| 1. |
- Persson, Mats, 1987-, et al.
(författare)
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Sub-pixel information retrieval from spectral x-ray images
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The detector pixel size can be a severe limitation in projection x-ray imaging of fine details inthe human body, but developing higher resolution detectors is technically challenging. Wedemonstrate a novel method of using spectral x-ray measurements, from an energy-resolvingdetector or from multiple acquisitions with different beam quality, to obtain information aboutthe spatial distribution of the linear attenuation coefficient on a length scale smaller than onepixel. The method builds on the fact that the linear attenuation coefficient of all materials inthe human body can be expressed as linear combinations of a small number of basis functions.However, an interface parallel to the x-ray beam has a unique spectral responose which makesit distinguishable from homogeneous materials.To demonstrate the method experimentally, a 120 mm polyethylene phantom with a 6 mmiodine-filled hole in its centre was imaged in a projection geometry using a photon-countingsilicon-strip detector with eight energy bins. X-ray transmission measurements of differentthicknesses of polyethylene and iodine were used to calibrate a forward model describing thedetector response for different objects in the beam. Using the proposed method, an imagespecific to the spectral response of an iodine-polyethylene interface was generated. Theresults show that the borders of the iodine insert are highlighted in the resulting image, ingood agreement with simulations.Our study demonstrates that spectral x-ray measurements can be used to distinguish betweensharp and gradual transitions in an x-ray image. The method may potentially be used forimproving visualization of blood vessel boundaries in stroke care.
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| 2. |
- Persson, Mats, 1987-, et al.
(författare)
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Subpixel x-ray imaging with an energy-resolving detector
- 2018
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Ingår i: Journal of Medical Imaging. - : SPIE - International Society for Optical Engineering. - 2329-4302 .- 2329-4310. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- The detector pixel size can be a severe limitation in x-ray imaging of fine details in the human body. We demonstrate a method of using spectral x-ray measurements to image the spatial distribution of the linear attenuation coefficient on a length scale smaller than one pixel, based on the fact that interfaces parallel to the x-ray beam have a unique spectral response, which distinguishes them from homogeneous materials. We evaluate the method in a simulation study by simulating projection imaging of the border of an iodine insert with 200 mg/ml I in a soft tissue phantom. The results show that the projected iodine profile can be recovered with an RMS resolution of 5% to 34% of the pixel size, using an ideal energy-resolving detector. We also validate this method in an experimental study by imaging an iodine insert in a polyethylene phantom using a photon-counting silicon-strip detector. The results show that abrupt and gradual transitions can be distinguished based on the transmitted x-ray spectrum, in good agreement with simulations. The demonstrated method may potentially be used for improving visualization of blood vessel boundaries, e.g., in acute stroke care.
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| 3. |
- Ahmed, Niaz, et al.
(författare)
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The SITS Open Study: A Prospective, Open Label Blinded Evaluation Study of Thrombectomy in Clinical Practice.
- 2021
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Ingår i: Stroke. - 1524-4628. ; 52:3, s. 792-801
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Tidskriftsartikel (refereegranskat)abstract
- We designed SITS (Safe Implementation of Treatment in Stroke) Open to determine benefit and safety of thrombectomy in clinical practice for large artery occlusion stroke, using selected stent retrievers plus standard care versus standard care alone.SITS Open was a prospective, open, blinded evaluation, international, multicenter, controlled, nonrandomized registry study. Centers lacking access to thrombectomy contributed controls. Primary end point was categorical shift in modified Rankin Scale score at 3 months in the per protocol (PP) population. Principal secondary outcomes were symptomatic intracranial hemorrhage, functional independency (modified Rankin Scale score 0-2) and death at 3 months. Patients independently evaluated by video-recorded modified Rankin Scale interviews blinded to treatment or center identity by central core laboratory were regarded as PP population. Propensity score matching with covariate adjusted analysis was performed.During 2014 to 2017, 293 patients (257 thrombectomy, 36 control) from 26 centers in 10 countries fulfilled intention-to-treat and 200 (170 thrombectomy, 30 control) PP criteria; enrollment of controls was limited by rapid uptake of thrombectomy. In PP analysis, median age was 71 versus 71 years, and baseline National Institutes of Health Stroke Scale 17 versus 17 in the thrombectomy and control arms, respectively. The propensity score matching analysis for PP showed a significant shift for modified Rankin Scale at 3 months favoring the thrombectomy group (odds ratio, 3.8 [95% CI, 1.61-8.95]; P=0.002). Regarding safety, there were 4 cases of symptomatic intracranial hemorrhage in the thrombectomy group (2.4%) and none in the control group.In clinical practice, thrombectomy for patients with large artery occlusion stroke is superior to standard of care in our study. Registration: URL: https://www.clinicaltrials.gov. Unique Identifier: NCT02326428.
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| 4. |
- Al-Saadi, Jonathan, et al.
(författare)
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Endovascular transplantation of mRNA-enhanced mesenchymal stromal cells results in superior therapeutic protein expression in swine heart
- 2024
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Ingår i: Molecular therapy. Methods & clinical development. - : Elsevier BV. - 2399-6951 .- 2329-0501. ; 32:2
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure has a poor prognosis and no curative treatment exists. Clinical trials are investigating gene- and cell-based therapies to improve cardiac function. The safe and efficient delivery of these therapies to solid organs is challenging. Herein, we demonstrate the feasibility of using an endovascular intramyocardial delivery approach to safely administer mRNA drug products and perform cell transplantation procedures in swine. Using a trans-vessel wall (TW) device, we delivered chemically modified mRNAs (modRNA) and mRNA-enhanced mesenchymal stromal cells expressing vascular endothelial growth factor A (VEGF-A) directly to the heart. We monitored and mapped the cellular distribution, protein expression, and safety tolerability of such an approach. The delivery of modRNA-enhanced cells via the TW device with different flow rates and cell concentrations marginally affect cell viability and protein expression in situ. Implanted cells were found within the myocardium for at least 3 days following administration, without the use of immunomodulation and minimal impact on tissue integrity. Finally, we could increase the protein expression of VEGF-A over 500-fold in the heart using a cell-mediated modRNA delivery system compared with modRNA delivered in saline solution. Ultimately, this method paves the way for future research to pioneer new treatments for cardiac disease.
