- Email: [email protected]
Mechanical embolectomy for acute ischemic stroke beyond six hours from symptom onset using MRI based perfusion imaging
Accepted Manuscript Mechanical embolectomy for acute ischemic stroke beyond six hours from symptom onset using MRI based perfusion imaging
Ryan A. McTaggart, Shadi Yaghi, Daniel C Sacchetti, Richard A. Haas, Morgan Hemendinger, Daniel Arcuri, Jeffrey M. Rogg, Karen L. Furie, Mahesh V. Jayaraman PII: DOI: Reference:
S0022-510X(17)30140-5 doi: 10.1016/j.jns.2017.02.044 JNS 15179
To appear in:
Journal of the Neurological Sciences
Received date: Revised date: Accepted date:
9 December 2016 14 February 2017 20 February 2017
Please cite this article as: Ryan A. McTaggart, Shadi Yaghi, Daniel C Sacchetti, Richard A. Haas, Morgan Hemendinger, Daniel Arcuri, Jeffrey M. Rogg, Karen L. Furie, Mahesh V. Jayaraman , Mechanical embolectomy for acute ischemic stroke beyond six hours from symptom onset using MRI based perfusion imaging. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Jns(2017), doi: 10.1016/j.jns.2017.02.044
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ACCEPTED MANUSCRIPT Mechanical Embolectomy for Acute Ischemic Stroke Beyond Six Hours from Symptom Onset Using MRI based perfusion imaging Ryan A. McTaggart1*, Shadi Yaghi2*, Daniel C Sacchetti 2, Richard A. Haas 1, Morgan Hemendinger2, Daniel Arcuri 1, Jeffrey M. Rogg 1, Karen L. Furie2, Mahesh V. Jayaraman1,2,3 *= co-first authors
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1 Department of Diagnostic Imaging, The Warren Alpert Medical School of Brown University, Providence, RI
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2 Department of Neurology, The Warren Alpert Medical School of Brown University, Providence, RI
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Word count: 1,864 words, Figure: 1, Tables: 2
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3 Department of Neurosurgery, The Warren Alpert Medical School of Brown University, Providence, RI
Key words: Stroke; Thrombectomy; Treatment Window; MRI; Imaging; Perfusion; outcome
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Corresponding author:
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Shadi Yaghi, MD
Providence, RI, 02903
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593 Eddy St, APC 530
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Tel: 401-444-8806, Fax: 401-444-8781
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Email: [email protected]
ACCEPTED MANUSCRIPT Disclosures: Dr. Yaghi received funding from the New York Stroke Trials Network of Columbia and Cornell (NYCCSTN, NINDS U10NS086728). Dr. McTaggart, Dr. Sacchetti, Dr. Haas, Ms. Hemendinger, Mr. Arcuri, Dr. Rogg, Dr. Furie, and Dr. Jayaraman have no disclosures.
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Author contribution
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Ryan McTaggart: Data collection, study concept and design, and manuscript revision
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Shadi Yaghi: Data collection, study concept and design, and manuscript preparation
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Daniel Sacchetti: manuscript preparation Richard Hass: Manuscript revision
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Morgan Hemendinger: Data collection
Jeffrey Rogg: Manuscript revision
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Karen L. Furie: Manuscript revision
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Daniel Arcuri: Manuscript revision
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Mahesh Jayaraman: Study planning and manuscript revision
ACCEPTED MANUSCRIPT Abstract Introduction: There is very limited data on the use of MRI based perfusion imaging to select patients with acute ischemic stroke and large vessel occlusion (LVO) for intraarterial therapy
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beyond 6 hours from onset. Our aim is to report the outcome of patients with acute ischemic
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stroke and large artery occlusion who presented beyond 6 hours from onset, had favorable MRI
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imaging profile, and underwent mechanical embolectomy.
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Methods: This is a single institution (Rhode Island Hospital) retrospective study between December 1st, 2015, and July 30th, 2016 that included patients with acute ischemic stroke and
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proximal LVO with CT ASPECTS of 6 or more and 6-24 hours from symptom onset who were
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assessed for mechanical embolectomy using MRI based perfusion imaging. Favorable imaging profile was defined based on prior studies as 1) DWI lesion volume (as defined as apparent
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diffusion coefficient < 620 X 10-6 mm2/s) of 70 mL or less AND 2) Penumbra volume (as defined
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by volume of tissue with Tmax >6 sec) of 15 mL or greater AND 3) A mismatch ratio of 1.8 or
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more AND 4) Volume of tissue with perfusion lesion with Tmax > 10 sec is less than 100 mL. Good outcome was defined as a 90-day mRS≤2.
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RESULTS: 41 patients met the inclusion criteria; 22 (53.7%) had favorable imaging profile and underwent mechanical embolectomy. The rate of good outcomes in this series was similar to that in a patient level pooled meta-analysis of the recent endovascular trials (63.6% vs. 46%, p=0.13). None of the patients in our cohort had symptomatic intracereberal hemorrhage. CONCLUSIONS: MRI perfusion based imaging may help select patients with acute ischemic stroke and proximal emergent LVO for embolectomy beyond the treatment window used in
ACCEPTED MANUSCRIPT most endovascular trials. This provides compelling evidence for stroke centers to participate in ongoing trials using advanced imaging to study endovascular treatment in this patient
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population.
ACCEPTED MANUSCRIPT Introduction Mechanical embolectomy using stent retrievers is the standard of care for most patients with acute ischemic stroke and evidence of proximal large vessel occlusion who are within six hours
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from stroke onset.1 While the benefit of revascularization declines with time, infarct growth
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varies dramatically among patients depending on the site of arterial occlusion and the degree
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of collaterals.2-4 In fact, studies have shown that some patients have a small core infarct many hours after onset while others develop a large core infarction quickly after symptom onset.5, 6
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Therefore, it is possible that some patients would benefit from revascularization beyond the
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standard time window for treatment.7
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Recently, advanced imaging has been used to assist in treatment decisions in patients with acute ischemic stroke and proximal large vessel occlusion. 8 A standardized post-processing
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software program RAPID (iSchemaView, Menlo Park) automatically outlines and calculates
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diffusion-weighted imaging (DWI) lesion and perfusion-weighted imaging (PWI) thresholds to
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provide data on the volume of tissue that is irreversibly injured or will likely progress into infarction if reperfusion is not achieved. Details of this software have been described in prior
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studies.9, 10
Incorporating RAPID in the evaluation of acute ischemic stroke patients with evidence of large vessel occlusion could possibly identify patients who may benefit from treatment beyond the currently accepted time window. Although the DEFUSE-2 study reported outcomes of patients treated with favorable imaging who were treated beyond 6 hours from onset, the endovascular therapy used in this study were prior generation embolectomy and thromboaspiration devices
ACCEPTED MANUSCRIPT which do not match the rate or rapidity of recanalization which can be achieved routinely using modern techniques.8 Therefore, we aim to report the outcomes of patients with favorable advanced imaging profiles treated with mechanical embolectomy using stent retrievers beyond the six-hour treatment window, and compare these outcomes to those of patients treated in
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recent endovascular trials.
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Methods
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Study cohort
We retrospectively queried our prospective acute ischemic stroke database from December 1 st
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2015 until July 30th, 2016 and included all consecutive patients with acute ischemic stroke and
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evidence of proximal large vessel occlusion who presented beyond 6 hours and were
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considered for treatment with mechanical embolectomy. The start date of the study was decided based on when the RAPID software was installed at our institution and utilized to offer
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Study Protocol
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treatment for patients in the extended window.
