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Computed Tomography (CT) Perfusion in the Treatment of Acute Stroke
WORLD Neurosurgery
Computed Tomography (CT) Perfusion in the Treatment of Acute Stroke Peter Kan, Kenneth V. Snyder, Mandy Jo Binning, Adnan H. Siddiqui, L. Nelson Hopkins, Elad I. Levy
Despite ongoing advances in pharmacologic and mechanical thrombolytic therapy, the treatment of acute ischemic stroke remains challenging because of the limited time window during which therapy must be administered. Recent studies suggest that clinical improvement is noted even in patients receiving late reperfusion with large penumbras identified on computed tomography (CT) perfusion imaging (1, 3). We review the clinical application of CT perfusion in the setting of acute stroke and our perfusion-based guidelines for patient selection for endovascular treatment.
TECHNIQUES, PARAMETERS, AND PERFUSION PATTERNS IN ISCHEMIA CT perfusion imaging involves the injection of a single bolus of iodinated contrast agent followed by spiral CT imaging. The commonly available parameters include cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), and mean transit time (MTT). With normal brain perfusion, there is symmetric perfusion with higher CBF and CBV in gray matter than in white matter (Figure 1).
Figure 1. Normal perfusion maps with symmetric perfusion: CBF (bottom left), CBV (top middle), TTP (top right), MTT (bottom middle), and delay map (bottom right).
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Figure 2. Matched reduction in CBF and CBV and increase in TTP and MTT, indicating an area of core infarct.
Regions of irreversible core infarct show matched areas of significant decrease in CBF and CBV owing to the loss of cerebral autoregulation, with increased TTP and MTT on perfusion maps (Figure 2). Reperfusion of such necrotic core is ineffective and would likely increase the risk of hemorrhage (2). By contrast, ischemic penumbra shows increased TTP and MTT, normal or mildly decreased CBF, and relatively spared CBV (as a result of autoregulation with early ischemia) (Figure 3). By limiting recanalization to patients with large areas of ischemic penumbra, neuronal function may be restored without increasing the risk of hemorrhage (2). Several disease states mimic the perfusion patterns seen in acute cerebral ischemia. In extracranial carotid artery stenosis, proximal intracranial stenosis, atrial fibrillation, and congestive heart failure, MTT prolongation is frequently seen, mimicking or overestimating the ischemic penumbra (the algorithm to generate CT perfusion parameters is sensitive to contrast delay). Concurrent CT angiography is critical in every CT perfusion study to assess the extracranial and intracranial vasculature. Delay perfusion maps that correct for the effect of the contrast delay
74 [6]: 550-554, DECEMBER 2010 WORLD NEUROSURGERY
News items of interest may be forwarded to: Felipe C. Albuquerque, M.D. Section Editor, WORLD Neurosurgery News E-mail: [email protected]
Figure 3. Large ischemic penumbra in left middle cerebral artery distribution on CT perfusion imaging with increased TTP and preserved CBF and CBV.
also help distinguish these chronic disease states from acute ischemia. Given the lack of consensus on operational thresholds and potential variations in the absolute values of CT perfusion parameters from different scanners, our group and many other clinicians favor the use of relative CT perfusion values (with the contralateral unaffected hemisphere serving as the control) in clinical decision making. MILLARD FILLMORE GATES PERFUSION-BASED ACUTE STROKE PROTOCOL All patients with suspected cerebrovascular accidents undergo immediate cranial CT scanning, cranial and cervical CT angiog-
REFERENCES 1. Abou-Chebl A: Endovascular treatment of acute ischemic stroke may be safely performed with no time window limit in appropriately selected patients. Stroke 41:1996-2000, 2010.
Felipe C. Albuquerque, M.D.
Issam Awad, M.D.