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| 5. |
- Chireh, Arvin, et al.
(författare)
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Micro-biopsy for detection of gene expression changes in ischemic swine myocardium : A pilot study
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:4, s. e0250582-
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Tidskriftsartikel (refereegranskat)abstract
- Micro-endomyocardial biopsy (micro-EMB) is a novel catheter-based biopsy technique, aiming to increase flexibility and safety compared to conventional EMB. The technique was developed and evaluated in healthy swine. Therefore, the ability to detect disease related tissue changes could not be evaluated. The aim of the present pilot study was to investigate the ability to detect disease related gene expression changes using micro-EMB. Myocardial infarction was induced in three swine by coronary artery balloon occlusion. Micro-EMB samples (n = 164) were collected before, during, and after occlusion. RNA-sequencing was performed on 85 samples, and 53 of these were selected for bioinformatic analysis. A large number of responding genes was detected from the infarcted area (n = 1911). The early responding genes (n = 1268) were mostly related to apoptosis and inflammation. There were fewer responding genes two days after infarction (n = 6), which were related to extra-cellular matrix changes, and none after 14 days. In contrast to the infarcted area, samples harvested from a non-infarcted myocardial region showed considerably fewer regulated genes (n = 33). Deconvolution analysis, to estimate the proportion of different cell types, revealed a higher proportion of fibroblasts and a reduced proportion of cardiomyocytes two days after occlusion compared to baseline (p < 0.02 and p < 0.01, respectively. S5 File). In conclusion, this pilot study demonstrates the capabilities of micro-EMB to detect local gene expression responses at an early stage after ischemia, but not at later timepoints.
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| 6. |
- Franzén, Erika, et al.
(författare)
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The EXPANd trial : effects of exercise and exploring neuroplastic changes in people with Parkinson's disease
- 2019
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Ingår i: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Parkinson's disease (PD) affects many physiological systems essential for balance control. Recent studies suggest that intensive and cognitively demanding physical exercise programs are capable of inducing plastic brain changes in PD. We have developed a highly challenging balance training (the HiBalance) program that emphasizes critical aspects of balance control through progressively introducing more challenging exercises which incorporates dual-tasking. Earlier studies have shown it to be effective in improving balance, gait and dual-tasking. The study design has thereafter been adjusted to link intervention-induced behavioral changes to brain morphology and function. Specifically, in this randomized controlled trial, we will determine the effects of the HiBalance program on balance, gait and cognition and relate this to task-evoked functional MRI (fMRI), as well as brain-derived neurotrophic factor (BDNF) in participants with mild-moderate PD.Methods: One hundred participants with idiopathic PD, Hoehn & Yahr stage 2 or 3, >= 60 years of age, >= 21 on Montreal Cognitive Assessment will be recruited in successive waves and randomized into either the HiBalance program or to an active control group (the HiCommunication program, targeting speech and communication). Both interventions will be performed in small groups, twice a week with 1 h sessions for 10 weeks. In addition, a 1 h, once a week, home exercise program will also be performed. A double-blinded design will be used. At the pre- and post-assessments, participants will be assessed on balance (main outcome), gait, cognitive functions, physical activity, voice/speech function, BDNF in serum and fMRI (3 T Philips) during performance of motor-cognitive tasks.Discussion: Since there is currently no cure for PD, findings of neuroplastic brain changes in response to exercise would revolutionize the way we treat PD, and, in turn, provide new hope to patients for a life with better health, greater independence and improved quality of life.
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| 7. |
- Gahm, Caroline, et al.
(författare)
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Reduced neuronal injury after treatment with NG-nitro-L-arginine methyl ester (L-NAME) or 2-sulfo-phenyl-N-tert-butyl nitrone (S-PBN) following experimental brain contusion
- 2005
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Ingår i: Neurosurgery. - : Ovid Technologies (Wolters Kluwer Health). - 0148-396X .- 1524-4040. ; 57:6, s. 1272-1281
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Nitric oxide (NO) and oxygen free radicals are implicated in the pathophysiology of traumatic brain injury (TBI). Peroxynitrite formation from NO and superoxide contributes to secondary neuronal injury but the neuroprotective effects of nitric oxide synthase (NOS)-inhibitors have been contradictory. This study was undertaken to examine whether PTtic administration of the (NOS)-inhibitor N-nitro-l-arginine methyl ester (L-NAME), and a combination of L-NAME and the nitrone radical scavenger 2-sulfo-phenyl-N-tert-butyl nitrone (S-PBN) favorable affects neuronal injury in a model of TBI. METHODS: A weight-drop model of TBI was used. The animals received L-NAME, S-PBN or a combination of the drugs 15 minutes prothrombin time (PT) and sacrificed after 24 hours or six days. NOS activity was measured by the conversion of L-[U-C]arginine to L-[U-C]citrulline. Peroxynitrite formation, cellular apoptosis, neuronal degeneration and survival were assessed by nitrotyrosine-, TUNEL-, Fluoro-Jade- and NeuN-stainings. RESULTS: eNOS and nNOS activity was significantly reduced in animals that received L-NAME alone or the combination with S-PBN. iNOS activity or iNOS immunoreactivity was not affected. All treatments significantly reduced neuronal degeneration and nitrotyrosine immunoreactivity at 24 hours and increased neuronal survival at six days PT. No differences were detected between L-NAME and L-NAME + S-PBN groups. CONCLUSION: NO from NOS contributes to secondary neuronal injury in this TBI-model. PTtic treatment does not inhibit early beneficial NO-related effects. L-NAME and S-PBN limit peroxynitrite formation, promoting neuronal survival. The combination of L-NAME and S-PBN was neuroprotective; surprisingly no additive effects were found on nitrotyrosine formation, apoptosis or neuronal survival.
