| 1. |
- Arnberg, Fabian
(författare)
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Cerebral blood flow and glucose metabolism in ischemic stroke : multimodal imaging investigations in a clinically relevant rat model
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ischemic stroke is one of the leading causes of death worldwide. Ischemic stroke is also a major cause of long-term disability with vast socioeconomic results for patients, their relatives and health services. Over the last decades, experimental research has resulted in significant progress of our understanding of mechanisms leading to brain injury after ischemic stroke. However, so far, translational research targeting these mechanisms has failed. This failure has resulted in a general consensus that a more integrative approach is needed to account for not only neurobiology under ischemia, but also the ischemic impact on the neurovascular interface. Accordingly, new tools for simultaneously imaging and perturbing this interface needs to be established. The aims of the present work were firstly to develop an ischemic stroke model in rats that more closely mimics human stroke. Secondly, our goal was to incorporate the model with perfusion- and metabolic imaging using high-field magnetic resonance imaging (HF-MRI) and positron emission tomography (PET). Finally we wanted to apply the model in a treatment study targeting the neurovascular interface, and use HF-MRI and PET to assess treatment outcome. We translated endovascular techniques from bedside to bench in the interest of realizing a new rat model for focal cerebral ischemia, in which a microwire is navigated under X-ray fluoroscopy to an occluding position in the middle cerebral artery (MCA). Furthermore, we were able to use the endovascular technique to facilitate intra-arterial microcatheter access to the cerebrovascular system in the rat accommodating injections with varying degree of selectivity. Next, we established protocols for HF-MRI and PET to obtain imaging of pathophysiological events following acute and subacute ischemic stroke. Finally we applied the aforementioned techniques in a treatment study targeting vascular endothelial growth factor B (VEGF-B) in ischemic stroke. We found that the translation of clinical endovascular techniques to the experimental setting opened up several possibilities to access and perturb the neurovascular interface. In comparison with earlier models for focal stroke in the rat, the model for ischemic stroke presented in Paper I produces an injury and pathophysiology more resembling human stroke. Furthermore, the model showed to be highly compatible with small animal imaging systems with the possibility to occlude the MCA and to inject substances directly to the cerebrovascular supply before, during and after imaging (Paper II). The model also makes it possible to control blood flow during scanning with various modalities. HF-MRI and [2-18F]-2-Fluoro-2-deoxy-D-glucose PET investigations of acute ischemia in Paper III provided evidence for hypermetabolism of glucose occurring in parallel with diffusion restriction of brain water, suggesting an extension of the current paradigm of the mechanisms behind infarct-related diffusion restriction of water. In Paper IV, we found that VEGF-B antagonism result in a reduction of stroke volume, indicating a mechanism of action of VEGF-B in ischemic stroke warranting further treatment studies targeting VEGF-B in ischemic stroke.
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| 2. |
- 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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| 3. |
- El-Hajj, Victor Gabriel, et al.
(författare)
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The negative impact of treatment delays on the long-term neurological outcomes of spinal dural arteriovenous fistulas : a longitudinal cohort study
- 2024
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Ingår i: Neurosurgical Focus. - : American Association of Neurological Surgeons. - 1092-0684. ; 56:3
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Dural arteriovenous fistulas are rare vascular malformations that affect the brain and spinal cord. Spinal dural arteriovenous fistulas (sdAVFs) are the most frequently encountered vascular malformation affecting the spinal cord. The object of this study was to evaluate the impact of treatment delays on the long-term neurological outcomes of either open surgical or interventional treatment of sdAVFs.METHODS: In this retrospective, population-based cohort study, the authors examined consecutive patients with diagnosed sdAVFs at a tertiary care center between 2005 and 2020. Patients were assessed using the Aminoff-Logue disability scale (ALS) at various time points including symptom onset, primary care visit, first specialist outpatient visit, as well as both short and long-term follow-ups. The postoperative long-term ALS gait and bladder grades constituted the primary outcomes of the study.RESULTS: Among the 34 patients included in the study, the median age was 65 years, and there was a male predominance (71%). Most lesions were in the lumbar region (47%). Significant worsening in ALS gait and bladder grades was observed preoperatively, followed by postoperative improvements (p < 0.05). There was no difference in outcomes between surgical and endovascular treatments. Older age (OR 1.10, 95% CI 1.03-1.17, p = 0.007), worse preoperative ALS gait grades (OR 5.12, 95% CI 2.18-12.4, p < 0.001), and longer time from first specialist outpatient visit to first treatment (OR 1.00, 95% CI 1.00-1.01, p = 0.040) were independently associated with worse long-term gait outcomes. Only the preoperative ALS bladder score was a predictor of worse long-term bladder function (OR 92.7, 95% CI 28.0-306.7, p < 0.001).CONCLUSIONS: Both surgical and endovascular treatments for sdAVFs led to significant neurological improvements. However, treatment delays were associated with less favorable long-term outcomes. Prompt diagnosis and early intervention prior to symptom progression may enhance recovery and help to preserve neurological function.
