Summary of current indications for mechanical thrombectomy for stroke.
\r\n\tThe following book will aim to explain clearly the main principles of mammography - advantages, disadvantages, benefits, and risks. Also, it has to offer detailed information about the screening, the early mammographic findings in breast cancer and the normal imaging anatomy of the breast and the process of aging. A significant part of the book will be dedicated to successful differentiation between benign and malignant breast calcifications. Another important task is to focus attention to the potential for radiation-induced breast cancer and to the screening of people with a family history of malignant breast tumors. Тhere will be included also practical advice and mammographic guidelines useful in daily medical practice.
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Since 2010, he has worked as a radiologist in the Department of Diagnostic Imaging at the University Hospital, Stara Zagora. Between 2013 and 2018, he was assistant professor in the Department of Radiology in the Medical Faculty, Trakia Universtity, Stara Zagora. Since 2018, he has been an associate professor in Radiology at the same university. In his practice, he presents lectures and tutorials in Bulgarian to medical, nursing, midwifery and rehabilitation students, in subject areas including X-ray, CT, MRI, angiography, mammography, ultrasound and DSG. Dr Manchev also delivers lectures and tutorials in English to medical students from the United Kingdom and the Republic of Ireland. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"51427",title:"Updates in Mechanical Thrombectomy",doi:"10.5772/64398",slug:"updates-in-mechanical-thrombectomy",body:'\nStrokes are the third leading cause of death globally and the leading cause of acquired adult disability [1, 2]. There are approximately 700,000 strokes annually in the United States and 4.5 million stroke survivors suffering from disability and loss of independence [3]. Proximal large vessel occlusions (LVOs) are particularly devastating, with an approximate 60–80% risk of 90-day mortality or severe morbidity [4, 5]. Costs associated with the treatment of stroke patients are more than 22 billion dollars annually [3, 6]. With an aging global population, the incidence of stroke is expected to increase over time, making improvements in detection, treatment, and management essential.
\nThe pathophysiology of ischemic strokes, which accounts for 85–90% of all strokes, is an ischemic cascade in the cerebral vasculature that leads to cellular bioenergetic failure. This injury is caused by cerebral hypoperfusion and subsequent excitotoxicity, oxidative stress, blood-brain barrier dysfunction, and post-ischemic inflammation that culminate in the death of neurons, glia, and endothelial cells [2]. Therapies targeting these deleterious pathways have been shown to improve cerebral perfusion and decrease secondary injury [7, 8], although rapid restoration of blood flow to affected areas remains the ultimate goal in stroke treatment.
\nEvidence-based indications (all criteria met) | \n
Pre-stroke mRS 0–1 | \n
Acute ischemic stroke of ICA or proximal MCA receiving tPA within 4.5 hours | \n
Age ≥ 18 years | \n
NIHSS/ASPECTS ≥ 6 | \n
Thrombectomy initiated within 6 hours of symptom onset | \n
\nThrombectomy may be considered (no definitive data and imaging to determine infarct core/penumbra may be helpful) | \n
>6 hours from symptom onset | \n
Patients with contraindications to tPA | \n
Distal MCA, ACA, and posterior circulation occlusions | \n
<18 years of age | \n
Pre-stroke mRS > 1, NIHSS/ASPECTS < 6 | \n
Summary of current indications for mechanical thrombectomy for stroke.
\nAbbreviations: ACA, anterior cerebral artery; ASPECTS, Alberta Stroke Program Early CT score; ICA, internal cerebral artery; MCA, middle cerebral artery; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; tPA, tissue plasminogen activator.
The long-standing gold standard for restoration of blood flow to ischemic brain is intravenous administration of the thrombolytic agent tissue plasminogen activator (tPA) within 3–4.5 hours of symptom onset [9, 10]. Tissue plasminogen activator leads to a 30% decreased risk of having no or minimal disability at 30 days [11]. However, strict parameters for tPA administration, such as its narrow treatment window and requirement that the patient has no recent surgeries, recent stroke, or prior hemorrhagic stroke, leave tPA underutilized. Only 3–5% of all stroke patients receive tPA, and less than half of patients that would be eligible for tPA actually receive treatment [12]. tPA is also associated with a 6% rate of hemorrhagic strokes and a 2% risk of systemic hemorrhage [13]. Most importantly, in high-risk patients with LVO, tPA has only modest rates of early reperfusion and thus limited efficacy [4, 5, 14, 15]. The limitations and risks of medical stroke therapies, particularly in patients with LVO, have led to the exploration of other reperfusion techniques by mechanical clot removal (thrombectomy). Recently, multiple large randomized trials demonstrated improved outcomes in patients with LVO [5, 16–19]. Based on this data, mechanical thrombectomy is now a standard of care in appropriately selected stroke patients with LVO (Table 1) [20]. This chapter focuses on the theory, technical aspects, current data, and future directions of mechanical thrombectomy for stroke.
\nMechanical thrombectomy employs direct arterial access to physically remove a thrombus from the cerebral circulation, providing in theory immediate and definitive reversal of hypoperfusion. While intuitively appealing, optimizing the technical aspects of this approach has delayed its widespread implementation. Early-generation devices included the MERCI Retriever (Concentric Medical Inc/Stryker Corp., Kalamazoo, MI), a flexible helical nitinol wire that is deployed through a microcatheter into the clot under balloon vessel occlusion and large-bore direct aspiration catheters with or without mechanical clot separators (Penumbra, Inc., Alameda, CA). Intra-arterial application of tPA directly to the site of the lesion was also explored in parallel to the above early techniques.
\nInitial randomized clinical trials with these devices/techniques demonstrated their safety but failed to show their superiority to intravenous tPA [4, 21, 22]. Potential reasons for the non-superiority of endovascular interventions in these trials include prolonged durations between symptom onset and intervention, poor patient selection as LVO was not in the selection criteria, and suboptimal recanalization rates likely resulting from use of early generation thrombectomy devices.
\nNewer generation stent retrievers, such as Solitaire FR (Covidien, Ltd., Mansfield, OH) and TREVO (Stryker Corp.), act as stents that are deployed within the clot and then retrieved to complete the thrombectomy. These devices have demonstrated superiority to older products like MERCI [23, 24] and are associated with significantly reduced endothelial damage [25]. Multiple large randomized trials have recently been published demonstrating improved outcomes in patients with LVO treated with stent retrievers as compared to intravenous tPA [5, 16–19], with clinical guideline updates including these therapies as standard of care.
\nThe American Heart Association (AHA)/American Stroke Association (ASA) released a set of updated guidelines for the management of patients with acute ischemic disease regarding endovascular treatment in 2015 after recent randomized controlled trial data clearly demonstrated the safety and efficacy of mechanical thrombectomy as compared to tPA for large vessel occlusion [20]. A summary of this clinical data follows and is highlighted in Table 2.
