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Contribution of 18F-sodium fluoride PET/CT to the study of the carotid atheroma calcification
Caracterizacion de la calcificacion del ateroma carotideo mediante 18F-fluoruro PET/TAC
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"apellidos" => "Rubio-Vassallo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 9 => array:3 [ "nombre" => "F." "apellidos" => "Ortega-Nava" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 10 => array:3 [ "nombre" => "R." "apellidos" => "Del Castillo-Matos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 11 => array:3 [ "nombre" => "J.M." "apellidos" => "Carril" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Medicina Nuclear, Hospital Universitario “Marqués de Vadecilla”, Universidad de Cantabria, Santander, Spain" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Neurología, Hospital Universitario “Marqués de Vadecilla”, Universidad de Cantabria, Santander, Spain" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Caracterizacion de la calcificacion del ateroma carotideo mediante <span class="elsevierStyleSup">18</span>F-fluoruro PET/TAC" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1021 "Ancho" => 1604 "Tamanyo" => 80178 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Graph representing the distribution of the plaques according to the intensity and symptomatology.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The indication of invasive procedures such as endarterectomy or angioplasty in patients with carotid atheromatosis is still unclear and, therefore, new markers to identify the vulnerable plaques are needed, so that the appropriate invasive technique, which involves high risk of morbidity, is indicated.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> The pathophysiological mechanisms involved in the development of symptoms include changes in the blood flow secondary to the stenosis or the embolic events caused by the rupture of the plaque; the latter associated with vulnerability of the plaque. Therefore, if the composition of the plaque could be determined “in vivo”, the criteria to select the patients under risk of developing these neurovascular events would be the candidates for those invasive therapies. This is the key of the “in vivo” metabolic imaging of the atheroma plaque as, potentially, they could help to characterize the different phases of the atherogenesis to select the appropriate therapy and to monitor and measure the response to it.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Atheromatosis is considered nowadays an immune inflammatory process characterized by accumulation of lipids, monocytes and macrophages, and by the calcification of vessels.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> This led to the evaluation of different radiotracers to image the inflammation associated with the atheroma.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> As result, <span class="elsevierStyleSup">18</span>F-FDG PET an PET/CT became the accepted technique for the assessment of the inflammatory process and for monitoring and measuring the response to new therapies.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">However, there are other mechanisms which can be involved in the development of the plaque and could not be investigated until now. Thus, the most recent guidelines for the management of patients with extracranial carotid disease, published in 2011, emphasize on the need for identifying new data related with the vulnerability of the plaque.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Arterial calcification is an active process regulated in a similar way as bone formation, and although it is considered as the final phase of the plaque development, which would be in accordance with the absence of <span class="elsevierStyleSup">18</span>F-FDG uptake,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> it also can be seen in the early phases.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> In this sense, it seems justified to study in depth this physiological process in the atherogenesis.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Recently, Derlin et al. from The University Medical Center Hamburg-Eppendorf have reported the uptake of <span class="elsevierStyleSup">18</span>F-sodium fluoride by the plaques that are found incidentally in a retrospective review of oncologic patients in whom the scan was done for the study of bone metastasis.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9–11</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Calcification may be one of the processes involved in the growth progression of the arterial wall which is in accordance with the new pathophysiological theories of the atherogenesis and vascular calcification. It opens new lines of research for molecular imaging not only to study the atherogenesis in depth but also to evaluate the introduction of new therapies and to monitor and measure the efficacy of the response.