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| 4. |
- El-Hajj, Victor Gabriel, et al.
(författare)
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The negative impact of treatment delays on the long-term neurological outcomes of spinal dural arteriovenous fistulas : a longitudinal cohort study
- 2024
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Ingår i: Neurosurgical Focus. - : American Association of Neurological Surgeons. - 1092-0684. ; 56:3
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Dural arteriovenous fistulas are rare vascular malformations that affect the brain and spinal cord. Spinal dural arteriovenous fistulas (sdAVFs) are the most frequently encountered vascular malformation affecting the spinal cord. The object of this study was to evaluate the impact of treatment delays on the long-term neurological outcomes of either open surgical or interventional treatment of sdAVFs.METHODS In this retrospective, population-based cohort study, the authors examined consecutive patients with diagnosed sdAVFs at a tertiary care center between 2005 and 2020. Patients were assessed using the Aminoff-Logue disability scale (ALS) at various time points including symptom onset, primary care visit, first specialist outpatient visit, as well as both short and long-term follow-ups. The postoperative long-term ALS gait and bladder grades constituted the primary outcomes of the study.RESULTS Among the 34 patients included in the study, the median age was 65 years, and there was a male predominance (71%). Most lesions were in the lumbar region (47%). Significant worsening in ALS gait and bladder grades was observed preoperatively, followed by postoperative improvements (p < 0.05). There was no difference in outcomes between surgical and endovascular treatments. Older age (OR 1.10, 95% CI 1.03-1.17, p = 0.007), worse preoperative ALS gait grades (OR 5.12, 95% CI 2.18-12.4, p < 0.001), and longer time from first specialist outpatient visit to first treatment (OR 1.00, 95% CI 1.00-1.01, p = 0.040) were independently associated with worse long-term gait outcomes. Only the preoperative ALS bladder score was a predictor of worse long-term bladder function (OR 92.7, 95% CI 28.0-306.7, p < 0.001).CONCLUSIONS Both surgical and endovascular treatments for sdAVFs led to significant neurological improvements. However, treatment delays were associated with less favorable long-term outcomes. Prompt diagnosis and early intervention prior to symptom progression may enhance recovery and help to preserve neurological function.
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| 5. |
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| 6. |
- 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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| 7. |
- Nilsson, Inga-Lena, et al.
(författare)
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Thyroid incidentaloma detected by fluorodeoxyglucose positron emission tomography/computed tomography : practical management algorithm
- 2011
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Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 35:12, s. 2691-2697
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundOur aim was to design a practical algorithm for management of an increasing number of incidental findings of thyroid lesions identified by 18F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT).MethodsThe reports of 3641 patients examined by FDG-PET/CT for evaluation of nonthyroid cancer were reviewed. The anatomic locations and standardized uptake values (SUV) of any focally increased thyroid FDG uptake were reanalyzed and related to surrounding normal thyroid (TSUVmax/thySUVmean ratio) and liver (TSUVmax/liverSUVmean).ResultsFocal FDG uptakes in the thyroid were reported in 37 cases (1%; 26 women). Neoplastic thyroid lesions were diagnosed in 16 patients: papillary thyroid cancer in 9, follicular neoplasia in 5, and metastatic lesions (lung cancer and squamous cell carcinoma) in 2. Benign lesions were diagnosed in 11 patients. Ten patients with malignancy elsewhere did not undergo thyroid examination. In all, 11 patients underwent thyroid surgery (8 with papillary cancer, 3 with follicular adenoma); the median tumor size was 12 mm (8–40 mm). The TSUVmax/thySUVmean ratio was higher for the malignant lesions [median 5.53 (2.75–30.81) vs. 3.70 (1.82–31.70); P < 0.05], albeit with a considerable overlap between individual patients. The TSUVmax and TSUVmax/liverSUVmean did not differ between groups. The TSUVmax/thySUVmean and / thySUVmean ratios correlated with the tumor size (r = 0.64 and r = 0.66; P < 0.05).ConclusionsAn incidental finding of focal uptake of FDG in the thyroid is associated with a significant risk of thyroid cancer. If the patient would benefit from thyroidectomy if a malignancy were identified, further diagnostic workup with ultrasonography-guided fine-needle aspiration and cytology is recommended.
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| 8. |
- Ullberg, Teresa, et al.
