Can a computed tomography angiography (CTA) brain scan show no large vessel occlusion (LVO) but computed tomography (CT) perfusion still show significant penumbra in a patient with suspected acute ischemic stroke?

Can CTA Show No LVO While CT Perfusion Still Shows Significant Penumbra?

Yes, CT perfusion can demonstrate significant penumbra even when CTA shows no large vessel occlusion, because penumbral tissue represents severely ischemic but salvageable brain tissue that can result from various mechanisms beyond proximal large vessel occlusion, including distal branch occlusions, critical stenoses, poor collateral flow, or microvascular dysfunction. 1

Understanding the Imaging Discordance

Why This Scenario Occurs

CTA and CT perfusion measure fundamentally different aspects of cerebral ischemia:

• CTA provides anatomic visualization of vessel patency and can reliably detect large vessel occlusions (internal carotid artery, M1 segment) with 92-100% sensitivity, but has limitations in detecting distal branch occlusions or assessing tissue-level perfusion 1

• CT perfusion measures tissue-level hemodynamics including cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT), which can identify ischemic penumbra (preserved CBV with prolonged MTT) even when proximal vessels appear patent 1

Clinical Mechanisms Explaining CTA-Negative/CTP-Positive Findings

Several pathophysiological scenarios can produce significant penumbra without visible LVO on CTA:

• Distal medium vessel occlusions (M2, M3 branches) that fall below CTA's reliable detection threshold but still produce substantial penumbral volumes 1

• Critical stenoses without complete occlusion that reduce perfusion pressure sufficiently to create penumbra while maintaining some antegrade flow visible on CTA 2

• Poor collateral circulation despite patent proximal vessels, where multiphase CTA would show inadequate collateral opacification and CT perfusion would demonstrate resulting tissue hypoperfusion 1

• Microvascular dysfunction or distal embolic showers causing tissue-level ischemia without discrete large vessel occlusion 3

Clinical Significance and Decision-Making

Prognostic Value of CT Perfusion Findings

CT perfusion penumbra volume represents independent prognostic information that cannot be predicted from clinical data, NCCT, or CTA alone:

• Penumbra volume is a strong predictor of clinical outcome, particularly when considered with recanalization status (P<0.001 for interaction term) 4

• Patients with large penumbra volumes show greater benefit from reperfusion therapies, even in the absence of traditional LVO 3, 4

• The presence of significant penumbra identifies "tissue at risk" that may be salvageable with appropriate intervention 2

Treatment Implications

The presence of significant penumbra on CT perfusion, even without LVO on CTA, should influence clinical decision-making:

• Consider the patient for reperfusion therapy based on tissue-level ischemia rather than solely on anatomic vessel occlusion, as penumbral imaging may identify patients who benefit from treatment despite lacking traditional LVO 3

• Evaluate for medium vessel occlusions that may be amenable to endovascular therapy, as EVT is increasingly performed for distal occlusions when significant penumbra is present 1

• Assess collateral status using multiphase CTA, as poor collaterals with patent proximal vessels can explain the perfusion deficit and predict worse outcomes 1

Important Caveats and Limitations

Technical Considerations for CT Perfusion

Be aware of CT perfusion's significant limitations that can produce false-positive penumbra findings:

• CTP has technical failure rates up to 30% due to motion artifact, inadequate contrast bolus, or processing errors 1

• Quantification of core and penumbra is neither standardized nor validated and varies substantially among different vendor software platforms 1

• A subgroup analysis from the MR CLEAN trial indicated that CTP did not add value to treatment decision-making in the context of proven LVO, though this doesn't address the CTA-negative scenario 1

The Core-Penumbra Concept Is Being Challenged

Recent evidence questions the validity of traditional perfusion imaging interpretations:

• In regions classified as "ischemic core," selective neuronal loss rather than pan-necrosis may be present, and no reliable imaging marker currently differentiates these 1

• Some initially abnormal diffusion-weighted imaging (DWI) regions are reversible, and visually thresholded perfusion volumes may overestimate true penumbra 1

• It is questionable whether we should refrain from treating patients due to apparently large ischemic core volumes, particularly given the natural history of untreated acute ischemic stroke 1

Recommended Diagnostic Algorithm

When CTA shows no LVO but CT perfusion demonstrates significant penumbra:

1. Verify CT perfusion technical quality - Review source images for motion artifact, confirm adequate contrast bolus timing, and check for processing errors that could produce spurious perfusion deficits 1, 5

2. Reassess CTA for subtle findings - Look specifically for distal branch occlusions, critical stenoses, or poor collateral flow that might explain the perfusion deficit 1

3. Correlate with clinical severity - Significant clinical deficits (high NIHSS) support true ischemia, while mild symptoms with large perfusion deficits suggest artifact 4

4. Consider multiphase CTA if not already performed - This provides superior assessment of collateral status and predicts outcome better than single-phase CTA or CT perfusion alone 1

5. Evaluate for reperfusion therapy candidacy - The presence of salvageable penumbra may justify treatment even without traditional LVO, particularly in extended time windows where tissue-based selection is established 1, 3

Practical Clinical Pearls

For patients presenting within 6 hours, CT perfusion is not necessary for clinical decision-making according to current expert consensus - NCCT and multiphase CTA provide sufficient information for treatment decisions in this early window 1

For patients presenting beyond 6 hours or with unknown onset, CT perfusion adds value by identifying salvageable tissue and guiding patient selection, though the scenario of significant penumbra without LVO is uncommon in this population 1

Never rely on CT perfusion alone - Always integrate findings with clinical assessment, NCCT ASPECTS score, and vascular imaging to avoid treating artifacts or overestimating salvageable tissue 1, 5