphy; Warthin tumour (hot) and pleomorphic adenoma (cold) (schematic).

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18.2 Oesophageal Transit Scintigraphy3 questions

Basic Principles

Oesophageal transit scintigraphy is a non-invasive method that assesses oesophageal motor function and bolus transport.

Indications

•
Assessment of achalasia
•
Scleroderma (systemic sclerosis) → oesophageal dysmotility
•
Diffuse oesophageal spasm
•
Aetiology of dysphagia
•
Functional assessment after oesophageal surgery/treatment

Protocol

•
Radiopharmaceutical: Tc-99m sulphur colloid, 150-300 μCi (5.5-11 MBq) → in 10-15 mL of water
•
Patient sitting or supine
•
Single-swallow or multiple-swallow technique
•
Dynamic imaging: 0.5-1 s/frame
•
Condensed image: All frames arranged side by side → oesophageal transit pattern

Assessment

•
Transit time: In classical sources the normal value is <15 seconds (sitting, single swallow); in the EANM protocol the upper limit of normal is ≤30 seconds
•
Retention: Normal → <10% retention (at 10 seconds)
•
Normal on the condensed image → a smooth diagonal line (the bolus progresses regularly)
•
EANM: There is no consensus on a standard protocol. 50 mL of apple purée (50 MBq) as semi-solid, 1 g of pâté (37 MBq) as solid, or 3.7-37 MBq in 10-30 mL of water may be used
•
The patient swallows the bolus in one go, then dry-swallows several times; the study is repeated upright and supine. Frame duration 0.5 s, acquisition time 30-60 s
•
EANM (≤30 s threshold): Sensitivity 95%, specificity 96% in achalasia and scleroderma
•
Manometry is the gold standard for diagnosis. ETS shows peristalsis directly; quantitative measurement of total oesophageal emptying is useful for monitoring treatment response in achalasia
•
Preparation: Fasting for at least 6 hours in the morning; prokinetic drugs are stopped 3 days before. 9.1 µSv/MBq, i.e. 0.3-0.5 mSv
•
Why multiple swallows are performed: ~25% of swallows may be abnormal; a dry swallow performed immediately afterwards suppresses the first peristaltic wave and produces a false delay. The supine position removes the effect of gravity and increases the sensitivity for detecting dysmotility
•
Transit time: The time from entry of the bolus into the oesophagus until 90% of the initial activity has cleared. The disorder to which scintigraphy is most sensitive is achalasia

Pathological patterns:

•
Achalasia: Retention at the lower oesophageal sphincter (LOS) → "bird's beak" pattern → transit absent/delayed
•
Scleroderma: Loss of peristalsis in the lower 2/3 of the oesophagus → retention (smooth muscle involvement)
•
Diffuse spasm: Irregular, segmental retention → "serrated" pattern
•
In diffuse spasm the bolus fragments and moves backwards, and multiple peaks are seen on the time-activity curves. In a Zenker diverticulum an oval or round persistent focus of retention is seen in the upper segment
BOARD TIP
▸
"Oesophageal involvement in scleroderma?"

→ Lower 2/3 (smooth muscle) → loss of peristalsis.

▸
"Scintigraphic finding in achalasia?"

→ Retention at the LOS, transit into the stomach absent/delayed.

▸
"Normal oesophageal transit time?"

→ <15 seconds.

A Normal 0 15 30 Time (s) Smooth diagonal line; transit <15 s B Achalasia 0 15 30 Time (s) Retention at LOS; no/delayed transit C Scleroderma 0 15 30 Time (s) Retention in lower 2/3 (loss of peristalsis) D Diffuse spasm 0 15 30 Time (s) Irregular, segmental retention ("serrated") proximal middle LOS stomach

Figure 18.2: Condensed image patterns on oesophageal transit scintigraphy: normal, achalasia, scleroderma and diffuse spasm (schematic).

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18.3 Gastro-oesophageal Reflux Scintigraphy1 questions

Basic Principles

Gastro-oesophageal reflux (GOR) scintigraphy is a non-invasive method that assesses backflow of gastric contents into the oesophagus. It is preferred especially in paediatric patients (low radiation, non-invasive).

Indications

•
Assessment of paediatric GOR (the commonest indication)
•
Suspected recurrent aspiration pneumonia
•
Situations in which pH monitoring cannot be performed
•
Assessment of pulmonary aspiration (activity in the lungs on delayed images)

Protocol

Adult:

•
Tc-99m sulphur colloid, 0.5-1 mCi (18.5-37 MBq) → in 300 mL of acidic orange juice
•
Graded pressure increase with an abdominal binder (0-100 mmHg)
•
Dynamic imaging in the supine position (30-60 minutes)

Paediatric:

•
Tc-99m sulphur colloid → in milk or formula
•
No abdominal binder is used
•
Dynamic imaging + delayed images (2-24 hours) → assessment of pulmonary aspiration

Assessment

•
Retrograde activity seen in the oesophagus → GOR positive
•
A reflux index can be calculated
•
Classical adult protocol: 150 mL orange juice and 150 mL 0.1 N HCl are given (acid relaxes the LES and increases sensitivity); a reflux index >4% is abnormal
•
Activity in the lungs on delayed images → pulmonary aspiration (clinically very important)
•
EANM: Sulphur colloid is not broken down by gastric acid and is not absorbed by the mucosa. 18.5-185 MBq is given with 100-300 mL of milk or fruit juice, followed by 50-100 mL of unlabelled fluid
•
Imaging: Supine posterior dynamic imaging, frame duration 15 s, for up to 1 hour (~200 frames); fasting for at least 6 hours
•
Diagnosis of GOR: At least one reflux episode seen as sharp spikes of activity extending from the stomach into the oesophagus or airways
•
First-line tests are oesophageal pH monitoring and multichannel intraluminal impedance; GOR scintigraphy no longer has a place in initial assessment
•
In children it remains important for objectively demonstrating reflux into the airways (recurrent infection, refractory asthma, apnoea, failure to thrive)
•
Because of lack of standardisation, sensitivity has been reported between 15-100% and specificity between 81-100%; dose 0.16-1.6 mSv
•
Interpretation and pitfalls (EANM Technologists' Guide 2023): new activity in the oesophagus is a reflux episode; the number and level of episodes (distal, proximal oesophagus, oropharynx) are noted, and the number of frames with oesophageal activity divided by the total gives a crude residence time. Motion brings gastric counts into the oesophageal ROI and distorts the curve. Labelled milk spilled during feeding or brought up by vomiting may mimic or hide aspiration over the lungs; continuing feeding with the unlabelled portion of the meal clears residual activity from the mouth and oesophagus. Sedation and anaesthesia are prohibited because they impair swallowing; a naso-jejunal tube is replaced by a nasogastric tube. For aspiration, static chest images are acquired at 1 and 4 hours (rarely at 24 hours)
–
A single reflux episode may be physiological postprandial reflux; a negative result does not exclude GER disease. NASPGHAN/ESPGHAN (2018) do not recommend scintigraphy for diagnosing GER disease in children (expert opinion); the role of scintigraphy is to show aspiration and gastric emptying
•
Radionuclide salivagram: A small amount of Tc-99m sulphur colloid is dropped on the tongue and dynamic images are acquired; activity in the tracheobronchial tree shows salivary aspiration (independent of reflux)
BOARD TIP
▸
"Lung activity on delayed images in GOR scintigraphy?"

→ Pulmonary aspiration → a clinically very important finding.

▸
"Preferred method for assessing paediatric GOR?"

→ Scintigraphy (non-invasive, low radiation).

▸
"Agent used in GOR scintigraphy?"

→ Tc-99m sulphur colloid (in acidic liquid).

18.4 Gastric Emptying Scintigraphy (Solid and Liquid)14 questions

Basic Principles

Gastric emptying scintigraphy is the gold-standard method for quantitatively assessing the rate at which the stomach empties solid and/or liquid food.

Indications

•
Diagnosis and follow-up of gastroparesis (the commonest indication)
•
Diabetic gastroparesis
•
Assessment of gastric emptying after vagotomy/surgery
•
Functional dyspepsia
•
Dumping syndrome (rapid emptying)
•
Assessment of the efficacy of drug treatment (prokinetic agents)

Patient Preparation

•
Drugs affecting gastric emptying should be stopped 48-72 hours before:
–
Prokinetics (metoclopramide, erythromycin, domperidone)
–
Opioids (slow gastric emptying)
–
Anticholinergics
•
Fasting: At least 4-6 hours
•
In diabetic patients: Blood glucose should be ≤275 mg/dL (hyperglycaemia slows gastric emptying)
•
Smoking affects gastric emptying → should not smoke on the day of the test
BOARD TIP
▸
"Which drugs should be stopped before gastric emptying scintigraphy?"

→ Prokinetics, opioids, anticholinergics (48-72 hours before).

▸
"Blood glucose limit in a diabetic patient?"

→ ≤275 mg/dL (hyperglycaemia mimics gastroparesis).

▸
"Effect of smoking?"

→ Affects gastric emptying → prohibited on the day of the test.