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Patients with acute ischemic stroke and documented anterior circulation proximal large vessel occlusion (ICA and M1) and an ASPECTS ≥ 6 who presented between 6 and 24 hours from last known normal underwent a hyperacute MRI protocol that included RAPID software analysis of DWI and perfusion imaging data. The inclusion/selection criteria for embolectomy were: 1) DWI lesion volume (as defined as apparent diffusion coefficient <620 X 10-6 mm2/s) of 70 mL or less AND 2) Penumbra volume (as defined by volume of tissue with Tmax >6 sec) of 15 mL or
ACCEPTED MANUSCRIPT greater AND 3) A mismatch ratio of 1.8 or more AND 4) Volume of tissue with perfusion lesion with Tmax > 10 sec is less than 100 mL. These criteria were based on prior studies.8-10 If these criteria were met, patients were immediately transported to the angiography suite to undergo mechanical embolectomy. In patients in whom DWI but not perfusion weighted imaging could
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be completed, decision was made to select them for mechanical thrombectomy if the DWI lesion volume of less than 60 mL. Standard protocols were implemented in monitoring patients
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after embolectomy and all patients had a repeat MRI within 24 hours from the procedure to
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assess for radiological infarct growth.
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MRI protocol
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All patients underwent a brain MRI on a 1.5 Tesla scanner and the sequences obtained included DWI and perfusion-weighted imaging (PWI), with automatic calculation of mismatch maps using
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RAPID software (iSchemaView, Menlo Park). Additional sequences including Fluid-Attenuated
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Inversion Recovery (FLAIR) sequence and gradient echo (GRE) sequence were performed at the
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discretion of the treating team, but typically only when the angiography suite was not immediately available. PWI was acquired on all but three patients (one due to poor renal
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function and two due to agitation). These sequences could be performed in an average of 10 minutes to eliminate significant delays in treatment if the patient was a candidate for mechanical embolectomy. Vessel imaging was not acquired as the ELVO was demonstrated on a CTA that immediately preceded the MRI. Embolectomy technique
ACCEPTED MANUSCRIPT All patients were treated by one of three experienced neurointerventional radiologists. All procedures were performed using conscious sedation, without general anesthesia. A standardized setup using a 6 French sheath in the carotid artery, a distal aspiration catheter, and microcatheter were used in all cases. Our embolectomy technique incorporated the use of
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a stent-retriever in all cases, in conjunction with a novel modification of local aspiration. We
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did not use primary aspiration (ADAPT) alone in any cases. 11 The goal was to achieve modified
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thrombolysis in cerebral ischemia (mTICI) 2b/3 reperfusion. Adjunctive intra-arterial
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thrombolytic agents were not used in any cases.
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Study variables
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We recorded baseline demographics (age and sex); clinical variables (history of hypertension, history of diabetes, history of hyperlipidemia, history of stroke, history of atrial fibrillation,
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baseline modified Rankin Scale (mRS), NIHSS score); time from symptom onset to groin
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puncture in minutes, time from symptom onset to recanalization in minutes; radiological
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findings (site of occlusion; ASPECTS score on initial CT; collateral score on CTA defined as poor, intermediate, or good; infarct volume on MRI in mL; mismatch volume in mL; mismatch ratio;
Outcomes
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and final mTICI score after treatment).
The clinical outcome recorded in our database included: discharge mRS, discharge NIHSS score, and 90 day mRS. Imaging outcomes included infarct growth and final infarct volume. Good outcome was defined as a 90 day mRS ≤ 2.
ACCEPTED MANUSCRIPT Analytic plan We compared the percentage of patients with good outcome in our cohort to those of patients who underwent mechanical embolectomy in the recent endovascular trials.12-17 In order to
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increase the number of patients who received mechanical embolectomy beyond the six hour
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time window, we ran an additional analysis combining our patient cohort with the DEFUSE-2
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trial cohort, in which the same imaging analysis software (RAPID) was used to identify a favorable (target mismatch) imaging profile, patients were treated 6 hours after symptom
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onset, and had reperfusion.7 Analysis was done using SPSS (Chicago, IL) version 16.0. We used t-
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test for continuous variables and Fisher’s exact test for categorical variables , and p < 0.05 was
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considered statistically significant.
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Results
In the study period, we evaluated 41 patients with anterior circulation proximal large vessel
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occlusion who were beyond 6 hours from symptom onset and had an ASEPCTS score of 6 or
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more on initial non-contrast brain CT. Out of this cohort, 22 patients (53.7%) had favorable imaging profile and underwent mechanical embolectomy. Reasons for exclusion were DWI
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lesion volume more than or equal to 70 ml (n = 13), Tmax 10 seconds volume > 100 ml (n = 2), mismatch ratio < 1.8 (n = 3), and family declined procedure (n = 1) (Figure 1). The median age was 75 years (59-92), 68.2% were males; the median time from last known normal to groin puncture was 684.5 minutes (range 363-1628) and the median admission NIHSS score was 17.5 (range 4-28). Of the 22 patients, 36.4% were transfers from other facilities. The median CSC arrival to puncture times for patients transferred from other facilities was 41 minutes and that
ACCEPTED MANUSCRIPT for those presenting to our CSC first was 86 minutes; 90.1% achieved good reperfusion (TICI 2B/3).The baseline characteristics, imaging findings, and outcomes are shown in Table 1. Figure 2 shows the imaging findings of one patient selected for mechanical embolectomy.
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The rate of good outcomes in this series was 63.6% (14/22). This compares very favorably with
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the 46.0% rate of good outcomes in a large, patient level pooled meta-analysis of the five
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recent endovascular stroke trials (Table 2).17 Notably, five of our patients had a pre-morbid mRS of 3 and when those are excluded (as they would have been in the recent endovascular
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stroke trials and DEFUSE-2), the rate of good outcome rises to 82.3% (14/17). In addition, when
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our data was combined with data from DEFUSE-2 (n = 24, 54.2% good outcome at 90 days), the percentage of patient with good outcome was similar between the pool of patients treated
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with mechanical embolectomy in recent endovascular trials and the pool of patients with
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favorable imaging who underwent mechanical embolectomy in the extended time window
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[58.6% (27/46) vs. 46.0% (291/633) p = 0.12] (Table 2). Among the recent embolectomy trials, only the EXTEND-IA trial required the use of mismatch
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imaging criteria using the RAPID software, although based on CT perfusion rather than MRI.18
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When our patient cohort was compared to patients treated in this trial, the rates of good outcome were similar between the two groups [63.6% (14/22) vs. 71.0% (25/35); p = 0.57] (Table 2), despite our patients being treated beyond 6 hours from symptom onset. As in EXTEND-IA, none of the patients in our study who underwent mechanical embolectomy had symptomatic intracranial hemorrhage. Discussion
ACCEPTED MANUSCRIPT Our study suggests that advanced neuroimaging can select patients for mechanical embolectomy likely to achieve a good outcome even beyond 6 hours from symptom onset. Approximately 50% of patients who presented beyond the currently accepted time window had a favorable imaging profile and these patients gained similar benefit from mechanical
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embolectomy compared to those reported in recent endovascular stroke trials 12-17, with minimal rates of hemorrhagic complications. In addition, endovascular treatment led to a
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reduction in infarct growth (Table 1) which translated into a good outcome in most patients.
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Therefore, excluding patients with evidence of large vessel occlusion and ASPECTS ≥ 6 who are beyond 6 hours from last known normal may exclude a large and important population of
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patients who could potentially benefit from mechanical embolectomy. Obtaining advanced
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neuroimaging did not result in significant delays in treatment times, as MRI completion was
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typically less than 15 minutes and ran in parallel with endovascular team activation.
