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Labelled White Cell Scanning for Infection

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Labelled White Cell Scanning for Infection

Guide to labelled white cell scintigraphy for diagnosing musculoskeletal infection including prosthetic joint infection and chronic osteomyelitis.

Medium Yield
complete
Updated: 2026-01-16
High Yield Overview

Labelled White Cell Scanning for Infection

—PJI Accuracy
90%Greater than (combined)
—Labelling Time
2-3hours
—Imaging Time
4-24hours post-injection
—Labels Used
111In- or Tc-99m HMPAO

Combined WBC/Marrow Interpretation

Positive for infection: WBC uptake WITHOUT matching marrow

Negative for infection: No WBC uptake OR matched WBC/marrow

Equivocal: Partially matched or borderline

Key: Spatial and intensity mismatch between WBC and marrow indicates infection

Critical Must-Knows

  • Patient's own WBCs are labelled ex vivo
  • WBCs accumulate at sites of infection
  • Combined with marrow scan for PJI (gold standard)
  • Mismatch pattern: WBC positive, marrow negative = infection
  • Better specificity than bone scan for chronic/hardware infection

Examiner's Pearls

  • "
    WBC scan: 80-90% sensitivity, greater than 90% specificity for infection
  • "
    Marrow scan (sulphur colloid): Shows marrow distribution
  • "
    Matched uptake = marrow hyperplasia (not infection)
  • "
    Spine infection: Poor sensitivity due to normal marrow uptake
  • "
    Time-consuming technique: 2-3 days to complete

Exam Warning

Labelled WBC scanning is the gold standard nuclear medicine technique for prosthetic joint infection. Know the combined WBC/marrow scan technique and how to interpret mismatch patterns. Remember that this technique has limitations in the spine where normal marrow is present.

Mnemonic

SCAN Indications

S
Suspected osteomyelitis - MRI equivocal or contraindicated
Suspected osteomyelitis - MRI equivocal or contraindicated
C
Chronic infection (>6 weeks) - distinguish from acute
Chronic infection (>6 weeks) - distinguish from acute
A
Arthroplasty - evaluate for prosthetic joint infection
Arthroplasty - evaluate for prosthetic joint infection
N
Non-diagnostic MRI - alternative imaging modality
Non-diagnostic MRI - alternative imaging modality

Memory Hook:SCAN when MRI is unclear or chronic infection suspected

Labelling Technique

White Cell Labelling Agents

AgentHalf-lifeAdvantagesDisadvantages
In-111 oxine67 hoursStable label, delayed imaging possibleHigher radiation dose, longer imaging times
Tc-99m HMPAO6 hoursBetter image quality, same-day imagingLess stable label, faster preparation needed
Tc-99m sulesomab (antigranulocyte)6 hoursNo blood handling requiredNot true WBC scan, less specific

Labelling Process

Patient's blood is drawn (40-60mL). WBCs are separated from red cells and plasma. WBCs are incubated with In-111 oxine or Tc-99m HMPAO. Labelled cells are quality checked for labelling efficiency. Cells are reinjected into the patient. The process takes 2-3 hours and requires specialised laboratory facilities.

Combined WBC/Marrow Scan

Combined WBC and Marrow Scan Protocol

StepTimingAgentPurpose
WBC injectionDay 1In-111 labelled WBCsLabels circulating neutrophils
WBC imaging4h and 24hN/ADelayed images improve specificity
Marrow injectionDay 2 or same dayTc-99m sulphur colloidMaps bone marrow distribution
Marrow imaging30 minutes postN/ACompare with WBC distribution

Interpretation of Combined Scan

WBC ScanMarrow ScanInterpretation
Positive (focal uptake)Negative (no uptake at same site)INFECTION - mismatch
PositivePositive (matched distribution)Marrow hyperplasia - NOT infection
NegativeAnyNo infection at imaged site
PositivePartially matchedEquivocal - may need further workup
Mnemonic