Protocol – Solid Food (Standard)

SNMMI/EANM Consensus Protocol:

•
Standard meal: Egg-white sandwich labelled with Tc-99m sulphur colloid
–
2 egg whites (Egg Beaters® or equivalent)
–
2 slices of bread + 30 g strawberry jam
–
120 mL water
•
Tc-99m sulphur colloid: 0.5-1 mCi (18.5-37 MBq)
•
Imaging times: 0, 1, 2 and 4 hours (the 4-hour protocol is standard)
•
Anterior and posterior images at each time point → geometric mean calculated
•
Decay correction is applied (Tc-99m, T½ = 6 hours)
•
EANM standard meal: A well-cooked omelette made with 1-2 eggs (white and yolk mixed), toast, jam and water; labelled with 18-37 MBq sulphur colloid
•
Cooking the egg well changes the structure of the albumin cage, so the label stays bound to the meal for hours in an acid and pepsin environment
•
In a patient with egg allergy, porridge or pancakes can be used; the same meal should be given in all repeat studies
•
Effective dose 9.1 µSv/MBq, i.e. 0.16-0.34 mSv
•
With an orally administered labelled meal the large bowel wall receives the highest absorbed dose, because activity accumulates in the colon
•
Why the geometric mean is used: As the meal moves from the posterior fundus to the anterior antrum, anterior counts increase only because attenuation decreases; if a single projection is used, emptying appears slower than it is
•
Radiation-free alternative: C-13 octanoic acid breath test. After leaving the stomach, octanoic acid is absorbed in the duodenum and oxidised to CO2 in the liver; labelled CO2 in the breath reflects the emptying rate of the solid phase

Normal Values (Solid Food – 4-Hour Protocol)

TimeNormal Retention
0 hours100% (baseline)
1 hour90% → >90% retention abnormal (delayed emptying)
2 hours60% → >60% retention → abnormal
4 hours10% → >10% retention → gastroparesis

Critical value: >10% retention at 4 hours → diagnosis of gastroparesis

Grading of gastroparesis (4-hour retention):

•
Mild: 11-20%
•
Moderate: 21-35%
•
Severe: >35% (36-50%; >50% very severe)
•
EANM grading (retention at 3 or 4 hours): Grade 0 <10%, Grade 1 11-20%, Grade 2 21-35%, Grade 3 >35%
•
The relationship between delayed emptying and symptoms is weak; rapid and slow emptying cause similar symptoms but are treated differently
•
Opiates and anticholinergic antispasmodics delay emptying, prokinetics accelerate it; smoking slows emptying
•
Other causes of delayed emptying: Anorexia nervosa, atrophic gastritis or pernicious anaemia, renal failure (uraemia), hypothyroidism, scleroderma, amyloidosis, vagotomy
•
Other indications: IBS, chronic liver disease, hypothyroidism, before and after heart-lung and kidney-pancreas transplantation
•
Physiology: The fundus empties liquids by tonic contraction, the antrum empties solids by grinding. The commonest cause of chronic gastroparesis is diabetes; diabetes prolongs the lag phase of the solid phase
•
Truncal vagotomy: Because receptive relaxation of the fundus is lost, liquids empty rapidly; because antral grinding is impaired, solids are delayed (if a drainage procedure or antrectomy is added, solid emptying may also accelerate)
•
Meal volume, caloric density, content (fat), particle size and consistency change the emptying rate; a standard meal should therefore be used. In a mixed meal the solid phase slows liquid emptying

Protocol – Liquid Food

•
Water or liquid labelled with In-111 DTPA (dual-isotope study simultaneous with the solid)
•
Liquid emptying → exponential kinetics (no lag phase)
•
Solid emptying → linear kinetics (lag phase present → slow at first, then linear)
•
Liquid emptying is generally faster than solid
•
In a single-isotope liquid-only study, Tc-99m sulphur colloid in water is used. The solid phase is more sensitive in gastroparesis; a liquid study is added in a patient who cannot tolerate a solid meal or when solid emptying is normal
•
Normal liquid T½: <20 minutes
BOARD TIP
▸
"Kinetics of solid gastric emptying?"

→ Linear (lag phase + linear phase).

▸
"Kinetics of liquid food?"

→ Exponential (no lag phase).

▸
">10% retention at 4 hours?"

→ Gastroparesis.

▸
"Standard meal?"

→ Egg-white sandwich (labelled with Tc-99m sulphur colloid).

▸
"Why is the geometric mean used?"

→ For attenuation correction (square root of anterior × posterior).

Rapid Gastric Emptying (Dumping Syndrome)

•
<30% retention at 1 hour → rapid emptying
•
Usually post-surgical (Billroth I/II, Roux-en-Y, vagotomy + pyloroplasty)
•
Early dumping (15-30 min): Vasomotor symptoms (sweating, tachycardia, hypotension)
•
Late dumping (1-3 hours): Reactive hypoglycaemia
•
Non-surgical causes of rapid emptying: Zollinger-Ellison syndrome, duodenal ulcer, hyperthyroidism, malabsorption (pancreatic insufficiency, sprue)
•
Report content (ANMS/SNM consensus 2008): in addition to the common items (see 27), how much of the meal was eaten and over what time, whether vomiting occurred after the meal, drugs taken in the previous 24 hours that affect emptying, fasting blood glucose in diabetic patients. Findings: percentage retained in the stomach at each time point with normal values (solid meal: 1 hour 37-90%, 2 hours 30-60%, 4 hours 0-10%); optionally a graph of retention over time; unusual findings such as oesophageal retention of the meal, hiatal hernia, fundoplication wrap, lack of fundic accommodation and retained old food
BOARD TIP
▸
"<30% retention at 1 hour?"

→ Rapid gastric emptying (dumping).

▸
"When is dumping syndrome most commonly seen?"

→ Post-surgical (gastric resection, vagotomy).

Left: anterior diagram of the stomach; solid meal particles (orange squares) are ground down in the antrum and pass the pylorus, while the liquid (green circles) empties at once. Right: percent retention curves for solid and liquid with the 1, 2 and 4 h thresholds.

Continuous stream · no seeking

The solid meal is first ground in the antrum (lag), then empties roughly linearly; >10% at 4 h is gastroparesis and <30% at 1 h is rapid emptying.

Source: thresholds and kinetics from book 18.4 (SNMMI/EANM consensus). Curves from a power-exponential model (Elashoff 1982; β = 2 solid, β = 1 liquid), values representative. Anatomy: OpenStax A&P 2e §23.4.

How to use: a single click on the drawing pauses and resumes; in the second step ↑ ↓ or the buttons under the chart change the scenario (normal, gastroparesis, rapid emptying); ← → change steps.

Speed
Test yourself:Chapter 18 · question 9Chapter 18 · question 2
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Figure 18.3: Solid gastric emptying curves and threshold values (A); solid (lag + linear) and liquid (exponential) emptying kinetics (B) (schematic).

Colonic Transit Scintigraphy (EANM)

•
Agents: In-111 DTPA in orange or apple juice (3.7-37 MBq), a capsule containing In-111 bound to amberlite resin (3.7 MBq) or Ga-67 citrate (3 MBq); none is absorbed and all are excreted in the faeces
•
Indications: Chronic constipation, irritable bowel syndrome; objective assessment if surgery is considered for severe transit delay
•
Assessment: The percentage of activity remaining in colonic segments and the geometric centre are calculated; with normal transit ~70% of the activity has been excreted at 48 hours (70.7 ± 9.1%, mean ± SEM, in 7 healthy men after In-111 DTPA instilled into the caecum through a tube; Krevsky 1986)
•
Imaging times and geometric centre: Images are acquired up to 6 hours on the first day and then at 24, 48 and 72 hours. The geometric centre is the weighted average of the fraction of counts in each colonic region multiplied by the region number; a low value means the activity is near the caecum, a high value that it is in the rectosigmoid or has been evacuated
•
Reference ranges (seven-region method; 7 = evacuated stool): 2.0-7.0 at 24 hours, 4.6-7.0 at 48 hours, 6.0-7.0 at 72 hours. Healthy individuals typically empty the colon completely by 72 hours; the 72-hour image is needed in particular to recognise functional rectosigmoid outlet obstruction
•
The five-region method with a delayed-release capsule has its own reference ranges (1.6-3.8 at 24 hours, 3.0-4.8 at 48 hours); numbers from the two methods are not interchangeable
Regions of the colon Anterior view: patient's right is on the left 1 2 3 4 5 6 7 stool caecum Geometric centre The fraction of counts in each region is multiplied by the region number and summed (weighted average). Reference ranges 24 h 2.0-7.0 48 h 4.6-7.0 72 h 6.0-7.0 1 2 3 4 5 6 7 low: activity near the caecum high: in the rectosigmoid or evacuated 1 Ascending colon 2 Hepatic flexure 3 Transverse colon 4 Splenic flexure 5 Descending colon 6 Rectosigmoid 7 Evacuated stool

Figure 18.3a: The seven regions in colon transit scintigraphy and the reference ranges of the geometric centre (schematic).

•
Patterns: In colonic inertia diffuse slow transit is seen throughout the colon; in functional rectosigmoid (outlet) obstruction proximal transit is normal and activity accumulates in the rectosigmoid
•
Drugs affecting motility are stopped 1 week before; pregnancy is a relative contraindication
•
Report content (SNMMI/EANM 2013): in addition to the common items (see 27), method used (radiolabelled charcoal in a delayed-release capsule or an In-111 DTPA liquid meal) and region scheme (5 or 7 regions), imaging times and any deviation from the standard meal. Findings: geometric centre at each time point with the method-specific reference values; the pattern (generalised slow transit, suspected colonic inertia or functional rectosigmoid outlet obstruction); it is stated that colonic inertia and outlet obstruction patterns need confirmation by manometry or defecography
•
Other GI function tests: The amount excreted in urine after oral Cr-51 EDTA shows small-bowel permeability (increased in coeliac disease, Crohn disease and alcohol use); Tc-99m human serum albumin shows loss into the bowel in protein-losing enteropathy
•
Bile acid malabsorption (Se-75 SeHCAT): A synthetic bile acid labelled with Se-75 (tauroselcholic acid) is swallowed as a capsule and absorbed like natural bile acids. A baseline count is taken within 3 hours of the capsule on day 1 and a second count one week later (day 8); the ratio of the second to the first gives the percentage retained. Bile acid diarrhoea is diagnosed when about 15% or less remains. Antidiarrhoeal drugs may affect the result and may need to be stopped for the duration of the test. The method is used in Europe

18.5 Meckel's Diverticulum Scintigraphy7 questions

Basic Principles

Meckel's diverticulum is a remnant of the vitellointestinal (omphalomesenteric) duct. It is the commonest congenital anomaly of the small bowel.