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Our study has several limitations including its retrospective nature and the small sample size. Furthermore, since all patients with favorable imaging were treated with mechanical
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embolectomy, it is unclear whether the relatively high rate of good outcomes achieved were
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due to a treatment effect of embolectomy or due to the fact that patients with favorable imaging may be more likely to have a good outcome regardless of treatment. Ideally, randomized clinical trials will address this important distinction. Previous studies, however, showed that patients with favorable imaging who have a significant perfusion delay (Tmax > 6sec) will likely extend the infarct and go on to have to a poor functional outcome if no reperfusion is achieved.19 In addition, the percentage of patients with good outcome was similar to that in EXTEND-IA, which used the RAPID software with CT perfusion. Another
ACCEPTED MANUSCRIPT limitation of this study is that we exclusively select patients with an MRI-based favorable imaging profile using RAPID software (iSchemaView, Menlo Park) at our institution access to which may not be readily available in most institutions on an urgent basis , making this study not generalizable to most stroke centers. Furthermore, we used discharge mRS on a group of
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patients without 90-day mRS. This, however, may have underestimated the percentage of patients with good outcomes in our cohort since stroke patients in general are expected to
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have some recovery in the first 90 days. Lastly, since a core lab was not used to score the
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degree of reperfusion, the higher degree of reperfusion could have been possibly overestimated by our readers. It could also be possible that patients with favorable imaging profile
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were more likely have a better degree of reperfusion than those with a large core infarct.
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Therefore, this data should urge the stroke community to participate in randomized clinical
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trials targeting patients with acute ischemic stroke and evidence of proximal large vessel
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occlusion beyond 6 hours from symptom onset (NCT02586415, NCT02142283), since a large proportion of these patients have favorable imaging profiles and may obtain significant benefit
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Conclusion
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from endovascular treatment without excess hemorrhagic risk.
Advanced imaging may help select patients with acute ischemic stroke and proximal emergent large vessel occlusion for embolectomy beyond the treatment window used in most endovascular trials. This provides compelling evidence for stroke centers to participate in ongoing trials using advanced imaging to study the effect of endovascular treatment in patients who present in the extended window.
ACCEPTED MANUSCRIPT References
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1. Powers WJ, Derdeyn CP, Biller J, et al. 2015 American Heart Association/American Stroke Association Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2015;46:3020-3035. 2. Vagal AS, Khatri P, Broderick JP, Tomsick TA, Yeatts SD, Eckman MH. Time to angiographic reperfusion in acute ischemic stroke: decision analysis. Stroke 2014;45:3625-3630. 3. Cheng-Ching E, Frontera JA, Man S, et al. Degree of Collaterals and Not Time Is the Determining Factor of Core Infarct Volume within 6 Hours of Stroke Onset. AJNR Am J Neuroradiol 2015;36:12721276. 4. Souza LC, Yoo AJ, Chaudhry ZA, et al. Malignant CTA collateral profile is highly specific for large admission DWI infarct core and poor outcome in acute stroke. AJNR Am J Neuroradiol 2012;33:13311336. 5. Wheeler HM, Mlynash M, Inoue M, et al. The growth rate of early DWI lesions is highly variable and associated with penumbral salvage and clinical outcomes following endovascular reperfusion. Int J Stroke 2015;10:723-729. 6. Hakimelahi R, Vachha BA, Copen WA, et al. Time and diffusion lesion size in major anterior circulation ischemic strokes. Stroke 2014;45:2936-2941. 7. Lansberg MG, Cereda CW, Mlynash M, et al. Response to endovascular reperfusion is not time dependent in patients with salvageable tissue. Neurology 2015;85:708-714. 8. Lansberg MG, Straka M, Kemp S, et al. MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study. Lancet Neurol 2012;11:860-867. 9. Kakuda W, Lansberg MG, Thijs VN, et al. Optimal definition for PWI/DWI mismatch in acute ischemic stroke patients. J Cereb Blood Flow Metab 2008;28:887-891. 10. Straka M, Albers GW, Bammer R. Real-time diffusion-perfusion mismatch analysis in acute stroke. Journal of magnetic resonance imaging : JMRI 2010;32:1024-1037. 11. McTaggart RA, Tung EL, Yaghi S, et al. Continuous aspiration prior to intracranial vascular embolectomy (CAPTIVE): a technique which improves outcomes. Journal of neurointerventional surgery 2016. 12. Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015;372:11-20. 13. Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 2015;372:2296-2306. 14. Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 2015;372:1009-1018. 15. Saver JL, Goyal M, Bonafe A, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 2015;372:2285-2295. 16. Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015;372:1019-1030. 17. Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after large -vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 2016;387:1723-1731. 18. Campbell BC, Mitchell PJ, Yan B, et al. A multicenter, randomized, controlled study to investigate EXtending the time for Thrombolysis in Emergency Neurological Deficits with Intra-Arterial therapy (EXTEND-IA). Int J Stroke 2014;9:126-132.
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19. Shih LC, Saver JL, Alger JR, et al. Perfusion-weighted magnetic resonance imaging thresholds identifying core, irreversibly infarcted tissue. Stroke 2003;34:1425-1430.
ACCEPTED MANUSCRIPT Table 1. Clinical characteristics, Imaging findings, and outcome of our patient cohort Medical history Imaging findings Procedure details Follow up imaging
AF Premorbid mRS 0 NIHSS 17
Patient 5
HTN, HLPD Premorbid mRS 0 NIHSS 17
Patient 6
HTN, HLPD, AF Premorbid mRS 0 NIHSS 24
Patient 7
HTN, HLPD, Stroke Premorbid mRS 3 NIHSS 10
Patient 8
HTN, AF Premorbid mRS 0 NIHSS 18
Patient 9
HTN, HLPD Premorbid mRS 0 NIHSS 26
Patient 10
Supraventricular tachycardia Premorbid mRS 0 NIHSS 19
Patient 11
HTN Premorbid mRS 0 NIHSS 28
Patient 12
HTN, HLPD, AF Premorbid mRS 3 NIHSS 21
Patient 13
HTN, AF Premorbid mRS 0 NIHSS 22
Patient 14
HTN Premorbid mRS 0
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Infarct volume 20.5 ml No hemorrhage
Discharge mRS 3 Discharge NIHSS 5 90 day mRS 3
LKW to puncture: 480 min LKW to recanalization: 513 min TICI score 3
Infarct volume 1.0 ml No hemorrhage
Discharge mRS 0 Discharge NIHSS 0 90 day mRS 0
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Patient 4
LKW to puncture: 697 min LKW to recanalization: 719 min TICI score 2B
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HTN, AF Premorbid mRS 0 NIHSS 9
Discharge mRS 0 Discharge NIHSS 1 90 day mRS 0
LKW to puncture: 390 min LKW to recanalization: 420 min TICI score 3
Infarct volume 2.0 ml No hemorrhage
