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The use of transcranial ultrasound and clinical assessment to diagnose ischaemic stroke due to large vessel occlusion in remote and rural areas.

ABSTRACT: Rapid endovascular thrombectomy, which can only be delivered in specialist centres, is the most effective treatment for acute ischaemic stroke due to large vessel occlusion (LVO). Pre-hospital selection of these patients is challenging, especially in remote and rural areas due to long transport times and limited access to specialist clinicians and diagnostic facilities. We investigated whether combined transcranial ultrasound and clinical assessment ("TUCA" model) could accurately triage these patients and improve access to thrombectomy. We recruited consecutive patients within 72 hours of suspected stroke, and performed non-contrast transcranial colour-coded ultrasonography within 24 hours of brain computed tomography. We retrospectively collected clinical information, and used hospital discharge diagnosis as the "gold standard". We used binary regression for diagnosis of haemorrhagic stroke, and an ordinal regression model for acute ischaemic stroke with probable LVO, without LVO, transient ischaemic attacks (TIA) and stroke mimics. We calculated sensitivity, specificity, positive and negative predictive values and performed a sensitivity analysis. We recruited 107 patients with suspected stroke from July 2017 to December 2019 at two study sites: 13/107 (12%) with probable LVO, 50/107 (47%) with acute ischaemic stroke without LVO, 18/107 (17%) with haemorrhagic stroke, and 26/107 (24%) with stroke mimics or TIA. The model identified 55% of cases with probable LVO who would have correctly been selected for thrombectomy and 97% of cases who would not have required this treatment (sensitivity 55%, specificity 97%, positive and negative predictive values 75% and 93%, respectively). Diagnostic accuracy of the proposed model was superior to the clinical assessment alone. These data suggest that our model might be a useful tool to identify pre-hospital patients requiring mechanical thrombectomy, however a larger sample is required with the use of CT angiogram as a reference test.

SUBMITTER: Antipova D

PROVIDER: S-EPMC7531787 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The use of transcranial ultrasound and clinical assessment to diagnose ischaemic stroke due to large vessel occlusion in remote and rural areas.

Antipova Daria D Eadie Leila L Makin Stephen S Shannon Helen H Wilson Philip P Macaden Ashish A

PloS one 20201002 10

Rapid endovascular thrombectomy, which can only be delivered in specialist centres, is the most effective treatment for acute ischaemic stroke due to large vessel occlusion (LVO). Pre-hospital selection of these patients is challenging, especially in remote and rural areas due to long transport times and limited access to specialist clinicians and diagnostic facilities. We investigated whether combined transcranial ultrasound and clinical assessment ("TUCA" model) could accurately triage these p ...[more]

PMID: 33007053

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Project description:Pre-clinically, High Intensity Focused Ultrasound (HIFU) has been shown to safely and effectively occlude placental blood vessels in the acute setting, when applied through the uterus. However, further development of the technique to overcome the technical challenges of targeting and occluding blood vessels through intact skin remains essential to translation into human studies. So too does the assessment of fetal wellbeing following this procedure, and demonstration of the persistence of vascular occlusion. At 115?±?10 d gestational age (term~147 days) 12 pregnant sheep were exposed to HIFU (n?=?6), or to a sham (n?=?6) therapy through intact abdominal skin (1.66?MHz, 5?s duration, in situ ISPTA 1.3-4.4?kW.cm-2). Treatment success was defined as undetectable colour Doppler signal in the target placental vessel following HIFU exposures. Pregnancies were monitored for 21 days using diagnostic ultrasound from one day before HIFU exposure until term, when post-mortem examination was performed. Placental vessels were examined histologically for evidence of persistent vascular occlusion. HIFU occluded 31/34 (91%) of placental vessels targeted, with persistent vascular occlusion evident on histological examination 20 days after treatment. The mean diameter of occluded vessels was 1.4?mm (range 0.3-3.3?mm). All pregnancies survived until post mortem without evidence of significant maternal or fetal iatrogenic harm, preterm labour, maternal or fetal haemorrhage or infection. Three of six ewes exposed to HIFU experienced abdominal skin burns, which healed without intervention within 21 days. Mean fetal weight, fetal growth velocity and other measures of fetal biometry were not affected by exposure to HIFU. Fetal Doppler studies indicated a transient increase in the umbilical artery pulsatility index (PI) and a decrease in middle cerebral artery PI as a result of general anaesthesia, which was not different between sham and treatment groups. We report the first successful application of fully non-invasive HIFU for occlusion of placental blood flow in a pregnant sheep model, with a low risk of significant complications. This proof of concept study demonstrates the potential of this technique for clinical translation.

Project description:INTRODUCTION:A number of pre-hospital clinical assessment tools have been developed to triage subjects with acute stroke due to large vessel occlusion (LVO) to a specialised endovascular centre, but their false negative rates remain high leading to inappropriate and costly emergency transfers. Transcranial ultrasonography may represent a valuable pre-hospital tool for selecting patients with LVO who could benefit from rapid transfer to a dedicated centre. METHODS:Diagnostic accuracy of transcranial ultrasonography in acute stroke was subjected to systematic review. Medline, Embase, PubMed, Scopus, and The Cochrane Library were searched. Published articles reporting diagnostic accuracy of transcranial ultrasonography in comparison to a reference imaging method were selected. Studies reporting estimates of diagnostic accuracy were included in the meta-analysis. RESULTS:Twenty-seven published articles were selected for the systematic review. Transcranial Doppler findings, such as absent or diminished blood flow signal in a major cerebral artery and asymmetry index ≥ 21% were shown to be suggestive of LVO. It demonstrated sensitivity ranging from 68 to 100% and specificity of 78-99% for detecting acute steno-occlusive lesions. Area under the receiver operating characteristics curve was 0.91. Transcranial ultrasonography can also detect haemorrhagic foci, however, its application is largely restricted by lesion location. CONCLUSIONS:Transcranial ultrasonography might potentially be used for the selection of subjects with acute LVO, to help streamline patient care and allow direct transfer to specialised endovascular centres. It can also assist in detecting haemorrhagic lesions in some cases, however, its applicability here is largely restricted. Additional research should optimize the scanning technique. Further work is required to demonstrate whether this diagnostic approach, possibly combined with clinical assessment, could be used at the pre-hospital stage to justify direct transfer to a regional thrombectomy centre in suitable cases.