"Rule of 2's":

•
Seen in 2% of the population
•
2 feet (60 cm) proximal to the ileocaecal valve
•
2 inches (5 cm) long
•
Becomes symptomatic under 2 years of age (most commonly)
•
Two types of ectopic mucosa: Gastric mucosa (in ~60% of symptomatic cases, >90% of those that bleed, but only ~15-30% of all Meckel's diverticula) and pancreatic mucosa (5-15%)
•
EANM: Located 40-150 cm proximal to the ileocaecal valve; prevalence 1-3%; 70-80% of cases are asymptomatic; ectopic gastric mucosa is present in 60-85%
•
Presents with painless rectal bleeding in children and with diverticulitis, intussusception, volvulus or perforation in adults; bleeding is not an expected finding after 40 years of age
•
Male/female ratio: 2:1
•
Indication (SNMMI/EANM 2.0, 2014): to localise ectopic gastric mucosa in a Meckel diverticulum as the source of unexplained gastrointestinal bleeding; bleeding Meckel diverticula usually occur in young children. The study is performed when the patient is not actively bleeding; active bleeding, even in children, is best studied with labelled red cell scintigraphy (18.6). About 57% of Meckel diverticula contain ectopic gastric mucosa, but almost all diverticula in children presenting with lower GI bleeding do
–
Up to 2 years of age the thorax is included in the field of view (bronchopulmonary foregut malformation with ectopic mucosa). In a patient with significant recent bleeding and no other cause found over several weeks, a negative scan may be repeated after pretreatment with an H2 blocker or proton pump inhibitor

Radiopharmaceutical and Mechanism

•
Tc-99m pertechnetate IV injection
•
Pertechnetate is taken up by ectopic gastric mucosa (NIS and mucus-secreting cells)
•
Pertechnetate is taken up mainly by the mucus-secreting cells of the surface epithelium; scintigraphy can therefore be positive even in ectopic gastric mucosa without parietal cells
•
Gastric mucosa within the diverticulum → pertechnetate uptake → focal activity in the right lower quadrant
•
Detects only Meckel's diverticula containing gastric mucosa
•
Pancreatic mucosa → does not take up pertechnetate → scintigraphy negative

Protocol

•
Dose: 5-10 mCi (185-370 MBq) Tc-99m pertechnetate IV
•
Imaging: Dynamic (1 min/frame, 30-60 minutes) + static images
•
Patient supine, anterior projection
•
Bladder activity → may mask a Meckel's → a lateral or post-void image should be acquired
•
EANM: Adult 200 MBq (child at least 20 MBq); 13 µSv/MBq, i.e. ~2.6 mSv; breastfeeding is interrupted for 12 hours
•
Preparation: The patient should be fasting; no barium bowel study should have been performed in the last 3 days; drugs affecting motility are stopped 3 days before
•
The thyroid should not be blocked with perchlorate: perchlorate also blocks pertechnetate uptake by the gastric mucosa and causes a false-negative result
•
SPECT/CT increases sensitivity and helps to distinguish false-positive foci

Pharmacological Interventions (To Increase Sensitivity)

Pentagastrin:

•
Increases pertechnetate uptake by gastric mucosa but also increases secretion
•
No longer widely used

Cimetidine (H2 receptor blocker):

•
The most commonly used premedication
•
Does not affect pertechnetate uptake by gastric mucosa but blocks its secretion → pertechnetate accumulates in the gastric mucosa → signal increases
•
Dose: 20 mg/kg/day, started 2 days before (or 300 mg IV, 1 hour before)
•
EANM: Among H2 blockers ranitidine is preferred (IV 1 mg/kg, maximum 50 mg; orally 2 × 150 mg in adults, 2-4 mg/kg/day in children); cimetidine is given as 3 × 200 mg in adults
•
Pentagastrin carries a risk of false negatives from washout into the lumen and of peptic ulcer; the effect of omeprazole is unknown

Glucagon:

•
Reduces bowel peristalsis → reduces motion artefact
•
Slows secretion of pertechnetate into the lumen
BOARD TIP
▸
"Drug most commonly used to increase sensitivity in Meckel's scintigraphy?"

→ Cimetidine (H2 blocker) → blocks secretion → pertechnetate accumulates in the gastric mucosa.

▸
"Which mucosa does Meckel's scintigraphy detect?"

→ Ectopic gastric mucosa (pertechnetate-avid).

▸
"Is pancreatic mucosa detected?"

→ NO.

Normal and Pathological Findings

Normal: Uptake in the stomach and bladder (both take up pertechnetate), thyroid, salivary glands

Positive Meckel's:

•
Focal activity in the right lower quadrant (usually)
•
Appears at the same time as the stomach (both are gastric mucosa)
•
Intensity increases over time
•
Fixed location, independent of bowel activity

Causes of false positives:

•
Intussusception
•
Duplication cyst (may contain gastric mucosa)
•
Ectopic kidney
•
Ureteropelvic junction obstruction
•
Inflammatory bowel disease
•
Arteriovenous malformation

Causes of false negatives:

•
Meckel's diverticulum without gastric mucosa
•
Active bleeding → pertechnetate is washed out
•
Small diverticulum
•
Inadequate premedication

Diagnostic Accuracy

•
In children: Sensitivity 85-95%, specificity 95%
•
In adults: Lower sensitivity (60-70%) → lower rate of ectopic gastric mucosa
•
EANM: Sensitivity is ~85% in children and ~60% in adults. Neither a negative scintigram nor a normal barium follow-through excludes Meckel's diverticulum
•
Other causes of false positives: Uterine blush, free pertechnetate in the lumen, renal pelvis, ureter or bladder diverticulum, haemangioma, abscess, small-bowel tumours
•
Other causes of false negatives: Small (<1 cm²) diverticulum, rapid secretion, perchlorate, pentagastrin-induced washout, barium, overlapping bladder
•
Report content (SNMMI/EANM 2.0, 2014): in addition to the common items (see 27), duration of dynamic acquisition (e.g. 30 minutes or 1 hour) and frame rate, projections acquired (anterior, lateral), field of view (stomach to bladder) and whether images were reviewed in cine mode, premedication if given. Findings: times of appearance of gastric mucosa and of ectopic activity (early or late, whether simultaneous with the stomach), site, size and shape of ectopic activity (focal, round, oblong, diffuse) and whether it moves; confounding factors (bladder, ureter, active bleeding). The interpretation is given as positive, negative or indeterminate
BOARD TIP
▸
"If focal activity in the right lower quadrant appears at the same time as the stomach on Meckel's scintigraphy?"

→ Positive Meckel's (ectopic gastric mucosa).

▸
"Sensitivity in children?"

→ 85-95%.

▸
"Why is it lower in adults?"

→ The proportion with ectopic gastric mucosa decreases with age.

▸
"Rule of twos?"

→ 2%, 2 feet, 2 inches, 2 years, 2 types of mucosa, 2:1 male/female.

~5 min Right Left kidney ~15 min Right Left ~30 min Right Left stomach Meckel's (RLQ) bladder Focus appears with the stomach, intensifies over time; fixed site (independent of bowel activity). Bladder may mask the focus → post-void or lateral image. Increasing sensitivity • H2 blocker (cimetidine; EANM: ranitidine): uptake same, luminal secretion blocked → stays in mucosa • Glucagon: peristalsis ↓, motion artefact ↓ • Pentagastrin: uptake ↑ but secretion also ↑ (now rare) • Perchlorate NOT given (gastric mucosal uptake is also blocked → false negative)

Figure 18.4: Meckel's diverticulum scintigraphy: a right-lower-quadrant focus appearing at the same time as the stomach and intensifying over time; agents that increase sensitivity (schematic).

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18.6 GI Bleeding Scintigraphy (Tc-99m Labelled Red Blood Cells)10 questions

Basic Principles

GI bleeding scintigraphy is used to localise active gastrointestinal bleeding. Tc-99m labelled red blood cells remain in the intravascular space → extravasation at the bleeding site → focal accumulation of activity.

Indications

•
Active lower GI bleeding (the commonest indication)
•
Upper GI bleeding (if endoscopy is negative or cannot be performed)
•
Intermittent bleeding
•
Localisation of bleeding before angiography
•
The commonest cause of lower GI bleeding in the elderly is diverticulosis; in upper GI bleeding the first and most reliable method is endoscopy

Red Blood Cell Labelling Methods

A) In-vivo method:

•
Stannous (tin) pyrophosphate IV → wait 20 min → Tc-99m pertechnetate IV
•
Tin enters the red cell → Sn²⁺ reduces pertechnetate → Tc-99m binds to haemoglobin
•
Labelling efficiency: 75-80% (lowest)
•
Advantage: Easy, fast
•
Disadvantage: Low labelling efficiency → free pertechnetate → uptake in the stomach, thyroid, kidney → artefact
•
If tin is insufficient, free pertechnetate increases; if tin is excessive, pertechnetate is reduced outside the cell and cannot enter the red cell. In both cases labelling efficiency falls and background activity rises

B) Modified in-vivo (in-vivtro) method:

•
Stannous pyrophosphate IV → wait 20 min → blood is drawn → Tc-99m is added in the syringe → 10 min incubation → reinjection
•
Labelling efficiency: 85-90%

C) In-vitro method:

•
Blood is drawn from the patient and whole blood is incubated with stannous citrate (red cells need not be separated); sodium hypochlorite oxidises extracellular tin, then Tc-99m pertechnetate is added and the blood is returned to the patient
•
Labelling efficiency: >95% (highest)
•
UltraTag® RBC kit → standardised in-vitro method
•
Advantage: Highest labelling efficiency → fewest artefacts
•
Disadvantage: Time-consuming (~30 min), requires blood handling
BOARD TIP
▸
"Highest red cell labelling efficiency?"

→ In-vitro method (>95%).

▸
"Lowest?"

→ In-vivo (75-80%).

▸
"Where is free pertechnetate taken up?"

→ Stomach, thyroid, kidney → artefact.

▸
"UltraTag® kit?"

→ In-vitro method.