Section Editor, WORLD Neurosurgery News
Section Editor, WORLD Neurosurgery News
raphy, and brain CT perfusion imaging. All scans are performed on the Toshiba Aquilion 320-slice CT scanner (Toshiba America Medical Systems, Tustin, CA, USA). Perfusion maps of the whole brain are derived using the Vitrea software (Vital Images Inc., Minnetonka, MN, USA), generating the standard perfusion parameters of TTP, MTT, CBF, CBV, and a delay map. If hemorrhage is identified on the noncontrast cranial CT scan, the protocol is aborted. CT angiography helps to identify structural lesions that can be targets for endovascular therapy and extracranial stenoses. CT perfusion imaging is used to identify core infarcts and ischemic penumbra. Ischemic penumbra is defined as the area of mismatch between increased MTT and the loss of CBV on color perfusion maps. Core infarct is defined by a significant loss in CBV (relative CBV of ⬍30%). Time of onset, patient characteristics, and CT perfusion patterns are used to select patients for therapy. Unless contraindicated, patients presenting less than 4.5 hours from symptom onset are treated with intravenous tissue plasminogen activator. Eligible patients treated 4.5– 6 hours after symptom onset usually receive a combination of intra-arterial thrombolytics and mechanical thrombolysis. Beyond 6 hours, only patients with a significant deficit (National Institutes of Health Stroke Scale score of ⱖ8 or severe aphasia), a large penumbra (⬎50% of the occluded vessel territory) with limited core infarct (⬍30% of the occluded vessel territory) on CT perfusion imaging, and a proximal lesion (M2 segment of the middle cerebral artery or proximal) on CT angiography would be selected for mechanical revascularization. Pharmacologic thrombolysis is minimized in this late presentation group because of increased risk of hemorrhage. Patients with core infarct of more than 30% of the occluded vessel territory or patients with core infarct within the basal ganglia are excluded because of increased risk of hemorrhage.
2. Lui YW, Tang ER, Allmendinger AM, Spektor V: Evaluation of CT perfusion in the setting of cerebral ischemia: patterns and pitfalls. AJNR Am J Neuroradiol Feb 3 2010.
3. Natarajan SK, Snyder KV, Siddiqui AH, Ionita CC, Hopkins LN, Levy EI: Safety and effectiveness of en-
WORLD NEUROSURGERY 74 [6]: 550-554, DECEMBER 2010
dovascular therapy after 8 hours of acute ischemic stroke onset and wake-up strokes. Stroke 40: 3269-3274, 2009. 1878-8750/$ - see front matter © 2010 Elsevier Inc. All rights reserved. DOI: 10.1016/j.wneu.2010.10.012
www.WORLDNEUROSURGERY.org
551
Computed Tomography (CT) Perfusion in the Treatment of Acute Stroke Peter Kan, Kenneth V. Snyder, Mandy Jo Binning, Adnan H. Siddiqui, L. Nelson Hopkins, Elad I. Levy
Despite ongoing advances in pharmacologic and mechanical thrombolytic therapy, the treatment of acute ischemic stroke remains challenging because of the limited time window during which therapy must be administered. Recent studies suggest that clinical improvement is noted even in patients receiving late reperfusion with large penumbras identified on computed tomography (CT) perfusion imaging (1, 3). We review the clinical application of CT perfusion in the setting of acute stroke and our perfusion-based guidelines for patient selection for endovascular treatment.
TECHNIQUES, PARAMETERS, AND PERFUSION PATTERNS IN ISCHEMIA CT perfusion imaging involves the injection of a single bolus of iodinated contrast agent followed by spiral CT imaging. The commonly available parameters include cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), and mean transit time (MTT). With normal brain perfusion, there is symmetric perfusion with higher CBF and CBV in gray matter than in white matter (Figure 1).
Figure 1. Normal perfusion maps with symmetric perfusion: CBF (bottom left), CBV (top middle), TTP (top right), MTT (bottom middle), and delay map (bottom right).
550
www.SCIENCEDIRECT.com
Figure 2. Matched reduction in CBF and CBV and increase in TTP and MTT, indicating an area of core infarct.