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| 8. |
- Holmin, Staffan
(författare)
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Inflammation in brain contusion
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The immune system is essential for host defense against microbial pathogens and for wound healing processes. Inflammatory reactions, however, invariably cause tissue damage. Intracerebral inflammatory processes are known to be pathogenically important in conditions such as multiple sclerosis and infectious meningitis, but they have not been extensively studied in traumatic brain injuries (TBI). Contusions are a form of TBI that frequently leads to delayed neurological deterioration. This study was undertaken to explore whether intracerebral inflammatory processes occur following cerebral contusions and to analyze the pathophysiological role of such processes. A maximal inflammatory response with infiltration of monocytes/macrophages, CD4 and CD8 positive T-lymphocytes, NK-cells, and MHC-II expression was detected four to six days after experimentally-induced contusions of the rat brain. Production of the proinflammatory cytokines interleukin (IL)-1-beta, tumor necrosis factor (TNF)-alpha and IL-6 showed similar temporal profiles, with maximal levels on day six after the trauma. Inflammatory activation persisted at least three months after the trauma. The development of edema was biphasic. The first peak occurred one day after the trauma. The second peak was detected five to seven days after the trauma and thus correlated in time with maximal inflammation. Anti-inflammatory treatment with dexamethasone, colchicine or chloroquine during the posttraumatic phase reduced inflammation and the delayed phase of edema. Cellular DNA-fragmentation in the perilesional zone, indicative of cell death, persisted for at least six days after the trauma. Microinjections of IL-1-beta into normal rat brain induced transient and dose-dependent neuronal DNA-fragmentation, encephalitis and vasogenic edema. Infiltrating inflammatory cells that strongly expressed nitric oxide synthase of the neuronal isoform correlated anatomically and temporally with neuronal DNA-fragmentation, indicating a possible role of nitric oxide in mediating neuronal cytotoxicity. Microinjections of TNF-alpha caused a less pronounced but more protracted vasogenic edema than IL-1-beta. Thus, these cytokines induced some of the pathogenic effects seen after contusions. Brain biopsies from patients undergoing surgery because of cerebral contusions were examined. We found intracerebral inflammation with monocytes/macrophages, CD4 and CD8 positive T-lymphocytes, MHC-II expression and IL-1-beta expression. The inflammation was more pronounced in patients who underwent surgery on days three to five than in those operated on within 24 hours after the trauma. Since the findings in humans and rodents are similar, the results of our experiments may be applicable also to man. The present study demonstrates that a pathogenically important delayed intracerebral inflammatory reaction occurs following cerebral contusions. The maximal inflammatory response correlates in time with a delayed deterioration frequently seen in the first week after a contusion. The persisting inflammatory activation also makes long-term effects on CNS physiology possible. Pharmacological modulation of the inflammatory response may improve the outcome.
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| 9. |
- Jaff, Nasren, et al.
(författare)
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Transcriptomic analysis of the harvested endothelial cells in a swine model of mechanical thrombectomy
- 2018
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Ingår i: Neuroradiology. - : SPRINGER. - 0028-3940 .- 1432-1920. ; 60:7, s. 759-768
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Tidskriftsartikel (refereegranskat)abstract
- In mechanical thrombectomy (MT) for ischemic stroke, endothelial cells (ECs) from intracranial blood vessels adhere to the stent retriever device and can be harvested. However, understanding the molecular biology and the role of the endothelium in different pathological conditions remains insufficient. The purpose of the study was to characterize and analyze the molecular aspect of harvested ECs using cell culture and transcriptomic techniques in an MT swine model relevant to clinical ischemic stroke. In swine, preformed thrombi were injected into the external carotid and subclavian arteries to occlude their branches. MT was performed according to clinical routine. The stent retriever device and thrombus were treated with cell dissociation buffer. The resulting cell suspension was analyzed by immunohistochemistry and was cultured. Cultured cells were analyzed using single-cell RNA sequencing (scRNA-seq) after fluorescence-activated cell sorting (FACS). A total number of 37 samples were obtained containing CD31-positive cells. Cell culture was successful in 90% of samples, and the cells expressed multiple typical EC protein markers. Eighty-nine percent of the sorted cells yielded high-quality transcriptomes, and single-cell transcriptomes from cultured cells showed that they expressed typical endothelial gene patterns. Gene expression analysis of ECs from an occluded artery did not show distinctive clustering into subtypes. ECs harvested during MT can be cultured and analyzed using single-cell transcriptomic techniques. This analysis can be implemented in clinical practice to study the EC gene expression of comorbidities, such as hypertension, diabetes mellitus, and metabolic syndrome, in patients suffering from acute ischemic stroke.
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| 10. |
- Jonsson, Magnus, et al.
(författare)
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Carotid Endarterectomy After Intracranial Endovascular Thrombectomy for Acute Ischaemic Stroke in Patients with Carotid Artery Stenosis
- 2022
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier. - 1078-5884 .- 1532-2165. ; 63:3, s. 371-378
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Recent randomised controlled trials demonstrated the benefit of intracranial endovascular thrombectomy (EVT) in acute ischaemic stroke. There is no consensus, however, on how to treat concomitant extracranial carotid artery stenosis after EVT. The aim of this study was to evaluate the outcome in patients treated with carotid endarterectomy (CEA) after EVT, comparing complication rates among patients undergoing CEA for stroke without previous EVT.Methods: This was a registry study of all patients (n = 3 780) treated with CEA after stroke in Sweden and the capital Helsinki region, Finland, from January 2011 to September 2020. Sixty three patients (1.7%; 0.5% 2011, 4.3% 2019) underwent EVT prior to CEA. The primary outcome was 30 day stroke and death rate.Results: The EVT+CEA group had major stroke as the qualifying neurological event (QNE) in 79%, but just 5.9% had this in the CEA only group (p < .001). Intravenous thrombolysis was administered before EVT in 54% of patients in the EVT+CEA group, but in just 12% in those receiving CEA only (p < .001). The combined stroke and death rate at 30 days for EVT+CEA was 0.0% (95% confidence interval [CI] 0.0 - 5.7). One patient had a post-operative TIA, none had post-operative intracerebral or surgical site haemorrhage. CEA was performed within a median of seven days (interquartile range 4, 15) after QNE, and 75% had CEA <= 14 days from QNE. The main reason to postpone CEA was an infarct larger than one third of the middle cerebral artery territory. The stroke and death rate in patients treated with CEA only was 3.7% (95% CI 3.2 - 4.4), CEA was performed a median of eight days after QNE, and in 79.7% in <= 14 days. The three year survival after EVT+CEA was 93% (95% CI 85 - 100), compared with 87% (95% CI 86 - 88) after CEA only. Cox regression analysis adjusting for age showed no increased all cause mortality after EVT+CEA (HR 1.3, 95% CI 0.6 - 2.7, p = .52).Conclusion: These results indicate that CEA is safe to perform after previous successful EVT for acute ischaemic stroke. Results were comparable with those undergoing CEA only, despite the EVT+CEA patients having more severe stroke symptoms prior to surgery, and timing was similar.