Common mechanism: Sn²⁺ (stannous ion) enters RBC → TcO₄⁻ is reduced → Tc-99m binds haemoglobin A In vivo Stannous pyrophosphate IV wait 20 min Tc-99m pertechnetate IV (directly in patient) Labelling efficiency: 75-80% (lowest) Easy, fast; free TcO₄⁻ → stomach, thyroid, kidney artefact B Modified in vivo (in vivtro) Stannous pyrophosphate IV blood drawn after 20 min Tc-99m added in syringe, 10 min incubation → reinjection Labelling efficiency: 85-90% (intermediate) Intermediate option C In vitro (UltraTag®) Whole blood + stannous citrate (no separation) Hypochlorite → Tc-99m labelling (in tube) Reinjection Labelling efficiency: >95% (highest) Fewest artefacts; time-consuming (~30 min), blood handling

Figure 18.5: Tc-99m red blood cell labelling methods and labelling efficiencies.

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Protocol

•
Dose: 20-30 mCi (740-1110 MBq) Tc-99m labelled red blood cells IV
•
Dynamic imaging: Continuous for the first 60 minutes (1 min/frame)
•
Delayed images: At 2, 4, 6 and if necessary up to 24 hours
•
The 6-hour half-life of Tc-99m → imaging possible up to 24 hours (red cells remain intravascular)
•
EANM: Adult 550-1110 MBq (child at least 20 MBq); 7 µSv/MBq, i.e. ~3.9-7.8 mSv. If scintigraphy is going to be positive, it mostly becomes positive within the first 4 hours
•
With in-vivo labelling, free pertechnetate may accumulate in breast tissue; breastfeeding is interrupted for 12 hours
–
Preparation (SNMMI/EANM 2.0): no preparation and no fasting are needed (fasting may be required for subsequent angiography or surgery); the patient voids just before imaging. Written safety policies prevent labelled blood being given to the wrong patient. In vitro labelling is the method of choice (≥95%; if efficiency is low, a centrifugation salvage can be tried); the in vivo method is not recommended and is used only for patients who do not accept injection of blood. No interruption of breastfeeding is needed with in vitro labelled red cells
–
Acquisition: anterior abdomen and pelvis, matrix at least 128 × 128; the angiographic phase is optional. Dynamic acquisition follows (longest frame 60 seconds; 10-20-second frames improve localisation and are later summed); serial intermittent static images are not recommended. If no bleeding is seen, imaging continues for at least 60 minutes. Delayed images are optional and are also acquired dynamically. Because a full bladder may hide sigmoid and rectal bleeding, lateral, posterior or subpubic views are added; in one study SPECT/CT was needed in 37% of patients for localisation or exclusion
•
In-111 labelled red cells are a theoretical option but image quality is poor. Tc-99m sulphur colloid is useful only if injected while bleeding is ongoing, and delayed images cannot be acquired
•
In a Tc-99m red cell study the critical organ is the heart wall (blood pool)

Detection Threshold

•
Scintigraphy: Can detect bleeding at a rate of 0.1-0.4 mL/min
•
Angiography: 0.5-1.0 mL/min (higher threshold than scintigraphy)
•
Scintigraphy is more sensitive than angiography but anatomical localisation is less precise
•
CT angiography: 0.3-0.5 mL/min
•
EANM: The probability of a positive result is highest in patients who have required transfusion of at least 500 mL of blood in the last 24 hours; mild bleeding at <0.5 mL/min mostly cannot be demonstrated
•
GI bleeding scintigraphy is not performed for chronic occult bleeding, because the guaiac test detects much smaller bleeds. It is indicated in mid and lower GI bleeding after upper GI bleeding has been excluded by nasogastric lavage or endoscopy
BOARD TIP
▸
"Detection threshold of GI bleeding scintigraphy?"

→ 0.1-0.4 mL/min.

▸
"Threshold of angiography?"

→ 0.5-1.0 mL/min.

▸
"Which is more sensitive?"

→ Scintigraphy.

▸
"Which localises better?"

→ Angiography.

Assessment

Criteria for a positive study:

•
Appearance of focal activity in an area where there is normally no activity
•
Movement of the activity over time (with peristalsis → antegrade or retrograde)
•
Focal activity that does not move and does not change shape over time suggests a vascular or blood-pool focus rather than bleeding (ectatic aorta, aneurysm, varix, collateral, haemangioma, accessory spleen)
•
Increase in activity over time

Localisation of bleeding:

•
The first focal activity to appear → shows the bleeding site
•
Small-bowel bleeding: Centrally located, rapidly moving, curvilinear (serpiginous) activity. Colonic bleeding: Peripherally framing, haustral-contoured and more slowly moving activity
•
On delayed images activity may move along the bowel → risk of mislocalisation
•
Dynamic (continuous) imaging is therefore critical → to capture the moment of first extravasation
•
Dynamic frames should be viewed in cinematic (cine) mode; the movement of activity and the site of first extravasation are then much easier to distinguish

Causes of false positives:

•
Free pertechnetate → uptake in the stomach, kidney
–
If activity is seen in the stomach, the thyroid and salivary glands are checked: if they also show activity, free pertechnetate is present; if not, true gastric or upper GI bleeding is considered
•
Accessory spleen
•
Renal pelvis activity
•
Vascular structures (aortic aneurysm, varices)
•
Genital organ activity (uterus → menstruation)
•
Other false-positive causes in the pelvis: Ectopic or transplant kidney, uterine fibroid
•
Activity seen only in the colon at 24 hours confirms bleeding but does not show its source; the blood may have come from any level of the GI tract and accumulated in the colon
•
Hepatic haemangioma
•
Diagnostic criteria (SNMMI/EANM 2.0): activity outside the expected blood pool structures, a change in intensity on consecutive images, and movement in a pattern consistent with bowel; all three must be present. The bleeding site is where activity is first seen, not the most intense, largest or most proximal focus. Bleeding appearing after 1 hour with activity less intense than the liver suggests a low rate; early appearance with activity equal to or greater than the liver suggests a high rate
–
Bowel activity on the first frame of delayed imaging after a period without imaging shows only that bleeding occurred in the interim; it is not taken as the bleeding site
–
Other pitfalls: penile blood pool (distinguished with a lateral view or by repositioning the penis), uterine activity with the ovulatory cycle and leiomyoma, a pelvic or horseshoe kidney and urinary diversion, aneurysms and vascular grafts, splenosis, gallbladder activity in renal failure or after transfusion (excretion of labelled haem) and haemobilia, hyperaemia after surgical resection or in Crohn's disease, and a catheter site. Retroperitoneal bleeding increases in intensity but does not move along a bowel lumen
•
Report content (SNMMI/EANM 2.0): in addition to the common items (see 27), signs of bleeding and time of the last bleed, endoscopy and other imaging, haemoglobin and transfusion; red cell labelling method (in vitro, in vivo, modified in vivo), duration of dynamic imaging, delayed images and SPECT/CT. Findings: whether bleeding is present, time and site of first appearance, movement and direction of activity, the most likely source by bowel segment; in a negative study the total imaging time is stated and that intermittent bleeding cannot be excluded
BOARD TIP
▸
"Most important rule for localisation on GI bleeding scintigraphy?"

→ Look at the first focal activity to appear.

▸
"Why does mislocalisation occur on delayed images?"

→ Blood moves along the bowel with peristalsis.

▸
"Advantage in intermittent bleeding?"

→ Delayed imaging can be performed up to 24 hours.

A Detection threshold 0.1-0.4 Scintigraphy (Tc-99m RBC) 0.3-0.5 CT angiography 0.5-1.0 Conventional angiography 0.1 0.2 0.5 1 2 more sensitive Lowest detectable bleeding rate (mL/min) B Localisation: based on site of first extravasation 10 min Right Left Blood pool only (normal distribution) 25 min Right Left New focal focus = bleed (descending colon) 50 min Right Left Focus grows, moves antegrade Blood pool: liver, spleen, aorta, iliac arteries. Faint band: colonic frame (guide only).

Figure 18.6: Detection thresholds of methods in GI bleeding (A) and localisation by site of first extravasation (B) (schematic).

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18.7 Hepatobiliary Scintigraphy (Tc-99m HIDA/DISIDA)16 questions

Basic Principles

Hepatobiliary scintigraphy (HIDA scan) is a functional imaging method that assesses hepatocyte function and biliary patency. Radiopharmaceuticals: Tc-99m labelled iminodiacetic acid (IDA) derivatives

•
Tc-99m HIDA (Hepatic IDA – lidofenin)
•
Tc-99m DISIDA (Diisopropyl IDA – disofenin) → sufficient with bilirubin <5 mg/dL
•
Tc-99m mebrofenin (BrIDA) → highest hepatic extraction → preferred in hyperbilirubinaemia

Mechanism:

•
IDA agents are taken up by hepatocytes via the organic anion transport system (the same route as bilirubin)
•
Secreted from hepatocytes into bile canaliculi → bile ducts → gallbladder → duodenum
•
Competitive uptake with bilirubin → uptake falls in hyperbilirubinaemia
•
EANM: Mebrofenin is used most often because of its high hepatic extraction; unlike bilirubin, IDA derivatives are secreted into bile without being conjugated
•
Activity: Adult 111-185 MBq (upper end of the range in hyperbilirubinaemia; child at least 20 MBq); 16 µSv/MBq, i.e. 1.8-3.0 mSv
•
The gallbladder starts to fill at 10 minutes and usually fills by 30-40 min (up to 60 min is normal); ~1/3 of bile goes to the gallbladder and ~2/3 directly to the duodenum
•
IDA is structurally an analogue of lidocaine and is a bifunctional chelate: its polar-anionic end binds Tc-99m (two IDA molecules per Tc atom), and its lipophilic end determines its biological behaviour
•
Hepatic extraction: 98% for mebrofenin, 88% for disofenin; renal excretion <1% for mebrofenin, ~9% for disofenin. Because they are protein-bound in plasma, normally very little is excreted by the kidneys
•
Functional liver reserve: Hepatic clearance is measured with a dynamic Tc-99m mebrofenin study (safe limit for the future liver remnant before major hepatectomy ~2.7 %/min/m²); the alternative agent is Tc-99m GSA (asialoglycoprotein receptor)
•
Cardiac blood-pool activity normally clears by 5 minutes. In hepatocyte dysfunction or jaundice the blood pool is prolonged and renal excretion increases (kidneys and bladder seen); a posterior image helps to distinguish kidney from bowel

Bilirubin Level and Choice of Agent

Bilirubin LevelPreferred AgentExplanation
<5 mg/dLTc-99m DISIDAStandard agent, adequate uptake
5-20 mg/dLTc-99m mebrofenin (BrIDA)High hepatic extraction
>20 mg/dLEven mebrofenin may be inadequatePoor image quality
BOARD TIP
▸
"Which IDA agent is preferred in hyperbilirubinaemia (>5 mg/dL)?"

