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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 ToolsDWIFLAIRCT

Penumbra 10-17 mL/100 g per min

Imaging:CTPMRPPETXe-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 achievedMedian 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

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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):66-73Furlan 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

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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 placebo90mcg 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

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

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DEFUSE-2

MRI/MRP and endovascular therapy 1.8

Favorable Mismatch

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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

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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

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NCCT NINDS

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

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

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.

Key value is score of ≥8

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 inNINDS rtPA Stroke Study. Stroke. 2005 Oct;36(10):2110-5

CT Perfusion

Reduced CBV correlates with ischemic core CBV

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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 (/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 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

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

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 BrainImproves 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 BrainImproves 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 BRAINPrompt treatment is less brain hemorrhage

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TIME is BRAINPrompt treatment is less brain hemorrhage