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In this setting, we designed a prospective study to evaluate the role of molecular imaging in a selected population with carotid stenosis detected by contrast enhanced CT by assessing the calcification process using <span class="elsevierStyleSup">18</span>F-sodium fluoride PET/CT scan.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Material and methods</span><p id="par0040" class="elsevierStylePara elsevierViewall">A prospective study was designed to evaluate the calcification process in the carotid plaques detected by CT in patients investigated for first time by Vascular Unit of the Neurology Department. The study was approved by the Ethics Committee of our hospital and informed consent was signed by all the patients.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Patients and carotid atheroma plaques</span><p id="par0045" class="elsevierStylePara elsevierViewall">The study included 15 patients, 10 men and 5 women. The age ranged from 52 to 82 years, and the mean age was 69 years. All patients showed at least one carotid plaque detected by contrast enhanced CT. Of the 15, 8 had neurovascular symptoms: transient ischemic attack (TIA) in 3, cerebrovascular accident (CVA) in 3, CVA and contralateral TIA in 1 and retinal ischaemia in 1. The other 7 have no neurovascular symptoms or signs.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The 8 symptomatic patients had 16 plaques, 10 of them ipsilaterals to the cerebral hemisphere of the vascular event and the other 6 asymptomatic. The 7 asymptomatic patients had 13 plaques in total. Altogether there were 29 carotid plaques, 10 in the 8 symptomatic patients and potentially related with the ipsilateral vascular event and 19 in the 7 asymptomatic patients.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Acquisition and processing of <span class="elsevierStyleSup">18</span>F-sodium fluoride PET/CT scan</span><p id="par0055" class="elsevierStylePara elsevierViewall">All patients underwent a PET/CT examination using a Siemens Biograph PICO 3D LSO. Images of chest and neck were acquired during 3<span class="elsevierStyleHsp" style=""></span>minutes per bed 180<span class="elsevierStyleHsp" style=""></span>minutes after the i.v. injection of 370 MBq of <span class="elsevierStyleSup">18</span>F-sodium fluoride. For image reconstruction, attenuation correction was applied and an iterative algorithm including 2 iterations and 16 subsets was employed.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Interpretation of the PET/CT scans</span><p id="par0060" class="elsevierStylePara elsevierViewall">A visual reading of each examination was done and an intensity grading was applied according to a scale raging from 0 (absence of uptake) to 5 (uptake the same or higher than cervical spine) (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Analysis of the results</span><p id="par0065" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleSup">18</span>F-sodium fluoride uptake by each plaque in the symptomatic population was compared with the asymptomatic populations.</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0070" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a> shows the distribution of the plaques according to the intensity of the uptake and for each of the 2 groups, symptomatic and asymptomatic. It can be seen that all the plaques in the group of patients with symptomatology showed an intensity of uptake of 2 or higher, whereas in the asymptomatic group the distribution was more heterogeneous 6 plaques showing an uptake lower than 2.</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">In a more detailed analysis of the data, <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the number and the percentage of plaques according to the thresholds of intensity of the uptake rating. All plaques, symptomatic or not, revealed some degree of uptake; however, the percentage of symptomatic plaques with uptake above 2 was higher than in the asymptomatic group, although the difference was not significant.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0080" class="elsevierStylePara elsevierViewall">This is the first study prospectively designed to assess the metabolism of the carotid atheroma plaque using the <span class="elsevierStyleSup">18</span>F-sodium fluoride as a marker of calcification. While <span class="elsevierStyleSup">18</span>F-FDG can be already considered an established technique to evaluate the atheroma inflammation and to monitor anti-inflammatory therapies,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> the introduction of <span class="elsevierStyleSup">18</span>F-fluoride offers a new approach based on the previous and recent retrospective reports on findings of systemic atheromatosis in oncologic population.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> From the publication of the first article, several authors have approached this topic,<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,11,13,14</span></a> but none of them focused on the carotid atheromatosis in a prospective way.