→ Tc-99m mebrofenin (BrIDA) → highest hepatic extraction fraction.

▸
"Why do IDA agents compete with bilirubin?"

→ They are taken up by the same organic anion transport system.

▸
"What happens at bilirubin >20 mg/dL?"

→ Even mebrofenin may be inadequate → image quality falls.

Patient Preparation

•
Fasting: Minimum 2 hours (ideally 4 hours); fasting >24 hours causes false positives
•
Very prolonged fasting (>24 hours) → gallbladder chronically full → false positive (mimics acute cholecystitis)
•
Patients fasting >24 hours or on TPN → sincalide (CCK-8) premedication (0.02 μg/kg, 30-60 min IV infusion) → empties the gallbladder → HIDA is performed 30-60 min later
•
Opioids contract the sphincter of Oddi, so passage of bile into the bowel is delayed and partial common bile duct obstruction is mimicked; opioids should be stopped at least 4 half-lives (~6 hours) before the test

Protocol

•
Dose: 5-10 mCi (185-370 MBq) Tc-99m DISIDA or mebrofenin IV
•
Dynamic imaging: 1 min/frame, 60 minutes
•
Normal sequence: Liver → bile ducts → gallbladder → duodenum
•
Normal timing:
–
Liver uptake: 1-2 minutes
–
Bile ducts visualised: 10-15 minutes
–
Gallbladder filling: 30-60 minutes
–
Duodenal activity: 30-60 minutes
•
In 10-20% of normal individuals passage of bile into the bowel exceeds 60 min; to distinguish this from partial common bile duct obstruction, delayed images are acquired or sincalide is given. Other causes: opiates, chronic cholecystitis, intra-abdominal inflammation
•
Visualisation of the liver at the same time as the spleen in the flow phase suggests hepatic arterialisation (cirrhosis, tumour). Reflux of bile into the stomach (enterogastric) is non-specific and has not been associated with gastritis

Assessment of Acute Cholecystitis

Commonest indication: Suspected acute cholecystitis Pathophysiology: Cystic duct obstruction (usually a gallstone) → the gallbladder does not fill

Diagnostic criterion:

•
If the gallbladder is not seen at 60 minutes → delayed images (3-4 hours) or morphine augmentation
•
If the gallbladder is still not seen at 3-4 hours → consistent with acute cholecystitis

Morphine augmentation:

•
If the gallbladder is not seen at 60 minutes → morphine sulphate 0.04 mg/kg IV (2 mg, slowly)
•
Morphine is given only after bowel activity has been seen, i.e. after the common bile duct has been shown to be patent; imaging for 30 minutes after morphine has similar accuracy to 3-4 hours of delayed imaging and shortens the study
•
Morphine → contraction of the sphincter of Oddi → biliary pressure rises → the gallbladder fills if the cystic duct is patent
•
Imaging for a further 30 minutes after morphine
•
If the gallbladder is still not seen → acute cholecystitis (sensitivity 95-98%, specificity 90%)
•
If the gallbladder fills → acute cholecystitis excluded
•
EANM: Accuracy in acute cholecystitis is 90-95%; morphine is given IV at 0.04 mg/kg over 2-5 minutes; in a patient with an intact gallbladder the fasting period is 2-6 hours
•
Conditions other than acute cholecystitis causing non-visualisation of the gallbladder: fasting <2 hours or >24 hours, hyperalimentation (TPN), severe hepatocellular dysfunction, severe illness, cholecystectomy
•
Cystic duct sign (nubbin): Small focal activity in the cystic duct stump proximal to the obstruction; if mistaken for the gallbladder it gives a false-negative result, and it is distinguished with a lateral or delayed image
•
The main cause of false negatives is acalculous cholecystitis: because the cystic duct can remain patent, sensitivity falls
•
Acalculous cholecystitis (mostly in intensive care patients) has a worse course than the calculous form; if suspicion persists despite a normal HIDA, labelled leucocyte scintigraphy (uptake in the gallbladder wall) may help
BOARD TIP
▸
"The gallbladder is not seen on HIDA — what is done?"

→ Morphine augmentation (0.04 mg/kg IV).

▸
"Mechanism of morphine?"

→ Contraction of the sphincter of Oddi → biliary pressure rises → the gallbladder fills if the cystic duct is patent.

▸
"If the gallbladder is still not seen after morphine?"

→ Acute cholecystitis.

▸
"Contraindication to morphine?"

→ Morphine allergy, acute pancreatitis.

Fasting at least 2 h (ideally 4) >24 h fasting / TPN → first sincalide 0.02 µg/kg, 30-60 min infusion Tc-99m mebrofenin / DISIDA IV 60 min dynamic 60 min gallbladder seen? Yes Cystic duct patent → acute cholecystitis excluded No If bowel seen (CBD patent): morphine 0.04 mg/kg IV (slow, ~2 mg) Sphincter of Oddi contracts → biliary pressure ↑ → +30 min imaging (alternative: 3-4 h delayed image) Gallbladder filled? Yes Acute cholecystitis excluded No ACUTE CHOLECYSTITIS (sensitivity 95-98%, specificity 90%) Additional tips • Rim sign: in liver around GB fossa ↑ activity → gangrenous cholecystitis / perforation → emergency surgery • Morphine contraindication: morphine allergy, acute pancreatitis • Other causes of non-visualised GB: <2 or >24 h fasting, TPN, severe liver disease • False negative: acalculous cholecystitis; cystic duct stump (nubbin) may mimic GB

Figure 18.7: Algorithm for assessing acute cholecystitis on HIDA scintigraphy and morphine augmentation.

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Sincalide (CCK-8) augmentation:

•
In patients with prolonged fasting (>24 hours) or on TPN
•
Sincalide 0.02 μg/kg, 30-60 minutes IV infusion (should be given slowly)
•
Empties the gallbladder → given before HIDA
•
Rapid injection → gallbladder spasm → falsely low ejection fraction
•
Sincalide: The synthetic C-terminal octapeptide of CCK; it contracts the gallbladder and relaxes the sphincter of Oddi; its serum half-life is ~2.5 min. Because morphine abolishes the effect of sincalide, it is not given after morphine; if given as pretreatment it may delay the passage of bile into the bowel

Chronic Cholecystitis / Gallbladder Dyskinesia

•
Calculation of gallbladder ejection fraction (GBEF)
•
In chronic cholecystitis the gallbladder usually fills normally within 1 hour; delayed filling between 1-4 hours and visualisation of the bowel before the gallbladder suggest chronic cholecystitis but are non-specific
•
Sincalide (CCK-8) infusion: 0.02 μg/kg, 60 minutes IV infusion (standardised)
•
GBEF is calculated: (Maximum counts − Minimum counts) / Maximum counts × 100
•
Normal GBEF: ≥38% (with a 60 min sincalide infusion, the SNMMI multicentre normal value); in EANM practice >40% is usually considered normal
•
If sincalide is unavailable, a standard fatty liquid meal (e.g. 240 mL Ensure Plus) may be given; GBEF is calculated at 60 minutes and the lower limit of normal is ~33%
•
GBEF <38% → gallbladder dyskinesia / chronic cholecystitis → cholecystectomy may be considered
•
EANM: The Rome IV criteria recommend HIDA scintigraphy when biliary dyskinesia is suspected, after structural causes have been excluded
•
Up to 95% of patients selected because of an abnormal GBEF have lasting improvement after cholecystectomy (observational data)
•
Causes of falsely low GBEF: Obesity, diabetes, calcium channel blockers, oral contraceptives
•
Sphincter of Oddi dysfunction (SOD; pain after cholecystectomy): Hilum-to-duodenum transit >10 min, entry into the bowel delayed >30-60 min, drainage not accelerating after sincalide
•
In the SOD protocol sincalide (0.02 µg/kg over 3 min) is given ~15 min before the radiopharmaceutical; the Sostre score gives 0-12 points based on six visual and quantitative criteria, and ≥5 points favours SOD
BOARD TIP
▸
"How is gallbladder ejection fraction (GBEF) calculated?"

→ After sincalide (CCK-8) infusion.

▸
"Normal GBEF?"

→ ≥38%.

▸
"GBEF <38%?"

→ Gallbladder dyskinesia.

▸
"Why is the sincalide infusion time important?"

→ Rapid infusion → spasm → falsely low GBEF. Standard: 60-minute infusion.

Left: anterior HIDA image showing activity in the liver, bile ducts, gallbladder and bowel over time. Right: blood, liver, gallbladder and bowel time-activity curves. The steps show a normal study, morphine in acute cholecystitis, biliary atresia and GBEF measurement with sincalide.

Continuous stream · no seeking

No gallbladder at 60 minutes and 30 minutes after morphine means acute cholecystitis; no bowel even at 24 hours means complete obstruction or biliary atresia; GBEF <38% with sincalide is dyskinesia.

Source: visualization times, morphine and sincalide doses and the GBEF threshold from book 18.7 (SNMMI/EANM). Image and curves from a representative compartment model. Anatomy: OpenStax A&P 2e §23.6.

How to use: a single click on the drawing pauses and resumes; ↑ ↓ or the buttons below change the scenario of that step; use the time bar below to go to any minute; ← → change steps.

Speed
Test yourself:Chapter 18 · question 17Chapter 18 · question 24
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Figure 18.8: Gallbladder time-activity curve during sincalide infusion and calculation of GBEF (schematic).

