MRI carotid plaque imaging predicts future stroke in patients with mild to moderate stenosis ICAD study

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MRI carotid plaque imaging predicts future stroke in patients with mild to moderate stenosis ICAD study Richard Simpson, Senior Clinical Vascular Scientist and Stroke Association Junior Research Training Fellow Hosseini AA, Bath PM, MacSweeney ST, Auer DP. Radiological Sciences, Division of Clinical Neuroscience, University of Nottingham and Department of Vascular Surgery, Nottingham University Hospitals NHS Trust

Introduction Carotid Endarterectomy reduces risk of recurrent stroke in patients with symptomatic carotid artery stenosis

Introduction Pooled analysis of NASCET, ECST and VA trials: n = 6092 patients Rothwell et al, Lancet 2003; 361: 107-116

Introduction Pooled analysis of NASCET, ECST and VA trials: n = 6092 patients Rothwell et al, Lancet 2003; 361: 107-116

Introduction Pooled analysis of NASCET, ECST and VA trials: n = 6092 patients Rothwell et al, Lancet 2003; 361: 107-116

Introduction Pooled analysis of NASCET, ECST and VA trials: n = 6092 patients Rothwell et al, Lancet 2003; 361: 107-116

Introduction Rothwell et al, Lancet 2005; 365: 256-265

Introduction Rothwell et al, Lancet 2005; 365: 256-265

Introduction Unstable/vulnerable carotid plaque Beyond the luminal stenosis Plaque imaging Naghavi et al, Circulation, 2003; 108: 1664-1672.

Introduction Hosseini et al, Ann Neurol, 2013; 73(6): 774 784.

Aim & outcomes To determine whether MRI-PH can predict future stroke in patients with symptomatic mild-moderate carotid stenosis 1 outcome Ipsilateral ischaemic stroke or DWI+TIA 2 outcomes Stroke only All recurrent ipsilateral cerebrovascular event

Methods Prospective observational study Adults with a recent TIA, stroke or AmFx Symptomatic 30-99% carotid stenosis No planned carotid intervention Excluded if contraindication to MRI, unable to consent, planned CEA Cerebrovascular events, vascular risk factors, comorbidities and medications 6 monthly clinical/telephone follow-up

Methods Brain and carotid imaging DTI, FLAIR, DWI, fmri Time of Flight MRA ± CE-MRA MRI carotid wall imaging Coronal T 1 -weighted 3D MPRAGE (Black-blood and fat-saturation) Signal Intensity Ratio = SI plaque /SI muscle MRIPH+ve if > 1.5 MRIPH-ve if < 1.5

Results Over 4000 were patients screened 38 excluded: 10 did not have MRI 1 poor quality MRI 2 <30% carotid stenosis 5 occluded ipsilateral carotid artery 12 asymptomatic carotid disease 6 contralateral carotid stenosis 2 posterior circulation stroke 190 agreed to participate 152 recruited (92M, 60F) 1 lost to follow-up 17 70-99% stenosis 134 patients in 30-69% analysis 79 males, 55 females. Median age: 76

Results MRIPH in ICAD study

Results MRIPH in ICAD study

Results 47 (35.1%) patients showed ipsilateral MRI-PH Of which 36 were male; χ² = 9.3, P=0.002 Ipsilateral carotid stenosis (P=0.97) MRIPH positive MRIPH negative 30-49% 22 40 50-59% 17 33 60-69% 8 14 No other demographic or risk factor was significantly associated with MRIPH presence.

Results Follow-up period Median = 656 days, IQR = 349-994 For 30-69% stenosis Event MRIPH positive MRIPH negative Total Stroke 8 4 12 DWI+ TIA 1 0 1 TIA 1 2 3 AmFx 0 1 1 CEA 3 2 5 Death 7 12 19

Results Presence of MRIPH Infarction: HR = 4.4 (95%CI 1.36 14.43, P=0.013) Stroke only: HR = 4.08 (95% CI 1.23 13.58, P=0.02) Controlling for stenosis HR for stroke was 4.69 (95%CI 1.40 15.74, P=0.012)

Results For 50-69% stenosis 72 participants 9 strokes HR = 4.1 95%CI 1.01 16.81, P=0.049 50-69% Risk difference 35% at 3 years

Results For 30-49% stenosis 62 participants 4 infarctions HR = 4.6 95%CI 0.47 44.3, P=0.19 Low power due to number of events 30-49%

Conclusions In symptomatic patients with moderate carotid stenosis, MRI-PH is a significant predictor of future cerebral infarction and stroke. This study builds on previous evidence for MRIPH in moderate stenosis * *Hosseini et al, Ann Neurol, 2013; 73(6): 774 784.

Conclusions MRI-PH status can thus offer decision support when there is clinical uncertainty regarding the benefit of carotid intervention. MRIPH is stable for up to 2 years * Inclusion of MRIPH into clinical risk tools. Easily accessible and quick technique, MRIPH should be implemented into clinical practice as standard care. * Simpson et al, AJNR, 2015;

Acknowledgements Dr Akram Hosseini Mr Nishath Altaf Professor Philip Bath Mr Shane MacSweeney Professor Dorothee Auer Dr Robert Dineen Anita French Dr Daniel Rodriguez Dr Solomon Akwei Dr Tim England Dr Mohana Maddula Funders Stroke Association Junior Research Training Fellowship Rosetrees Trust Nottingham Vascular Research Fund NIHR Research for Patient Benefit programme Declaration: This presentation presents independent research funded by the NIHR under its RfPB Programme (Ref: PB-PG-0107-11438). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. None of the sponsors had any role in study design, data collection, data analysis, data interpretation, writing the report, or in decision making to submit for publication.