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Optimization of Perfusion Imaging for Acute Cerebral Ischemia: Review of Recent Clinical Trials and Recommendations for Future Studies

¹ Department of Radiology, Duke University Medical Center, Box 3808, Durham, NC 27710.
² Departments of Radiology, Biomedical Engineering and Medicine, Emory University School of Medicine, Atlanta, GA.
³ Department of Radiology, University of California, San Francisco, San Francisco, CA.

View larger version (110K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A —MRI depiction of a diffusion–perfusion mismatch in 70-year-old man with right hemiparesis. Axial diffusion-weighted image shows multiple foci of hyperintense signal within relatively small portion of left middle cerebral artery territory, consistent with acute infarction. These foci corresponded to regions of hyperintense signal on T2-weighted images (not shown). On apparent diffusion coefficient map (not shown), these regions were seen to have lowered apparent diffusion coefficients, consistent with acute infarction.

View larger version (126K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B —MRI depiction of a diffusion–perfusion mismatch in 70-year-old man with right hemiparesis. Axial MR mean transit time (MTT) image obtained at same time as A shows region of prolonged MTT (depicted in orange) in left middle cerebral artery territory that is much larger than diffusion-weighted abnormality seen in A. Area of mismatch, that is, region showing abnormal MTT, but no abnormal diffusion, is usually considered as representing ischemic penumbra or tissue at risk.

View larger version (97K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A —Pretreatment and early posttreatment imaging in 64-year-old man with 2 hours of aphasia and right hemiparesis who underwent IV recombinant tissue plasminogen activator therapy within 3-hour time window recommended for IV therapy. Pretreatment axial maximum-intensity-projection image from CT angiogram (A) shows almost complete occlusion of M1 segment of the left middle cerebral artery. Pretreatment perfusion CT image (B) shows cerebral blood volume deficit (dark blue) in posterior left temporal lobe with sparing of anterior left temporal lobe. However, cerebral blood flow image (C) shows decreased cerebral blood flow and mean transit time (MTT) image (D) shows prolonged MTT (dark blue) in both anterior portion and posterior portion of left temporal lobe. Thus, posterior temporal lobe likely represents infarcted tissue (both MTT/cerebral blood flow and cerebral blood volume abnormality) and anterior temporal lobe may represent salvageable tissue or ischemic penumbra (MTT/cerebral blood flow abnormality with normal cerebral blood volume).

View larger version (111K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B —Pretreatment and early posttreatment imaging in 64-year-old man with 2 hours of aphasia and right hemiparesis who underwent IV recombinant tissue plasminogen activator therapy within 3-hour time window recommended for IV therapy. Pretreatment axial maximum-intensity-projection image from CT angiogram (A) shows almost complete occlusion of M1 segment of the left middle cerebral artery. Pretreatment perfusion CT image (B) shows cerebral blood volume deficit (dark blue) in posterior left temporal lobe with sparing of anterior left temporal lobe. However, cerebral blood flow image (C) shows decreased cerebral blood flow and mean transit time (MTT) image (D) shows prolonged MTT (dark blue) in both anterior portion and posterior portion of left temporal lobe. Thus, posterior temporal lobe likely represents infarcted tissue (both MTT/cerebral blood flow and cerebral blood volume abnormality) and anterior temporal lobe may represent salvageable tissue or ischemic penumbra (MTT/cerebral blood flow abnormality with normal cerebral blood volume).

View larger version (108K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2C —Pretreatment and early posttreatment imaging in 64-year-old man with 2 hours of aphasia and right hemiparesis who underwent IV recombinant tissue plasminogen activator therapy within 3-hour time window recommended for IV therapy. Pretreatment axial maximum-intensity-projection image from CT angiogram (A) shows almost complete occlusion of M1 segment of the left middle cerebral artery. Pretreatment perfusion CT image (B) shows cerebral blood volume deficit (dark blue) in posterior left temporal lobe with sparing of anterior left temporal lobe. However, cerebral blood flow image (C) shows decreased cerebral blood flow and mean transit time (MTT) image (D) shows prolonged MTT (dark blue) in both anterior portion and posterior portion of left temporal lobe. Thus, posterior temporal lobe likely represents infarcted tissue (both MTT/cerebral blood flow and cerebral blood volume abnormality) and anterior temporal lobe may represent salvageable tissue or ischemic penumbra (MTT/cerebral blood flow abnormality with normal cerebral blood volume).