Bile Leak

•
After cholecystectomy or liver surgery
•
Focal accumulation of activity outside the bile ducts → bile leak
•
Usually from the gallbladder bed or cystic duct stump
•
Delayed images (2-4 hours) increase sensitivity
•
After liver transplantation the commonest complication detected on scintigraphy is bile leak (most often from the anastomosis); rejection and cholestasis cannot be distinguished scintigraphically (both show slow clearance and prolonged retention)
•
Hepatic artery thrombosis causes ischaemic necrosis of the bile ducts (leak, biloma, sepsis); the first diagnostic method is Doppler US

Biliary Obstruction

Complete obstruction:

•
Liver uptake present but no passage into the bile ducts and bowel
•
No bowel activity even on 24-hour delayed images
•
Activity may be seen in the kidneys and bladder (alternative excretion route)
•
In acute obstruction liver uptake is rapid as long as hepatocyte function is preserved. Absence of bowel visualisation at 1 hour in adults is also seen in severe intrahepatic cholestasis; it is therefore not specific for complete obstruction

Partial obstruction:

•
Delayed transit → retention in the bile ducts
•
Bowel activity delayed but present
•
Specific findings in partial obstruction: Segmental narrowing of the common bile duct, abrupt or gradual cut-off, filling defect, ductal activity not decreasing on delayed images. Duct diameter is assessed with US, not scintigraphy
•
In acute obstruction HIDA may become positive before dilatation develops on US (in the first 24-72 hours). If there is persistent dilatation after a relieved obstruction, free passage of bile into the bowel excludes obstruction

Neonatal jaundice – Biliary atresia vs Neonatal hepatitis:

•
Biliary atresia: no passage into the bowel at 24 hours → surgery (Kasai procedure) required
•
Neonatal hepatitis: Delayed, but bowel activity PRESENT
•
In early (<3 months) biliary atresia hepatic extraction is preserved and the blood pool clears rapidly; in neonatal hepatitis extraction is reduced and the blood pool is prolonged, but bile passes into the bowel
•
Phenobarbital premedication: 5 mg/kg/day for 5 days → hepatic enzyme induction → increases bile flow → bowel activity becomes conspicuous in neonatal hepatitis
•
In biliary atresia the sensitivity of scintigraphy is higher than its specificity (false positives occur in severe intrahepatic cholestasis and with very high bilirubin); the Kasai operation is most successful when performed before 60 days, so early diagnosis is critical
•
Absence of passage into the bowel is not specific for biliary atresia; severe neonatal hepatitis, Alagille syndrome, alpha-1 antitrypsin deficiency, cystic fibrosis and TPN-related cholestasis can give the same appearance
•
Choledochal cyst: Seen initially as a cold defect, fills over time (a delayed image may be needed), rarely remains cold throughout the study; it does not respond to CCK because it contains no contractile structure
•
Caroli disease: There are saccular dilatations of the intrahepatic bile ducts; these areas are photopenic initially, fill over time and show pooling of activity on delayed images; hepatointestinal transit is prolonged
•
Dubin-Johnson syndrome: Hepatic uptake is rapid (extraction intact), biliary excretion is impaired; hepatic retention is prolonged and the bile ducts and gallbladder are seen late
BOARD TIP
▸
"Distinguishing biliary atresia from neonatal hepatitis in neonatal jaundice?"

→ HIDA scintigraphy.

▸
"Finding in biliary atresia?"

→ NO passage into the bowel at 24 hours.

▸
"In neonatal hepatitis?"

→ Delayed, but bowel activity PRESENT.

▸
"Why is phenobarbital given?"

→ Hepatic enzyme induction → increases bile flow → makes bowel transit conspicuous in neonatal hepatitis.

▸
"Phenobarbital dose and duration?"

→ 5 mg/kg/day, 5 days.

Rim Sign on HIDA Scintigraphy

•
Increased activity in the liver parenchyma around the gallbladder fossa → "rim sign"
•
Associated with gangrenous cholecystitis or perforation
•
Indicator of poor prognosis → indication for emergency surgery
•
Rim sign + non-visualised gallbladder → complicated acute cholecystitis
•
The rim sign is seen in about a quarter of acute cholecystitis cases; it increases the likelihood of gangrene or perforation but is not specific. Hyperaemia of the gallbladder fossa in the flow phase also supports acute cholecystitis
•
Report content (SNM 4.0, 2010): in addition to the common items (see 27), duration of fasting, opioid use, parenteral nutrition, bilirubin and liver tests, phenobarbital pretreatment; pharmacological intervention (morphine dose and timing; sincalide dose and infusion duration, or a standard fatty meal). Findings: hepatic extraction and blood pool clearance, times of gallbladder and bowel visualisation, gallbladder ejection fraction with method and normal range if measured; additional findings such as leak, rim sign and duodenogastric reflux
BOARD TIP
▸
"What does the rim sign mean on HIDA?"

→ Gangrenous cholecystitis / perforation → poor prognosis → emergency surgery. This is a frequently asked finding in board exams!

Left: anterior HIDA image showing activity in the liver, bile ducts, gallbladder and bowel over time. Right: blood, liver, gallbladder and bowel time-activity curves. The steps show a normal study, morphine in acute cholecystitis, biliary atresia and GBEF measurement with sincalide.

Continuous stream · no seeking

No gallbladder at 60 minutes and 30 minutes after morphine means acute cholecystitis; no bowel even at 24 hours means complete obstruction or biliary atresia; GBEF <38% with sincalide is dyskinesia.

Source: visualization times, morphine and sincalide doses and the GBEF threshold from book 18.7 (SNMMI/EANM). Image and curves from a representative compartment model. Anatomy: OpenStax A&P 2e §23.6.

How to use: a single click on the drawing pauses and resumes; ↑ ↓ or the buttons below change the scenario of that step; use the time bar below to go to any minute; ← → change steps.

Speed
Test yourself:Chapter 18 · question 5Chapter 18 · question 13Chapter 18 · question 8
Did this animation help you understand the topic?

Figure 18.9: HIDA scintigraphy patterns: normal, acute cholecystitis, complete obstruction/biliary atresia and rim sign (schematic).

18.8 Liver-Spleen Scintigraphy (Tc-99m Sulphur Colloid)7 questions

Basic Principles

Tc-99m sulphur colloid is taken up by phagocytosis by reticuloendothelial system (RES) cells (Kupffer cells).

•
It clears rapidly from the blood (half-life ~2-3 min). Particle size determines distribution: small particles go to the bone marrow, large particles to the liver; very large particles or flocculation cause lung uptake
•
Preparation of sulphur colloid requires boiling; the alternative Tc-99m albumin colloid does not require heating (IDA kits are also prepared at room temperature)
•
The smallest detectable lesion is ~2-3 cm on planar imaging and ~1-1.5 cm on SPECT; routine SPECT increases sensitivity, but specificity falls
•
Preparation and acquisition (EANM Technologists' Guide 2023): no specific preparation is needed; the study is done before any examination with iodinated or barium contrast (retained bowel contrast causes artefacts). Sulphur colloid (particles 0.1-1.0 µm) 111-222 MBq (3-6 mCi) for planar imaging and 370 MBq (10 mCi) for SPECT; in children 1.8 MBq/kg (minimum 15 MBq). Uptake peaks at 10-20 minutes and imaging begins at about 20 minutes; with a low-energy collimator the anterior image (about 1 million counts) is acquired first, and a lead marker is placed on the costal margin for size estimation. SPECT: 128 × 128 matrix, 60 projections per head, 3°
–
For spleen-specific studies (functioning splenic tissue, ectopic spleen, splenule, functional asplenia), heat-damaged Tc-99m red cells are used (see Chapter 20 for the protocol)

Normal distribution:

•
Liver: 85-90%
•
Spleen: 5-10%
•
Bone marrow: 3-5%
–
EANM Technologists' Guide 2023 (approximate, at the time of imaging): liver 80%, spleen 15%, bone marrow 5%; the bone marrow is not normally seen on anterior abdominal images. The right lobe of the liver normally measures about 15 cm from the dome, and the spleen at most 14 cm diagonally. Visualisation of the bone marrow (colloid shift) occurs in diffuse liver disease and after splenectomy

Indications

•
Assessment of diffuse liver disease (cirrhosis)
•
Focal liver lesions (FNH, adenoma, metastasis)
•
Hepatosplenomegaly
•
Assessment of functional asplenia
•
Budd-Chiari syndrome
•
Superior vena cava obstruction

Pathological Findings

Cirrhosis:

•
Liver uptake reduced and heterogeneous
•
Splenic and bone marrow uptake increased → "colloid shift"
•
Colloid shift = Kupffer cell function reduced → spleen and bone marrow take up more as compensation
•
Diffuse lung uptake with sulphur colloid: Seen in advanced cirrhosis or chronic liver disease and is a poor prognostic indicator; a preparation error (flocculation due to excess Al³⁺) gives the same appearance
BOARD TIP
▸
"What is colloid shift?"

→ In cirrhosis liver uptake falls → splenic and bone marrow uptake increase.

▸
"Mechanism of colloid shift?"

→ Kupffer cell function reduced → RES function shifts to the spleen and bone marrow.

