What are the neuroimaging guidelines for a patient presenting with symptoms of a window period stroke, considering their medical history and potential eligibility for thrombolytic therapy with tissue plasminogen activator (tPA)?

Neuroimaging Guidelines for Window Period Stroke

Primary Imaging Mandate

Either non-contrast CT or MRI must be performed immediately to exclude intracranial hemorrhage before administering tPA, but imaging is performed to exclude hemorrhage—not to confirm ischemia—and the absence of visible ischemic changes does not preclude thrombolytic treatment within the therapeutic window. 1, 2, 3

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Time-Based Imaging Algorithm

Within 0-3 Hour Window

Obtain non-contrast CT or MRI immediately to exclude hemorrhage only; proceed with tPA if no contraindications exist, regardless of whether acute ischemic changes are visible. 1, 2

• Non-contrast CT is the most practical and widely available initial imaging modality, with target completion and interpretation within 45 minutes of emergency department arrival 3, 4
• CT has limited sensitivity (16%) for hyperacute ischemia in the first 3 hours, compared to MRI-DWI sensitivity of 77%, but this does not affect treatment decisions 3, 5
• Frank hypodensity involving >1/3 of MCA territory is a relative contraindication due to increased hemorrhagic transformation risk, but early ischemic signs of any extent are NOT contraindications to treatment 1
• MRI with DWI, FLAIR, and GRE/SWI can be completed in approximately 10 minutes and is acceptable if it does not delay tPA administration 1, 3

Within 3-4.5 Hour Window

Apply the same imaging principles as the 0-3 hour window: exclude hemorrhage with CT or MRI, then proceed with standard tPA eligibility criteria. 1, 2

• Advanced imaging (CTA, MRA, perfusion studies) is justifiable but cannot delay tPA administration 1
• Vascular imaging should be obtained if endovascular therapy is available, but do not wait for results before starting IV tPA 1, 4

Beyond 4.5 Hours or Wake-Up Stroke

Perform multimodal imaging with DWI-FLAIR mismatch (MRI) or CT perfusion to identify salvageable tissue and select patients for late-window reperfusion therapy. 1, 2, 4

• DWI-FLAIR mismatch identifies patients with unclear onset time who may benefit from thrombolysis 2
• CT or MR perfusion studies identify ischemic penumbra versus irreversibly infarcted core 1, 3
• Vascular imaging (CTA or MRA) is necessary for mechanical thrombectomy consideration 1, 4

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Critical Hemorrhage Exclusion Standards

MRI gradient-echo (GRE) or susceptibility-weighted imaging (SWI) detects hemorrhage with equal or superior sensitivity to CT. 1, 3

• Both CT and MRI have very high sensitivity and specificity for detecting acute intracranial hemorrhage 1
• Small numbers of microbleeds (<5) on GRE/SWI do not contraindicate IV tPA 1, 2
• MRI is superior for detecting subacute/chronic hemorrhage and hemorrhagic transformation 1

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Advanced Imaging Considerations

Vascular Imaging Integration

Obtain CTA (head and neck) or MRA alongside initial brain imaging if endovascular capability exists, but do not delay IV tPA while waiting for vascular imaging results. 1, 3, 4

• CTA-source imaging (CTA-SI) approaches DWI sensitivity for large ischemic regions but is less effective for small lesions and posterior fossa 1
• Vascular imaging identifies large vessel occlusions that may benefit from mechanical thrombectomy 4
• Administer IV tPA immediately even if mechanical thrombectomy is planned; do not wait to assess response 2

MRI Protocol Specifications

A standardized acute stroke MRI protocol includes DWI, FLAIR, and GRE/SWI sequences without contrast. 3

• DWI has 91% sensitivity and 95% specificity for acute ischemia within 6 hours, far exceeding CT's 61% sensitivity 3
• FLAIR detects 91% of ischemic lesions and is useful for wake-up stroke DWI-FLAIR mismatch 3
• GRE/SWI excludes hemorrhage with superior sensitivity to CT 3
• Contrast administration provides no additional diagnostic benefit for acute stroke evaluation 3

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Common Pitfalls and How to Avoid Them

Pitfall #1: Delaying Treatment for "Positive" Imaging

The absence of visible ischemia on CT or MRI is NOT a contraindication to thrombolysis within the treatment window. 2, 3

• Standard CT shows no acute changes in many hyperacute strokes; only 32% of CT scans are positive within 12 hours 5
• Treat based on clinical stroke syndrome and time from onset, not imaging confirmation of ischemia 2

Pitfall #2: Waiting for Advanced Imaging

Emergency treatment should not be delayed to obtain multimodal imaging studies beyond basic hemorrhage exclusion. 1

• Door-to-needle time should be <60 minutes, ideally <30 minutes 2
• Advanced imaging is for patient selection beyond standard windows, not for routine early-window cases 1

Pitfall #3: Misinterpreting Early Ischemic Signs

Early ischemic changes on CT (loss of gray-white differentiation, insular ribbon sign, sulcal effacement) are associated with poor outcomes but are NOT contraindications to treatment unless involving >1/3 MCA territory. 1

• These signs appear in up to 82% of MCA strokes within 6 hours 1
• Only frank hypodensity >1/3 MCA territory is a strong contraindication 1

Pitfall #4: Overreliance on CT in Posterior Circulation Strokes

CT is relatively insensitive for posterior fossa and small cortical/subcortical infarctions; consider MRI if clinical suspicion is high and CT is negative. 1, 4

• MRI detects 93.5% of strokes after 48 hours versus 85% for CT 5
• MRI is particularly superior for lacunar infarcts (75% vs 50% detection) 5

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Practical Implementation Strategy

Step 1: Rapid Clinical Assessment

• Document NIHSS score to quantify deficit severity 1
• Verify acute focal neurological deficit consistent with vascular territory 2
• Exclude stroke mimics (hypoglycemia, seizure) through glucose measurement and clinical assessment 2

Step 2: Immediate Imaging (Target <45 Minutes)

• Obtain non-contrast CT (most facilities) or MRI (if immediately available) 3, 4
• Interpret for hemorrhage exclusion and extent of hypodensity 1
• Add CTA/MRA if endovascular capability exists, but do not delay tPA 1, 4

Step 3: Treatment Decision

• Within 3 hours: Treat all eligible patients regardless of imaging findings beyond hemorrhage exclusion 1, 2
• Within 3-4.5 hours: Apply standard inclusion/exclusion criteria; negative imaging does not preclude treatment 2
• Beyond 4.5 hours: Use multimodal imaging to identify salvageable tissue 1, 2

Step 4: Administer tPA Without Delay

• Give alteplase 0.9 mg/kg (maximum 90 mg) with 10% bolus over 1 minute, remainder over 60 minutes 2, 6
• Blood pressure must be <185/110 mmHg before initiating treatment 2
• Symptomatic ICH risk is 6.4% with tPA versus 0.6% with placebo, but mortality benefit and functional outcomes favor treatment 6