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| 11. |
- Keselman, Boris, et al.
(författare)
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Analysis and modelling of mistriage in the Stockholm stroke triage system
- 2022
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Ingår i: European Stroke Journal. - : Sage Publications. - 2396-9873 .- 2396-9881. ; 7:2, s. 126-133
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The Stockholm Stroke Triage System (SSTS) is a prehospital triage system for detection of patients eligible for endovascular thrombectomy (EVT). Assessment of hemiparesis combined with ambulance-hospital teleconsultation is used to route patients directly to the thrombectomy centre. Some patients are not identified and require secondary transport for EVT (undertriage) while others taken to the thrombectomy centre do not undergo EVT (overtriage). The aims of this study were to characterize mistriaged patients, model for and evaluate alternative triage algorithms.Patients and methods: Patients with suspected stroke transported by priority 1 ground ambulance between October 2017 and October 2018 (n = 2905) were included. Three triage algorithms were modelled using prehospital data. Decision curve analysis was performed to calculate net benefit (correctly routing patients for EVT without increasing mistriage) of alternative models vs SSTS.Results: Undertriage for EVT occurred in n = 35/2582 (1.4%) and overtriage in n = 239/323 (74.0%). Compared to correct thrombectomy triages, undertriaged patients were younger and had lower median NIHSS (10 vs 18), despite 62.9% with an M1 occlusion. In overtriaged patients, 77.0% had a stroke diagnosis (29.7% haemorrhagic). Hemiparesis and FAST items face and speech were included in all models. Decision curve analysis showed highest net benefit for SSTS for EVT, but lower for large artery occlusion (LAO) stroke.Discussion: Undertriaged patients had lower NIHSS, likely due to better compensated proximal occlusions. SSTS was superior to other models for identifying EVT candidates, but lacked information allowing comparison to other prehospital scales.Conclusion: Using prehospital data, alternative models did not outperform the SSTS in finding EVT candidates.
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| 12. |
- Keselman, Boris, et al.
(författare)
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The Stockholm Stroke Triage Project : Outcomes of Endovascular Thrombectomy Before and After Triage Implementation
- 2022
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Ingår i: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 53:2, s. 473-481
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: The Stockholm Stroke Triage System (SSTS) is a prehospital algorithm for detection of endovascular thrombectomy (EVT)-eligible patients, combining symptom severity assessment and ambulance-to-hospital teleconsultation, leading to a decision on primary stroke center bypass. In the Stockholm Region (6 primary stroke centers, 1 EVT center), SSTS implementation in October 2017 reduced onset-to-EVT time by 69 minutes. We compared clinical outcomes before and after implementation of SSTS in an observational study.METHODS: We prospectively recruited patients transported by Code Stroke ambulance within the Stockholm region under the SSTS, treated with EVT during October 2017 to October 2019, and compared to EVT patients from 2 previous years.OUTCOMES: shift in modified Rankin Scale (mRS) scores, mRS score 0 to 1, mRS score 0 to 2, and death (all 3 months), National Institutes of Health Stroke Scale (NIHSS) score change 24-hour post-EVT, recanalization (Thrombolysis in Cerebral Infarction 2b-3), and symptomatic intracranial hemorrhage. mRS outcomes were adjusted for age and baseline NIHSS.RESULTS: Patients with EVT in the SSTS group (n=244) were older and had higher baseline NIHSS versus historical controls (n=187): median age 74 (interquartile range, 63-81) versus 71 (61-78); NIHSS score 17 (11.5-21) versus 15 (10-20). During SSTS, median onset-to-puncture time was 136 versus 205 minutes (P<0.001). Adjusted common odds ratio for lower mRS in SSTS patients was 1.7 (95% CI, 1.2-2.3) versus controls. During SSTS, 83/240 (34.6%) versus 44/186 (23.7%) reached 3-month mRS score 0 to 1 (P=0.014), adjusted common odds ratio 2.3 (95% CI, 1.4-3.6). Median NIHSS change 24-hour post-EVT was 6 versus 4 (P=0.005). Differences in Thrombolysis in Cerebral Infarction, symptomatic intracranial hemorrhage, and death were nonsignificant.CONCLUSIONS: With an onset to arterial puncture time reduction by 69 minutes, outcomes in thrombectomy-treated patients improved significantly after region-wide large artery occlusion triage system implementation. These results warrant replication studies in other geographic and organizational circumstances.
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| 13. |
- Kong, Wan-Yee, et al.
(författare)
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Validation of Serial Alberta Stroke Program Early CT Score as an Outcome Predictor in Thrombolyzed Stroke Patients.