View larger version (100K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2D —Pretreatment and early posttreatment imaging in 64-year-old man with 2 hours of aphasia and right hemiparesis who underwent IV recombinant tissue plasminogen activator therapy within 3-hour time window recommended for IV therapy. Pretreatment axial maximum-intensity-projection image from CT angiogram (A) shows almost complete occlusion of M1 segment of the left middle cerebral artery. Pretreatment perfusion CT image (B) shows cerebral blood volume deficit (dark blue) in posterior left temporal lobe with sparing of anterior left temporal lobe. However, cerebral blood flow image (C) shows decreased cerebral blood flow and mean transit time (MTT) image (D) shows prolonged MTT (dark blue) in both anterior portion and posterior portion of left temporal lobe. Thus, posterior temporal lobe likely represents infarcted tissue (both MTT/cerebral blood flow and cerebral blood volume abnormality) and anterior temporal lobe may represent salvageable tissue or ischemic penumbra (MTT/cerebral blood flow abnormality with normal cerebral blood volume).

View larger version (97K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2E —Pretreatment and early posttreatment imaging in 64-year-old man with 2 hours of aphasia and right hemiparesis who underwent IV recombinant tissue plasminogen activator therapy within 3-hour time window recommended for IV therapy. Posttreatment axial maximum-intensity-projection image (E) from CT angiogram performed 24 hours after therapy now shows patency of left middle cerebral artery, consistent with complete recanalization. Posttreatment perfusion CT image now shows diminished cerebral blood volume (F), diminished cerebral blood flow (G), and prolonged MTT (H) in anterior temporal lobe, consistent with infarction, as well as previously noted hemodynamic alteration consistent with infarction in posterior temporal lobe. This figure shows that mere fact of recanalization does not guarantee salvage of tissue and may interfere with testing of prediction paradigm if not adequately documented. For instance, anterior temporal lobe may have progressed to infarction between time of imaging and time of therapy. Alternatively, as result of recanalization, distal emboli from initial thrombus may have propagated into arterial supply of anterior temporal lobe, causing infarction.

View larger version (121K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2F —Pretreatment and early posttreatment imaging in 64-year-old man with 2 hours of aphasia and right hemiparesis who underwent IV recombinant tissue plasminogen activator therapy within 3-hour time window recommended for IV therapy. Posttreatment axial maximum-intensity-projection image (E) from CT angiogram performed 24 hours after therapy now shows patency of left middle cerebral artery, consistent with complete recanalization. Posttreatment perfusion CT image now shows diminished cerebral blood volume (F), diminished cerebral blood flow (G), and prolonged MTT (H) in anterior temporal lobe, consistent with infarction, as well as previously noted hemodynamic alteration consistent with infarction in posterior temporal lobe. This figure shows that mere fact of recanalization does not guarantee salvage of tissue and may interfere with testing of prediction paradigm if not adequately documented. For instance, anterior temporal lobe may have progressed to infarction between time of imaging and time of therapy. Alternatively, as result of recanalization, distal emboli from initial thrombus may have propagated into arterial supply of anterior temporal lobe, causing infarction.

View larger version (111K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2G —Pretreatment and early posttreatment imaging in 64-year-old man with 2 hours of aphasia and right hemiparesis who underwent IV recombinant tissue plasminogen activator therapy within 3-hour time window recommended for IV therapy. Posttreatment axial maximum-intensity-projection image (E) from CT angiogram performed 24 hours after therapy now shows patency of left middle cerebral artery, consistent with complete recanalization. Posttreatment perfusion CT image now shows diminished cerebral blood volume (F), diminished cerebral blood flow (G), and prolonged MTT (H) in anterior temporal lobe, consistent with infarction, as well as previously noted hemodynamic alteration consistent with infarction in posterior temporal lobe. This figure shows that mere fact of recanalization does not guarantee salvage of tissue and may interfere with testing of prediction paradigm if not adequately documented. For instance, anterior temporal lobe may have progressed to infarction between time of imaging and time of therapy. Alternatively, as result of recanalization, distal emboli from initial thrombus may have propagated into arterial supply of anterior temporal lobe, causing infarction.

