Radiology - Research Publications

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    Sustaining a New Model of Acute Stroke Care: A Mixed- Method Process Evaluation of the Melbourne Mobile Stroke Unit
    Bagot, KL ; Purvis, T ; Hancock, S ; Zhao, H ; Coote, S ; Easton, D ; Campbell, BC ; Davis, SM ; Donnan, GA ; Foster, S ; Langenberg, F ; Smith, K ; Stephenson, M ; Bernard, S ; McGowan, S ; Yan, B ; Mitchell, P ; Middleton, S ; Cadilhac, DA (KERMAN UNIV MEDICAL SCIENCES, 2023-01)
    BACKGROUND: Internationally, Mobile Stroke Unit (MSU) ambulances have changed pre-hospital acute stroke care delivery. MSU clinical and cost-effectiveness studies are emerging, but little is known about important factors for achieving sustainability of this innovative model of care. METHODS: Mixed-methods study from the Melbourne MSU (operational since November 2017) process evaluation. Participant purposive sampling included clinical, operational and executive/management representatives from Ambulance Victoria (AV) (emergency medical service provider), the MSU clinical team, and receiving hospitals. Sustainability was defined as ongoing MSU operations, including MSU workforce and future model considerations. Theoretically-based on-line survey with Unified Theory of Acceptance and Use of Technology (UTAUT), Self Determination Theory (SDT, Intrinsic Motivation), and open-text questions targeting barriers and benefits was administered (June-September 2019). Individual/group interviews were conducted, eliciting improvement suggestions and requirements for ongoing use. Descriptive and regression analyses (quantitative data) and directed content and thematic analysis (open text and interview data) were conducted. RESULTS: There were 135 surveys completed. Identifying that the MSU was beneficial to daily work (β=0.61), not experiencing pressure/tension about working on the MSU (β=0.17) and thinking they did well working within the team model (β=0.17) were significantly associated with wanting to continue working within the MSU model [R2=0.76; F(15, 60)=12.76, P<.001]. Experiences varied between those on the MSU team and those working with the MSU. Advantages were identified for patients (better, faster care) and clinicians (interdisciplinary learning). Disadvantages included challenges integrating into established systems, and establishing working relationships. Themes identified from 35 interviews were MSU team composition, MSU vehicle design and layout, personnel recruitment and rostering, communication improvements between organisations, telemedicine options, MSU operations and dispatch specificity. CONCLUSION: Important factors affecting the sustainability of the MSU model of stroke care emerged. A cohesive team approach, with identifiable benefits and good communication between participating organisations is important for clinical and operational sustainability.
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    Prevalence and Significance of Impaired Microvascular Tissue Reperfusion Despite Macrovascular Angiographic Reperfusion (No-Reflow)
    Ng, FC ; Churilov, L ; Yassi, N ; Kleinig, TJ ; Thijs, V ; Wu, T ; Shah, D ; Dewey, H ; Sharma, G ; Desmond, P ; Yan, B ; Parsons, M ; Donnan, G ; Davis, S ; Mitchell, P ; Campbell, B (LIPPINCOTT WILLIAMS & WILKINS, 2022-02-22)
    BACKGROUND AND OBJECTIVES: The relevance of impaired microvascular tissue-level reperfusion despite complete upstream macrovascular angiographic reperfusion (no-reflow) in human stroke remains controversial. We investigated the prevalence and clinical-radiologic features of this phenomenon and its associations with outcomes in 3 international randomized controlled thrombectomy trials with prespecified follow-up perfusion imaging. METHODS: In a pooled analysis of the Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA; ClinicalTrials.gov NCT01492725), Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK; NCT02388061), and Determining the Optimal Dose of Tenecteplase Before Endovascular Therapy for Ischaemic Stroke (EXTEND-IA TNK Part 2; NCT03340493) trials, patients undergoing thrombectomy with final angiographic expanded Treatment in Cerebral Infarction score of 2c to 3 score for anterior circulation large vessel occlusion and 24-hour follow-up CT or MRI perfusion imaging were included. No-reflow was defined as regions of visually demonstrable persistent hypoperfusion on relative cerebral blood volume or flow maps within the infarct and verified quantitatively by >15% asymmetry compared to a mirror homolog in the absence of carotid stenosis or reocclusion. RESULTS: Regions