- 2017
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Ingår i: Journal of Stroke & Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057 .- 1532-8511. ; 26:10, s. 2264-2271
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Alberta Stroke Program Early CT Score (ASPECTS) on baseline imaging is an established predictor of functional outcome in anterior circulation acute ischemic stroke (AIS). We studied ASPECTS before intravenous thrombolysis (IVT) and at 24 hours to assess its prognostic value.METHODS: Data for consecutive anterior circulation AIS patients treated with IVT from 2006 to 2013 were extracted from a prospectively managed registry at our tertiary center. Pre-thrombolysis and 24-hour ASPECTS were evaluated by 2 independent neuroradiologists. Outcome measures included symptomatic intracranial hemorrhage (SICH), modified Rankin Scale (mRS) at 90 days, and mortality. Unfavorable functional outcome was defined by mRS >1. Dramatic ASPECTS progression (DAP) was defined as deterioration in ASPECTS by 6 points or more.RESULTS: Of 554 AIS patients thrombolyzed during the study period, 400 suffered from anterior circulation infarction. The median age was 65 years (interquartile range (IQR): 59-70) and the median National Institutes of Health Stroke Scale score was 18 points (IQR: 12-22). Compared with the pre-IVT ASPECTS (area under the curve [AUC] = .64, 95% confidence interval [CI]: .54-.65, P = .001), ASPECTS on the 24-hour CT scan (AUC = .78, 95% CI: .73-.82, P < .001), and change in ASPECTS (AUC = .69, 95% CI: .64-.74, P < .001) were better predictors of unfavorable functional outcome at 3 months. DAP, noted in 34 (14.4%) patients with good baseline ASPECTS (8-10 points), was significantly associated with unfavorable functional outcome (odds ratio [OR]: 9.91, 95% CI: 3.37-29.19, P ≤ .001), mortality (OR: 21.99, 95% CI: 7.98-60.58, P < .001), and SICH (OR: 8.57, 95% CI: 2.87-25.59, P < .001).CONCLUSION: Compared with the pre-thrombolysis score, ASPECTS measured at 24 hours as well as serial change in ASPECTS is a better predictor of 3-month functional outcome.
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| 14. |
- Lundberg, Johan, et al.
(författare)
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Access to the brain parenchyma using endovascular techniques and a micro-working channel
- 2017
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Ingår i: Journal of Neurosurgery. - 0022-3085 .- 1933-0693. ; 126:2, s. 511-517
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Several older studies report a low risk for parenchymal access to the CNS by surgical techniques. In more recent studies, including those with post-puncture CT scans, there are indications that the risk of bleeding might approach 8%. New therapies, such as those that use viral vectors, modified mRNA, or cell transplantation, will probably warrant more parenchymal access to the CNS. Other minimally invasive routes might then be tempting to explore. This study was designed in 2 parts to address the possibility of using the endovascular route. The first aim was to test the ability to create a parenchymal micro-working channel to the CNS in macaque monkeys through the vessel wall. Second, the biocompatibility of a device-associated, detached, distal securing plug that was made of nitinol was investigated in swine for 1 year. METHODS Trans-vessel wall intervention in the middle cerebral artery and associated cerebral parenchyma was performed in 4 rhesus macaque monkeys using a full clinical angiography suite. A contrast agent and methylene blue were injected to test the working channel and then detached at the distal end to act as a securing plug through the vessel wall. One-year follow-ups were also performed using angiography and histological analysis in 10 swine with 24 implants that were distributed in the external carotid artery tree. RESULTS The cerebral interventions were performed without acute bleeding. Both the contrast agent and methylene blue were infused into the brain parenchyma and subarachnoidal space via the endovascular micro-working channel (7 injections in 4 animals). In the 1-year follow-up period, the implant that was left in the external carotid vessel wall in the swine was covered by the endothelium, which was followed by dislodgement just outside the blood vessel with thin capsule formation. No stenosis in the artery was detected on 1-year angiography. The animals showed normal behavior and blood sample results during the follow-up period. This is the first histological demonstration of nitinol biocompatibility when the implant is positioned through an arterial wall and indicates that the trans-vessel wall technique is not comparable with stent placement and its ability to induce intimal hyperplasia and restenosis. CONCLUSIONS This study demonstrates that the trans-vessel wall technique is applicable to brain intervention in macaque monkeys, providing a micro-working channel for delivery or sampling. The long-term follow-up study of the detached device in swine showed no clinical or biochemical complications and a normal angiography appearance.
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| 15. |
- Lundberg, Johan, et al.
(författare)
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Long Term Follow-Up of the Endovascular Trans-Vessel Wall Technique for Parenchymal Access in Rabbit with Full Clinical Integration
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:8, s. e23328-
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Endovascular techniques are providing options to surgical/percutaneous cell transplantation methods. Some cells, e. g. insulin producing cells, are not suitable for intra-luminal transplantation and for such cells, other options must be found. We have constructed a "nanocatheter'' with a penetrating tip for vessel perforation, thereby creating a working channel for parenchymal access by endovascular technique. To finish the procedure safely, the distal tip is detached to provide a securing plug in the vessel wall defect. Materials and Methods: We have performed interventions with full clinical integration in the superior mesenteric artery (SMA), the subclavian artery and the external carotid artery in rabbits. No hemorrhagic-or thromboembolic events occurred during the procedure. Stenosis formation and distal embolisation were analyzed by angiography and macroscopic inspection during autopsy at five, 30 and 80 days. All animals and implanted devices were also evaluated by micro-dissections and histochemical analysis. Results: In this study we show safety data on the trans-vessel wall technique by behavioral, angiographical and histological analysis. No stenosis formation was observed at any of the follow-up time points. No animals or organs have shown any signs of distress due to the intervention. Histological examination showed no signs of hemorrhage, excellent biocompatibility with no inflammation and a very limited fibrous capsule formation around the device, comparable to titanium implants. Further, no histological changes were detected in the endothelia of the vessels subject to intervention. Conclusions: The trans-vessel wall technique can be applied for e. g. cell transplantations, local substance administration and tissue sampling with low risk for complications during the procedure and low risk for hemorrhage, stenosis development or adverse tissue reactions with an 80 days follow-up time. The benefit should be greatest in organs that are difficult or risky to reach with surgical techniques, such as the pancreas, the CNS and the heart.