\nThe Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) enrolled 500 patients with anterior cerebral circulation arterial occlusion and an National Institutes of Health Stroke Scale (NIHSS) score ≥2, who could be treated endovascularly within 6 hours of symptom onset [5]. The effects of intra-arterial treatment plus standard medical therapy (intervention) versus standard medical therapy alone (control; including intravenous tPA, if eligible) were assessed. Mechanical thrombectomy was performed in 195 of 233 patients randomized to the intervention group, with retrievable stents used in 190 of these 195 patients. A modified thrombolysis in cerebral infarction (TICI) score of 2b or 3 (indicating >50% or complete distal reperfusion, respectively) was achieved in 58.7% of patients in the intervention group. This study reported a 13.5% increase in functional independence in the intervention group (32.6 versus 19.1, p < 0.05 as determined by the primary study outcome 90-day modified Rankin Scale [mRS] ≤ 2), with no significant difference in mortality or intracerebral hemorrhage rates. Secondary outcomes of the 5- and 7-day NIHSS score, the absence of residual occlusion at 24 hours, and the infarct volume were also improved in the intervention group.
\nThe Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial enrolled 316 patients with proximal anterior circulation occlusions, moderate-to-good collateral circulation, and a small infarct core, up to 12 hours after symptom onset [16]. The effects of intra-arterial treatment plus standard medical therapy (intervention) versus standard medical therapy alone (control; including intravenous tPA, if eligible) were assessed. This study was terminated early after an interim analysis demonstrated clear treatment efficacy. One hundred and fifty-one of the 165 patients assigned to the intervention group received intra-arterial therapy, with retrievable stents used in 130 of these patients. A modified TICI 2b or 3 score was achieved in 72.4% of patients in the intervention group. This study reported a 23.7% increase in functional independence (90-day mRS ≤ 2) with intervention (53.0 versus 29.3%, p < 0.05; a primary study outcome) and a decrease in 90-day mortality (10.4 versus 19.0%; p = 0.04). Secondary quality of life outcomes including 90-day Barthel Index (BI), NIHSS, and EuroQoL Group 5-Dimension Self-Report Questionnaire (EQ-5D) all favored the intervention group as well.
\nThe Solitaire FR with the Intention for Thrombectomy as Primary Endovascular Treatment of Acute Ischemic Stroke (SWIFT PRIME) trial enrolled 196 patients with confirmed proximal anterior circulation occlusions and the absence of a large ischemic core that could be treated within 6 hours of symptom onset [17]. The effects of intravenous tPA (control) versus intravenous tPA plus stent-retriever thrombectomy (intervention) were assessed. This study was terminated early after an interim analysis demonstrated clear treatment efficacy. The intervention group of 98 patients had a median time from qualifying imaging to groin puncture of 57 minutes. At the end of the procedure, the rate of substantial reperfusion was 88%. This study reported a 25% increase in functional independence (90-day mRS ≤ 2) with intervention (60 versus 35%, p < 0.001; a primary study outcome). Secondary outcomes including 27-hour successful reperfusion and NIHSS were also significantly improved in the intervention group. There were no significant differences between the intervention and control group in 90-day mortality or symptomatic intracranial hemorrhage.
\nTrial name | \nYear | \nStudy design | \nGroups | \nNumber of patients | \nStudy criteria | \nInterventional outcome | \nClinical outcome | \nReference | \n
---|---|---|---|---|---|---|---|---|
Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) | \n2015 | \nRando-mized, contr-olled | \nIntra-arterial treatment + usual care versus usual care alone | \n500 (233 intra-arterial treatment [81% stent retriever]; 267 control) | \nProximal anterior circulation occlusions, NIHSS ≥ 2, treated within 6 hours | \n58.7% TICI 2b or 3 score with intervention | \n13.5% increase in rate of functional independence (90-day mRS ≤ 2) with intra-arterial intervention (32.6 versus 19.1%; p < 0.05). No significant difference in mortality or symptomatic intracerebral hemorrhage | \n[5] | \n
Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) | \n2015 | \nRando-mized, contr-olled | \nIntra-arterial treatment + usual care versus usual care alone | \n316 (165 intra-arterial treatment [78% stent retriever]; 150 control) | \nProximal anterior circulation occlusions, moderate-to-good collateral circulation, small infarct core, treated within 12 hours | \n72.4% TICI 2b or 3 score with intervention | \n23.7% increase in functional independence (90-day mRS ≤ 2) with intra-arterial intervention (53.0 versus 29.3%, p < 0.05) and a decrease in 90-day mortality (10.4 versus 19.0%; p = 0.04) | \n[16] | \n
Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment of Acute Ischemic Stroke (SWIFT PRIME) | \n2015 | \nRando-mized, contr-olled | \nStent-retriever thrombectomy + usual care versus usual care alone | \n196 (98 stent retriever; 98 control) | \nProximal anterior circulation occlusions, no large ischemic core, treated within 6 hours | \n88% rate of substantial reperfusion | \n25% increase in functional independence (90-day mRS ≤ 2) with intervention (60 versus 35%, p < 0.001). No significant difference in 90-day mortality or symptomatic intracranial hemorrhage | \n[17] | \n
Extending the Time for Thrombolysis in Emergency Neurological Deficits – Intra-Arterial (EXTEND-IA) | \n2015 | \nRando-mized, contr-olled | \nStent-retriever thrombectomy + usual care versus usual care alone | \n70 (35 stent retriever; 35 control) | \nProximal anterior circulation occlusions, no large ischemic core, treated within 6 hours | \n86% TICI 2b or 3 score with intervention | \n31% increase in functional independence (90-day mRS ≤ 2) with intervention (71 versus 40%; p = 0.01). No significant difference in 90-day mortality or symptomatic intracranial hemorrhage | \n[18] | \n
Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours (REVASCAT) | \n2015 | \nRando-mized, contr-olled | \nStent-retriever thrombectomy + usual care versus usual care alone | \n206 (103 intervention [98 stent retriever]; 103 control) | \nProximal anterior circulation occlusions, no large ischemic core, treated within 8 hours | \n65.7% TICI 2b or 3 score with intervention | \n15.5% increase in functional independence (90-day mRS ≤ 2) with intervention (43.7 versus 28.2%, p < 0.05). No significant difference in 90-day mortality or symptomatic intracranial hemorrhage | \n[19] | \n
Summary of randomized controlled trials for mechanical thrombectomy in stroke.
Abbreviations: mRS, modified Rankin Scale; TICI, thrombolysis in cerebral infarction score.