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,13</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">These results correspond to a preliminary evaluation of the designed study and although it includes a small number of patients and some lax criteria of inclusion (carotid plaque by CT) the findings are relevant enough to be reported so that they can encourage future research in this direction. This is especially true if the results are considered within the new paradigms of the origin and development of the vascular atheroesclerosis.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> This new approach to the identification “in vivo” of the calcification process involved in the atheroma plaque opens new possibilities for the development and monitoring of new therapies.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Previous retrospective studies have reported that the association between calcification and <span class="elsevierStyleSup">18</span>F-sodium fluoride uptake may vary depending on the vascular territory. According to Dweck et al.,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> it could be explained by the low resolution of the PET technology and by the heterogeneity of the populations included in the studies. In our study, as reported in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, all the plaques showed <span class="elsevierStyleSup">18</span>F-sodium fluoride uptake which should not be unexpected as all of them where detected already by CT deserving to be referred to the Neurovascular Unit because of carotid atheromatosis. This could be also in agreement with Dweck et al. who reported a correlation between the degree of calcification and the <span class="elsevierStyleSup">18</span>F-sodium fluoride uptake although it was lower for the high degrees of calcification due, perhaps, to the stability result of an old process.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> The different uptake time for <span class="elsevierStyleSup">18</span>F-sodium fluoride, before the PET/CT acquisition, 180<span class="elsevierStyleHsp" style=""></span>min compared with the 60<span class="elsevierStyleHsp" style=""></span>min used by other groups can also explain the different results obtained.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9–11,13,14</span></a> The long uptake time used in our protocol is the result of our research comparing early and delayed acquisitions to avoid the overlap of blood pool activity when applying <span class="elsevierStyleSup">18</span>F-FDG PET/CT to the study of vasculitis and atheroma. the delayed acquisition provides a higher plaque/backgroung contrast.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16–18</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Taking into account the symptomatology of the plaque and its correlation with the <span class="elsevierStyleSup">18</span>F-sodium fluoride uptake is crucial for the potential application of the technique as biomarker of the stability of the plaque. In this sense, an association between the intensity of <span class="elsevierStyleSup">18</span>F-FDG uptake and instability has been reported.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Also, Li et al.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> and Dweck et al.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> have reported, an association between the intensity of <span class="elsevierStyleSup">18</span>F-sodium fluoride uptake and the development of cardiovascular events.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Although plaques, regardless symptomatology, took up <span class="elsevierStyleSup">18</span>F-sodium fluoride, it is interesting that in all the plaques corresponding to symptomatic patients the uptake intensity was 2 or more. Therefore, we can hypothesized a correlation between neurovascular symptomatology and the active calcification.</p><p id="par0105" class="elsevierStylePara elsevierViewall">The metabolic pattern described here cannot be taken, until now, as a specific biomarker of the instability of the plaque as <span class="elsevierStyleSup">18</span>F-sodium fluoride has been shown in our study to be taken up also by the asymptomatic plaques (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). However, this can only be clarified by the follow-up of these patients and the corresponding plaques.</p><p id="par0110" class="elsevierStylePara elsevierViewall">Other limitations of the study, in addition to the small number of patients, are the difficulty to accurately determine the cause of the cerebrovascular event, and the clinical heterogeneity of the symptomatic group, a limitation, which could be overcome by increasing the patient population.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conclusions</span><p id="par0115" class="elsevierStylePara elsevierViewall">Although the number of patients is small, the results allow us to report the feasibility of <span class="elsevierStyleSup">18</span>F-sodium fluoride PET/CT to image the carotid plaque. The study showed that all the plaques took up the <span class="elsevierStyleSup">18</span>F-sodium fluoride, regardless the intensity. The study also showed an association between the intensity of uptake and symptomatology. This allows us to hypothesize a relationship between active calcification and the instability of the plaque associated or not to the effect of inflammation. Therefore, the results of this preliminary work are encouraging to include the number of patients to clarify the real meaning of these findings in order to contribute to the knowledge of the atherogenesis by in vivo imaging molecular techniques.