Discharge mRS 1 Discharge NIHSS 1 90 day mRS 1
LKW to puncture: 1151 min LKW to recanalization: 1179 min TICI score 3
Infarct volume 3.0 ml No hemorrhage
Discharge mRS 1 Discharge NIHSS 1 90 day mRS 0
LKW to puncture: 427 min LKW to recanalization: 442 min TICI score 3
Infarct volume 16.2 ml No hemorrhage
Discharge mRS 2 Discharge NIHSS 8 90 day mRS 4
LKW to puncture: 844 min LKW to recanalization: 891 min TICI score 2B
Infarct volume 112.6 ml No hemorrhage Re-occlusion of MCA
Discharge mRS 5 Discharge NIHSS 20 90 day mRS 6
LKW to puncture: 708 min LKW to recanalization: 729 min TICI score 3
Infarct volume 11.2 ml No hemorrhage
Discharge mRS 2 Discharge NIHSS 2 90 day mRS 0
LKW to puncture: 475 min LKW to recanalization: 491min TICI score 2B
Infarct volume 3.0 ml No hemorrhage
Discharge mRS 1 Discharge NIHSS 2 90 day mRS 1
LKW to puncture: 940 min LKW to recanalization: 959 min TICI score 3
Infarct volume 33.8 ml Asymptomatic hemorrhage
Discharge mRS 3 Discharge NIHSS 3 90 day mRS 2
LKW to puncture: 677 min LKW to recanalization: 738 min TICI score 2B
Infarct volume 30.0 ml Asymptomatic hemorrhage
Discharge mRS 3 Discharge NIHSS 4 90 day mRS 1
LKW to puncture: 1021 min LKW to recanalization: N/A TICI score 0
Infarct volume 90.0 ml Asymptomatic hemorrhage
Discharge mRS 5 Discharge NIHSS 25 90 day mRS 6
LKW to puncture: 363 min LKW to recanalization: 389 min TICI score 2C
Infarct volume 72.4 ml Asymptomatic hemorrhage
Discharge mRS 3 Discharge NIHSS 5 90 day mRS 2
LKW to puncture: 714 min LKW to recanalization: 725 min
Infarct volume 26.0 ml No hemorrhage
Discharge mRS 3 Discharge NIHSS 2
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Patient 3
Infarct volume 8.4 ml No hemorrhage
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HTN, HLPD, AF Premorbid mRS 0 NIHSS 17
Outcome
LKW to puncture: 470 min LKW to recanalization: 546 min TICI score 3
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Patient 2
Tandem lesion (ICA/M1) ASPECTS 10 good collaterals Infarct volume 10 ml Mismatch volume 134.6 ml M1 ASPECTS 10 Intermediate collaterals Infarct volume 14.9 ml Mismatch volume 112.1 ml M1 ASPECTS 10 Intermediate collaterals Infarct volume 1.0 ml Mismatch volume 124.6 ml M1 ASPECTS 8 Intermediate collaterals Infarct volume 2.0 ml Mismatch volume 67.0 ml M1 ASPECTS 10 Good collaterals Infarct volume 2.0 ml Mismatch volume: N/A M1 ASPECTS 10 Intermediate collaterals Infarct volume 11.6 ml Mismatch volume 109.3 ml M1 ASPECTS 6 Good collaterals Infarct volume 16.5 ml Mismatch volume 57.3 ml ICA ASPECTS 10 Intermediate collaterals Infarct volume 10.0 ml Mismatch volume 180.4 ml M1 ASPECTS 10 Intermediate collaterals Infarct volume 3.0 ml Mismatch volume N/A M1 ASPECTS 10 Intermediate collaterals Infarct volume 33.8 ml Mismatch volume 31.3 ml ICA ASPECTS 7 Intermediate collaterals Infarct volume 24.6 ml Mismatch volume 127.4 ml M1 ASPECTS 6 Intermediate collaterals Infarct volume 15.0 ml Mismatch volume N/A M1 ASPECTS 6 Intermediate collaterals Infarct volume 63.4 ml Mismatch Volume N/A M1 ASPECTS 8
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HTN, DM2, HLPD premorbid mRS 0 NIHSS 14
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Patient 1
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HTN, AF Premorbid mRS 4 NIHSS 25
Patient 19
HTN, AF Premorbid mRS 3 NIHSS 24
Patient 20
HTN, HLPD Premorbid mRS 0 NIHSS 4
Patient 21
HTN, HLPD, AF Premorbid mRS 1 NIHSS 9
Patient 22
HTN, DM2 Premorbid mRS 4 NIHSS 9
LKW to puncture: 595 min LKW to recanalization: 618 min TICI score 3
Infarct volume 10.0 ml No hemorrhage
Discharge mRS 2 Discharge NIHSS 0 90 day mRS 2
LKW to puncture: 692 min LKW to recanalization: 727 min TICI score 2B
Infarct volume 20.1 ml No hemorrhage
Discharge mRS 2 Discharge NIHSS 4 90 day mRS 1
LKW to puncture: 784 min LKW to recanalization: 910 min TICI score 3
Infarct volume 129 ml Asymptomatic hemorrhage Re-occlusion of MCA
Discharge mRS 6 Discharge NIHSS 24 90 day mRS 6
LKW to puncture: 513 min LKW to recanalization: 542 min TICI score 3
Infarct volume 45.4 ml Asymptomatic hemorrhage
Discharge mRS 5 Discharge NIHSS 10 90 day mRS 6
LKW to puncture: 427 min LKW to recanalization: 446 min TICI score 3
Infarct volume 1.0 ml No hemorrhage
Discharge mRS 0 Discharge NIHSS 1 90 day mRS 0
LKW to puncture: 843 min LKW to recanalization: 899 min TICI score 2B
Infarct volume 1.6 ml No hemorrhage
Discharge mRS 0 Discharge NIHSS 0 90 day mRS 0
LKW to puncture: 615 min LKW to recanalization: N/A TICI score 0
Infarct volume 210.4 No hemorrhage
Discharge mRS 6 Discharge NIHSS 24 90 day mRS 6
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Patient 18
Discharge mRS 4 Discharge NIHSS 13 90 day mRS 4
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None Premorbid mRS 1 NIHSS 19
Infarct volume 35 ml Asymptomatic hemorrhage
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Patient 17
LKW to puncture: 1628 min LKW to recanalization: 1641 min TICI score 3
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HTN, HLPD, AF Premorbid mRS 0 NIHSS 14
90 day mRS 2
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Patient 16
TICI score 2B
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None Premorbid mRS 0 NIHSS 20
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Patient 15
Intermediate collaterals Infarct volume 25.2 ml Mismatch Volume 75.6 ml M1 ASPECTS 7 Good collaterals Infarct volume 33.0 ml Mismatch Volume N/A ICA ASPECTS 6 Poor collaterals Infarct volume 8.0 ml Mismatch Volume 38.4 M1 ASPECTS 8 Good collaterals Infarct volume 18.6 ml Mismatch Volume N/A M1 ASPECTS 6 Intermediate collaterals Infarct volume 66.0 ml Mismatch Volume 82.2 ml M1 ASPECTS 6 Intermediate collaterals Infarct volume 40.0 ml Mismatch Volume 63.1 ml M1 ASPECTS 10 Good collaterals Infarct volume 1.0 ml Mismatch Volume 17.2 ml M1 ASPECTS 6 Poor collaterals Infarct volume 1.0 ml Mismatch Volume 58.5 M1 ASPECTS 6 Poor collaterals Infarct volume 55.8 ml Mismatch Volume 178.4 ml
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NIHSS 9
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Table 2. Functional outcome of patients in our study compared to endovascular trials RIH study cohort RIH study cohort & DEFUSE-2 HERMES cohort Good functional 14/22 (63.6%) 28/46 (60.8%) 291/633 (46.0%) outcome (mRS 0-2) Excellent functional 9/22 (40.9%) N/A 170/633 (26.9%) outcome (mRS 0-1) Symptomatic 0/22 (0%) N/A 28/634 (4.4%) hemorrhage
Extend IA cohort 25/35 (71.0%) 18/35 (51.0%) 0/35 (0%)
ACCEPTED MANUSCRIPT Figure 1. Study flow chart
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DWI lesion volume more than or equal to 70 ml (n = 13) Tmax 10 seconds volume > 100 ml (n = 2) Mismatch ratio < 1.8 (n = 3) Family declined procedure (n = 1)
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• • • •
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19 patients excluded
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41 patients with NIHSS ≥ 6, ASPECTS ≥ 6, and 6-24 hours from last known normal
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22 patients underwent mechanical thrombectomy
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14 patients had good 90-day functional outcome
8 patients had poor 90-day functional outcome
ACCEPTED MANUSCRIPT Figure 2 legend
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Images of a patient 1 from table 1. A. CTA showing right middle cerebral artery occlusion. B. MRI RAPID summary showing a 10.6 ml infarct and a 134.6 mL mismatch volume. C. Cerebral angiogram showing complete recanalization for right middle cerebral artery. D. Follow up RAPID showing an infarct volume of 8.3 mL and a mismatch volume of 9.2 mL .