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| 16. |
- Lundberg, Johan, et al.
(författare)
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New Endovascular Method for Transvascular Exit of Arteries and Veins : Developed in Simulator, in Rat and in Rabbit with Full Clinical Integration
- 2010
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:5, s. e10449-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Endovascular technique has benefits vis-a-vis surgical access to organs with less accessible anatomical locations. To minimize surgical risk we propose a novel endovascular technique, to create parenchymal access through endovascular methods. Methodology/Principal Findings: We have developed, manufactured and tested an endovascular catheter with a depth limiting collar and a penetrating tip that is used to perforate vessels, thereby creating a working channel to the extravascular space. Computer simulations and subsequent interventions have been performed ex vivo and in vivo in both small and large animals by testing different prototypes. All tests were designed for testing extravascular hemostasis and absence of thrombo-embolic complications when exiting the vessels from the inside to the extra vascular space. We have deposited prototypes after intervention in vascular walls over a period of 14 days in rat with no impairment on blood flow and no signs of thrombo-embolic complications upon re-exploration (n = 7). We have also incorporated the catheter system with clinically available systems both in an ex vivo simulator setting and in a full scale clinical angiographical setting in rabbit were no bleeding (0%) in any of the interventions performed (n = 40). To prevent hemorrhage during termination of the procedure, a hollow electrolysis detachment-zone leaves the distal tip in the vessel-wall after the intervention. This has also been tested with absolute hemostasis in large animals (n = 6). Conclusions/Significance: We have developed and tested a new system for transvascular tissue access in simulations, ex vivo and in vivo in small and large animals, integrating it with standard clinical catheters and angiographical environment, with absolute hemostasis and without thromboembolic complications. In a clinical setting for stem cell transplantation, local substance administration or tissue sampling, the benefit should be greatest in organs that are difficult or high-risk to access with other techniques, such as the pancreas, the central nervous system (CNS) and the heart.
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| 17. |
- Mazya, Michael V., et al.
(författare)
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Implementation of a Prehospital Stroke Triage System Using Symptom Severity and Teleconsultation in the Stockholm Stroke Triage Study
- 2020
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Ingår i: JAMA Neurology. - : American Mathematical Society (AMS). - 2168-6149 .- 2168-6157. ; 77:6, s. 691-699
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Tidskriftsartikel (refereegranskat)abstract
- Importance: To our knowledge, it is unknown whether a prehospital stroke triage system combining symptom severity and teleconsultation could accurately select patients for primary stroke center bypass and hasten delivery of endovascular thrombectomy (EVT) without delaying intravenous thrombolysis (IVT).Objective: To evaluate the predictive performance of the newly implemented Stockholm Stroke Triage System (SSTS) for large-artery occlusion (LAO) stroke and EVT initiation. Secondary objectives included evaluating whether the Stockholm Stroke Triage System shortened onset-to-puncture time for EVT and onset-to-needle time (ONT) for IVT.Design, Setting, and Participants: This population-based prospective cohort study conducted from October 2017 to October 2018 across the Stockholm region (Sweden) included patients transported by first-priority ("code stroke") ambulance to the hospital for acute stroke suspected by an ambulance nurse and historical controls (October 2016-October 2017). Exclusion criteria were in-hospital stroke and helicopter or private transport. Of 2909 eligible patients, 4 (0.14%) declined participation.Exposures: Patients were assessed by ambulance nurses with positive the face-arm-speech-time test or other stroke suspicion and were evaluated for moderate-to-severe hemiparesis (≥2 National Institutes of Health stroke scale points each on the ipsilateral arm and leg [A2L2 test]). If present, the comprehensive stroke center (CSC) stroke physician was teleconsulted by phone for confirmation of stroke suspicion, assessment of EVT eligibility, and direction to CSC or the nearest primary stroke center. If absent, the nearest hospital was prenotified.Main Outcomes and Measures: Primary outcome: LAO stroke. Secondary outcomes: EVT initiation, onset-to-puncture time, and ONT. Predictive performance measures included sensitivity, specificity, positive and negative predictive values, the overall accuracy for LAO stroke, and EVT initiation.Results: We recorded 2905 patients with code-stroke transports (1420 women [49%]), and of these, 323 (11%) had A2L2+ teleconsultation positive results and were triaged for direct transport to CSC (median age, 73 years [interquartile range (IQR), 64-82 years]; 55 women [48%]). Accuracy for LAO stroke was 87% (positive predictive value, 41%; negative predictive value, 93%) and 91% for EVT initiation (positive predictive value, 26%; negative predictive value, 99%). Endovascular thrombectomy was performed for 84 of 323 patients (26%) with triage-positive results and 35 of 2582 patients (1.4%) with triage-negative results. In EVT cases with a known onset time (77 [3%]), the median OPT was 137 minutes (IQR, 118-180; previous year, 206 minutes [IQR, 160-280]; n = 75) (P < .001). The regional median ONT (337 [12%]) was unchanged at 115 minutes (IQR, 83-164; previous year, 115 minutes [IQR, 85-161]; n = 360) (P = .79). The median CSC IVT door-to-needle time was 13 minutes (IQR, 10-18; 116 [4%]) (previous year, 31 minutes [IQR, 19-38]; n = 45) (P < .001).Conclusions and Relevance: The Stockholm Stroke Triage System, which combines symptom severity and teleconsultation, results in markedly faster EVT delivery without delaying IVT.
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| 18. |
- Sandell, Mikael, et al.