(författare)
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Endovascular thrombectomy for anterior circulation stroke beyond 6 hours of onset in Sweden 2015 to 2020 : rates and outcomes in a nationwide register-based study
- 2023
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Ingår i: Journal of neurointerventional surgery. - : BMJ Publishing Group Ltd. - 1759-8486 .- 1759-8478. ; 15:4, s. 330-335
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Endovascular thrombectomy (EVT) for ischemic stroke (IS) beyond 6 hours has been proven effective in randomized controlled trials. We present data on implementation and outcomes for EVT beyond 6 hours in Sweden.METHODS: We included all cases of anterior circulation IS caused by occlusion of the intracranial carotid artery, and the M1 or M2 segment of the middle cerebral artery, registered in two nationwide quality registers for stroke in 2015-2020. Three groups were defined from onset-to-groin-puncture (OTG) time: early window (<6 hours), late window (6-24 hours) known onset, late window last seen well (LSW). Favorable outcome (modified Rankin Scale (mRS) 0-2) and all-cause mortality at 90 days were the main outcomes, and symptomatic intracerebral hemorrhage (sICH) was the safety outcome.RESULTS: Late window EVT increased from 0.3% of all IS in 2015 to 1.8% in 2020, and from 17.4% of all anterior circulation EVTs in 2015 to 32.9% in 2020. Of 2199 patients, 76.9% (n=1690) were early window EVTs and 23.1% late window EVTs (n=509; 141 known onset, 368 LSW). Median age was 73 years, and 46.2% were female, with no differences between groups. Favorable outcome did not differ between groups (early window 42.4%, late window known onset 38.9%, late window LSW 37.3% (p=0.737)) and remained similar when adjusted for baseline differences. sICH rates did not differ (early window 4.0%, late window known onset 2.1%, late window LSW 4.9% (p=0.413)).CONCLUSION: Late window EVTs have increased substantially over time, and currently account for one third of anterior circulation treatments. Early and late window patients had similar outcomes.
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| 9. |
- Ullberg, Teresa, et al.
(författare)
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Survival and functional outcome following endovascular thrombectomy for anterior circulation acute ischemic stroke caused by large vessel occlusion in Sweden 2017-2019-a nationwide, prospective, observational study
- 2023
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Ingår i: Interventional Neuroradiology. - : Edizioni del Centauro. - 1591-0199 .- 2385-2011 .- 1123-9344. ; 29:1, s. 94-101
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Endovascular thrombectomy (EVT) is standard of care for anterior circulation acute ischemic stroke (AIS) caused by large vessel occlusion (LVO), but data on nationwide performance in routine healthcare are sparse. The study aims were to describe EVT patients with LVO AIS, analyze mortality and functional outcome, and compare results with randomized controlled trials (RCTs).METHODS: Data from the Riksstroke and the Swedish Endovascular Treatment of Acute Stroke Registry (RSEVAS) on pre-stroke independent patients, with LVO AIS in 2017-2019, defined as occlusion of the intracranial internal carotid artery, or the M1 or M2 segments of the middle cerebral artery, and groin puncture <6 h of onset, were compared to aggregated HERMES collaboration RCT data. We assessed 90-day survival and function, defined by the modified Rankin Scale. Specific analyzes were stratified by occlusion location.RESULTS: In all, 1011/2560 of RSEVAS patients matched RCT inclusion criteria. Compared with RCT data, patients were older (73 vs. 68), fewer received intravenous thrombolysis (63.1% vs. 83%), and M2 occlusions were more common (24.5% vs. 8%). 90-day survival in RSEVAS was 85.3%, 42.8% achieved good outcome and 5% had symptomatic intracerebral hemorrhage (sICH). Corresponding outcomes in RCT data were 84.7% survival, 46% good outcome, and 4.4% sICH. Functional outcome was most favorable following M2 occlusions.CONCLUSIONS: EVT patients from our large real-world national dataset differed from RCT patients in several baseline factors including distribution of vascular occlusion site. However, the overall outcome of EVT in our Swedish cohort appeared to well match the pivotal trial findings.
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| 10. |
- Wassélius, Johan, et al.
(författare)
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Endovascular thrombectomy for acute ischemic stroke
- 2022
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Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell Publishing Inc.. - 0954-6820 .- 1365-2796. ; 291:3, s. 303-316
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Forskningsöversikt (refereegranskat)abstract
- This review describes the evolution of endovascular treatment for acute ischemic stroke, current state of the art, and the challenges for the next decade. The rapid development of endovascular thrombectomy (EVT), from the first attempts into standard of care on a global scale, is one of the major achievements in modern medicine. It was possible thanks to the establishment of a scientific framework for patient selection, assessment of stroke severity and outcome, technical development by dedicated physicians and the MedTech industry, including noninvasive imaging for patient selection, and radiological outcome evaluation. A series of randomized controlled trials on EVT in addition to intravenous thrombolytics, with overwhelmingly positive results for anterior circulation stroke within 6 h of onset regardless of patient characteristics with a number needed to treat of less than 3 for any positive shift in outcome, paved the way for a rapid introduction of EVT into clinical practice. Within the "extended" time window of 6-24 h, the effect has been even greater for patients with salvageable brain tissue according to perfusion imaging with a number needed to treat below 2. Even so, EVT is only available for a small portion of stroke patients, and successfully recanalized EVT patients do not always achieve excellent functional outcome. The major challenges in the years to come include rapid prehospital detection of stroke symptoms, adequate clinical and radiological diagnosis of severe ischemic stroke cases, enabling effective recanalization by EVT in dedicated angiosuites, followed by personalized post-EVT stroke care.
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