The Extending the Time for Thrombolysis in Emergency Neurological Deficits – Intra-Arterial (EXTEND-IA) trial was designed similarly to SWIFT PRIME and enrolled 70 patients with confirmed proximal anterior circulation occlusions and the absence of a large ischemic core that could be treated within 6 hours of symptom onset [18]. Again, the effects of intravenous tPA (control) versus intravenous tPA plus stent-retriever thrombectomy (intervention) were assessed, and this study was also terminated early after an interim analysis demonstrated clear treatment efficacy. The 35 patients in the intervention group had a median time from qualifying imaging to groin puncture of 93 minutes. A modified TICI 2b or 3 score was achieved in 86% of patients in the intervention group. This study reported a significant increase in ischemic territory reperfusion at 24 hours with intervention (median 100 versus 37%; p < 0.001) and increased neurologic improvement at 3 days (80 versus 37%; p < 0.01). They also report a 31% increase in functional independence (90-day mRS ≤ 2) with intervention (71 versus 40%; p = 0.01), with no significant difference in rate of symptomatic intracerebral hemorrhage or death.
\nThe Endovascular Revascularization with Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke within 8 Hours (REVASCAT) trial enrolled 206 patients with occlusion of the proximal anterior circulation and the absence of a large ischemic core who could be treated within 8 hours of symptom onset [19]. The effects of stent-retriever thrombectomy plus standard medical therapy (intervention) versus standard medical therapy alone (control; including intravenous tPA, if eligible) were assessed. This study was terminated early after an interim analysis demonstrated clear treatment efficacy. Ninty-eight of the 103 patients in the intervention group underwent thrombectomy, with a median time from stroke onset to groin puncture of 269 minutes. A modified TICI 2b or 3 score was achieved in 65.7% of patients in the intervention group. This study reported a 15.5% increase in functional independence (90-day mRS ≤ 2) with intervention (43.7 versus 28.2%, p < 0.05; a primary study outcome). Secondary functional outcomes including 90-day BI, NIHSS, and EQ-5D all favored the intervention group, as did the median 24-hour infarct volume. There were no significant differences between the intervention and control groups in 90-day mortality or symptomatic intracranial hemorrhage.
\nThese five trials clearly demonstrate the therapeutic efficacy of mechanical thrombectomy with stent retrievers in stroke patients with LVO. The dramatic results from these studies (with multiple trials being stopped early for treatment efficacy) demanded a rapid update of clinical guidelines.
\nIn response to the above trials and other recent smaller studies, in 2015 the American Heart Association (AHA) and American Stroke Association (ASA) released a focused update of the 2013 guidelines for the endovascular treatment of patients presenting with acute ischemic stroke [20].
\nThese updated guidelines fall under several classifications of recommendation and levels of evidence. Class I recommendations imply that the benefits of the suggested procedure well outweighs the potential risks, and therefore indicate that the treatment should be administered. Class IIa recommendations indicate a moderate outweighing of benefit over risk and suggest that a treatment is reasonable to consider performing, but further studies are needed to ensure appropriate clinical application. Class IIb recommendations indicate that the benefits of the procedure may or may not outweigh its associated risks, and these procedures may be considered, although higher classifications of treatment recommendations take priority. Evidence pertaining to individual recommendations is stratified by level, indicating the strength of supporting data. Level A indicates that multiple populations have been evaluated and that data supporting the recommendation has been derived from multiple trials. Level B indicates that fewer populations have been evaluated or that the data supporting the recommendation has been derived from a single trial. Level C data indicates that the only data supporting the recommendation are the opinions of experts, case studies, or current standard of care [26].
\nA summary of the AHA/ASA 2015 guidelines detailing recommendations for treatment of patients using mechanical thrombectomy is as follows [20]. If patients meet all of the following criteria, mechanical thrombectomy using stent retriever is indicated and should be performed (Class I, Level of Evidence A): (a) prestroke mRS (modified Rankin Scale) score of 0 or 1, (b) presentation of acute ischemic stroke and receiving intravenous tPA within 4.5 hours of symptom onset, (c) causative occlusion of internal carotid artery or proximal MCA (M1), (d) age of at least 18 years, (e) NIHSS score of at least 6, (f) Alberta Stroke Program Early CT score (ASPECTS) of at least 6, and (g) treatment that can be initiated within 6 hours of symptom onset.
\nImportantly, eligible patients should receive tPA even if endovascular treatments are being considered, and contrary to previous guidelines, observation of patients after administration of tPA for clinical response is no longer required nor recommended prior to initiation of endovascular treatment (Class III, Level of Evidence B [randomized data]). Additionally, the ASA states that the use of stent retrievers is preferable to the MERCI device (Class I, Level of Evidence A) and that the use of alternate mechanical thrombectomy devices aside from stent retrievers may be acceptable in some cases (Class IIb, Level of Evidence B [non-randomized data]) [20].
\nThe new guidelines have also stipulated that the ultimate goal of mechanical thrombectomy should be a modified TICI score of 2b/3 in angiographic imaging (Class I, Level of Evidence A), as early as possible and within 6 hours of stroke onset (Class I, Level of Evidence B [randomized]) [20]. If mechanical thrombectomy following intravenous tPA administration is not adequate to achieve this angiographic result, the use of additional adjuncts including intra-arterial fibrinolysis is indicated to maximize the angiographic result (Class IIb, Level of Evidence B [randomized]). The treatment efficacy of mechanical thrombectomy initiated longer than 6 hours from symptom onset is unknown; however, additional trials are needed to determine the clinical benefit in this setting [20].
\nWhile adhering to the above recommendations is ideal for maximal clinical benefit, acute ischemic stroke patients are heterogeneous. The ASA thus included alternate recommendations for patient subpopulations/clinical situations not covered above. These expanded recommendations are as follows [20]. The use of stent retrievers alone is reasonable in patients presenting with anterior circulation occlusion even when intravenous tPA is contraindicated (i.e., outside of time window, prior stroke, head trauma, hemorrhagic coagulopathy, etc.) (Class IIa, Level of Evidence C). However, there is currently inadequate data definitively determining the clinical efficacy of monotherapy alone for this patient cohort. Intra-arterial fibrinolysis may be considered in these patients, but the clinical benefit of this approach has also yet to be established (Class IIb, Level of Evidence C).
\nAlthough no study-based evidence exists, the ASA recommendations include the use of stent retrievers in patients experiencing causative occlusions of the M2 or M3 portions of the MCA, anterior cerebral artery, vertebral arteries, basilar arteries, and posterior cerebral arteries, if treatment can be initiated within 6 hours of symptom onset (Class IIa, Level of Evidence C). Stent retrievers may also be appropriate in treatment of patients under 18 years of age with occlusion of large vessels and patients with an mRS score of >1, an ASPECTS score <6, or an NIHSS score <6 who present with causative occlusions of the internal carotid artery or proximal MCA (M1) (Class IIb, Level of Evidence C). However, randomized trials are required to provide data on the clinical efficacy of stent-retriever usage in such patients.
