One-day protocol for <span class="elsevierStyleSup">18</span>F-FDG and <span class="elsevierStyleSup">13</span>N-ammonia PET/CT with uptake decoupling score in differentiating untreated low-grade glioma from inflammation | Revista Española de Medicina Nuclear e Imagen Molecular (English Edition)

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Low-grade gliomas &#40;LGGs&#59; World Health Organization &#91;WHO&#93; grades I and II&#41; are a diverse group of primary brain tumors that often arise in young&#44; otherwise healthy patients&#59; these commonly follow an indolent course and exhibit long-term survival&#44; which contrasts with the prognosis of high-grade gliomas&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> Accurate diagnosis and grading are critical for management of LGGs&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Although histopathological examination of tissue remains the gold standard for diagnosis and grading of LGGs&#44; preoperative imaging is essential to distinguish between inflammation and tumor&#46; However&#44; gliomas are often histologically heterogeneous&#44; with evolving anaplastic areas within a low-grade tumor&#59; moreover&#44; contrast-enhancement on CT or MRI does not provide a good marker for anaplastic tissue detection&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The development of radiolabeled tracers has enabled metabolic and molecular imaging to play a major role in the management of gliomas&#44; such as PET&#46; To successfully use PET data in glioma treatment&#44; PET can be integrated in the planning of image-guided biopsy&#44; resection&#44; and radiosurgery&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Additionally&#44; amino acid tracers have a high sensitivity for detection of LGGs&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Notably&#44; fluorothymidine is useful in grading gliomas&#44; as is dynamic PET using fluoroethyltyrosine &#40;FET&#41; for tumor grading&#59;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;8</span></a> however&#44; these tracers are either complicated to synthesize&#44; with low yields&#44; or require a complex acquisition protocol&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">In a previous study&#44; we found that <span class="elsevierStyleSup">13</span>N-ammonia PET was superior to <span class="elsevierStyleSup">18</span>F-FDG PET and contrast-enhanced MRI for grading of untreated gliomas and that it could be used for the detection of high-grade gliomas and recurrent astrocytomas&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#8211;11</span></a> Thus far&#44; differentiation between neoplastic and non-neoplastic lesions has been evaluated in several studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13</span></a> However&#44; our recent study found that <span class="elsevierStyleSup">13</span>N-ammonia was effective in distinguishing high-grade gliomas from low-grade gliomas and inflammation&#44; but its role in differential diagnose of low-grade gliomas and brain inflammatory lesions was limited&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> This might be attributed to difficulty in discriminating between brain inflammation lesions &#40;BILs&#41; and LGGs by using conventional imaging modalities&#59; furthermore&#44; there are no established quantification approaches for image analysis using <span class="elsevierStyleSup">13</span>N-ammonia and <span class="elsevierStyleSup">18</span>F-FDG&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In this retrospective study&#44; we performed voxel-wise analysis of <span class="elsevierStyleSup">18</span>F-FDG and <span class="elsevierStyleSup">13</span>N-ammonia PET in tumor and inflammation-infiltrative brain lesions&#44; in an attempt to discriminate between benign lesions and LGGs using decoupling score&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Patients</span><p id="par0020" class="elsevierStylePara elsevierViewall">This study was performed between july 2011 and may 2016&#46; A total of 28 patients with a final diagnosis of LGG &#40;13 female and 15 male patients&#59; mean age&#44; 36&#46;53&#8239;&#177;&#8239;14&#46;59 years&#59; age range&#44; 14&#8211;67 years&#41; and 16 patients with a final diagnosis of BIL &#40;8 female and 8 male patients&#59; mean age&#44; 46&#46;38&#8239;&#177;&#8239;16&#46;49 years&#59; range&#44; 23&#8211;73 years&#41; were included in this study&#46; Patients with any previous treatments