Focal Nodular Hyperplasia (FNH):

•
TAKES UP sulphur colloid (normal or increased) → contains Kupffer cells
•
Important in the differential diagnosis from hepatic adenoma and metastases
•
Normal or increased uptake in 60-70% of FNH
•
FNH on IDA scintigraphy: Flow is increased, uptake rapid and clearance delayed. Some well-differentiated HCCs may also take up IDA and show retention in the late phase; other masses appear as cold defects in the hepatic phase

Hepatic adenoma:

•
Usually does NOT take up sulphur colloid (cold defect) → few or no Kupffer cells
•
May rarely show mild uptake
•
Adenoma is associated with oral contraceptive or anabolic steroid use and carries a risk of haemorrhage; FNH is not causally related to oral contraceptives, may contain a central scar and mostly requires no treatment

Metastasis:

•
Does NOT take up sulphur colloid → cold defect (photopenic area)
•
Radiotherapy: A sharply defined, rectangular uptake defect matching the radiation field
•
Combined assessment with Ga-67: In a cirrhotic liver, a lesion that is cold on colloid and shows intense Ga-67 uptake suggests HCC (a regenerative nodule does not take up Ga-67). A pyogenic abscess takes up Ga-67; an amoebic abscess is mostly seen with a cold centre (a peripheral rim may be present)

Budd-Chiari syndrome:

•
Hepatic vein thrombosis → hepatic congestion
•
Caudate lobe hypertrophy → increased uptake in the caudate lobe (the caudate lobe drains directly into the IVC → spared)
•
Reduced uptake in the rest of the liver
•
Hot quadrate lobe (segment IV): In a patient injected in the arm with superior vena cava obstruction, activity reaches the quadrate lobe directly via collateral and paraumbilical veins
BOARD TIP
▸
"Liver lesion that takes up sulphur colloid?"

→ FNH (contains Kupffer cells).

▸
"Lesions that do not take up sulphur colloid?"

→ Adenoma, metastasis, cyst, abscess.

▸
"Which lobe is spared in Budd-Chiari?"

→ Caudate lobe (direct IVC drainage). These distinctions are very frequently asked in board exams!

A Normal Liver 85-90% Spleen 5-10% Bone marrow 3-5% B Cirrhosis: colloid shift Liver ↓, heterogeneous Spleen ↑ (splenomegaly) Bone marrow ↑ (Kupffer function ↓) Anterior; image left is patient's right (liver left, spleen right). C Budd-Chiari (anterior) Right Left caudate lobe: ↑ uptake (direct IVC drainage → spared) Rest of parenchyma ↓ (hepatic vein thrombosis, congestion)

Figure 18.10: Tc-99m sulphur colloid distribution: normal, colloid shift in cirrhosis and spared caudate lobe in Budd-Chiari (schematic).

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Functional Asplenia

•
Sickle cell disease → recurrent splenic infarcts → autosplenectomy → functional asplenia
•
The spleen is not seen or is very small on sulphur colloid scintigraphy
•
Alternative: Heat-damaged red cell scintigraphy (detailed in Chapter 20 → cross-reference)

18.9 Hepatic Haemangioma with Tc-99m Labelled Red Blood Cells3 questions

Basic Principles

Cavernous haemangioma is the commonest benign tumour of the liver. It shows a characteristic perfusion-blood pool pattern on Tc-99m labelled red cell scintigraphy.

•
Indication and preparation (NVNG 2016): performed when a liver mass seen on US, CT or MRI cannot be distinguished between haemangioma and another lesion and biopsy carries risk. No patient preparation is needed; high labelling efficiency (90-95%) is important for image quality. The site and size of the lesion should be known beforehand: the flow study is acquired in the projection that best shows the lesion. The detection limit is about 1.5 cm; MRI is more sensitive for small (<1 cm) lesions. Results are always compared with US, CT and MRI findings

Mechanism

•
Haemangioma = vascular spaces (cavernous sinusoids) → red cells accumulate in these spaces
•
In the dynamic phase → slow filling (appears as a perfusion defect)
•
In the delayed phase → increased uptake (blood pool → red cells accumulate)

Protocol

•
Dose: 20-30 mCi (740-1110 MBq) Tc-99m labelled red blood cells IV
•
Three-phase study:

1. Flow phase: Dynamic, 2-3 s/frame → reduced or normal perfusion in the haemangioma 2. Blood pool phase: 5-10 minutes → uptake beginning to increase in the haemangioma 3. Delayed phase: 1-2 hours → markedly increased uptake in the haemangioma (more intense than the liver parenchyma)

Diagnostic Pattern

•
Flow phase: Reduced or normal (NO hyperperfusion → distinguishes it from malignant tumours)
•
Early blood pool: Peripheral filling begins
•
Delayed images: Uptake more intense than the liver parenchyma → diagnostic
•
This pattern: "Fill-in" pattern → filling from the periphery towards the centre
BOARD TIP
▸
"Pattern of hepatic haemangioma on Tc-99m RBC scintigraphy?"

→ Reduced/normal in the flow phase, increased uptake in the delayed phase (fill-in pattern).

▸
"Is delayed-phase uptake more intense than the liver?"

→ YES → diagnostic.

▸
"Difference in a malignant tumour?"

→ In malignant tumours increased perfusion in the flow phase + reduced uptake in the delayed phase (the exact opposite).

Flow phase (2-3 s/frame) Blood pool (5-10 min) Delayed (1-2 h) Haemangioma Right Left reduced/normal (NO hyperperfusion) Right Left from periphery filling begins Right Left more intense than liver = diagnostic (fill-in) Malignant (e.g. metastasis) Right Left increased perfusion Right Left reduced Right Left reduced (opposite pattern)

Figure 18.11: Three-phase pattern of haemangioma and a malignant lesion on Tc-99m red cell scintigraphy (schematic).

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Diagnostic Accuracy

•
Sensitivity: 70-80% (90-95% for lesions >2 cm)
•
Specificity: 95-100% (very high)
•
Sensitivity falls for 1.5-2 cm lesions → MR is preferred
•
Today contrast-enhanced MR (gadolinium) → gold standard for the diagnosis of haemangioma
•
Tc-99m RBC scintigraphy → in patients who cannot have MR or when MR is inconclusive
•
Blood-pool SPECT (preferably SPECT/CT) markedly increases sensitivity over planar (~1-1.5 cm lesions can be shown; on planar lesions smaller than ~2-3 cm are often missed); the positive predictive value of a positive result is >99%
•
In large cavernous haemangiomas filling is heterogeneous because of internal thrombosis or fibrosis, and a central defect may be seen
•
Rare false positives on blood pool: Angiosarcoma, haemangioendothelioma, some HCCs and hypervascular metastases. In infantile haemangioendothelioma activity is markedly increased in the flow and delayed blood-pool phases
•
Report content (NVNG 2016): in addition to the common items (see 27), red cell labelling method, projection of the flow study, timing of delayed images and SPECT/CT. Findings: number and site of lesions, their perfusion on the flow phase and their intensity relative to liver on delayed blood pool images; matching of each finding to the lesions on US, CT or MRI, and that the result does not apply to lesions below the detection limit (~1.5 cm)

Differential Diagnosis

LesionFlow PhaseDelayed PhaseSulphur Colloid
HaemangiomaReduced/NormalIncreased (fill-in)No uptake
FNHIncreasedNormal/Mildly increasedUptake
AdenomaIncreasedNormal/ReducedNo uptake
MetastasisIncreasedReducedNo uptake
CystReducedReduced (photopenic)No uptake
BOARD TIP
▸
"This table is very frequently asked in board exams!"

→ "Reduced in the flow phase, increased in the delayed phase?" → Haemangioma.

▸
"Lesion that takes up sulphur colloid?"

→ FNH.

▸
"Increased in the flow phase, reduced in the delayed phase?"

→ Malignant lesion (metastasis).

18.10 C-14 Urea Breath Test (H. pylori)2 questions

Basic Principles

Helicobacter pylori is a bacterium that lives in the gastric mucosa and produces the enzyme urease. The urea breath test detects this urease activity.

Mechanism

•
The patient drinks C-14 (or C-13) labelled urea
•
If H. pylori is present → urease breaks down urea:

14C-urea →(urease) 14CO2 + NH3

•
¹⁴CO₂ is absorbed into the blood → exhaled through the lungs → measured in the breath
•
If H. pylori is absent → urea is not broken down → no ¹⁴CO₂ forms

C-14 vs C-13

FeatureC-14 UreaC-13 Urea
Radioactive?YES (β emitter)NO (stable isotope)
Measurement methodScintillation counterMass spectrometry
Radiation doseVery low (~1 μCi)None
Use in pregnancyContraindicatedSafe
Use in childrenNot recommendedPreferred
CostCheaperMore expensive

Protocol

•
Fasting: At least 6 hours
•
Drug withdrawal:
–
Antibiotics: Should be stopped at least 4 weeks before
–
PPIs (proton pump inhibitors): Should be stopped at least 2 weeks before
–
H2 blockers: Should be stopped at least 24-48 hours before
–
Bismuth preparations: Should be stopped at least 4 weeks before
•
A C-14 urea capsule is swallowed → wait 10-20 minutes → a breath sample is collected

Assessment

•
Positive: ¹⁴CO₂ detected in the breath → active H. pylori infection
•
Negative: No ¹⁴CO₂ detected → no H. pylori or eradicated
•
Sensitivity: >95%, Specificity: >95%
•
False positives: Overgrowth of urease-producing bacteria other than H. pylori in achlorhydria or atrophic gastritis. False negatives: Recent antibiotic, bismuth or PPI use. The test is less reliable after gastric resection

Clinical Use

•
Diagnosis of H. pylori (non-invasive)
•
Check after eradication therapy (the commonest indication) → at least 4 weeks after treatment
•
In patients in whom endoscopy is not possible or not wanted
BOARD TIP
▸
"When should PPIs be stopped before a urea breath test?"

→ 2 weeks before.

▸
"Antibiotics?"

→ 4 weeks before.

▸
"Which isotope is used in pregnancy?"

→ C-13 (non-radioactive).

▸
"C-14 in pregnancy?"

→ Contraindicated.

▸
"When is eradication checked?"

→ 4 weeks after treatment.

H. pylori PRESENT → test positive ¹⁴C-urea capsule swallowed H. pylori in the stomach urease splits urea ¹⁴CO₂ + NH₃ is formed ¹⁴CO₂ → blood → via the lungs exhaled after 10-20 min, breath sample → scintillation counter: ¹⁴CO₂ (+) H. pylori ABSENT → urea not split → no ¹⁴CO₂ in breath → test negative (or eradicated) C-13 urea: non-radioactive (mass spectrometry) → preferred in pregnancy and children. Drugs to stop to avoid false negatives Antibiotics ≥4 wk • Bismuth ≥4 wk • PPI ≥2 wk • H2 blocker 24-48 h Eradication check: at least 4 weeks after treatment

Figure 18.12: Mechanism of the C-14 urea breath test and drugs to be stopped before the test.