WBC + Marrow = Match (Normal), WBC - Marrow = INFECTIONMismatch = Infection

W
WBC uptake WITH matching marrow = bone marrow hyperplasia (normal post-op)
W
WBC uptake WITHOUT matching marrow = infection
T
The spatial mismatch indicates WBCs are accumulating due to infection, not marrow

Memory Hook:Around prosthetic joints, marrow can expand and show both WBC and sulphur colloid uptake - this is normal, not infection

Clinical Applications

Gold Standard for PJI

Combined WBC/marrow scan has greater than 90% accuracy for prosthetic joint infection. Superior to bone scan (which remains positive for years post-arthroplasty) and MRI (artefact limitations). Mismatch pattern is highly specific for infection. Should be performed before antibiotic therapy if possible.

Performance in PJI

ParameterWBC Scan AloneCombined WBC/Marrow
Sensitivity80-90%80-90%
Specificity70-80%Greater than 90%
Accuracy75-85%Greater than 90%
False positivesMarrow hyperplasiaSignificantly reduced

Chronic Osteomyelitis Assessment

WBC scan useful in chronic osteomyelitis when bone scan is non-specific (stays positive for months after cure). Helps assess activity of chronic infection and response to treatment. Less useful in acute osteomyelitis where MRI is preferred. Diabetic foot infection: WBC scan can help, but complex anatomy limits accuracy.

Spine Infection Limitation

WBC scanning has POOR sensitivity in vertebral osteomyelitis/discitis. Normal vertebral marrow shows variable WBC uptake, making interpretation difficult. Cold or photopenic areas may be seen with infection (counterintuitive). MRI is the preferred modality for spine infection. If nuclear medicine needed, consider FDG-PET or gallium scan instead.

Comparison with Other Modalities

Imaging for Musculoskeletal Infection

ModalitySensitivitySpecificityBest Use
3-phase bone scanGreater than 90%40-70%Screening, rule out osteomyelitis
WBC scan alone80-90%70-80%Appendicular infection
Combined WBC/marrow80-90%Greater than 90%PJI (gold standard)
FDG-PETGreater than 90%70-80%Spine infection, fever workup
MRIGreater than 90%80-90%Acute osteomyelitis, anatomic detail
Gallium-67ModerateModerateHistorical, largely replaced

Exam Viva Scenarios

Practice these scenarios to excel in your viva examination

VIVA SCENARIOStandard

EXAMINER

"A patient 2 years after total hip replacement presents with groin pain and elevated inflammatory markers. Aspiration is equivocal. You are asked about nuclear medicine imaging options."

EXCEPTIONAL ANSWER
I would recommend combined labelled white cell scan and bone marrow (sulphur colloid) scan, which is the gold standard nuclear medicine technique for prosthetic joint infection with greater than 90% accuracy. The technique involves: (1) Labelling the patient's own WBCs with In-111 or Tc-99m HMPAO ex vivo, (2) Imaging at 4 and 24 hours to see where WBCs accumulate, (3) Injecting Tc-99m sulphur colloid to map bone marrow distribution, (4) Comparing the two scans spatially. Interpretation: If WBC uptake occurs WITHOUT matching marrow uptake at the same site (mismatch), this indicates infection. If both WBC and marrow uptake are present and matched, this indicates marrow hyperplasia (normal post-arthroplasty change) rather than infection. Plain bone scan is not helpful as it remains positive for years after arthroplasty.
KEY POINTS TO SCORE
Combined WBC/marrow scan is gold standard for PJI
Greater than 90% accuracy when combined
Mismatch (WBC without marrow) = infection
Match (WBC and marrow) = marrow hyperplasia, not infection
Bone scan not helpful (positive for years post-op)
COMMON TRAPS
✗Recommending bone scan alone (not specific)
✗Using WBC scan alone (lower specificity)
✗Not understanding mismatch interpretation
VIVA SCENARIOStandard

EXAMINER

"A diabetic patient with a foot ulcer and suspected osteomyelitis has had a bone scan that is positive. The referring team asks if further nuclear medicine imaging would help."