of no-reflow were identified in 33 of 130 patients (25.3%), encompassed a median of 60.2% (interquartile range 47.8%-70.7%) of the infarct volume, and involved both subcortical (n = 26 of 33, 78.8%) and cortical (n = 10 of 33, 30.3%) regions. Patients with no-reflow had a median 25.2% (interquartile range 16.4%-32.2%, p < 0.00001) relative cerebral blood volume interside reduction and 19.1% (interquartile range 3.9%-28.3%, p = 0.00011) relative cerebral blood flow reduction but similar mean transit time (median -3.3%, interquartile range -11.9% to 24.4%, p = 0.24) within the infarcted region. Baseline characteristics were similar between patients with and those without no-reflow. The presence of no-reflow was associated with hemorrhagic transformation (adjusted odds ratio [aOR] 1.79, 95% confidence interval [CI] 2.32-15.57, p = 0.0002), greater infarct growth (β = 11.00, 95% CI 5.22-16.78, p = 0.00027), reduced NIH Stroke Scale score improvement at 24 hours (β = -4.06, 95% CI 6.78-1.34, p = 0.004) and being dependent or dead at 90 days as assessed by the modified Rankin Scale (aOR 3.72, 95% CI 1.35-10.20, p = 0.011) in multivariable analysis. DISCUSSION: Cerebral no-reflow in humans is common, can be detected by its characteristic perfusion imaging profile using readily available sequences in the clinical setting, and is associated with posttreatment complications and being dependent or dead. Further studies evaluating the role of no-reflow in secondary injury after angiographic reperfusion are warranted. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that cerebral no-reflow on CT/MRI perfusion imaging at 24 hours is associated with posttreatment complications and poor 3-month functional outcome.
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    Endovascular Thrombectomy Versus Medical Management in Isolated M2 Occlusions: Pooled Patient-Level Analysis from the EXTEND-IA Trials, INSPIRE, and SELECT Studies
    Sarraj, A ; Parsons, M ; Bivard, A ; Hassan, AE ; Abraham, MG ; Wu, T ; Kleinig, T ; Lin, L ; Chen, C ; Levi, C ; Dong, Q ; Cheng, X ; Butcher, KS ; Choi, P ; Yassi, N ; Shah, D ; Sharma, G ; Pujara, D ; Shaker, F ; Blackburn, S ; Dewey, H ; Thijs, V ; Sitton, CW ; Donnan, GA ; Mitchell, PJ ; Yan, B ; Grotta, JG ; Albers, GW ; Davis, SM ; Campbell, B (WILEY, 2022-05)
    OBJECTIVE: The objective of this study was to evaluate functional and safety outcomes of endovascular thrombectomy (EVT) versus medical management (MM) in patients with M2 occlusion and examine their association with perfusion imaging mismatch and stroke severity. METHODS: In a pooled, patient-level analysis of 3 randomized controlled trials (EXTEND-IA, EXTEND-and IA-TNK parts 1 and 2) and 2 prospective nonrandomized studies (INSPIRE and SELECT), we evaluated EVT association with 90-day functional independence (modified Rankin Scale [mRS] = 0-2) in isolated M2 occlusions as compared to medical management overall and in subgroups by mismatch profile status and stroke severity. RESULTS: We included 517 patients (EVT = 195 and MM = 322), baseline median (interquartile range [IQR]) National Institutes of Health Stroke Scale (NIHSS) was 13 (8-19) in EVT versus 10 (6-15) in MM, p < 0.001. Pretreatment ischemic core did not differ (EVT = 10 [0-24] ml vs MM = 9 [3-21] ml, p = 0.59). Compared to MM, EVT was more frequently associated with functional independence (68.3 vs 61.6%, adjusted odds ratio [aOR] = 2.42, 95% confidence interval [CI] = 1.25-4.67, p = 0.008, inverse probability of treatment weights [IPTW]-OR = 1.75, 95% CI = 1.00-3.75, p = 0.05) with a shift toward better mRS outcomes (adjusted cOR = 2.02, 95% CI:1.23-3.29, p = 0.005), and lower mortality (5 vs 10%, aOR = 0.32, 95% CI = 0.12-0.87, p = 0.025). EVT was associated with higher functional independence in patients with a perfusion mismatch profile (EVT = 70.7% vs MM = 61.3%, aOR = 2.29, 95% CI = 1.09-4.79, p = 0.029, IPTW-OR = 2.02, 1.08-3.78, p = 0.029), whereas no difference was found in those without mismatch (EVT = 43.8% vs MM = 62.7%, p = 0.17, IPTW-OR: 0.71, 95% CI = 0.18-2.78, p = 0.62). Functional independence was more frequent with EVT in patients with moderate or severe strokes, as defined by baseline NIHSS above any thresholds from 6 to 10, whereas there was no difference between groups with milder strokes below these thresholds. INTERPRETATION: In patients with M2 occlusion, EVT was associated with improved clinical outcomes when compared to MM. This association was primarily observed in patients with a mismatch profile and those with higher stroke severity. ANN NEUROL 2022;91:629-639.