ACCEPTED MANUSCRIPT Highlights
Over 50% of stroke patients had a favorable imaging profile 6-24 hours from onset
MRI perfusion imaging may help select ischemic stroke patients for thrombectomy
Over 60% of patients with favorable imaging achieved independence with thrombectomy
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Ryan A. McTaggart, Shadi Yaghi, Daniel C Sacchetti, Richard A. Haas, Morgan Hemendinger, Daniel Arcuri, Jeffrey M. Rogg, Karen L. Furie, Mahesh V. Jayaraman PII: DOI: Reference:
S0022-510X(17)30140-5 doi: 10.1016/j.jns.2017.02.044 JNS 15179
To appear in:
Journal of the Neurological Sciences
Received date: Revised date: Accepted date:
9 December 2016 14 February 2017 20 February 2017
Please cite this article as: Ryan A. McTaggart, Shadi Yaghi, Daniel C Sacchetti, Richard A. Haas, Morgan Hemendinger, Daniel Arcuri, Jeffrey M. Rogg, Karen L. Furie, Mahesh V. Jayaraman , Mechanical embolectomy for acute ischemic stroke beyond six hours from symptom onset using MRI based perfusion imaging. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Jns(2017), doi: 10.1016/j.jns.2017.02.044
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Mechanical Embolectomy for Acute Ischemic Stroke Beyond Six Hours from Symptom Onset Using MRI based perfusion imaging Ryan A. McTaggart1*, Shadi Yaghi2*, Daniel C Sacchetti 2, Richard A. Haas 1, Morgan Hemendinger2, Daniel Arcuri 1, Jeffrey M. Rogg 1, Karen L. Furie2, Mahesh V. Jayaraman1,2,3 *= co-first authors
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1 Department of Diagnostic Imaging, The Warren Alpert Medical School of Brown University, Providence, RI
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2 Department of Neurology, The Warren Alpert Medical School of Brown University, Providence, RI
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Word count: 1,864 words, Figure: 1, Tables: 2
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3 Department of Neurosurgery, The Warren Alpert Medical School of Brown University, Providence, RI
Key words: Stroke; Thrombectomy; Treatment Window; MRI; Imaging; Perfusion; outcome
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Corresponding author:
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Shadi Yaghi, MD
Providence, RI, 02903
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593 Eddy St, APC 530
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Tel: 401-444-8806, Fax: 401-444-8781
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Email: [email protected]
ACCEPTED MANUSCRIPT Disclosures: Dr. Yaghi received funding from the New York Stroke Trials Network of Columbia and Cornell (NYCCSTN, NINDS U10NS086728). Dr. McTaggart, Dr. Sacchetti, Dr. Haas, Ms. Hemendinger, Mr. Arcuri, Dr. Rogg, Dr. Furie, and Dr. Jayaraman have no disclosures.
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Author contribution
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Ryan McTaggart: Data collection, study concept and design, and manuscript revision
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Shadi Yaghi: Data collection, study concept and design, and manuscript preparation
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Daniel Sacchetti: manuscript preparation Richard Hass: Manuscript revision
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Morgan Hemendinger: Data collection
Jeffrey Rogg: Manuscript revision
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Karen L. Furie: Manuscript revision
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Daniel Arcuri: Manuscript revision
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Mahesh Jayaraman: Study planning and manuscript revision
ACCEPTED MANUSCRIPT Abstract Introduction: There is very limited data on the use of MRI based perfusion imaging to select patients with acute ischemic stroke and large vessel occlusion (LVO) for intraarterial therapy
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beyond 6 hours from onset. Our aim is to report the outcome of patients with acute ischemic
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stroke and large artery occlusion who presented beyond 6 hours from onset, had favorable MRI
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imaging profile, and underwent mechanical embolectomy.
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Methods: This is a single institution (Rhode Island Hospital) retrospective study between December 1st, 2015, and July 30th, 2016 that included patients with acute ischemic stroke and
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proximal LVO with CT ASPECTS of 6 or more and 6-24 hours from symptom onset who were
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assessed for mechanical embolectomy using MRI based perfusion imaging. Favorable imaging profile was defined based on prior studies as 1) DWI lesion volume (as defined as apparent
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diffusion coefficient < 620 X 10-6 mm2/s) of 70 mL or less AND 2) Penumbra volume (as defined
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by volume of tissue with Tmax >6 sec) of 15 mL or greater AND 3) A mismatch ratio of 1.8 or
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more AND 4) Volume of tissue with perfusion lesion with Tmax > 10 sec is less than 100 mL. Good outcome was defined as a 90-day mRS≤2.
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RESULTS: 41 patients met the inclusion criteria; 22 (53.7%) had favorable imaging profile and underwent mechanical embolectomy. The rate of good outcomes in this series was similar to that in a patient level pooled meta-analysis of the recent endovascular trials (63.6% vs. 46%, p=0.13). None of the patients in our cohort had symptomatic intracereberal hemorrhage. CONCLUSIONS: MRI perfusion based imaging may help select patients with acute ischemic stroke and proximal emergent LVO for embolectomy beyond the treatment window used in
ACCEPTED MANUSCRIPT most endovascular trials. This provides compelling evidence for stroke centers to participate in ongoing trials using advanced imaging to study endovascular treatment in this patient
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population.
ACCEPTED MANUSCRIPT Introduction Mechanical embolectomy using stent retrievers is the standard of care for most patients with acute ischemic stroke and evidence of proximal large vessel occlusion who are within six hours
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from stroke onset.1 While the benefit of revascularization declines with time, infarct growth
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varies dramatically among patients depending on the site of arterial occlusion and the degree
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of collaterals.2-4 In fact, studies have shown that some patients have a small core infarct many hours after onset while others develop a large core infarction quickly after symptom onset.5, 6
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Therefore, it is possible that some patients would benefit from revascularization beyond the
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standard time window for treatment.7
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Recently, advanced imaging has been used to assist in treatment decisions in patients with acute ischemic stroke and proximal large vessel occlusion. 8 A standardized post-processing
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software program RAPID (iSchemaView, Menlo Park) automatically outlines and calculates
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diffusion-weighted imaging (DWI) lesion and perfusion-weighted imaging (PWI) thresholds to
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provide data on the volume of tissue that is irreversibly injured or will likely progress into infarction if reperfusion is not achieved. Details of this software have been described in prior
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studies.9, 10
Incorporating RAPID in the evaluation of acute ischemic stroke patients with evidence of large vessel occlusion could possibly identify patients who may benefit from treatment beyond the currently accepted time window. Although the DEFUSE-2 study reported outcomes of patients treated with favorable imaging who were treated beyond 6 hours from onset, the endovascular therapy used in this study were prior generation embolectomy and thromboaspiration devices
ACCEPTED MANUSCRIPT which do not match the rate or rapidity of recanalization which can be achieved routinely using modern techniques.8 Therefore, we aim to report the outcomes of patients with favorable advanced imaging profiles treated with mechanical embolectomy using stent retrievers beyond the six-hour treatment window, and compare these outcomes to those of patients treated in
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recent endovascular trials.
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Methods
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Study cohort
We retrospectively queried our prospective acute ischemic stroke database from December 1 st
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2015 until July 30th, 2016 and included all consecutive patients with acute ischemic stroke and
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evidence of proximal large vessel occlusion who presented beyond 6 hours and were
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considered for treatment with mechanical embolectomy. The start date of the study was decided based on when the RAPID software was installed at our institution and utilized to offer
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Study Protocol
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treatment for patients in the extended window.