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Key Points for the Board

Salivary Gland Scintigraphy:

•
Agent: Tc-99m pertechnetate (taken up via NIS)
•
Stimulation: Lemon juice (at 15-20 minutes)
•
Sjögren syndrome: Reduced uptake + absent/reduced secretion
•
Pertechnetate-avid tumour: Warthin tumour (hot nodule)
•
Commonest salivary gland tumour: Pleomorphic adenoma → does not take up pertechnetate (cold)

Oesophageal Transit Scintigraphy:

•
Agent: Tc-99m sulphur colloid (in liquid)
•
Normal transit time: <15 seconds (classical); EANM upper limit ≤30 seconds
•
Scleroderma: Retention in the lower 2/3 of the oesophagus (smooth muscle involvement)
•
Achalasia: Retention at the LOS

GOR Scintigraphy:

•
Agent: Tc-99m sulphur colloid (in acidic liquid/milk)
•
Lung activity on delayed images → pulmonary aspiration
•
The preferred non-invasive method in paediatric patients

Gastric Emptying Scintigraphy:

•
Gold-standard method
•
Standard meal: Egg-white sandwich (Tc-99m sulphur colloid)
•
<30% retention at 1 hour → rapid emptying (dumping)
•
>10% retention at 4 hours → gastroparesis (Mild 11-20%, Moderate 21-35%, Severe >35%)
•
Solid food: Linear kinetics (lag phase + linear phase)
•
Liquid food: Exponential kinetics
•
Geometric mean: For attenuation correction (square root of anterior × posterior)
•
Blood glucose in a diabetic patient: ≤275 mg/dL
•
Drug withdrawal: Prokinetics, opioids, anticholinergics → 48-72 hours before
•
Truncal vagotomy: Liquids empty rapidly (loss of fundic relaxation), solids are delayed (impaired antral grinding)

Meckel's Diverticulum Scintigraphy:

•
Agent: Tc-99m pertechnetate IV → uptake by ectopic gastric mucosa
•
Rule of twos: 2%, 2 feet, 2 inches, 2 years, 2 types of mucosa, 2:1 M/F
•
Premedication: Cimetidine (H2 blocker) → blocks secretion → signal increases
•
Positive finding: Focal activity in the right lower quadrant → appears at the same time as the stomach
•
Sensitivity in children: 85-95%; in adults: 60-70%
•
Pancreatic mucosa → does not take up pertechnetate → scintigraphy negative

GI Bleeding Scintigraphy:

•
Agent: Tc-99m labelled red blood cells
•
Labelling efficiency: In-vivo 75-80%, In-vivtro 85-90%, In-vitro >95%
•
Detection threshold: 0.1-0.4 mL/min (angiography: 0.5-1.0 mL/min)
•
Localisation: The first focal activity to appear is the most reliable
•
Delayed imaging up to 24 hours → advantage in intermittent bleeding
•
Free pertechnetate → uptake in the stomach, thyroid, kidney → artefact
•
Gastric activity + thyroid/salivary glands seen → free pertechnetate; not seen → true gastric/upper GI bleeding

Hepatobiliary Scintigraphy (HIDA):

•
Agents: Mebrofenin/BrIDA (most common; preferred in hyperbilirubinaemia), DISIDA (sufficient at bilirubin <5 mg/dL)
•
Bilirubin >5 mg/dL → mebrofenin; >20 mg/dL → even mebrofenin may be inadequate
•
Acute cholecystitis: 60 min without gallbladder visualisation → morphine augmentation (0.04 mg/kg IV)
•
Mechanism of morphine: Contraction of the sphincter of Oddi → biliary pressure rises
•
Rim sign → gangrenous cholecystitis / perforation → emergency surgery
•
Morphine is given only after bowel activity (common bile duct patency) has been seen; the main cause of false negatives is acalculous cholecystitis
•
GBEF: Sincalide (CCK-8) 60 min infusion → normal ≥38%; <38% → dyskinesia
•
Neonatal jaundice: Phenobarbital 5 mg/kg/day for 5 days → distinguishes biliary atresia from hepatitis
•
Biliary atresia: NO passage into the bowel at 24 hours (not specific: severe neonatal hepatitis, Alagille, α1-antitrypsin deficiency); Kasai <60 days most successful
•
Bile leak: Focal accumulation of activity outside the bile ducts

Liver-Spleen Scintigraphy (Sulphur Colloid):

•
Normal distribution: Liver 85-90%, Spleen 5-10%, Bone marrow 3-5%
•
Colloid shift → cirrhosis (splenic and bone marrow uptake increased)
•
FNH → takes up sulphur colloid (contains Kupffer cells)
•
Adenoma, metastasis, cyst, abscess → do not take up sulphur colloid
•
Budd-Chiari → increased caudate lobe uptake (direct IVC drainage)

Hepatic Haemangioma (Tc-99m Labelled Red Blood Cells):

•
Flow phase: Reduced/normal perfusion
•
Delayed phase: Increased uptake (more intense than the liver) → fill-in pattern
•
Sensitivity: >2 cm lesions 90-95%; at 1.5 cm low → MR preferred
•
Specificity: 95-100%
•
Malignant tumour: Increased in the flow phase, reduced in the delayed phase (the exact opposite)

C-14 Urea Breath Test:

•
Detects H. pylori urease activity
•
C-14: Radioactive → contraindicated in pregnancy; C-13: Non-radioactive → safe
•
PPI withdrawal: 2 weeks; Antibiotic/bismuth withdrawal: 4 weeks
•
Eradication check: 4 weeks after treatment
•
Sensitivity and specificity: >95%

Additional Notes from EANM Guidelines:

•
Salivary gland: 37 MBq, maximum uptake at ~30 min; increased uptake + reduced secretion in sialadenosis; breastfeeding 12 hours
•
ETS: Normal transit ≤30 s; sensitivity 95%, specificity 96% in achalasia/scleroderma; manometry is the gold standard
•
GOR: First-line pH-metry/impedance; valuable for airway reflux in children; 15 s/frame, 1 hour
•
Gastric emptying: Omelette 18-37 MBq; normal ≤90% (1 h), ≤60% (2 h), ≤10% (4 h); < 30% at 1 hour rapid; Grade 1-3: 11-20% / 21-35% / >35%
•
Meckel's: 200 MBq; ranitidine preferred; NO thyroid blockade with perchlorate; sensitivity ~85% in children, ~60% in adults
•
GIBS: 550-1110 MBq; high success with transfusion ≥500 mL/24 hours; not performed for chronic occult bleeding
•
HIDA: Mebrofenin most common; 111-185 MBq; GBEF >40% normal (EANM); obesity/diabetes/CCB/OCP give falsely low GBEF; SOD criteria
•
Colonic transit: In-111 DTPA; ~70% excreted at 48 hours is normal

Current guidelines on this chapter's topics

The latest guidelines and consensus documents on the procedures covered in this chapter (official EANM index and primary sources, November 2026). Comparison of the text with these versions is in progress; consult the guideline itself for details.

  1. 2023Joint EANM/SNMMI/IHPBA procedure guideline for [99mTc]Tc-mebrofenin hepatobiliary scintigraphy SPECT/CT in the quantitative assessment of the future liver remnant function (opens in a new tab)
  2. 2014SNMMI Procedure Standard/EANM Practice Guideline for Gastrointestinal Bleeding Scintigraphy 2.0 (opens in a new tab)
  3. 2014The SNMMI and EANM Practice Guidelines for Meckel Diverticulum Scintigraphy 2.0 (opens in a new tab)
  4. 2013The SNMMI and EANM Practice Guideline for Small-Bowel and Colon Transit (opens in a new tab)

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Step 1/2

Solid and liquid phases

In a dual-isotope study the solid meal is labelled with Tc-99m sulfur colloid and the liquid with In-111 DTPA. The fundus pushes liquids by tonic contraction; liquids empty monoexponentially with no lag (normal T½ <20 min). Solid particles are first ground down in the antrum (lag phase) and only then pass the pylorus; emptying is then roughly linear.

Stomach (anterior, schematic)t = 0.0 hfundusbodyantrumpylorusduodenumjejunumsolid (Tc-99m SC, egg)liquid (In-111 DTPA)
Activity remaining in stomach (%)0255075100lagliquid T½ ≈ 15 min01234time (h)% leftNow: solid 100% · liquid 100%Solid: lag + linear; liquid: monoexponentialSchematic; curves representative.

Once the gallbladder has filled, sincalide (CCK-8) 0.02 µg/kg is infused over 60 minutes; the gallbladder contracts and bile passes through the CBD into the duodenum. GBEF = (maximum − minimum) / maximum × 100; normal is ≥38% (>40% in EANM practice). A low GBEF suggests chronic cholecystitis or biliary dyskinesia; rapid injection gives a falsely low value.

Sincalide infusiont = 0 minRLlivergallbladderCBDduodenum
Gallbladder counts and GBEFsincalide 0.02 µg/kg over 60 minGBEF 38% limit015304560time (min)counts (each curve to its own peak)GBEF = 0%Schematic; compartment model, values representative.

Step 1/3

Normal HIDA

Tc-99m mebrofenin is taken up by hepatocytes through the same organic anion pathway as bilirubin and secreted into bile without conjugation. The cardiac blood pool clears in ~5 minutes; the liver appears at 1-2 minutes, the bile ducts at 10-15 minutes, the gallbladder and duodenum within 30-60 minutes. About 1/3 of bile goes to the gallbladder and 2/3 directly to the duodenum.

Normal HIDA (anterior)t = 0 minRLliverheart (blood pool)gallbladderCBDduodenum
Time-activity curvesbloodlivergallbladderbowel015304560time (min)counts (each curve to its own peak)Liver → bile ducts → GB and duodenum ≤60 minSchematic; compartment model, values representative.