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    Healthy Life-Year Costs of Treatment Speed From Arrival to Endovascular Thrombectomy in Patients With Ischemic Stroke A Meta-analysis of Individual Patient Data From 7 Randomized Clinical Trials
    Almekhlafi, MA ; Goyal, M ; Dippel, DWJ ; Majoie, CBLM ; Campbell, BCV ; Muir, KW ; Demchuk, AM ; Bracard, S ; Guillemin, F ; Jovin, TG ; Mitchell, P ; White, P ; Hill, MD ; Brown, S ; Saver, JL (AMER MEDICAL ASSOC, 2021-06)
    IMPORTANCE: The benefits of endovascular thrombectomy (EVT) are time dependent. Prior studies may have underestimated the time-benefit association because time of onset is imprecisely known. OBJECTIVE: To assess the lifetime outcomes associated with speed of endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion (LVO). DATA SOURCES: PubMed was searched for randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time, and for which a peer-reviewed, complete primary results article was published by August 1, 2020. STUDY SELECTION: All randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time were included. DATA EXTRACTION/SYNTHESIS: Patient-level data regarding presenting clinical and imaging features and functional outcomes were pooled from the 7 retrieved randomized clinical trials of stent retriever thrombectomy devices (entirely or predominantly) vs medical therapy. All 7 identified trials published in a peer-reviewed journal (by August 1, 2020) contributed data. Detailed time metrics were collected including last known well-to-door (LKWTD) time; last known well/onset-to-puncture (LKWTP) time; last known well-to-reperfusion (LKWR) time; door-to-puncture (DTP) time; and door-to-reperfusion (DTR) time. MAIN OUTCOMES AND MEASURES: Change in healthy life-years measured as disability-adjusted life-years (DALYs). DALYs were calculated as the sum of years of life lost (YLL) owing to premature mortality and years of healthy life lost because of disability (YLD). Disability weights were assigned using the utility-weighted modified Rankin Scale. Age-specific life expectancies without stroke were calculated from 2017 US National Vital Statistics. RESULTS: Among the 781 EVT-treated patients, 406 (52.0%) were early-treated (LKWTP ≤4 hours) and 375 (48.0%) were late-treated (LKWTP >4-12 hours). In early-treated patients, LKWTD was 188 minutes (interquartile range, 151.3-214.8 minutes) and DTP 105 minutes (interquartile range, 76-135 minutes). Among the 298 of 380 (78.4%) patients with substantial reperfusion, median DTR time was 145.0 minutes (interquartile range, 111.5-185.5 minutes). Care process delays were associated with worse clinical outcomes in LKW-to-intervention intervals in early-treated patients and in door-to-intervention intervals in early-treated and late-treated patients, and not associated with LKWTD intervals, eg, in early-treated patients, for each 10-minute delay, healthy life-years lost were DTP 1.8 months vs LKWTD 0.0 months; P < .001. Considering granular time increments, the amount of healthy life-time lost associated with each 1 second of delay was DTP 2.2 hours and DTR 2.4 hours. CONCLUSIONS AND RELEVANCE: In this study, care delays were associated with loss of healthy life-years in patients with acute ischemic stroke treated with EVT, particularly in the postarrival time period. The finding that every 1 second of delay was associated with loss of 2.2 hours of healthy life may encourage continuous quality improvement in door-to-treatment times.