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Patients with acute ischemic stroke and documented anterior circulation proximal large vessel occlusion (ICA and M1) and an ASPECTS ≥ 6 who presented between 6 and 24 hours from last known normal underwent a hyperacute MRI protocol that included RAPID software analysis of DWI and perfusion imaging data. The inclusion/selection criteria for embolectomy were: 1) DWI lesion volume (as defined as apparent diffusion coefficient <620 X 10-6 mm2/s) of 70 mL or less AND 2) Penumbra volume (as defined by volume of tissue with Tmax >6 sec) of 15 mL or
ACCEPTED MANUSCRIPT greater AND 3) A mismatch ratio of 1.8 or more AND 4) Volume of tissue with perfusion lesion with Tmax > 10 sec is less than 100 mL. These criteria were based on prior studies.8-10 If these criteria were met, patients were immediately transported to the angiography suite to undergo mechanical embolectomy. In patients in whom DWI but not perfusion weighted imaging could
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be completed, decision was made to select them for mechanical thrombectomy if the DWI lesion volume of less than 60 mL. Standard protocols were implemented in monitoring patients
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after embolectomy and all patients had a repeat MRI within 24 hours from the procedure to
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assess for radiological infarct growth.
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MRI protocol
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All patients underwent a brain MRI on a 1.5 Tesla scanner and the sequences obtained included DWI and perfusion-weighted imaging (PWI), with automatic calculation of mismatch maps using
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RAPID software (iSchemaView, Menlo Park). Additional sequences including Fluid-Attenuated
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Inversion Recovery (FLAIR) sequence and gradient echo (GRE) sequence were performed at the
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discretion of the treating team, but typically only when the angiography suite was not immediately available. PWI was acquired on all but three patients (one due to poor renal
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function and two due to agitation). These sequences could be performed in an average of 10 minutes to eliminate significant delays in treatment if the patient was a candidate for mechanical embolectomy. Vessel imaging was not acquired as the ELVO was demonstrated on a CTA that immediately preceded the MRI. Embolectomy technique
ACCEPTED MANUSCRIPT All patients were treated by one of three experienced neurointerventional radiologists. All procedures were performed using conscious sedation, without general anesthesia. A standardized setup using a 6 French sheath in the carotid artery, a distal aspiration catheter, and microcatheter were used in all cases. Our embolectomy technique incorporated the use of
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a stent-retriever in all cases, in conjunction with a novel modification of local aspiration. We
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did not use primary aspiration (ADAPT) alone in any cases. 11 The goal was to achieve modified
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thrombolysis in cerebral ischemia (mTICI) 2b/3 reperfusion. Adjunctive intra-arterial
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thrombolytic agents were not used in any cases.
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Study variables
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We recorded baseline demographics (age and sex); clinical variables (history of hypertension, history of diabetes, history of hyperlipidemia, history of stroke, history of atrial fibrillation,
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baseline modified Rankin Scale (mRS), NIHSS score); time from symptom onset to groin
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puncture in minutes, time from symptom onset to recanalization in minutes; radiological
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findings (site of occlusion; ASPECTS score on initial CT; collateral score on CTA defined as poor, intermediate, or good; infarct volume on MRI in mL; mismatch volume in mL; mismatch ratio;
Outcomes
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and final mTICI score after treatment).
The clinical outcome recorded in our database included: discharge mRS, discharge NIHSS score, and 90 day mRS. Imaging outcomes included infarct growth and final infarct volume. Good outcome was defined as a 90 day mRS ≤ 2.
ACCEPTED MANUSCRIPT Analytic plan We compared the percentage of patients with good outcome in our cohort to those of patients who underwent mechanical embolectomy in the recent endovascular trials.12-17 In order to
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increase the number of patients who received mechanical embolectomy beyond the six hour
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time window, we ran an additional analysis combining our patient cohort with the DEFUSE-2
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trial cohort, in which the same imaging analysis software (RAPID) was used to identify a favorable (target mismatch) imaging profile, patients were treated 6 hours after symptom
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onset, and had reperfusion.7 Analysis was done using SPSS (Chicago, IL) version 16.0. We used t-
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test for continuous variables and Fisher’s exact test for categorical variables , and p < 0.05 was
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considered statistically significant.
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Results
In the study period, we evaluated 41 patients with anterior circulation proximal large vessel
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occlusion who were beyond 6 hours from symptom onset and had an ASEPCTS score of 6 or
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more on initial non-contrast brain CT. Out of this cohort, 22 patients (53.7%) had favorable imaging profile and underwent mechanical embolectomy. Reasons for exclusion were DWI
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lesion volume more than or equal to 70 ml (n = 13), Tmax 10 seconds volume > 100 ml (n = 2), mismatch ratio < 1.8 (n = 3), and family declined procedure (n = 1) (Figure 1). The median age was 75 years (59-92), 68.2% were males; the median time from last known normal to groin puncture was 684.5 minutes (range 363-1628) and the median admission NIHSS score was 17.5 (range 4-28). Of the 22 patients, 36.4% were transfers from other facilities. The median CSC arrival to puncture times for patients transferred from other facilities was 41 minutes and that
ACCEPTED MANUSCRIPT for those presenting to our CSC first was 86 minutes; 90.1% achieved good reperfusion (TICI 2B/3).The baseline characteristics, imaging findings, and outcomes are shown in Table 1. Figure 2 shows the imaging findings of one patient selected for mechanical embolectomy.
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The rate of good outcomes in this series was 63.6% (14/22). This compares very favorably with
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the 46.0% rate of good outcomes in a large, patient level pooled meta-analysis of the five
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recent endovascular stroke trials (Table 2).17 Notably, five of our patients had a pre-morbid mRS of 3 and when those are excluded (as they would have been in the recent endovascular
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stroke trials and DEFUSE-2), the rate of good outcome rises to 82.3% (14/17). In addition, when
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our data was combined with data from DEFUSE-2 (n = 24, 54.2% good outcome at 90 days), the percentage of patient with good outcome was similar between the pool of patients treated
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with mechanical embolectomy in recent endovascular trials and the pool of patients with
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favorable imaging who underwent mechanical embolectomy in the extended time window
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[58.6% (27/46) vs. 46.0% (291/633) p = 0.12] (Table 2). Among the recent embolectomy trials, only the EXTEND-IA trial required the use of mismatch
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imaging criteria using the RAPID software, although based on CT perfusion rather than MRI.18
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When our patient cohort was compared to patients treated in this trial, the rates of good outcome were similar between the two groups [63.6% (14/22) vs. 71.0% (25/35); p = 0.57] (Table 2), despite our patients being treated beyond 6 hours from symptom onset. As in EXTEND-IA, none of the patients in our study who underwent mechanical embolectomy had symptomatic intracranial hemorrhage. Discussion
ACCEPTED MANUSCRIPT Our study suggests that advanced neuroimaging can select patients for mechanical embolectomy likely to achieve a good outcome even beyond 6 hours from symptom onset. Approximately 50% of patients who presented beyond the currently accepted time window had a favorable imaging profile and these patients gained similar benefit from mechanical
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embolectomy compared to those reported in recent endovascular stroke trials 12-17, with minimal rates of hemorrhagic complications. In addition, endovascular treatment led to a
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reduction in infarct growth (Table 1) which translated into a good outcome in most patients.
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Therefore, excluding patients with evidence of large vessel occlusion and ASPECTS ≥ 6 who are beyond 6 hours from last known normal may exclude a large and important population of
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patients who could potentially benefit from mechanical embolectomy. Obtaining advanced
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neuroimaging did not result in significant delays in treatment times, as MRI completion was
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typically less than 15 minutes and ran in parallel with endovascular team activation.