EXCEPTIONAL ANSWER
In diabetic foot infection, the three-phase bone scan is sensitive (greater than 90%) but has low specificity because Charcot neuroarthropathy, fractures, and other diabetic changes also cause positive scans. WBC scanning can improve specificity in this setting. However, there are important limitations: (1) Complex foot anatomy makes spatial correlation difficult, (2) Charcot joints may show some WBC uptake due to inflammation, (3) Combined WBC/marrow technique is less validated in the foot compared to PJI. Despite these limitations, WBC scan can help differentiate osteomyelitis from Charcot by showing more focal, intense WBC uptake with osteomyelitis. However, MRI remains the preferred modality for diabetic foot osteomyelitis as it provides better anatomic detail and can identify abscess, extent of infection, and differentiate from Charcot based on pattern.
KEY POINTS TO SCORE
Bone scan sensitive but non-specific in diabetic foot
WBC scan improves specificity over bone scan
Limitations: Charcot can cause WBC uptake
Complex anatomy makes interpretation difficult
MRI preferred for anatomic detail and pattern
COMMON TRAPS
✗Expecting WBC scan to be definitive in diabetic foot
✗Not recognising Charcot limitation
✗Not recommending MRI as alternative
VIVA SCENARIOStandard

EXAMINER

"A patient with chronic low back pain and mildly elevated inflammatory markers is referred for suspected vertebral osteomyelitis. The clinician asks about WBC scanning."

EXCEPTIONAL ANSWER
I would NOT recommend WBC scanning for suspected vertebral osteomyelitis. WBC scans have poor sensitivity in the spine due to: (1) Normal vertebral bone marrow shows variable, unpredictable WBC uptake, (2) Paradoxically, vertebral infection may appear 'cold' or photopenic rather than hot, (3) Interpretation is unreliable. For suspected spine infection, I would recommend: (1) MRI as first choice - highly sensitive (greater than 90%), excellent anatomic detail, can show disc involvement (key distinguishing feature from tumour), epidural abscess, and paraspinal extension. (2) If MRI contraindicated, FDG-PET/CT is an alternative - better performance than WBC scan in spine, can assess entire spine, and helps differentiate infection from degenerative changes. (3) CT-guided biopsy for microbiological diagnosis if imaging suggests infection.
KEY POINTS TO SCORE
WBC scan has POOR sensitivity in spine infection
Vertebral marrow causes variable uptake
Infection may appear cold (counterintuitive)
MRI is modality of choice for spine infection
FDG-PET alternative if MRI contraindicated
COMMON TRAPS
✗Recommending WBC scan for spine (poor performance)
✗Not knowing about the spine limitation
✗Not recommending MRI as first-line

Evidence Base

Diagnostic Accuracy

1

2

Clinical Applications

3

4

Limitations and Considerations

  • Spine infections: Poor performance due to normal bone marrow presence
  • Chronic infections: May have less inflammatory cell activity
  • Neutropenic patients: Limited utility if neutrophil count low
  • Technique: Requires specialist nuclear medicine laboratory

WBC Scan Quick Reference

High-Yield Exam Summary

Labelling Agents

  • •In-111 oxine: Stable, delayed imaging
  • •Tc-99m HMPAO: Better images, same-day
  • •Patient's own WBCs labelled ex vivo
  • •Process takes 2-3 hours

Combined WBC/Marrow

  • •Gold standard for PJI (greater than 90% accuracy)
  • •WBC scan + Sulphur colloid marrow scan
  • •Mismatch = infection
  • •Match = marrow hyperplasia (not infection)

Interpretation Pattern

  • •WBC +, Marrow - = INFECTION (mismatch)
  • •WBC +, Marrow + = Marrow hyperplasia
  • •WBC -, Any = No infection

Limitations

  • •Spine: POOR sensitivity (use MRI/PET)
  • •Time-consuming (2-3 days)
  • •Requires specialised lab
  • •Diabetic foot: Moderate performance
Quick Stats
Reading Time34 min
Related Topics

Nuclear Medicine in Orthopaedics

Infection Imaging: MRI & Nuclear Medicine

Bone Scintigraphy: Three-Phase Interpretation

PET-CT in Orthopaedic Oncology