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Multimodal Imaging Using Ct, Mri, and Angiography in Stroke

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1/18/2014 MULTIMODAL IMAGING USING CT, MRI, AND ANGIOGRAPHY IN STROKE Jefferson T Miley MD Seton Brain and Spine Institute Department of Neurology UT-Southwestern Austin Outline Focus of Imaging on Acute Ischemic Stroke Physiology Basics Imaging Computerized Tomography NCCT CT-Perfusion Magnetic Resonance Imaging DWI PWI FLAIR Digital Subtraction Angiography Conclusions Physiology CBF = CBV/MTT Benign oligemia; >17 mL/100 g per minute Penumbra 17 to 10 mL/100 g per minute infarct core 10mL/100 g per minute Latchaw RE, Yonas H, Hunter GJ, Yuh WT, et al. Guidelines and recommendations for perfusion imaging in cerebral ischemia:a scientific statement for healthcare professionals by the writing group on perfusion imaging, from the Council on Cardiovascular Radiology of the American Heart Association. Stroke. 2003;34: 1084–1104. 1 1/18/2014 Oligemia? Penumbra? Infarct? infarct core 10mL/100 g per minute Imaging Tools DWI FLAIR CT Penumbra 10-17 mL/100 g per min Imaging: CTP MRP PET Xe-CT 2 1/18/2014 Benign oligemia; >17 mL/100 g per min CBV CBF = CBV/MTT CBV= mL/100g of brain MTT Time 3 1/18/2014 Summary AUC=CBV MRI DWI DWI lesions are regions of cytotoxic edema which proceed to infarction Lesions can reverse if reperfusion is achieved Median reversal DWI volume 43% in DEFUSE trial Reversibility correlates with good clinical outcome Jean-Marc Olivot, MD, PhD; Michael Mlynash, MD, MS; Vincent N. Thijs, MD, PhD, et al. Relationships Between Cerebral Perfusion and Reversibility of Acute Diffusion Lesions in DEFUSE Insights from RADAR. Stroke. 2009;40:1692-1697. 4 1/18/2014 MRI FLAIR Acute imaging: DWI positive/FLAIR negative: images correlate with stroke of under 4.5hrs Thomalla G, Cheng B, Ebinger M, et al. DWI-FLAIR mismatch for the identification of patients with acute ischaemic stroke within 4·5 h of symptom onset (PRE-FLAIR): a multicentre observational study.. Lancet Neurol. 2011 Nov;10(11):978-86.Epub 2011 Oct 4. Samuel Emeriau, PhD; Isabelle Serre, MD; Olivier Toubas, MD;et al. Can Diffusion-Weighted Imaging–Fluid-Attenuated Inversion Recovery Mismatch (Positive Diffusion-Weighted Imaging/ Negative Fluid-Attenuated Inversion Recovery) at 3 Tesla Identify Patients With Stroke at <4.5 Hours? Stroke. 2013 Jun;44(6):1647-51Epub 2013 May 2. MRI FLAIR MR WITNESS SIR= lesion/nL Ona Wu, Lawrence L Latour, Shlee S Song. MR WITNESS: A Phase IIa Safety Study of Intravenous Thrombolysis with Alteplase in MRI-Selected Patients. ISC 2012. MRI PWI-DWI mismatch DIAS EPITHET DEFUSE MR RESCUE 5 1/18/2014 DIAS-2 IV Desmoteplase 3-9h in patients selected on perfusion mismatch DIAS & DEDAS (2005,2006) Used DWI/MR-P only Phase II studies demonstrated better outcomes in desmoteplase patients Hacke W, Albers G, Al-Rawi Y et al. The Desmoteplase in Acute Ischemic Stroke Trial (DIAS): a phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase. Stroke. 2005 Jan;36(1):66-73 Furlan AJ, Eyding D, Albers GW et al. Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS): evidence of safety and efficacy 3 to 9 hours after stroke onset. Stroke. 2006 May;37(5):1227-31 DIAS-2 DIAS-2 Perfusion Mismatch 6 1/18/2014 DIAS-2 DIAS-2 (2009) 186 pts 90mcg/kg vs 125mcg/kg vs placebo Included MR-P and CT-P with a visually demonstrated perfusion mismatch with >20% salvageable penumbra No threshold values included Study failed to demonstrate benefit when compared with placebo 90mcg 47% 125mcg 36% Placebo 46%; p=0.47 Hacke W, Furlan AJ, Al-Rawi Y et al. Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study. Lancet Neurol. 2009 Feb;8(2):141-50 EPITHET Phase II study Alteplase 3-6hr 101 pts Perfusion mismatch was not used for selection of patients PWI threshold Tmax ≥2s (time to peak) Davis SM, Donnan GA, Parsons MW, et al. Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial. Lancet Neurol. 2008 Apr;7(4):299-309 EPITHET 7 1/18/2014 EPITHET EPITHET EPITHET Alteplase Associated lower infarct growth* 1.24 vs 1.78 p=0.69 Associated with increased reperfusion p=0.001 Reperfusion associated with better clinical outcomes p<0.0001 Phase III study? ECASS study 8 1/18/2014 DEFUSE-2 MRI/MRP and endovascular therapy <12hrs of onset Prospective Eligible for endovascular therapy and tolerate MRI where main inclusion criteria 104 pts Lansberg MG, Straka M, Kemp S. MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study. Lancet Neurol. 