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Our study has several limitations including its retrospective nature and the small sample size. Furthermore, since all patients with favorable imaging were treated with mechanical
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embolectomy, it is unclear whether the relatively high rate of good outcomes achieved were
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due to a treatment effect of embolectomy or due to the fact that patients with favorable imaging may be more likely to have a good outcome regardless of treatment. Ideally, randomized clinical trials will address this important distinction. Previous studies, however, showed that patients with favorable imaging who have a significant perfusion delay (Tmax > 6sec) will likely extend the infarct and go on to have to a poor functional outcome if no reperfusion is achieved.19 In addition, the percentage of patients with good outcome was similar to that in EXTEND-IA, which used the RAPID software with CT perfusion. Another
ACCEPTED MANUSCRIPT limitation of this study is that we exclusively select patients with an MRI-based favorable imaging profile using RAPID software (iSchemaView, Menlo Park) at our institution access to which may not be readily available in most institutions on an urgent basis , making this study not generalizable to most stroke centers. Furthermore, we used discharge mRS on a group of
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patients without 90-day mRS. This, however, may have underestimated the percentage of patients with good outcomes in our cohort since stroke patients in general are expected to
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have some recovery in the first 90 days. Lastly, since a core lab was not used to score the
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degree of reperfusion, the higher degree of reperfusion could have been possibly overestimated by our readers. It could also be possible that patients with favorable imaging profile
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were more likely have a better degree of reperfusion than those with a large core infarct.
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Therefore, this data should urge the stroke community to participate in randomized clinical
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trials targeting patients with acute ischemic stroke and evidence of proximal large vessel
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occlusion beyond 6 hours from symptom onset (NCT02586415, NCT02142283), since a large proportion of these patients have favorable imaging profiles and may obtain significant benefit
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Conclusion
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from endovascular treatment without excess hemorrhagic risk.
Advanced imaging may help select patients with acute ischemic stroke and proximal emergent large vessel occlusion for embolectomy beyond the treatment window used in most endovascular trials. This provides compelling evidence for stroke centers to participate in ongoing trials using advanced imaging to study the effect of endovascular treatment in patients who present in the extended window.
ACCEPTED MANUSCRIPT References
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1. Powers WJ, Derdeyn CP, Biller J, et al. 2015 American Heart Association/American Stroke Association Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2015;46:3020-3035. 2. Vagal AS, Khatri P, Broderick JP, Tomsick TA, Yeatts SD, Eckman MH. Time to angiographic reperfusion in acute ischemic stroke: decision analysis. Stroke 2014;45:3625-3630. 3. Cheng-Ching E, Frontera JA, Man S, et al. Degree of Collaterals and Not Time Is the Determining Factor of Core Infarct Volume within 6 Hours of Stroke Onset. AJNR Am J Neuroradiol 2015;36:12721276. 4. Souza LC, Yoo AJ, Chaudhry ZA, et al. Malignant CTA collateral profile is highly specific for large admission DWI infarct core and poor outcome in acute stroke. AJNR Am J Neuroradiol 2012;33:13311336. 5. Wheeler HM, Mlynash M, Inoue M, et al. The growth rate of early DWI lesions is highly variable and associated with penumbral salvage and clinical outcomes following endovascular reperfusion. Int J Stroke 2015;10:723-729. 6. Hakimelahi R, Vachha BA, Copen WA, et al. Time and diffusion lesion size in major anterior circulation ischemic strokes. Stroke 2014;45:2936-2941. 7. Lansberg MG, Cereda CW, Mlynash M, et al. Response to endovascular reperfusion is not time dependent in patients with salvageable tissue. Neurology 2015;85:708-714. 8. Lansberg MG, Straka M, Kemp S, et al. MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study. Lancet Neurol 2012;11:860-867. 9. Kakuda W, Lansberg MG, Thijs VN, et al. Optimal definition for PWI/DWI mismatch in acute ischemic stroke patients. J Cereb Blood Flow Metab 2008;28:887-891. 10. Straka M, Albers GW, Bammer R. Real-time diffusion-perfusion mismatch analysis in acute stroke. Journal of magnetic resonance imaging : JMRI 2010;32:1024-1037. 11. McTaggart RA, Tung EL, Yaghi S, et al. Continuous aspiration prior to intracranial vascular embolectomy (CAPTIVE): a technique which improves outcomes. Journal of neurointerventional surgery 2016. 12. Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015;372:11-20. 13. Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 2015;372:2296-2306. 14. Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 2015;372:1009-1018. 15. Saver JL, Goyal M, Bonafe A, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 2015;372:2285-2295. 16. Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015;372:1019-1030. 17. Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after large -vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 2016;387:1723-1731. 18. Campbell BC, Mitchell PJ, Yan B, et al. A multicenter, randomized, controlled study to investigate EXtending the time for Thrombolysis in Emergency Neurological Deficits with Intra-Arterial therapy (EXTEND-IA). Int J Stroke 2014;9:126-132.
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19. Shih LC, Saver JL, Alger JR, et al. Perfusion-weighted magnetic resonance imaging thresholds identifying core, irreversibly infarcted tissue. Stroke 2003;34:1425-1430.
ACCEPTED MANUSCRIPT Table 1. Clinical characteristics, Imaging findings, and outcome of our patient cohort Medical history Imaging findings Procedure details Follow up imaging
AF Premorbid mRS 0 NIHSS 17
Patient 5
HTN, HLPD Premorbid mRS 0 NIHSS 17
Patient 6
HTN, HLPD, AF Premorbid mRS 0 NIHSS 24
Patient 7
HTN, HLPD, Stroke Premorbid mRS 3 NIHSS 10
Patient 8
HTN, AF Premorbid mRS 0 NIHSS 18
Patient 9
HTN, HLPD Premorbid mRS 0 NIHSS 26
Patient 10
Supraventricular tachycardia Premorbid mRS 0 NIHSS 19
Patient 11
HTN Premorbid mRS 0 NIHSS 28
Patient 12
HTN, HLPD, AF Premorbid mRS 3 NIHSS 21
Patient 13
HTN, AF Premorbid mRS 0 NIHSS 22
Patient 14
HTN Premorbid mRS 0
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Infarct volume 20.5 ml No hemorrhage
Discharge mRS 3 Discharge NIHSS 5 90 day mRS 3
LKW to puncture: 480 min LKW to recanalization: 513 min TICI score 3
Infarct volume 1.0 ml No hemorrhage
Discharge mRS 0 Discharge NIHSS 0 90 day mRS 0
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Patient 4
LKW to puncture: 697 min LKW to recanalization: 719 min TICI score 2B
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HTN, AF Premorbid mRS 0 NIHSS 9
Discharge mRS 0 Discharge NIHSS 1 90 day mRS 0
LKW to puncture: 390 min LKW to recanalization: 420 min TICI score 3
Infarct volume 2.0 ml No hemorrhage
Discharge mRS 1 Discharge NIHSS 1 90 day mRS 1
LKW to puncture: 1151 min LKW to recanalization: 1179 min TICI score 3