\nAdditionally, the updated guidelines discuss multiple technical aspects of endovascular intervention in strokes [20]. Specifically, they state the use of a proximal balloon guide catheter or a large-bore distal access catheter to provide flow stasis, and/or simultaneous aspiration as opposed to a cervical guide catheter alone during stent-retriever thrombectomy may be beneficial (Class IIa, Level of Evidence C). Future studies are nonetheless needed to determine the optimal technical approach with regard to recanalization and distal embolization rates. They also state that angioplasty and stenting of proximal cervical atherosclerotic stenoses or occlusions at the time of thrombectomy are reasonable (Class IIb, Level of Evidence C), although the utility of this intervention is currently unknown.
\nLastly, the guidelines addressed the issue of conscious sedations versus general anesthesia during mechanical thrombectomy. However, given a lack of randomized trial data, they state that anesthetic selection should be patient-based after considering individual risk factors, tolerance of procedure, other clinical characteristics, and evaluation of a patient’s medical history [20].
\nDespite being the new gold standard for large vessel acute stroke, there remain multiple unknown technical and clinical variables regarding the optimization of mechanical thrombectomy for strokes. As alluded to in the above guideline summary, outstanding clinical questions requiring further study include the use of adjunct imaging modalities to further define an acceptable pre-intervention ischemic core/penumbra (e.g., CT-perfusion/diffusion and perfusion-weighted imaging), the utility of simultaneous lesional catheter aspiration versus standard carotid balloon occlusion, the efficacy of thrombectomy in the posterior circulation, and the maximal acceptable timing of intervention from symptom onset.
\nMoreover, many technical aspects of the devices employed are still being optimized. Future device designs will center on reduction of the endothelial footprint both by changing device design and optimizing device size relative to the vasculature. Additionally, reduction of embolic complications beyond those afforded by direct lesional aspiration, and increasing first pass success, will be major driving forces behind future iterations of stent-retriever devices.
\nGuiding these changes is a fundamental inquiry into stroke physiology, and how device characteristics beyond efficacy of clot removal can affect outcomes. For example, an area of ongoing and future study is the potential role of iatrogenic endothelial damage on post-thrombectomy secondary neurologic injury (Figure 1). The potential importance of endothelial injury becomes apparent upon close analysis of existing clinical data. Specifically, while the initial equivocal thrombectomy clinical trial data is likely due in part to lower recanalization rates than with more recent studies [4, 5, 16–19, 21, 22], another potential explanation may relate to the increased iatrogenic endothelial injury generated by older thrombectomy devices when studied in both in vitro and in vivo models [25]. When combined with the known deleterious effects of physiologic blood flow disruptions on endothelial cell homeostasis and cytokine signaling [27–37], these findings necessitate future studies to determine how iatrogenic endothelial damage affects secondary neuronal injury in post-thrombectomy stroke patients. This line of study is critical to next generation device design.
\nSchematic illustration of the potential negative effects of iatrogenic endothelial damage during thrombectomy on downstream neurons/glia. Proposed deleterious mechanisms include upregulation of inflammatory pathways, blood-brain barrier (BBB) disruption, and flow disturbances. Ongoing work to understand these effects will inform future thrombectomy device design.
In summary, mechanical thrombectomy for selected patients with large vessel acute stroke is the new standard of care based on overwhelming clinical efficacy data. Future studies and technical and procedural refinements will undoubtedly increase the indications for this intervention.
\nThe authors acknowledge Victor W. Wong for contributing his original artwork to this chapter.
\nThe fusion-fission hybrid energy reactor, consisting of a low-power magnetic confinement fusion assembly and a subcritical blanket, is one of the advanced reactors of applying fusion technology to solve the present energy crisis. Natural thorium contains one isotope 232Th. Thorium is a fertile element that can be applied in the conceptual blanket design of a fusion-fission hybrid reactor [1, 2]. The actual neutron spectrum in the subcritical blanket based on the Th/U fuel cycle is composed of fast and thermal spectra. The 232Th capture cross section at fast neutron is slightly larger than that of 238U, and 232Th is more suitable to breed 233U under fast spectrum. Since 232Th capture cross section for thermal neutron is about 2.7 times larger than that of 238U, the conversion rate in the Th/U fuel cycle is more than that in the U/Pu fuel cycle and the neutron economy of thorium is better. Moreover, the 233U capture cross section for thermal neutron is smaller than that of 239Pu and 233U needs to absorb neutrons many times to produce Pu and long-life Minor Actinides (MA, such as 237Np, 241Am, and 242Cm), whereas Pu and MA produced in the Th/U fuel cycle are one order of magnitude less than those in the U/Pu fuel cycle. Therefore, the Th/U fuel cycle is beneficial to reduce the long-life nuclear waste and prevent nuclear proliferation. The feasibility and reliability of the physical design for the subcritical blanket based on thorium depend on the accuracy of 232Th nuclear data and calculational tool. It is essential to carry out the fusion neutronics experiments for validating the evaluated 232Th nuclear data and studying the breeding properties.
A small number of fusion neutronics experiments on thorium were carried out, and there exist essential differences between the calculations and experiments [3, 4, 5]. The 232Th fission rate with fast neutrons was determined by detecting the gamma rays emitted from 140Ba and 140La, and the calculated-to-experimental ratio was 0.9 based on ENDF/B-IV [4]. The thorium fission reaction rate in a metallic sphere setup was determined by absolute measurement of the gamma-emission from 143Ce, the experimental uncertainty was 5.2%, and the calculation to experiment ratio was 1.17 employing ENDF/B-IV [5].
The integral fusion neutronics benchmark experiments for macroscopic thorium assemblies with a D-T fusion neutron source were carried out at Institute of Nuclear Physics and Chemistry (INPC) [6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17]. The method for measuring integral 232Th reaction rate and its application in an experimental assembly were developed and investigated [6, 7, 8]. In this chapter, the progress in the fusion neutronics experiments for thorium assemblies is described. The overview of main results is presented. The thorium assemblies with a D-T fusion neutron source consist of a polyethylene shell, depleted uranium shell, and thorium oxide cylinder. The 232Th reaction rates in the assemblies and leakage neutron spectra are measured separately. The benchmark experiments on fuel and neutron breeding properties derived from the 232Th reaction rates in representative thorium assemblies are carried out and analyzed. The breeding properties are valuable to the breeding ratio in the conceptual design of subcritical blanket based on the Th/U fuel cycle. The experimental results are simulated by using the MC code with different evaluated data. The ratios of calculation to experimental values are analyzed.
The fusion neutronics experiments contain the measurements of the 232Th(n,γ), 232Th(n, f), and 232Th(n,2n) reaction rates, and the neutron spectra for thorium assemblies with a D-T fusion neutron source.
The experimental method of activation of γ-ray off-line measurement of 232Th reaction rates is used. The activation γ-rays are measured by using an HPGe γ spectrometer.