Project description:BACKGROUND:Acute ischemic stroke (AIS) due to large vessel occlusion (LVO) is a devastating cerebrovascular disorder, which could benefit from collateral circulation. Proteins associated with acute LVO pathogenesis and endothelial function may appear in blood samples of AIS patients due to LVO, thus permitting development of blood-based biomarkers for its diagnosis and prognosis. METHODS:This study is a single-center, retrospective, observational case-control trial. Consecutive patients who presented at the Department of Neurology of Tongji Hospital were recruited from July 2016 to April 2018. In the discovery phase, a proteomic approach with iTRAQ-based LC-MS/MS was used to investigate the altered proteomic pattern in plasma from patients with AIS due to LVO. In the validation study, Western blots was used to identify biomarkers associated with stroke diagnosis as well as their prognostic value associated with different collateral statuses. RESULTS:For this exploratory study, the proteomic analysis of plasma from 40 patients with AIS due to LVO and 20 healthy controls revealed seven differentially expressed proteins with a 1.2/0.83-fold or greater difference between groups. The four elevated proteins, PPBP (1.58 ± 0.78 vs 0.98 ± 0.37; P < 0.001), THBS1 (1.13 ± 0.88 vs 0.43 ± 0.26; P < 0.001), LYVE1 (1.61 ± 0.55 vs 0.97 ± 0.50; P < 0.001), and IGF2 (1.19 ± 0.42 vs 0.86 ± 0.24; P < 0.001), were verified by Western blots analysis in an independent cohort including 33 patients and 33 controls. A strong interaction was observed between the four-protein panel and the diagnosis of AIS due to LVO (AUC 0.947; P < 0.001). Furthermore, IGF2, LYVE1, and THBS1 were closely associated with collateral status (IGF2 0.115, 95% CI 0.016-0.841, P = 0.033; LYVE1 0.183, 95% CI 0.036-0.918, P = 0.039; THBS1 4.257, 95% CI 1.273-14.228, P = 0.019), and proved to be independent predictors of good outcome (IGF2 0.115, 95% CI 0.015-0.866, P = 0.036; LYVE1 0.028, 95% CI 0.002-0.334, P = 0.005; THBS1 3.294, 95% CI 1.158-9.372, P = 0.025) at a 3-month follow-up. CONCLUSIONS:The identified 4-biomarker panel could provide diagnostic aid to the existing imaging modalities for AIS due to LVO, and the prognostic value of IGF2, LYVE1, and THBS1 was proved in predicting functional outcomes related to collateral status. Trial registration ClinicalTrials.gov NCT03122002. Retrospectively registered April 20, 2017. URL of trial registry record: https://www.clinicaltrials.gov/ct2/show/NCT03122002?term=NCT+03122002&rank=1.

Project description:BackgroundLow-intensity transcranial focused ultrasound (tFUS) has emerged as a new non-invasive modality of brain stimulation with the potential for high spatial selectivity and penetration depth. Anesthesia is typically applied in animal-based tFUS brain stimulation models; however, the type and depth of anesthesia are known to introduce variability in responsiveness to the stimulation. Therefore, the ability to conduct sonication experiments on awake small animals, such as rats, is warranted to avoid confounding effects of anesthesia.ResultsWe developed a miniature tFUS headgear, operating at 600 kHz, which can be attached to the skull of Sprague-Dawley rats through an implanted pedestal, allowing the ultrasound to be transcranially delivered to motor cortical areas of unanesthetized freely-moving rats. Video recordings were obtained to monitor physical responses from the rat during acoustic brain stimulation. The stimulation elicited body movements from various areas, such as the tail, limbs, and whiskers. Movement of the head, including chewing behavior, was also observed. When compared to the light ketamine/xylazine and isoflurane anesthetic conditions, the response rate increased while the latency to stimulation decreased in the awake condition. The individual variability in response rates was smaller during the awake condition compared to the anesthetic conditions. Our analysis of latency distribution of responses also suggested possible presence of acoustic startle responses mixed with stimulation-related physical movement. Post-tFUS monitoring of animal behaviors and histological analysis performed on the brain did not reveal any abnormalities after the repeated tFUS sessions.ConclusionsThe wearable miniature tFUS configuration allowed for the stimulation of motor cortical areas in rats and elicited sonication-related movements under both awake and anesthetized conditions. The awake condition yielded diverse physical responses compared to those reported in existing literatures. The ability to conduct an experiment in freely-moving awake animals can be gainfully used to investigate the effects of acoustic neuromodulation free from the confounding effects of anesthesia, thus, may serve as a translational platform to large animals and humans.

Dataset Information

The use of transcranial ultrasound and clinical assessment to diagnose ischaemic stroke due to large vessel occlusion in remote and rural areas.

Publications

The use of transcranial ultrasound and clinical assessment to diagnose ischaemic stroke due to large vessel occlusion in remote and rural areas.

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