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of interest</span><p id="par0120" class="elsevierStylePara elsevierViewall">No conflict of interests.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:2 [ "identificador" => "xres119578" "titulo" => array:5 [ 0 => "Abstract" 1 => "Aim" 2 => "Material and methods" 3 => "Results" 4 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec106858" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres119577" "titulo" => array:5 [ 0 => "Resumen" 1 => "Objetivo" 2 => "Material y métodos" 3 => "Resultados" 4 => "Conclusiones" ] ] 3 => array:2 [ "identificador" => "xpalclavsec106857" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients and carotid atheroma plaques" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Acquisition and processing of F-sodium fluoride PET/CT scan" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Interpretation of the PET/CT scans" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Analysis of the results" ] ] ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0045" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflict of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-08-01" "fechaAceptado" => "2012-08-24" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec106858" "palabras" => array:6 [ 0 => "Carotid atheroma" 1 => "<span class="elsevierStyleSup">18</span>F-sodium fluoride PET/CT" 2 => "Calcification" 3 => "Atherosclerosis" 4 => "Stroke" 5 => "Molecular imaging" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec106857" "palabras" => array:6 [ 0 => "Ateromatosis carotídea" 1 => "PET/TAC con <span class="elsevierStyleSup">18</span>F-Fluoruro Sódico" 2 => "Calcificación" 3 => "Ateroesclerosis" 4 => "Accidente cerebro vascular" 5 => "Imagen molecular" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle">Aim</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To assess the calcification process of the carotid plaque by <span class="elsevierStyleSup">18</span>F-sodium fluoride PET/CT imaging.</p> <span class="elsevierStyleSectionTitle">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A prospectively designed study including 15 patients in whom an atheroma plaque was detected by contrast enhanced CT scan during a neurological work-up was performed. A total of 29 plaques, 19 asymptomatic and 10 symptomatic, were studied. An <span class="elsevierStyleSup">18</span>F-sodium fluoride PET/CT scan was acquired 180<span class="elsevierStyleHsp" style=""></span>min after the i.v. injection of 370 MBq of <span class="elsevierStyleSup">18</span>F-sodium fluoride in all the patients. The images obtained were analyzed visually according to the intensity of the uptake.</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">All the plaques showed <span class="elsevierStyleSup">18</span>F-sodium fluoride uptake, regardless of the intensity. However, the plaques of the symptomatic group showed a level of 2 or greater intensity while the intensity in 6 of the 19 in the asymptomatic group was lower than 2.</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Although the study is limited by the small number of cases, the results show the feasibility of the technique to study the calcification of the atheroma using <span class="elsevierStyleSup">18</span>F-sodium fluoride and suggest an association between symptomatology and higher uptake of <span class="elsevierStyleSup">18</span>F-sodium fluoride. Thus, these results encourage us to continue this study, with the inclusion of a larger number of patients.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Estudiar el proceso de calcificación de la placa de ateroma carotideo mediante <span class="elsevierStyleSup">18</span>F-fluoruro sódico PET/TAC.</p> <span class="elsevierStyleSectionTitle">Material y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo en 15 pacientes con ateromatosis carotidea detectada por angio-TAC durante su estudio neurológico. El total de placas de ateroma estudiadas fue de 29, 19 asintomáticas y 10 sintomáticas. En todos los pacientes se adquirió un estudio PET/TAC a los 180<span class="elsevierStyleHsp" style=""></span>min De la administración intravenosa de 370 MBq de <span class="elsevierStyleSup">18</span>F-fluoruro sódico. Las imágenes se analizaron visualmente considerando la intensidad de captación.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Todas las placas captaron <span class="elsevierStyleSup">18</span>F-fluoruro sódico, con independencia de la intensidad. Sin embargo las placas del grupo sintomático mostraron una intensidad de 2 o mayor mientras que 6 de las 19 del grupo asintomático mostraron una intensidad inferior a 2.