The 232Th capture reaction rate (THCR) indicates the fuel breeding, that is, the production rate of fissile 233U (233Pa decay). THCR can be deduced by measuring 311.98 keV γ rays emitted from 233Pa [6, 7]. The reaction process is as follows:
The 232Th fission (with threshold of 0.7 MeV) reaction rate (THFR) indicates energy amplification and neutron breeding. The fission fragment yield correction method is used [8]. THCR can be deduced by measuring 151.16 keV γ rays emitted from the decay of 85mKr from 232Th (n, f) reaction. The reaction process is as follows:
The 232Th(n,2n) 231Th (with threshold of 6.5 MeV) reaction rate (THNR) indicates neutron breeding. THNR is obtained from measuring 84.2 keV γ rays emitted from 231Th [9]. The reaction process is as follows:
The 232Th reaction rates are deduced from the measured activity and corrections, which include detection efficiency of the HPGe γ spectrometer, cited value of branching ratio, D-T neutron yield during irradiation, self-absorption of gamma rays in the foils, 85mKr yield only for THFR, etc. The 232Th reaction rates are normalized to one source neutron and one 232Th atom.
The breeding ratio in the conceptual design of subcritical blanket is more than one [1]. The experiment on breeding properties of thorium is used to support the design [17]. The breeding properties are relevant to the reaction type, cross section, and neutron spectrum. The breeding properties contain the fuel breeding and neutron breeding. The fuel breeding is derived from the reaction rate ratio of 232Th capture to fission, and neutron breeding from the 232Th(n,2n) and fission reaction rates. The different neutron spectra are constructed by using the macroscopic assemblies in which the material is relevant to that of the conceptual design. The breeding properties under different assemblies are obtained and analyzed from the measured 232Th reaction rates.
The neutron spectra leaking from the ThO2 cylinders of different thickness are measured by the proton recoil method and the liquid scintillator [16]. The n-γ pulse shape discrimination is based on the cross-zero method. The spectra are resolved by using iterative method, and their range is from 0.5 to 16 MeV.
The experimental assemblies are composed of polyethylene shell, depleted uranium shell, and ThO2 cylinder with a D-T fusion neutron source and thorium samples.
One can assume the elastic scattering cross sections of H and C, which are widely used as standard cross sections [18] to be reliable. The polyethylene (PE) shell is adopted for checking the method of measuring the 232Th reaction rates. The inner radius (IR) and the outer radius (OR) of the PE shell are 80 and 230 mm [11], respectively. Five slices of ThO2 (concentration > 99.95%) foils are put in the radial channel at 0° to the incident D+ beam, as shown in Figure 1. The mass and size of foils are about 4.2 g and ϕ30 × 1 mm, respectively.
Polyethylene shell assembly.
A D-T fusion neutron source is located in the center of the shell. The 14 MeV neutrons are produced by a neutron generator at INPC. The energy of D+ beam bombarding a T-Ti target is 225 keV. An Au-Si surface barrier semiconductor detector is at an angle of 178.2° to the incident D+ beam in the drift tube and used to measure the absolute yield by counting associated α particles [19, 20]. D-T neutron yield is about 3 × 1010/s.
In the conceptual design of a subcritical blanket based on thorium, the neutrons from the U reaction process are used to maintain the Th/U fuel cycle. The depleted uranium (DU) shell is adopted for studying Th reaction. The IR/OR of the DU shell is 131/300 mm [12]. Six slices of ThO2 samples are put in the radial channel at 90° to the incident D+ beam, as shown in Figure 2. ThO2 samples are foils made from ThO2 powder filling a plexiglass box with IR/OR of 9/9.5 mm. The mass of ThO2 powder is about 0.45 g, and the thickness is about 0.7 mm. The D-T neutron source is located in the center of the shell.
Depleted uranium shell assembly.
The thorium oxide (ThO2) cylindrical assembly with the thickness of 150 mm is produced and consists of three ThO2 cylinders with the thickness of 50 mm and the diameter of 300 mm. The ThO2 cylinders are made by pressing ThO2 powder using PEO (CH2CH2O) as the binder and their densities are 4.25–5.59 g/cm3 [9, 10]. The structure of the ThO2 cylinders as benchmark is simple. To change neutron spectra in ThO2 cylinders, the latter can be combined with DU cylinders. The combination of two ThO2 cylinders and one DU cylinders is shown in Figure 3. Three slices of the ThO2 samples are put in axial channel of the assembly. The front surface of the assembly is 113 mm from the center of a tritium target.
ThO2/DU assembly.
Based on thorium oxide powder, the ThO2 assembly is produced, as shown in Figure 4 [13, 14, 15]. ThO2 powder fills a stainless steel/aluminum cylinder container with IR/OR of 93.4/96.2 mm. The height of the ThO2 cylinder is 168.9 mm and the density 1.5 g/cm3. Five pieces of ThO2 foils are put at 0° to the incident D+ beam and fixed using holders consisting of aluminum plate and stainless steel. The mass and size of ThO2 foils are about 5.0 g and ϕ30 × 1 mm, respectively. The distance between the tritium target center and the front end of the cylinder is 78.8 mm.
ThO2 powder cylindrical assembly.
The neutron spectra in PE, DU, and ThO2 assemblies are simulated by using the MCNP4B code [21] with ENDF/B-VII.0 [22], in which the S (α, β) thermal scattering model in PE is considered. The angular dependences of the source neutron energy and intensity are calculated by “DROSG-2000” code [23]. The neutron spectra at foils with different distances d to the neutron source in three assemblies are relatively compared, as shown in Figure 5. The ordinate is a normalized neutron fraction, that is, the proportion of the neutron number in each energy segment to the one in the whole energy range [11, 13]. The results show that the differences of the fractions are very obvious, especially in the low-energy region.
Neutron spectra at foils in three assemblies.
The PE shell assembly for measuring 232Th reaction rates is shown in Figure 1. THCR is deduced from measuring 311.98 keV γ rays emitted from 233Pa (its half-life is 26.967 days, it is obtained from 233Th decay). THFR is deduced from measuring 151.16 keV γ rays emitted from 85mKr decay (its half-life is 4.48 hour), which is one of the fragments of 232Th(n,f) reaction, and using the fragment yield correction method. THNR is deduced from measuring 84.2 keV γ rays emitted from 231Th (its half-life is 25.52 hour).
The experimental uncertainty of THCR is 3.1%, including neutron yield 2.5%, γ-ray detection efficiency 1.0% (HPGe-GEM 60P), self-absorption 1.0%, characteristic gamma branch ratio 1.0%, 232Th nucleus number 0.5%, and counting statistics 0.3–0.6%.
