Developments in Imaging Criteria for Ischemic Stroke Treatment
Introduction. Ischemic strokes make up 85% of strokes and can be caused by thrombi.1 Tissue affected by ischemia can be categorized by probability of infarction. Penumbra is tissue likely to infarct but is still salvageable with timely intervention.1,2 Standard treatment for stroke is reperfusion therapy via tissue plasminogen activator (tPA) and/or thrombectomy, the retrieval of the thrombus.1,2 However, these interventions have strict indications due to the rising risk of intracerebral hemorrhage (ICH) over time. Reperfusion cannot be performed after 4.5 hours or 6 hours from stroke symptom onset for tPA or thrombectomy, respectively.1,2 Due to these strict indications for reperfusion therapy, only 6% of ischemic stroke patients receive tPA.3 14-27% of patients are not eligible for therapy due to unknown time of stroke onset.4 In addition, individuals have variable collateral circulation and could benefit from reperfusion past the indicated timeline.2 The use of different imaging modalities is hypothesized to determine whether reperfusion could benefit patients by quantifying penumbral volume defined by hypo-perfusion without restricted diffusion associated with transmembrane ion gradient disruption, cytotoxic edema, or estimating ICH risk via presence of vascular macromolecule leakage, vasogenic edema.4-7 Methods. Perfusion weighted (PWI), diffusion weighted (DWI) and/or fluid attenuated inversion recovery (FLAIR) imaging were used to evaluate ischemic changes (hypo-perfusion, cytotoxic edema, and vasogenic edema, respectively) in rat brains after large artery occlusion compared to controls. Lesion volume on imaging was compared with final infarct volume via histological analysis.5,8-11 Results. PWI showed significant increase in the travel time of contrast agent to and from tissue affected by artery occlusion.5 In DWI, significantly restricted diffusion was observed in affected tissue.5,10,11 FLAIR studies showed hyperintensity lesions starting at 3 hours.5,9 DWI and FLAIR correlated well with areas of ischemia past 3.5 hours.9 DWI lesion volume grew to match PWI hypo-perfusion lesion volume over time, and DWI lesion volume decreased in size after reperfusion therapy.5,10,11 Conclusions. Recent clinical trials have developed imaging criteria based on penumbral or vasogenic changes to determine if reperfusion could benefit patients past current indications. These trials have shown there is benefit with reperfusion for patients chosen with imaging criteria with unknown time of onset and extended-window therapy up to 9 hours and 16 hours for tPA or thrombectomy, respectively, without increased risk of ICH.4,6,7 Therefore, perfusion, diffusion and/or FLAIR imaging may be important adjuncts in the evaluation of stroke in patients who could benefit from reperfusion but are excluded under current indications.
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- Fonarow GC, Zhao X, Smith EE, et al. Door-to-Needle Times for Tissue Plasminogen Activator Administration and Clinical Outcomes in Acute Ischemic Stroke Before and After a Quality Improvement Initiative. JAMA. 2014;311(16):1632-1640.
- Thomalla G, Simonsen C, Boutitie F, et al. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset. The New England Journal of Medicine. 2018;379(7):611-622.
- Quast MJ, Huang NC, Hillman GR, Kent TA. The evolution of acute stroke recorded by multimodal magnetic resonance imaging. Magnetic Resonance Imaging. 1993;11(4):465-471.
- Albers GW, Marks MP, Kemp S, et al. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. New England Journal of Medicine. 2018;378(8):708-718.
- Ma H, Campbell BCV, Parsons MW, et al. Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke. New England Journal of Medicine. 2019;380(19):1795-1803.
- Noguchi K, Ogawa T, Inugami A, et al. MRI of acute cerebral infarction: a comparison of FLAIR and T2-weighted fast spin-echo imaging. Neuroradiology. 1997;39(6):406-410.
- Loubinoux I, Volk A, Borredon J, et al. Spreading of Vasogenic Edema and Cytotoxic Edema Assessed by Quantitative Diffusion and T2 Magnetic Resonance Imaging. Stroke. 1997;28(2):419-427.
- Mintorovitch J, Moseley ME, Chileuitt L, Shimizu H, Cohen Y, Weinstein PR. Comparison of diffusion- and T2-weighted MRI for the early detection of cerebral ischemia and reperfusion in rats. Magnetic Resonance in Medicine. 1991;18(1):39-50.
- Dijkhuizen RM, Knollema S, Worp HBvd, et al. Dynamics of Cerebral Tissue Injury and Perfusion After Temporary Hypoxia-Ischemia in the Rat. Stroke. 1998;29(3):695-704.