2012 Oct;11(10):860-7. DEFUSE-2 RAPID software DEFUSE-2 Favorable Mismatch DWI vol <70mL Ratio >1.8 Tmax >6s 9 1/18/2014 DEFUSE-2 DEFUSE-2 NIHSS improvement ≥8 or return to 0-1 Randomized trial in the horizon? MR RESCUE CT and MR Perfusion Endovascular stroke therapy Images obtained processed by “Box” to evaluate penumbral pattern and then allocate into embolectomy or standard of care Favorable penumbra Infarct core ≤90mL Estimated infarct ≤70% of area at risk Chelsea S. Kidwell, M.D., Reza Jahan, M.D., Jeffrey Gornbein, Dr.P.H. et at. A Trial of Imaging Selection and Endovascular Treatment for Ischemic Stroke. N Engl J Med 2013; 368:914-923 10 1/18/2014 MR RESCUE MR RESCUE Among all patients (mRS) embolectomy 3.9 standard care 3.9 (P=0.99) Favorable penumbral pattern embolectomy 3.9 standard care 3.4 (P=0.23) Non-penumbral pattern Embolecomy 4.0 Standard care 4.4 (p=0.32) MR RESCUE “Findings do not support the efficacy of using CT or MRI to select patients for acute stroke treatment or the efficacy of mechanical embolectomy with first- generation devices” Chelsea S. Kidwell, M.D., Reza Jahan, M.D., Jeffrey Gornbein, Dr.P.H. et at. A Trial of Imaging Selection and Endovascular Treatment for Ischemic Stroke. N Engl J Med 2013; 368:914-923 11 1/18/2014 NCCT NINDS NCCT NINDS Baseline CT that showed no evidence of ICH Early Ischemic Change Did not change treatment eligibility Present in 31% 12 1/18/2014 ASPECTS ASPECTS Alberta Stroke Programme Early CT Score Max score 10 Min score 0 With thrombolytics High Score correlates with favorable outcomes Low Score correlates with ICH related to thrombolytics Key value is score of ≥8 Barber PA, Demchuk AM, Zhang J, Buchan AM. Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy. ASPECTS Study Group. Alberta Stroke Programme Early CT Score. Lancet. 2000 May 13;355(9216):1670-4. ASPECTS 13 1/18/2014 ASPECTS NINDS Demchuk AM, Hill MD, Barber PA, Silver B, Patel SC, Levine SR; NINDS rtPA Stroke Study Group, NIH. Importance of early ischemic computed tomography changes using ASPECTS in NINDS rtPA Stroke Study. Stroke. 2005 Oct;36(10):2110-5 CT Perfusion Reduced CBV correlates with ischemic core CBV <2mL/100g Ischemia Penumbra CBF MTT Wintermark M, Flanders AE, Velthuis B, et al. Perfusion-CT assessment of infarct core and penumbra: receiver operating characteristic curve analysis in 130 patients suspected of acute hemispheric stroke. Stroke 2006; 37:979-985. CT Perfusion Phase III Studies DIAS-2 (also MRI) MR RESCUE (also MRI) Many series published comparing different variables for treatment decision against CTP 14 1/18/2014 CT Perfusion CTP guided Endovascular Stroke Therapy vs Time Retrospective Qualitative perfusion analysis (visual) Hassan: CTP-guided endovascular treatment did not increase the rate of short-term favorable outcomes among patients with acute ischemic stroke Chalouhi: CTP guided therapy (<8hrs) was associated with lower ICH and mortality. No difference favorable outcomes. Turk: similar rates of good functional outcome and ICH on CTP guided therapy vs as if treated time-guided (>/<8hrs) Ameer E. Hassan, DO; Haralabos Zacharatos, DO; Gustavo J. Rodriguez, MD; et al. A Comparison of Computed Tomography Perfusion-Guided and Time-Guided Endovascular Treatments for Patients With Acute Ischemic Stroke. Stroke. 2010;41:1673-1678. Nohra Chalouhia, George Ghobriala, Stavropoula Tjoumakarisa, et al. CT perfusion-guided versus time-guided mechanical recanalization inacute ischemic stroke patients. Clinical Neurology and Neurosurgery 115 (2013). Aquilla S Turk, Jordan Asher Magarick, Don Frei, et al. CT perfusion-guided patient selection for endovascular recanalization in acute ischemic stroke: a multicenter study. J NeuroIntervent Surg 2013;5:523–527. CT Perfusion Agreement on Endovascular Treatment using initial CT vs CTP among stroke specialists There is lack of agreement when using a qualitative CT-P determination in selecting stroke patients for endovascular treatment Treatment using NCCT: 0.43 (moderate agreement 0.61-0.80) Treatment using CTP: 0.29 (fair agreement 0.21-0.40) Ameer E. Hassan; Haralabos Zacharatos; Saqib A. Chaudhry, et al. Agreement in Endovascular Thrombolysis Patient Selection Based on Interpretation of Presenting CT and CT-P Changes in Ischemic Stroke Patients. Neurocrit Care (2012) 16:88–94 Perfusion Imaging – Moving target Qualitative penumbra determination Often used and defies “scientific method” Quantitative penumbra determination Definitions not consistent MRP 10 different penumbra definitions CBF: <18,25,35,35,37 mL/100g/min MTT: >1.78, 4, 6,7,8 seconds relative to contralateral Tmax: >1.45, 2, 4, 5.4 seconds relative to contralateral CTP 8 different definitions CBF: 20.8, 34.6 mL/100g/min CBV: non viable <1.7, 2.4 mL/100g MTT: >4.94, 5.15 seconds relative to contralateral Krishna A. Dani, Ralph G.R.
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