The experimental uncertainty of THFR is 5.3%, including neutron yield 2.5%, γ-ray detection efficiency 1.0%, self-absorption 1.0%, average fission yield of 85mKr 4.3%, characteristic gamma branch ratio 0.7%, 232Th nucleus number 0.5%, and counting statistics 0.8–1.0%.
The experimental uncertainty of THNR is 6.8%, including neutron yield 2.5%, γ-ray detection efficiency 1.0%, self-absorption 1.0%, characteristic gamma branch ratio 6.1%, 232Th nucleus number 0.5%, and counting statistics 0.5–0.6%.
The experiment is simulated by using the MCNP code with evaluated nuclear data from different libraries, including ENDF/B-VII.0, ENDF/B-VII.1 [24] and JENDL-4.0 [25]. The model is completely consistent with the structure of the assembly; it takes into account the target chamber and experimental hall. The calculated statistical uncertainty is less than 1%. The ranges of C/E with ENDF/B-VII.0 are 0.96–1.02 for THCR, 0.95–0.97 for THFR, and 0.89–0.91 for THNR. The results show that the experiment and calculation for THCR and THFR are well consistent within the range of experimental uncertainties, respectively. It is shown that the γ-ray off-line method is feasible for determining the 232Th reaction rates.
The distributions of 232Th reaction rates obtained from the experiments and calculations with ENDF/B-VII.0 are shown in Figure 6. The reaction rate ratio of 232Th capture to fission gives fissile production rate in unit of fuel burn-up [12]. The relative ratios measured are about 10.76–20.17 with the increase of radius in PE shell.
232Th reaction rates in PE shell.
The ratios of calculation to experimental values (C/E) are analyzed. The C/E ratios of 232Th reaction rates are shown in Figure 7, and the 232Th(n,f) reaction results for different evaluated nuclear data are shown in Ref. [11]. The calculations with ENDF/B-VII.0 and ENDF/B-VII.1 for THNR underestimate the experimental values. Meanwhile, large differences still exist in the 232Th(n,2n)231Th cross sections among different evaluated data [26]. Fractions with different energies in the PE shell are calculated by using ENDF/B-VII.0, and neutrons of energy more than 6.5 MeV account for 33–48% in the whole energy range, as shown in Figure 5. Since the neutron spectra in the PE shell are reliable, it is suggested that 232Th(n,2n) reaction cross sections should be studied further.
C/E ratio of 232Th reaction rates in PE shell.
The DU shell assembly for measuring 232Th reaction rates is shown in Figure 2. The 232Th reaction rates are measured by the same method as described above.
The experimental uncertainties are 3.1% for THCR, 5.3–5.5% for THFR [6, 8], and 6.8% for THNR in DU shell.
The experiment is simulated using the MCNP code with different evaluated data, including ENDF/B-VII.0, ENDF/B-VII.1, JENDL-4.0, and CENDL-3.1 [27]. The distributions of 232Th reaction rates from the experiments and calculations with ENDF/B-VII.0 are shown in Figure 8. The ranges of C/E ratios with ENDF/B-VII.0 are 0.97–1.04 for THCR and 0.95–1.02 for THFR [8, 12], respectively. The results show that calculations and experiments are well consistent within the range of experimental uncertainties. The ratio of 232Th capture to fission is about 6.71–12.23 with the increase of radius in DU shell.
232Th reaction rates in DU shell.
The C/E ratios of 232Th reaction rates with different evaluated data are shown in Figure 9. The calculations for THNR overestimate the experiments. Meanwhile, large differences still exist in C/E of THNR. The range of C/E with ENDF/B-VII.0 is 1.07–1.12. Fractions with different energies in DU shell are calculated by using ENDF/B-VII.0, and neutrons of energy more than 6.5 MeV account for 4–9% in the whole energy range, as shown in Figure 5. Since U(n,f) cross sections are standard in the wide energy range, it is suggested that U inelastic cross sections and 232Th(n,2n) reaction cross sections should be studied further.
C/E ratio of 232Th reaction rates in the DU shell.
The ThO2 assembly for measuring 232Th reaction rates in three ThO2 cylinders with the thickness of 150 mm (without DU cylinder) is shown in Figure 3. The 232Th fission and (n,2n) reaction rates are measured by the same method as described above.
The experimental uncertainties are 5.3–5.5% for THFR and 7.1% for THNR [9, 10].
The 232Th reaction rates are calculated by using MCNP code with ENDF/B-VII.0. The ranges of C/E are 0.77–0.91 for THFR, and 0.92–1.0 [12] for THNR, respectively. The results show that the calculations generally underestimate the experiments for THFR. The PEO influence on THFR is described below. The distributions of 232Th reaction rates by the experiments and calculations are shown in Figure 10.
232Th reaction rates in ThO2 cylinder.
Experimental and simulative studies of THFR are carried out on three sets of ThO2/DU cylinder assemblies to validate the evaluated thorium fission cross section and code [9, 10]. The size of each ThO2 cylinder and DU cylinder is ϕ300 × 50 mm. The ThO2 cylinders with PEO contents of 7.28, 1.1, and 0.55% are named as number 1, number 2, and number 3, respectively. The DU cylinder is named as number 4. Three sets of cylinder assemblies are combined with different cylinders, and named as “3 + 2 + 1,” “4 + 2 + 1” (as shown in Figure 3) and “3 + 4 + 2 + 1” assembly, respectively.
THFR in the axial direction of the assemblies is obtained by using the activation method as described above, with experimental uncertainties about 5.6–5.9%.
THFRs are calculated by using MCNP code with ENDF/B-VII.0 and ENDF/B-VII.1. The calculations are 5–21% smaller than experimental ones, while the calculations with ENDF/B-VII.0 show better agreement with experimental ones. C/E distributions in the three assemblies are presented in Figure 11. The influence of the PEO in the ThO2 cylinders is also evaluated by MCNP simulation employing ENDF/B-VII.0. The results show that the PEO influence on THFR under the measured level is negligible.
C/E distribution in the three sets of assemblies.
In order to gain more experimental results, it is necessary to design a new integral experiment employing thorium transport medium in which the ingredient is single and precisely known, and to determine THFR based on more kinds of fission products, as described below. The stage results could provide reference for the evaluation of neutron-induced thorium fission cross section, and the conceptual design margin of the subcritical blanket.
The ThO2 power cylinder assembly for measuring 232Th reaction rates is shown in Figure 4. The 232Th reaction rates are measured by the same method as described above.
The experimental uncertainties are 3.1% for THCR, 5.5% for THFR, and 7.0% for THNR in the ThO2 powder cylinder.
The experiment is simulated by using the MCNP code with different evaluated data [10, 11]. The C/E ratio of 232Th reaction rates with ENDF/B-VII.0 are shown in Figure 12. The ranges of C/E ratio are 0.96–0.98 for THCR, 0.96–0.99 for THFR, and 0.74–0.76 for THNR. The results show that calculations and experiments for THCR and THFR are well consistent within the range of experimental uncertainties. The distributions of 232Th reaction rates in the experiments and calculations are shown in [13, 14, 15].