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    Antiplatelet resistance and thromboembolic complications in neurointerventional procedures.
    Oxley, TJ ; Dowling, RJ ; Mitchell, PJ ; Davis, S ; Yan, B (Frontiers Media SA, 2011)
    Antiplatelet resistance is emerging as a significant factor in effective secondary stroke prevention. Prevalence of aspirin and clopidogrel resistance is dependent upon laboratory test and remains contentious. Large studies in cardiovascular disease populations have demonstrated worse ischemic outcomes in patients with antiplatelet resistance, particularly in patients with coronary stents. Thromboembolism is a complication of neurointerventional procedures that leads to stroke. Stroke rates related to aneurysm coiling range from 2 to 10% and may be higher when considering silent ischemia. Stroke associated with carotid stenting is a major cause of morbidity. Antiplatelet use in the periprocedure setting varies among different centers. No guidelines exist for use of antiplatelet regimens in neurointerventional procedures. Incidence of stroke in patients post procedure may be partly explained by resistance to antiplatelet agents. Further research is required to establish the incidence of stroke in patients with antiplatelet resistance undergoing neurointerventional procedures.
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    Proximal Hyperdense Middle Cerebral Artery Sign Predicts Poor Response to Thrombolysis
    Li, Q ; Davis, S ; Mitchell, P ; Dowling, R ; Yan, B ; Baron, J-C (PUBLIC LIBRARY SCIENCE, 2014-05-07)
    The aim of our study was to compare the rapid neurological improvement after intravenous recombinant tissue-type plasminogen activator (rtPA) in patients with proximal hyperdense middle cerebral artery sign (p-HMCAS) to those without the sign and those with the distal hyperdense middle cerebral artery sign (d-HMCAS). Admission and 24 hour non-contrast CT scans of 120 patients with middle cerebral artery (MCA) territory stroke who were treated with intravenous rtPA were assessed for the presence of p-HMCAS and d-HMCAS. The sign was classified according to the site of occlusion. Rapid neurological improvement was defined as ≥ 50% improvement in the NIHSS score at 24 hours after thrombolysis. Rapid neurological recovery after thrombolysis was assessed and compared between the subgroups. Rapid neurological recovery was less common in the pooled group of patients with either p-HMCAS or d-HMCAS than those without the sign (p<0.01). Patients with p-HMCAS were less likely to have rapid neurological recovery than those with d-HMCAS (p<0.01). However, there was no difference in early neurological recovery between patients with d-HMCAS and those without any hyperdense sign. Our study showed that poor neurological recovery post rtPA was confined to p-HMCAS and not to d-HMCAS, indicating that these signs have quite different prognostic significance.
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    Blood Pressure May Be Associated with Arterial Collateralization in Anterior Circulation Ischemic Stroke before Acute Reperfusion Therapy
    Jiang, B ; Churilov, L ; Kanesan, L ; Dowling, R ; Mitchell, P ; Dong, Q ; Davis, S ; Yan, B (KOREAN STROKE SOC, 2017-05)
    BACKGROUND AND PURPOSE: Leptomeningeal collaterals maintain arterial perfusion in acute arterial occlusion but may fluctuate subject to arterial blood pressure (ABP). We aim to investigate the relationship between ABP and collaterals as assessed by computer tomography (CT) perfusion in acute ischemic stroke. METHODS: We retrospectively analyzed acute anterior circulation ischemic stroke patients with CT perfusion from 2009 to 2014. Collateral status using relative filling time delay (rFTD) determined by time delay of collateral-derived contrast opacification within the Sylvian fissure, from 0 seconds to unlimited count. The data were analyzed by zero-inflated negative binomial regression model including an appropriate interaction examining in the model in terms of occlusion location and onset-to-CT time (OCT). RESULTS: Two hundred and seventy patients were included. We found that increment of 10 mm Hg in BP, the odds that a patient would have rFTD equal to 0 seconds increased by 27.9% in systolic BP (SBP) (p=0.001), by 73.9% in diastolic BP (DBP) (p<0.001) and by 68.5% in mean BP (MBP) (p<0.001). For patients with rFTD not necessarily equal to 0 seconds, every 10 mm Hg increase in BP, there was a 7% decrease in expected count of seconds for rFTD in SBP (p=0.002), 10% decrease for rFTD in DBP and 11% decrease for rFTD in MBP. The arterial occlusion location and OCT showed no significant interaction in the BP-rFTD relationship (p>0.05). CONCLUSIONS: In acute ischemic stroke, higher ABP is possibly associated with improved leptomeningeal collaterals as identified by decreased rFTD.