(författare)
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3 D-printed micrograters for sampling of the blood vessel wall
- 2021
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Ingår i: 2021 34th IEEE international conference on micro electro mechanical systems (MEMS 2021). - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 548-550
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Konferensbidrag (refereegranskat)abstract
- Endothelial cells lining blood vessels have phenotypic variations that indicate the health/disease status for a variety of conditions, including atherosclerosis and hypertension. Current sampling strategies lead to a high variation in the sampled amount, and we are not aware of sampling tools specifically targeting endothelial cells. Here, we present a new type of endovascular catheter for sampling of the blood vessel wall. The catheter is a 380 mu m nitinol tube over which 3D printed graters are threaded. The catheter is designed to be non-invasive during the axial motion and to interact with the blood vessel wall when rotated. Initial results indicate successful in-vivo sampling - with minimal blood contamination - of the wall of blood vessels less than 0.5 mm in diameter.
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| 19. |
- Sandell, Mikael, et al.
(författare)
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A novel noble metal stent coating reduces in vitro platelet activation and acute in vivo thrombosis formation : a blinded study
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Inherent to any stenting procedure is the prescription of dual antiplatelet therapy (DAPT) to reduce the platelet response. Clinical guidelines recommend 6 - 12 months of DAPT, depending on stent type, clinical picture and patient factors. Our hypothesis is that a nanostructured noble metal coating has the potential to reduce protein deposition and platelet activation, which in turn could reduce the need for DAPT. Here, a noble metal nanostructure coating on stents is investigated. Twelve pigs underwent endovascular implantation of coated and non-coated stents for paired comparisons in a double-blinded study design. The non-coated control stent was placed at the contralateral corresponding artery. Volumetric analysis of angiographic data, performed by a treatment blinded assessor, demonstrated a significant thrombus reduction for one of the coatings compared to control. This effect was already seen one hour after implantation. This finding was supported by in vitro data showing a significant reduction of coagulation activation in the coated group. This novel coating shows promise as an implant material addition and could potentially decrease the need for DAPT in the acute clinical setting.
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| 20. |
- Sandell, Mikael, et al.
(författare)
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A novel noble metal stent coating reduces in vitro platelet activation and acute in vivo thrombosis formation : a blinded study
- 2023
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Inherent to any stenting procedure is the prescription of dual antiplatelet therapy (DAPT) to reduce the platelet response. Clinical guidelines recommend 6–12 months of DAPT, depending on stent type, clinical picture and patient factors. Our hypothesis is that a nanostructured noble metal coating has the potential to reduce protein deposition and platelet activation. These effects would reduce subsequent thrombo-inflammatory reactions, potentially mitigating the need for an extensive DAPT in the acute phase. Here, a noble metal nanostructure coating on stents is investigated. Twelve pigs underwent endovascular implantation of coated and non-coated stents for paired comparisons in a blinded study design. The non-coated control stent was placed at the contralateral corresponding artery. Volumetric analysis of angiographic data, performed by a treatment blinded assessor, demonstrated a significant thrombus reduction for one of the coatings compared to control. This effect was already seen one hour after implantation. This finding was supported by in vitro data showing a significant reduction of coagulation activation in the coated group. This novel coating shows promise as an implant material addition and could potentially decrease the need for DAPT in the early phases of stent implementation.
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| 21. |
- Sandell, Mikael, et al.
(författare)
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An Ultraminiaturized MEMS Microbiopsy Tool for Trans Blood Vessel Wall Biopsies
- 2020
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Ingår i: Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS). - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 10-12
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Konferensbidrag (refereegranskat)abstract
- We present a new type of microbiopsy tool (MBT) an order of magnitude smaller than commercially available biopsy catheters that, together with a trans-vessel wall catheter (Extroducer) successfully samples soft tissues with significantly less trauma to the tissue than commercial catheters. The MBT is mounted on a Nitinol wire. It features a gripping action that is actuated by the relative motion inside the Extroducer and has demonstrated repeated successful tissue sampling of approximately 500-1000 cells in ex-vivo tissue. This new catheter system can potentially allow super-selective, minimally invasive tissue sampling and transcriptomic analysis from hard to reach areas.
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| 22. |
- Sandell, Mikael, et al.
(författare)
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Endovascular Device for Endothelial Cell Sampling
- 2022
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Ingår i: Advanced NanoBiomed Research. - : Wiley. - 2699-9307 .- 2699-9307. ; 2:10, s. 2200023-2200023
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Tidskriftsartikel (refereegranskat)abstract
- Endothelial cells play an important role in several vascular diseases, and molecular analysis of these cells could provide valuable information on underlying tissue status. However, no clinically established procedure for harvesting endothelial cells exists. A micro-3D-printed device adapted for endovascular techniques to harvest endothelial cells for transcriptomic analysis is presented. In vivo evaluation in swine (n = 6) yielded tissue samples in 60 out of 65 cases, of which 80% show a substantial amount of tissue. The cytological evaluation indicates high selectivity towards endothelial cells, and RNA-sequencing shows gene expression signatures consistent with vascular tissue. It is found that there are no short-term safety risks compared to operation with a control wire of equal dimensions and acute complications are not detected. If translated to clinical use, the device could enable increased understanding of early-stage endothelial cell-mediated disease progression and earlier diagnosis of diseases such as atherosclerosis.
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| 23. |
- Sandell, Mikael, et al.
(författare)
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Hydraulic micropistons enable high-force operations through miniaturized catheters
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective: As catheter sizes decrease, traditional navigation techniques for endovascular catheter-based devices within small working channels may fail due to mechanical scaling laws. This study evaluates a novel solution employing micropistons mounted on an intraluminal device in a miniaturized catheter to increase force generation at the distal end. Methods: The force exerted by a wire at the distal end of a catheter was measured under various degrees of bending and in an artificial vascular path. Our micropiston solution was benchmarked against conventional flushing techniques and manual pushing. Results: Incorporating micropistons to the internal wire consistently increased the generated force across all measured instances. This effect was more pronounced at higher degrees of bending, where manual pushing was deemed unfeasible. Conclusion: Our findings demonstrate that micropistons can effectively augment the delivery and operation of small wires, potentially overcoming the problems associated with extremely downscaled intraluminal devices. Significance: This advancement may enable the use of catheter systems much smaller than what is currently used.