Infarct volume 3.0 ml No hemorrhage
Discharge mRS 1 Discharge NIHSS 1 90 day mRS 0
LKW to puncture: 427 min LKW to recanalization: 442 min TICI score 3
Infarct volume 16.2 ml No hemorrhage
Discharge mRS 2 Discharge NIHSS 8 90 day mRS 4
LKW to puncture: 844 min LKW to recanalization: 891 min TICI score 2B
Infarct volume 112.6 ml No hemorrhage Re-occlusion of MCA
Discharge mRS 5 Discharge NIHSS 20 90 day mRS 6
LKW to puncture: 708 min LKW to recanalization: 729 min TICI score 3
Infarct volume 11.2 ml No hemorrhage
Discharge mRS 2 Discharge NIHSS 2 90 day mRS 0
LKW to puncture: 475 min LKW to recanalization: 491min TICI score 2B
Infarct volume 3.0 ml No hemorrhage
Discharge mRS 1 Discharge NIHSS 2 90 day mRS 1
LKW to puncture: 940 min LKW to recanalization: 959 min TICI score 3
Infarct volume 33.8 ml Asymptomatic hemorrhage
Discharge mRS 3 Discharge NIHSS 3 90 day mRS 2
LKW to puncture: 677 min LKW to recanalization: 738 min TICI score 2B
Infarct volume 30.0 ml Asymptomatic hemorrhage
Discharge mRS 3 Discharge NIHSS 4 90 day mRS 1
LKW to puncture: 1021 min LKW to recanalization: N/A TICI score 0
Infarct volume 90.0 ml Asymptomatic hemorrhage
Discharge mRS 5 Discharge NIHSS 25 90 day mRS 6
LKW to puncture: 363 min LKW to recanalization: 389 min TICI score 2C
Infarct volume 72.4 ml Asymptomatic hemorrhage
Discharge mRS 3 Discharge NIHSS 5 90 day mRS 2
LKW to puncture: 714 min LKW to recanalization: 725 min
Infarct volume 26.0 ml No hemorrhage
Discharge mRS 3 Discharge NIHSS 2
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Patient 3
Infarct volume 8.4 ml No hemorrhage
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HTN, HLPD, AF Premorbid mRS 0 NIHSS 17
Outcome
LKW to puncture: 470 min LKW to recanalization: 546 min TICI score 3
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Patient 2
Tandem lesion (ICA/M1) ASPECTS 10 good collaterals Infarct volume 10 ml Mismatch volume 134.6 ml M1 ASPECTS 10 Intermediate collaterals Infarct volume 14.9 ml Mismatch volume 112.1 ml M1 ASPECTS 10 Intermediate collaterals Infarct volume 1.0 ml Mismatch volume 124.6 ml M1 ASPECTS 8 Intermediate collaterals Infarct volume 2.0 ml Mismatch volume 67.0 ml M1 ASPECTS 10 Good collaterals Infarct volume 2.0 ml Mismatch volume: N/A M1 ASPECTS 10 Intermediate collaterals Infarct volume 11.6 ml Mismatch volume 109.3 ml M1 ASPECTS 6 Good collaterals Infarct volume 16.5 ml Mismatch volume 57.3 ml ICA ASPECTS 10 Intermediate collaterals Infarct volume 10.0 ml Mismatch volume 180.4 ml M1 ASPECTS 10 Intermediate collaterals Infarct volume 3.0 ml Mismatch volume N/A M1 ASPECTS 10 Intermediate collaterals Infarct volume 33.8 ml Mismatch volume 31.3 ml ICA ASPECTS 7 Intermediate collaterals Infarct volume 24.6 ml Mismatch volume 127.4 ml M1 ASPECTS 6 Intermediate collaterals Infarct volume 15.0 ml Mismatch volume N/A M1 ASPECTS 6 Intermediate collaterals Infarct volume 63.4 ml Mismatch Volume N/A M1 ASPECTS 8
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HTN, DM2, HLPD premorbid mRS 0 NIHSS 14
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Patient 1
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HTN, AF Premorbid mRS 4 NIHSS 25
Patient 19
HTN, AF Premorbid mRS 3 NIHSS 24
Patient 20
HTN, HLPD Premorbid mRS 0 NIHSS 4
Patient 21
HTN, HLPD, AF Premorbid mRS 1 NIHSS 9
Patient 22
HTN, DM2 Premorbid mRS 4 NIHSS 9
LKW to puncture: 595 min LKW to recanalization: 618 min TICI score 3
Infarct volume 10.0 ml No hemorrhage
Discharge mRS 2 Discharge NIHSS 0 90 day mRS 2
LKW to puncture: 692 min LKW to recanalization: 727 min TICI score 2B
Infarct volume 20.1 ml No hemorrhage
Discharge mRS 2 Discharge NIHSS 4 90 day mRS 1
LKW to puncture: 784 min LKW to recanalization: 910 min TICI score 3
Infarct volume 129 ml Asymptomatic hemorrhage Re-occlusion of MCA
Discharge mRS 6 Discharge NIHSS 24 90 day mRS 6
LKW to puncture: 513 min LKW to recanalization: 542 min TICI score 3
Infarct volume 45.4 ml Asymptomatic hemorrhage
Discharge mRS 5 Discharge NIHSS 10 90 day mRS 6
LKW to puncture: 427 min LKW to recanalization: 446 min TICI score 3
Infarct volume 1.0 ml No hemorrhage
Discharge mRS 0 Discharge NIHSS 1 90 day mRS 0
LKW to puncture: 843 min LKW to recanalization: 899 min TICI score 2B
Infarct volume 1.6 ml No hemorrhage
Discharge mRS 0 Discharge NIHSS 0 90 day mRS 0
LKW to puncture: 615 min LKW to recanalization: N/A TICI score 0
Infarct volume 210.4 No hemorrhage
Discharge mRS 6 Discharge NIHSS 24 90 day mRS 6
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Patient 18
Discharge mRS 4 Discharge NIHSS 13 90 day mRS 4
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None Premorbid mRS 1 NIHSS 19
Infarct volume 35 ml Asymptomatic hemorrhage
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Patient 17
LKW to puncture: 1628 min LKW to recanalization: 1641 min TICI score 3
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90 day mRS 2
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Patient 16
TICI score 2B
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None Premorbid mRS 0 NIHSS 20
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Patient 15
Intermediate collaterals Infarct volume 25.2 ml Mismatch Volume 75.6 ml M1 ASPECTS 7 Good collaterals Infarct volume 33.0 ml Mismatch Volume N/A ICA ASPECTS 6 Poor collaterals Infarct volume 8.0 ml Mismatch Volume 38.4 M1 ASPECTS 8 Good collaterals Infarct volume 18.6 ml Mismatch Volume N/A M1 ASPECTS 6 Intermediate collaterals Infarct volume 66.0 ml Mismatch Volume 82.2 ml M1 ASPECTS 6 Intermediate collaterals Infarct volume 40.0 ml Mismatch Volume 63.1 ml M1 ASPECTS 10 Good collaterals Infarct volume 1.0 ml Mismatch Volume 17.2 ml M1 ASPECTS 6 Poor collaterals Infarct volume 1.0 ml Mismatch Volume 58.5 M1 ASPECTS 6 Poor collaterals Infarct volume 55.8 ml Mismatch Volume 178.4 ml
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NIHSS 9
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Table 2. Functional outcome of patients in our study compared to endovascular trials RIH study cohort RIH study cohort & DEFUSE-2 HERMES cohort Good functional 14/22 (63.6%) 28/46 (60.8%) 291/633 (46.0%) outcome (mRS 0-2) Excellent functional 9/22 (40.9%) N/A 170/633 (26.9%) outcome (mRS 0-1) Symptomatic 0/22 (0%) N/A 28/634 (4.4%) hemorrhage
Extend IA cohort 25/35 (71.0%) 18/35 (51.0%) 0/35 (0%)
ACCEPTED MANUSCRIPT Figure 1. Study flow chart
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DWI lesion volume more than or equal to 70 ml (n = 13) Tmax 10 seconds volume > 100 ml (n = 2) Mismatch ratio < 1.8 (n = 3) Family declined procedure (n = 1)
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19 patients excluded
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41 patients with NIHSS ≥ 6, ASPECTS ≥ 6, and 6-24 hours from last known normal
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22 patients underwent mechanical thrombectomy
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14 patients had good 90-day functional outcome
8 patients had poor 90-day functional outcome
ACCEPTED MANUSCRIPT Figure 2 legend
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Images of a patient 1 from table 1. A. CTA showing right middle cerebral artery occlusion. B. MRI RAPID summary showing a 10.6 ml infarct and a 134.6 mL mismatch volume. C. Cerebral angiogram showing complete recanalization for right middle cerebral artery. D. Follow up RAPID showing an infarct volume of 8.3 mL and a mismatch volume of 9.2 mL .
ACCEPTED MANUSCRIPT Highlights
Over 50% of stroke patients had a favorable imaging profile 6-24 hours from onset
MRI perfusion imaging may help select ischemic stroke patients for thrombectomy
Over 60% of patients with favorable imaging achieved independence with thrombectomy
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