View larger version (100K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2H —Pretreatment and early posttreatment imaging in 64-year-old man with 2 hours of aphasia and right hemiparesis who underwent IV recombinant tissue plasminogen activator therapy within 3-hour time window recommended for IV therapy. Posttreatment axial maximum-intensity-projection image (E) from CT angiogram performed 24 hours after therapy now shows patency of left middle cerebral artery, consistent with complete recanalization. Posttreatment perfusion CT image now shows diminished cerebral blood volume (F), diminished cerebral blood flow (G), and prolonged MTT (H) in anterior temporal lobe, consistent with infarction, as well as previously noted hemodynamic alteration consistent with infarction in posterior temporal lobe. This figure shows that mere fact of recanalization does not guarantee salvage of tissue and may interfere with testing of prediction paradigm if not adequately documented. For instance, anterior temporal lobe may have progressed to infarction between time of imaging and time of therapy. Alternatively, as result of recanalization, distal emboli from initial thrombus may have propagated into arterial supply of anterior temporal lobe, causing infarction.

View larger version (94K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3A —Catheter angiogram depiction of collateral circulation beyond site of arterial occlusion in 70-year-old woman. Catheter angiogram, anteroposterior projection, early arterial phase of left internal carotid artery injection, shows stenosis of left middle cerebral artery (arrowhead) with absence of opacification of suprasylvian branches (arrow). Note incidental finding of opacification of both posterior cerebral arteries and basilar artery via flow through left posterior communicating artery.

View larger version (111K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3B —Catheter angiogram depiction of collateral circulation beyond site of arterial occlusion in 70-year-old woman. Catheter angiogram, anteroposterior projection, midarterial phase, shows filling of suprasylvian branches via collateral flow (arrow) from anterior cerebral artery branches rather than through anterograde flow.

View larger version (120K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3C —Catheter angiogram depiction of collateral circulation beyond site of arterial occlusion in 70-year-old woman. Catheter angiogram, anteroposterior projection, late arterial phase, shows late filling of suprasylvian branches via collateral flow (arrow).

View larger version (94K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4A —Depiction of effect of lack of adequate collateral flow on final infarct volume in 70-year-old man with 4 hours of left hemiparesis. Thrombolytic therapy was not administered. Axial maximum-intensity-projection image from CT angiogram shows occlusion (arrow) of right middle cerebral artery. Note absence of filling of distal middle cerebral artery branches and no collateral circulation from other arteries.

View larger version (130K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4B —Depiction of effect of lack of adequate collateral flow on final infarct volume in 70-year-old man with 4 hours of left hemiparesis. Thrombolytic therapy was not administered. Unenhanced axial CT image of brain obtained 36 hours after A shows large infarction in essentially entire right middle cerebral artery territory. Inadequate collateral circulation led to development of large artery territory infarct.

View larger version (103K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5A —Illustration of effect of excellent collateral flow on minimizing of final infarct volume in 64-year-old woman with 6 hours of left hemiparesis. Thrombolytic therapy was not administered. Axial maximum-intensity-projection image from CT angiogram shows occlusion (arrow) of right middle cerebral artery. Note opacification of distal middle cerebral artery branches via collateral circulation from other arteries.

View larger version (140K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5B —Illustration of effect of excellent collateral flow on minimizing of final infarct volume in 64-year-old woman with 6 hours of left hemiparesis. Thrombolytic therapy was not administered. Unenhanced axial CT image of brain obtained 48 hours after A shows that resultant infarct is small and confined to right basal ganglia, whereas most of remainder of right middle cerebral artery territory is spared.

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