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| 24. |
- Sandell, Mikael
(författare)
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Minimally Invasive Catheter-Based Technologies
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A simple incision procedure in a blood vessel makes the entire vascular system accessible. Through contrast injection and X-ray visualization, the vascular tree can be mapped and navigated through manual manipulation of thin tubes and wires. This utilization of the vasculature as internal pathways is commonly referred to as the endovascular technique. This technique can be used to deliver implants and drugs, retrieve problematic lesions or objects from the vasculature, or take tissue samples. Compared to open surgery, the advantage of this technique lies in the reduced invasiveness, ideally only leaving a small incision scar at the point of entry. Some interventions, however, are still associated with certain risks, requiring medication or complicating further interventions. The development of sequencing technologies presents an opportunity to improve and miniaturize devices, reducing invasiveness. This thesis aims to mitigate these risks and capitalize on the potential of next generation sequencing through microfabrication technologies, producing devices that are less invasive than current methods or that enable a new procedure.Initially, the aspect of endovascular heart biopsy is covered. The first work presents the fabrication and in vivo evaluation of a nitinol-based catheter device designed for extracting myocardial tissue. The device is fabricated through picosecond laser machining of nitinol tubes and wires, producing a device that is substantially smaller than what is currently used. The samples are evaluated and compared to samples extracted with conventional devices through RNA-Sequencing, verifying the proof of concept. The second work further emphasizes the device's functionality by evaluating it in a disease model of endomyocardial infarction. Tissue that is affected by the infarct and surrounding healthy tissue is extracted and compared in terms of its genetic expression. This comparison reveals a genetic discrepancy between the sick and healthy tissue, verifying the potential of using the device with RNA-sequencing for diagnostic purposes. The third work evaluates the safety aspects of the novel device in a head-to-head comparison with a conventional device. The study reveals a clear benefit of using the smaller device in terms of the complication rate during the procedure.The fourth work presents the fabrication and in vivo evaluation of another nitinol based catheter device designed for endothelial cell sampling. The device is fabricated through two-photon polymerization technologies, producing sub-mm brush structures mounted on a nitinol wire. Currently, there are no devices in clinical use that are capable of exclusively extracting endothelial cells. The novel device presents a solution for selective interaction with the innermost layer of the blood vessel. It represents an important step toward sampling endothelial cells for diagnostic and research purposes.The fifth and sixth works collectively present two different aspects of a third nitinol based catheter device designed to sample tissue from soft organs anywhere in the body. The device is fabricated using laser micromachining, grinding, and two-photon polymerization. The work is separated in terms of the in vivo evaluation and the technical solution. The technical aspects of the device are examined in terms of force generation in miniaturized catheter systems and the problems that arise in terms of mechanical scaling. These problems are solved by attaching pistons along the wire surface coupled with applied pressure to increase the force generated. The sampling with this device is realized, similar to the fourth work, with sub-mm brushes mountedon the wire. In vivo evaluation of this device reveals successful sampling of minute tissue quantities from the liver and kidney, in the size range of 10-100 cells per sample.The seventh work presents the in vivo and in vitro performance of a nanostructure coating on nitinol-based stents. Patients with a stent implant are prescribed an extensive medication regimen to counteract the metal implant's effects on the blood and surrounding tissue. This issue is being continuously targeted by new stent platforms, either with a drug-eluting polymer layer or by being resorbable by the body or through various other means. These implants all have a transient behavior, resulting in different issues over time. Paper VII presents an alternative approach to this problem by instead applying a nanostructure coating that is designed to interact with the blood to a much lesser degree, as demonstrated by CT-angiography and the measurement of multiple biomarkers.
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| 25. |
- Sandell, Mikael, et al.
(författare)
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Sampling through a transvascular working channel
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Endovascular biopsies are widely utilized for many organs, either as standard practice or when there are contraindications to the percutaneous route. Depending on the target site, currently used devices for sampling through the endovascular route is either not possible to use, such as in the brain, or present certain risks due to their size, such as in the heart or liver. A recent development in catheter technology has opened up new possibilities for parenchymal access through a microscopic working channel. Through this method essentially all organs can be accessed safely without causing hemorrhagic complications. Here, an endovascular sampling device designed to be used through this channel is presented. The device contains 3D-printed brush structures and is tested in the liver and kidney. Cytological data reveals the presence of the tissue in question.
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| 26. |
- Yeo, Leonard L L, et al.
(författare)
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Nongated Cardiac Computed Tomographic Angiograms for Detection of Embolic Sources in Acute Ischemic Stroke
- 2017
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 48:5, s. 1256-1261
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: axis coverage of a non-ECG-gated computed tomographic angiogram performed in the primary evaluation of acute stroke without increasing the contrast dose.METHODS: Twenty consecutive patients with acute ischemic stroke within the 4.5 hours of symptom onset were prospectively recruited. We increased the longitudinal coverage to the domes of the diaphragm to include the heart. Contrast administration (Omnipaque 350) remained unchanged (injected at 3-4 mL/s; total 60-80 mL, triggered by bolus tracking). Images of the heart and aorta, reconstructed at 5 mm slice thickness in 3 orthogonal planes, were read by a radiologist and cardiologist, findings conveyed to the treating neurologist, and correlated with the transthoracic or transesophageal echocardiogram performed within the next 24 hours.RESULTS: Of 20 patients studied, 3 (15%) had abnormal findings: a left ventricular thrombus, a Stanford type A aortic dissection, and a thrombus of the left atrial appendage. Both thrombi were confirmed by transesophageal echocardiography, and anticoagulation was started urgently the following day. None of the patients developed contrast-induced nephropathy on follow-up. The radiation dose was slightly increased from a mean of 4.26 mSV (range, 3.88-4.70 mSV) to 5.17 (range, 3.95 to 6.25 mSV).CONCLUSIONS: Including the heart and ascending aorta in a routine non-ECG-gated computed tomographic angiogram enhances an existing imaging modality, with no increased incidence of contrast-induced nephropathy and minimal increase in radiation dose. This may help in the detection of high-risk cardiac and aortic sources of embolism in acute stroke patients.
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