</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Aunque el estudio está limitado por el pequeño número de casos, los resultados muestran la aplicabilidad de la técnica al estudio de la calcificación del ateroma con <span class="elsevierStyleSup">18</span>F-fluoruro sódico y sugieren una asociación entre la sintomatología y una mayor captación de <span class="elsevierStyleSup">18</span>F-fluoruro sódico. Por ello, estos resultados nos animan a continuar este estudio incluyendo un mayor número de pacientes.</p>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 750 "Ancho" => 2167 "Tamanyo" => 84886 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Sagittal slices in a patient with repeated TIAs during the previous year and on statin, antiaggregant and antihypertensive treatment. High uptake of <span class="elsevierStyleSup">18</span>F-sodium fluoride (intensity 4) is seen.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2237 "Ancho" => 2333 "Tamanyo" => 260833 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Images of the atheroma plaque in an asymptomatic patient with a 50% stenosis of the right internal carotid. There was a low intensity <span class="elsevierStyleSup">18</span>F-sodium fluoride uptake (intensity 1).</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1021 "Ancho" => 1604 "Tamanyo" => 80178 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Graph representing the distribution of the plaques according to the intensity and symptomatology.</p>" ] ] 3 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Intensity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Asymptomatic <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Symptomatic <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (100%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (100%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (68%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (100%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (42%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (50%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (11%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (20%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab207780.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Intensity of uptake vs. symptomatology.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:19 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Low risk of ipsilateral stroke in patients with asymptomatic carotid stenosis on best medical treatment: a prospective, population-based study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "L. 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Rothwell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/STROKEAHA.109.561837" "Revista" => array:6 [ "tituloSerie" => "Stroke" "fecha" => "2010" "volumen" => "41" "paginaInicial" => "e11" "paginaFinal" => "e17" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19926843" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guidelines for management of ischaemic stroke and transient ischaemic attack 2008" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "European Stroke Organisation (ESO) Executive Committee; ESO Writing Committee" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000131083" "Revista" => array:6 [ "tituloSerie" => "Cerebrovasc Dis" "fecha" => "2008" "volumen" => "25" "paginaInicial" => "457" "paginaFinal" => "507" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18477843" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effects of angiotensin-converting enzyme inhibition on endothelial dysfunction: potential role in myocardial ischemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "C.J. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2023 March | 2 | 0 | 2 |
| 2018 February | 6 | 1 | 7 |
| 2018 January | 1 | 0 | 1 |
| 2017 December | 8 | 0 | 8 |
| 2017 November | 6 | 1 | 7 |
| 2017 October | 12 | 3 | 15 |
| 2017 September | 7 | 0 | 7 |
| 2017 August | 10 | 1 | 11 |
| 2017 July | 5 | 2 | 7 |
| 2017 June | 11 | 19 | 30 |
| 2017 May | 10 | 0 | 10 |
| 2017 April | 13 | 2 | 15 |
| 2017 March | 10 | 3 | 13 |
| 2017 February | 16 | 6 | 22 |
| 2017 January | 14 | 1 | 15 |
| 2016 December | 8 | 4 | 12 |
| 2016 November | 11 | 8 | 19 |
| 2016 October | 18 | 1 | 19 |
| 2016 September | 14 | 4 | 18 |
| 2016 August | 10 | 2 | 12 |
| 2016 July | 16 | 1 | 17 |
| 2016 June | 16 | 8 | 24 |
| 2016 May | 22 | 1 | 23 |
| 2016 April | 17 | 3 | 20 |
| 2016 March | 13 | 5 | 18 |
| 2016 February | 13 | 5 | 18 |
| 2016 January | 17 | 6 | 23 |
| 2015 December | 8 | 5 | 13 |
| 2015 November | 7 | 6 | 13 |
| 2015 October | 17 | 5 | 22 |
| 2015 September | 5 | 6 | 11 |
| 2015 August | 6 | 1 | 7 |
| 2015 July | 4 | 3 | 7 |
| 2015 June | 4 | 4 | 8 |
| 2015 May | 15 | 3 | 18 |
| 2015 April | 14 | 3 | 17 |
| 2015 March | 15 | 5 | 20 |
| 2015 February | 14 | 0 | 14 |
| 2015 January | 28 | 6 | 34 |
| 2014 December | 32 | 6 | 38 |
| 2014 November | 14 | 0 | 14 |
| 2014 October | 30 | 1 | 31 |
| 2014 September | 10 | 0 | 10 |
| 2014 August | 16 | 0 | 16 |
| 2014 July | 24 | 0 | 24 |
| 2014 June | 10 | 1 | 11 |
| 2014 May | 10 | 0 | 10 |
| 2014 April | 14 | 0 | 14 |
| 2014 March | 19 | 3 | 22 |
| 2014 February | 12 | 3 | 15 |
| 2014 January | 15 | 3 | 18 |
| 2013 May | 3 | 0 | 3 |
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