C/E ratio of 232Th reaction rates in ThO2 powder cylinder.
The calculations for THNR underestimate the experiments. Fractions with different energies in ThO2 powder cylinder are calculated by using ENDF/B-VII.0, and neutrons of energy more than 6.5 MeV account for 62–72% in the whole energy range, which is the largest among the assemblies, as shown in Figure 5. The suggestion described above is that 232Th(n,2n) reaction cross sections should be studied further.
The ThO2 power cylinder assembly for developing the activation method of measuring THFR is shown in Figure 4. THFR in the axial direction of the cylinder is determined by measuring the 1260.409 keV gamma emitted from 232Th fission product 135I, with experimental uncertainties of 6.2% [14]. The experiment is simulated by using the MCNP code with ENDF/B-VII.0, ENDF/B-VII.1, JENDL-4.0, and CENDL-3.1. The calculations and experiments are in good agreement within experimental uncertainties. The activation method to determine THFR is developed and the data obtained in this work could provide reference for the validation of thorium fission parameters. The C/E ratio of 232Th fission rates based on different evaluated data is presented in the [14].
The primary conversion rate is one of the important parameters in the conceptual design of subcritical blanket. The relative reaction rate ratio of 232Th capture to fission as the fissile production rate indicates fuel breeding in the fuel burn-up unit [12]. The ratios of 232Th capture to fission measured in PE shell, DU shell, and ThO2 powder cylinder are obtained.
The ratios are about 10.76–20.17 with the increase in radius of the PE shell. It is demonstrated that the fuel breeding efficiency under the neutron spectra in the PE shell is quite high.
The ratios are about 6.71–12.23 with the increase in radius of the DU shell. It is demonstrated that the fuel breeding efficiency under the neutron spectra in DU shell is high.
The ratios are only about 0.11–0.19 with the increase in radius of the ThO2 powder cylinder. It is demonstrated that the fuel breeding efficiency under the neutron spectra in ThO2 powder cylinder is low.
The results show that the ratios are relevant to neutron spectra in the assemblies. The ratios in the three assemblies are compared and shown in Figure 13.
Ratios of 232Th capture to fission in the three assemblies.
The bred neutrons from 232Th(n,2n) and 232Th(n,f) react with thorium or relevant nuclides to maintain the Th/U fuel cycle. THNRs in three assemblies, that is, under different neutron spectra, are compared and shown in Figure 14. The results show that the 232Th(n,2n) reaction rates are relevant to the fraction of high-energy neutrons in the assemblies as described above, and the decreasing trend of THNR with the increase in distance to the neutron source are similar for three assemblies.
THNRs in the three assemblies.
Since 230Th half-life (7.54 × 104 years) is very long, measurement of 232Th(n,3n) 230Th (with threshold of 11.6 MeV) reaction rate by the activation method is very difficult. The 232Th(n,4n) reaction has high threshold 19 MeV and is not involved in this work.
The prompt neutron and delayed neutron yields from 232Th(n,f) reaction are about 3.7 and 0.0265 per fission at 14.1 MeV [28], respectively. THFRs in three assemblies, that is, under different neutron spectra, are compared and shown in Figure 15. From Figures 14 and 15, THNRs are higher than THFRs in the three assemblies.
THFRs in the three assemblies.
Three assemblies consist of the ThO2 cylinders with thicknesses of 50, 100, and 150 mm (without DU cylinder), respectively, as shown in Figure 3. The front surface of the assembly is 0.22 m from the center of a T-Ti target. The leakage neutron spectra are measured by using a 50.8 mm diameter and 50.8 mm length BC501A liquid scintillator coupled to a 50.8 mm diameter 9807B photomultiplier [16]. The distance from the detector to the neutron source is 10.75 m. The detector is at a 0° to the incident D+ beam and arranged in shielding room. The influence of background neutrons is negligible.
The leakage neutron spectra from the three assemblies are measured. The spectra are normalized to one source neutron and unit area. The experimental uncertainties are 9.7% for 0.5–1 MeV, 6.7% for 1–3 MeV, and 6.3% for 3–16 MeV. The experiments are calculated by using MCNP code with ENDF/B-VII.0. The results show that the experiments and calculations are generally consistent within the range of experimental uncertainties, and the spectra (<5 MeV) should be analyzed further, as shown in Figure 16.
Leakage neutron spectra from ThO2 cylinders.
To validate 232Th nuclear data, the fusion neutronics experiments for the three kinds of thorium assemblies with a D-T neutron source have been carried out. The two spherical assemblies based on the DU and PE shells, and the cylindrical assemblies based on ThO2 have been designed and established. The assembly materials are referable to the conceptual design of subcritical blanket of a hybrid reactor. The 232Th(n,γ), 232Th(n,f), and 232Th(n,2n) reaction rates in the assemblies are measured by the foil activation technique. The results show that the developed activation approach can work well for the experiments, and the 232Th reaction rates are relevant to neutron spectra in assemblies. The reaction rate ratios of 232Th capture to fission are obtained. The fuel and neutron breeding properties under different neutron spectra are compared and analyzed. The leakage neutron spectra from ThO2 cylinders are measured. The experimental results are compared to the numerical results calculated by using the MCNP code with different evaluated data. The results show that the experiments are benefit to validate Th nuclear data and support the conceptual design of subcritical blanket with thorium in a hybrid reactor. Furthermore, it should be beneficial to measure relevant 232Th excitation curve at white neutron source of China Spallation Neutron Source (CSNS) [29] for verifying 232Th nuclear data.
This work is supported by the National Special Magnetic Confinement Fusion Energy Research of China (No. 2015GB108001B), the National Natural Science Foundation of China (No. 11675155, 91226104), and the National Key Research and Development Program of China (No. 2016YFA0401603). The author wishes to acknowledge all participators of the projects, including Dr. Yiwei Yang, Dr. Lei Zheng, Dr. Song Feng, MS. Caifeng Lai, Prof. Xinxin Lu, MS. Zhujun Liu, Prof. Li Jiang, Prof. Mei Wang, MS. Zijie Han, et al. All participators would like to thank Prof. Benchao Lou and his group for operating the neutron generator. The author thanks the reviewers, comments and suggestion.
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\\n\\nMaterijali koji se pojavljuju na IntechOpenovoj stranici mogu sadržavati manje greške, tipfelere ili fotografske greške. IntechOpen može napraviti promjene na bilo kojem materijalu koji se nalazi na stranici u bilo koje vrijeme.