Regions of irreversible core infarct show matched areas of significant decrease in CBF and CBV owing to the loss of cerebral autoregulation, with increased TTP and MTT on perfusion maps (Figure 2). Reperfusion of such necrotic core is ineffective and would likely increase the risk of hemorrhage (2). By contrast, ischemic penumbra shows increased TTP and MTT, normal or mildly decreased CBF, and relatively spared CBV (as a result of autoregulation with early ischemia) (Figure 3). By limiting recanalization to patients with large areas of ischemic penumbra, neuronal function may be restored without increasing the risk of hemorrhage (2). Several disease states mimic the perfusion patterns seen in acute cerebral ischemia. In extracranial carotid artery stenosis, proximal intracranial stenosis, atrial fibrillation, and congestive heart failure, MTT prolongation is frequently seen, mimicking or overestimating the ischemic penumbra (the algorithm to generate CT perfusion parameters is sensitive to contrast delay). Concurrent CT angiography is critical in every CT perfusion study to assess the extracranial and intracranial vasculature. Delay perfusion maps that correct for the effect of the contrast delay
74 [6]: 550-554, DECEMBER 2010 WORLD NEUROSURGERY
News items of interest may be forwarded to: Felipe C. Albuquerque, M.D. Section Editor, WORLD Neurosurgery News E-mail: [email protected]
Figure 3. Large ischemic penumbra in left middle cerebral artery distribution on CT perfusion imaging with increased TTP and preserved CBF and CBV.
also help distinguish these chronic disease states from acute ischemia. Given the lack of consensus on operational thresholds and potential variations in the absolute values of CT perfusion parameters from different scanners, our group and many other clinicians favor the use of relative CT perfusion values (with the contralateral unaffected hemisphere serving as the control) in clinical decision making. MILLARD FILLMORE GATES PERFUSION-BASED ACUTE STROKE PROTOCOL All patients with suspected cerebrovascular accidents undergo immediate cranial CT scanning, cranial and cervical CT angiog-
REFERENCES 1. Abou-Chebl A: Endovascular treatment of acute ischemic stroke may be safely performed with no time window limit in appropriately selected patients. Stroke 41:1996-2000, 2010.
Felipe C. Albuquerque, M.D.
Issam Awad, M.D.
Section Editor, WORLD Neurosurgery News
Section Editor, WORLD Neurosurgery News
raphy, and brain CT perfusion imaging. All scans are performed on the Toshiba Aquilion 320-slice CT scanner (Toshiba America Medical Systems, Tustin, CA, USA). Perfusion maps of the whole brain are derived using the Vitrea software (Vital Images Inc., Minnetonka, MN, USA), generating the standard perfusion parameters of TTP, MTT, CBF, CBV, and a delay map. If hemorrhage is identified on the noncontrast cranial CT scan, the protocol is aborted. CT angiography helps to identify structural lesions that can be targets for endovascular therapy and extracranial stenoses. CT perfusion imaging is used to identify core infarcts and ischemic penumbra. Ischemic penumbra is defined as the area of mismatch between increased MTT and the loss of CBV on color perfusion maps. Core infarct is defined by a significant loss in CBV (relative CBV of ⬍30%). Time of onset, patient characteristics, and CT perfusion patterns are used to select patients for therapy. Unless contraindicated, patients presenting less than 4.5 hours from symptom onset are treated with intravenous tissue plasminogen activator. Eligible patients treated 4.5– 6 hours after symptom onset usually receive a combination of intra-arterial thrombolytics and mechanical thrombolysis. Beyond 6 hours, only patients with a significant deficit (National Institutes of Health Stroke Scale score of ⱖ8 or severe aphasia), a large penumbra (⬎50% of the occluded vessel territory) with limited core infarct (⬍30% of the occluded vessel territory) on CT perfusion imaging, and a proximal lesion (M2 segment of the middle cerebral artery or proximal) on CT angiography would be selected for mechanical revascularization. Pharmacologic thrombolysis is minimized in this late presentation group because of increased risk of hemorrhage. Patients with core infarct of more than 30% of the occluded vessel territory or patients with core infarct within the basal ganglia are excluded because of increased risk of hemorrhage.
2. Lui YW, Tang ER, Allmendinger AM, Spektor V: Evaluation of CT perfusion in the setting of cerebral ischemia: patterns and pitfalls. AJNR Am J Neuroradiol Feb 3 2010.
3. Natarajan SK, Snyder KV, Siddiqui AH, Ionita CC, Hopkins LN, Levy EI: Safety and effectiveness of en-
WORLD NEUROSURGERY 74 [6]: 550-554, DECEMBER 2010
dovascular therapy after 8 hours of acute ischemic stroke onset and wake-up strokes. Stroke 40: 3269-3274, 2009. 1878-8750/$ - see front matter © 2010 Elsevier Inc. All rights reserved. DOI: 10.1016/j.wneu.2010.10.012
www.WORLDNEUROSURGERY.org
551