Multimodal Imaging Using Ct, Mri, and Angiography in Stroke

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.

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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

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Benign oligemia; >17 mL/100 g per min

CBV

 CBF = CBV/MTT

CBV= mL/100g of brain

MTT

Time

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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.

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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

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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

Perfusion Mismatch

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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

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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

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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

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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

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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

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NCCT NINDS

 Baseline CT that showed no evidence of ICH

 Early Ischemic Change  Did not change treatment eligibility  Present in 31%

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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

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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

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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. Thomas, Francesca M. Chappell, et al. Computed Tomography and Magnetic Resonance Perfusion Imaging in Ischemic Stroke: Definitions and Thresholds. ANN NEUROL 2011;70:384–401

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Angiography

 Diagnostic and therapetic properties

 Gold standard for diagnosis of steno-occlusive disease

 Goal of stroke therapy is to achieve recanalization

Value of Collaterals

 ASITN/SIR Collateral Flow Grading System  Grade 0 (no collaterals visible to the ischemic site).  Grade 1 (slow collaterals to the periphery of the ischemic site with persistence of some of the defect).  Grade 2 (rapid collaterals to the periphery of ischemic site with persistence of some of the defect and to only a portion of the ischemic territory).  Grade 3 (collaterals with slow but complete angiographic blood flow of the ischemic bed by the late venous phase)  Grade 4 (complete and rapid collateral blood flow to the vascular bed in the entire ischemic territory by retrograde perfusion).

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Value of Collaterals

 SWIFT Trial (Solitaire vs MERCI)  Baseline Collateral Grade (n=119)  Grade 0-1: 27%  Grade 2: 40%  Grade 3: 29%  Grade 4: 3%  Smoking, elevated admission glucose & systolic blood pressure were associated with worse collateral  Better collaterals were associated with better revascularization; favorable NIHSS and mRS  Poor collaterals were associated with sICH

David S Liebeskind, MD. Impact of Collaterals on Successful Revascularization in SWIFT. International Stroke Conference. Honolulu, HI. 2013

Conclusions

 Prospective studies are required to validate the Perfusion Criteria (CT/MR) before incorporating perfusion imaging as a routine modality for patient selection for stroke treatment

 TIME and NCCT are still the most valuable tools in stroke therapy determination

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Time is Brain Improves outcomes

Hacke W, Donnan G, Fieschi C, et al. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet. 2004 Mar 6

Time is Brain Improves outcomes

Hacke W, Donnan G, Fieschi C, et al. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet. 2004 Mar 6

TIME is BRAIN Prompt treatment is less brain hemorrhage

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TIME is BRAIN Prompt treatment is less brain hemorrhage