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    Endovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost
    Campbell, BCV ; Mitchell, PJ ; Churilov, L ; Keshtkaran, M ; Hong, K-S ; Kleinig, TJ ; Dewey, HM ; Yassi, N ; Yan, B ; Dowling, RJ ; Parsons, MW ; Wu, TY ; Brooks, M ; Simpson, MA ; Miteff, F ; Levi, CR ; Krause, M ; Harrington, TJ ; Faulder, KC ; Steinfort, BS ; Ang, T ; Scroop, R ; Barber, PA ; McGuinness, B ; Wijeratne, T ; Phan, TG ; Chong, W ; Chandra, RV ; Bladin, CF ; Rice, H ; de Villiers, L ; Ma, H ; Desmond, PM ; Meretoja, A ; Cadilhac, DA ; Donnan, GA ; Davis, SM (FRONTIERS MEDIA SA, 2017-12-14)
    BACKGROUND: Endovascular thrombectomy improves functional outcome in large vessel occlusion ischemic stroke. We examined disability, quality of life, survival and acute care costs in the EXTEND-IA trial, which used CT-perfusion imaging selection. METHODS: Large vessel ischemic stroke patients with favorable CT-perfusion were randomized to endovascular thrombectomy after alteplase versus alteplase-only. Clinical outcome was prospectively measured using 90-day modified Rankin scale (mRS). Individual patient expected survival and net difference in Disability/Quality-adjusted life years (DALY/QALY) up to 15 years from stroke were modeled using age, sex, 90-day mRS, and utility scores. Level of care within the first 90 days was prospectively measured and used to estimate procedure and inpatient care costs (US$ reference year 2014). RESULTS: There were 70 patients, 35 in each arm, mean age 69, median NIHSS 15 (IQR 12-19). The median (IQR) disability-weighted utility score at 90 days was 0.65 (0.00-0.91) in the alteplase-only versus 0.91 (0.65-1.00) in the endovascular group (p = 0.005). Modeled life expectancy was greater in the endovascular versus alteplase-only group (median 15.6 versus 11.2 years, p = 0.02). The endovascular thrombectomy group had fewer simulated DALYs lost over 15 years [median (IQR) 5.5 (3.2-8.7) versus 8.9 (4.7-13.8), p = 0.02] and more QALY gained [median (IQR) 9.3 (4.2-13.1) versus 4.9 (0.3-8.5), p = 0.03]. Endovascular patients spent less time in hospital [median (IQR) 5 (3-11) days versus 8 (5-14) days, p = 0.04] and rehabilitation [median (IQR) 0 (0-28) versus 27 (0-65) days, p = 0.03]. The estimated inpatient costs in the first 90 days were less in the thrombectomy group (average US$15,689 versus US$30,569, p = 0.008) offsetting the costs of interhospital transport and the thrombectomy procedure (average US$10,515). The average saving per patient treated with thrombectomy was US$4,365. CONCLUSION: Thrombectomy patients with large vessel occlusion and salvageable tissue on CT-perfusion had reduced length of stay and overall costs to 90 days. There was evidence of clinically relevant improvement in long-term survival and quality of life. CLINICAL TRIAL REGISTRATION: http://www.ClinicalTrials.gov NCT01492725 (registered 20/11/2011).