What is the role of acetazolamide (carbonic anhydrase inhibitor) augmented Technetium-99m (TC 99m) ethyl cysteinate dimer (ECD) scan in diagnosing and managing cerebral blood flow in patients with Moya Moya disease?

Acetazolamide-Augmented Tc-99m ECD SPECT in Moyamoya Disease

Acetazolamide-augmented SPECT imaging (including Tc-99m ECD) is a valuable functional imaging modality for assessing cerebrovascular reserve and perfusion instability in moyamoya patients, helping guide surgical decision-making and evaluate post-revascularization outcomes. 1

Primary Role: Assessment of Cerebrovascular Reserve

SPECT with acetazolamide challenge directly measures vascular reserve capacity, which is a critical predictor of ischemic events and surgical candidacy in moyamoya disease. 1

• The acetazolamide challenge reveals regions with impaired vasodilatory capacity that cannot be detected on resting perfusion studies alone 2, 3
• Patients with moyamoya demonstrate paradoxical responses to acetazolamide, including "steal phenomenon" where acetazolamide administration can actually decrease perfusion in severely compromised territories 4
• Cerebrovascular reserve (CVR) measurements identify hemodynamically compromised regions before they become symptomatic, allowing for preemptive surgical intervention 2

Clinical Applications

Preoperative Assessment

• Identifies surgical candidates: Even asymptomatic patients with radiographic or functional evidence of impaired cerebral perfusion on acetazolamide-challenged studies should be considered for revascularization 5
• Quantifies severity: Regions showing negative CVR values (indicating steal phenomenon) represent the most severely compromised territories requiring urgent intervention 2, 4
• Maps hemodynamic compromise: Acetazolamide-challenged SPECT delineates specific vascular territories with inadequate perfusion reserve, guiding surgical planning 1

Postoperative Evaluation

• Documents functional improvement: Serial acetazolamide-challenged SPECT studies demonstrate restoration of cerebrovascular reserve after successful revascularization 1
• Quantifies surgical success: Studies show significant improvement in both resting cerebral blood flow and vasodilatory capacity following revascularization, with CVR improving from approximately -18% to -15% in treated territories 2
• Detects incomplete revascularization: Persistent impaired CVR on post-surgical acetazolamide challenge may indicate need for additional procedures 2

Technical Considerations

Imaging Protocol

• Baseline scan: Initial SPECT imaging performed at rest to establish baseline cerebral perfusion 1
• Acetazolamide administration: Typically 10 mg/kg IV or 1 g IV dose 2, 3
• Post-challenge imaging: Second SPECT acquisition performed 15-20 minutes after acetazolamide injection 2, 3

Important Caveat: Temporal Variability

Recent evidence reveals substantial temporal variation in CBF response to acetazolamide, with peak increases occurring at different time points (5,15, or 25 minutes) in individual patients. 6

• In 68% of affected vascular territories, maximum CBF increase did not occur at the standard 15-minute time point 6
• Individual CVR differences between time points ranged from 1-30 percentage points (mean 8 percentage points) 6
• Clinical implication: Single time-point measurements may overestimate disease progression or underestimate surgical benefit, potentially affecting surgical decision-making 6

Comparison with Alternative Modalities

SPECT vs. MR Perfusion

• SPECT advantages: Well-established methodology with extensive validation in moyamoya populations; can use either Tc-99m HMPAO or Tc-99m ECD tracers 1
• MR perfusion alternatives: Arterial spin labeling (ASL) or dynamic susceptibility contrast (DSC) techniques provide similar information without radiation exposure 1
• Both modalities are acceptable for assessing functional improvement after treatment 1

SPECT vs. CT Perfusion

• CT perfusion with acetazolamide challenge shows strong correlation with SPECT-derived CVR (r=0.89 for percentage change in CBF) 7
• However, CT perfusion requires repetitive brain imaging and higher radiation exposure in children 1
• Baseline CT perfusion parameters alone are unreliable for predicting impaired CVR; acetazolamide challenge is essential 7

Integration into Diagnostic Algorithm

When to Order Acetazolamide-Challenged SPECT

1. After anatomic diagnosis: Once moyamoya is confirmed by catheter angiography or MRA, functional perfusion assessment guides treatment decisions 1
2. Symptomatic patients: Those with TIAs, strokes, or cognitive decline require CVR assessment to determine surgical urgency 5
3. Asymptomatic patients: Even without symptoms, impaired CVR on acetazolamide challenge identifies candidates for preventive revascularization 5
4. Post-surgical follow-up: Serial studies at 12-24 months document hemodynamic improvement and detect disease progression 2

Interpretation Framework

• Normal CVR: >30% increase in regional CBF post-acetazolamide indicates adequate vascular reserve 2, 4
• Impaired CVR: 0-30% increase suggests compromised but present reserve capacity 2, 4
• Negative CVR (steal phenomenon): Decreased CBF post-acetazolamide indicates severe hemodynamic compromise requiring urgent intervention 2, 4

Role in the Broader Imaging Strategy

While catheter angiography remains the gold standard for definitive anatomic diagnosis of moyamoya, acetazolamide-challenged SPECT provides complementary functional information that anatomic imaging cannot reveal. 1

• MRI/MRA serves as the preferred initial noninvasive diagnostic modality for anatomic assessment 1
• Acetazolamide-challenged SPECT (or alternative perfusion techniques) adds functional hemodynamic data essential for treatment planning 1
• The combination of anatomic and functional imaging optimizes surgical candidate selection and timing 5