\\n\\nIntechOpen nije formalno povezan niti s jednom vanjskom stranicom čije poveznice vode na www.intechopen.com, osim ako to nije izravno navedeno. Iz tog razloga IntechOpen nije odgovoran za sadržaj koji se pojavljuje na takvim stranicama. Poveznica na IntechOpenovu stranicu ne implicira povezanost sa IntechOpenom. Korištenje takvih poveznica isključiva je odgovornost korisnika.
\\n\\nZadržavamo pravo vlasništva nad cjelokupnom stranicom www.intechopen.com i nad svim materijalom na toj stranici. Koristeći se našim uslugama, slažete se da maknete sve poveznice na našu stranicu odmah nakon što to od vas zatražimo. Također, zadržavamo pravo da ove Odredbe i uvjete, i politiku o poveznicama izmjenimo u bilo koje vrijeme. Koristeći se poveznicama na naše stranice slažete se s ovim Odredbama i uvjetima.
\\n\\nAko smatrate da je bilo koja poveznica na našoj stranici sumnjiva iz bilo kojeg razloga, molimo vas da nas kontaktirate. U tom slučaju razmotrit ćemo micanje poveznice s naše stranice, iako nismo obvezni to napraviti.
\\n\\nBez prethodne privole i izričite pisane dozvole, ne možete stvarati okvire oko naših stranica ili koristiti druge tehnike koje na bilo koji način mogu promijeniti prezentaciju ili izgled naše stranice.
\\n\\nIntechOpen može ove Odredbe izmijeniti u bilo koje vrijeme i bez prethodne obavijesti. Koristeći ovu stranicu vi se slažete s trenutnim Odredbama i uvjetima koje su na snazi.
\\n\\nOve Odredbe i uvjeti su sastavljeni u skladu s odredbama prava Ujedinjenog Kraljevstva, a za sve sporove nadležan je sud u Londonu, Ujedinjeno Kraljevstvo.
\\n"}]'},components:[{type:"htmlEditorComponent",content:"Pristupom na stranicu www.intechopen.com slažete se s ovim odredbama, sa svim primjenjivim zakonskim odredbama, te se slažete s poštovanjem svih lokalnih zakona. Korištenje i/ili pristup ovoj stranici temelji se na potpunom prihvaćanju ovih odredbi. Svi materijali na ovoj stranici zaštićeni su primjenjivim zakonima o autorskim pravima i žigu.
\n\nSljedeća terminologija odnosi se na Odredbe i uvjete, te na sve naše ugovore:
\n\nKlijent, stranka, vi, vaš odnosi se na vas, osobu koja pristupa ovoj stranici i prihvaća IntechOpenove Odredbe i uvjete;
\n\nKompanija, tvrtka, mi, naše odnosi se na tvrtku IntechOpen;
\n\nStranke, strane odnosi se na klijenta i na nas, ili samo na klijenta ili nas.
\n\nSve odredbe koje se odnose na ponudu, prihvat ili razmatranje plaćanja, a za koja mi pružamo asistenciju klijentu, bilo na ugovoreni ili fiksni način, a s ciljem da se ostvare potrebe i želje klijenta u svezi s našim uslugama, su podložne zakonskim odredbama Ujedinjenog Kraljevstva.
\n\nOsim ako nije suprotno navedeno, IntechOpen i/ili svi davatelji licence vlasnici su intelektualnog vlasništva nad svim materijalima na www.intechopen.com. Sva prava intelektualnog vlasništva su pridržana. Stranice sa www.intechopen.com možete gledati, preuzimati, dijeliti, dijeliti poveznice i printati za osobnu uporabu, a temeljem pravila sadržanih u ovim Odredbama i uvjetima.
\n\nMi koristimo kolačiće. Korištenjem IntechOpenove stranice slažete se s korištenjem kolačića u skladu s IntechOpenovom Politikom privatnosti. Većina modernih, interaktivnih stranica koristi kolačiće kako bi omogućila ponovno pronalaženje korisničkih detalja kod svakog posjeta. Na našoj stranici kolačići se uglavnom koriste kako bi omogućili funkcionalnost i olakšali posjetiteljima korištenje stranice.
\n\nIntechOpen ili njegovi suradnici niti u jednom slučaju neće biti odgovorni za štete (štete uključuju gubitak podataka ili profita, druge poslovne prekide, te sve ostale štete) koje nastanu zbog korištenja materijala na IntechOpenovoj stranici ili nemogućnosti da se iste koriste, čak i ako je IntechOpen ili njegov predstavnik o takvoj šteti obaviješten pismenim ili usmenim putem. Neke jurisdikcije ne dozvoljavaju ograničenja garancija ili ograničenja obveza za posljedične ili slučajne štete pa se u tom slučaju ova ograničenja možda ne odnose na vas.
\n\nMaterijali koji se pojavljuju na IntechOpenovoj stranici mogu sadržavati manje greške, tipfelere ili fotografske greške. IntechOpen može napraviti promjene na bilo kojem materijalu koji se nalazi na stranici u bilo koje vrijeme.
\n\nIntechOpen nije formalno povezan niti s jednom vanjskom stranicom čije poveznice vode na www.intechopen.com, osim ako to nije izravno navedeno. Iz tog razloga IntechOpen nije odgovoran za sadržaj koji se pojavljuje na takvim stranicama. Poveznica na IntechOpenovu stranicu ne implicira povezanost sa IntechOpenom. Korištenje takvih poveznica isključiva je odgovornost korisnika.
\n\nZadržavamo pravo vlasništva nad cjelokupnom stranicom www.intechopen.com i nad svim materijalom na toj stranici. Koristeći se našim uslugama, slažete se da maknete sve poveznice na našu stranicu odmah nakon što to od vas zatražimo. Također, zadržavamo pravo da ove Odredbe i uvjete, i politiku o poveznicama izmjenimo u bilo koje vrijeme. Koristeći se poveznicama na naše stranice slažete se s ovim Odredbama i uvjetima.
\n\nAko smatrate da je bilo koja poveznica na našoj stranici sumnjiva iz bilo kojeg razloga, molimo vas da nas kontaktirate. U tom slučaju razmotrit ćemo micanje poveznice s naše stranice, iako nismo obvezni to napraviti.
\n\nBez prethodne privole i izričite pisane dozvole, ne možete stvarati okvire oko naših stranica ili koristiti druge tehnike koje na bilo koji način mogu promijeniti prezentaciju ili izgled naše stranice.
\n\nIntechOpen može ove Odredbe izmijeniti u bilo koje vrijeme i bez prethodne obavijesti. Koristeći ovu stranicu vi se slažete s trenutnim Odredbama i uvjetima koje su na snazi.
\n\nOve Odredbe i uvjeti su sastavljeni u skladu s odredbama prava Ujedinjenog Kraljevstva, a za sve sporove nadležan je sud u Londonu, Ujedinjeno Kraljevstvo.
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