were excluded &#40;e&#46;g&#46;&#44; corticosteroids&#44; surgery&#44; chemotherapy&#44; radiotherapy&#44; or gamma-knife therapy&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> All patients underwent <span class="elsevierStyleSup">13</span>N-ammonia PET&#47;CT and <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT on the same day &#40;FDG PET&#47;CT was performed after ammonia PET&#47;CT&#44; with a minimum interval of 2&#8239;h&#41;&#46; In 34 patients&#44; pathological diagnosis was obtained by tumor resection or biopsy after PET examination&#46; Four patients had grade I glioma&#44; according to the WHO classification&#44; whereas 24 had WHO grade II glioma &#40;19 were astrocytoma&#44; 4 were oligodendroglioma&#44; and 1 was oligoastrocytoma&#41;&#46; The remaining patients had BILs &#40;3 were brain abscess&#44; 2 were demyelination&#44; and 1 was fungal infection&#41;&#46; In 10 patients&#44; the results of pathological examination could not be obtained&#59; thus&#44; the diagnosis of inflammation was based on radiological &#40;CT and MRI&#41; and clinical investigation&#46; The patients&#8217; characteristics are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The study of <span class="elsevierStyleSup">13</span>N-ammonia imaging has been approved by the ethics committee of our hospital&#46; Although formal consent was not required for this retrospective study&#44; all subjects agreed to participate in this study after receiving an explanation of detailed study purpose and imaging procedure&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">PET data acquisition</span><p id="par0030" class="elsevierStylePara elsevierViewall">Tracers were produced at our center by using standard techniques and commercially available system for isotope generation &#40;Cyclone-10&#44; Ion Beam Applications&#59; Louvain-La-Neuve&#44; Belgium&#41;&#46; PET&#47;CT imaging was performed with a Gemini GXL 16 scanner &#40;Philips&#44; Amsterdam&#44; Netherlands&#41; in a 3-dimensional &#40;3D&#41; acquisition mode&#46; The specific imaging protocol for the brain was selected as field of view &#40;FOV&#41; 180&#8239;mm&#44; and the transaxial spatial resolution was 2&#8239;mm full width at half maximum &#40;FWHM&#41; at the center of the FOV for <span class="elsevierStyleSup">18</span>F-FDG&#46; The spatial resolution of <span class="elsevierStyleSup">13</span>N-ammonia imaging was lower than that of <span class="elsevierStyleSup">18</span>F-FDG because of the difference in positron energy&#46; PET images were reconstructed by the Line of Response RAMLA algorithm with low-dose CT images for attenuation correction&#44; resulting in 3D images comprising 128&#8239;&#215;&#8239;128&#8239;&#215;&#8239;90 voxels of 2&#46;0&#8239;&#215;&#8239;2&#46;0&#8239;&#215;&#8239;2&#46;0 mm<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">All subjects fasted for at least 8&#8239;h before PET&#47;CT imaging&#46; Ammonia and FDG PET&#47;CT studies were performed on the same day&#44; as described above&#46; The 10-min PET acquisition began 5&#8239;min after an intravenous injection of <span class="elsevierStyleSup">13</span>N-ammonia &#40;555&#8211;740&#8239;MBq&#41; or 45&#8211;60&#8239;min after an intravenous injection of <span class="elsevierStyleSup">18</span>F-FDG &#40;5&#46;18&#8239;MBq&#47;kg&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Data analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">One experienced nuclear medicine physician&#44; who was blinded to the clinical and structural imaging findings&#44; evaluated the PET&#47;CT images&#46; PET images were converted to NII format and co-registered using SPM software &#40;Functional Imaging Laboratory&#44; Wellcome Trust Centre for Neuroimaging&#44; Institute of Neurology&#44; UCL&#44; London&#44; UK&#41;&#46; The registration of the images was confirmed visually&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Lesion uptake was evaluated by semiquantitative analysis&#46; Regions of interest &#40;ROIs&#41; for each lesion were outlined in the area with the highest activity&#44; and the location of the lesion was determined by using CT image guidance to avoid misplacement&#46; For lesions that did not show higher uptake than the surrounding tissue&#44; ROIs were defined on CT images after co-registering the PET and CT images&#46; All ROIs of each tumor were placed carefully to avoid areas of necrosis&#44; hemorrhage&#44; or normal tissue&#59; in addition&#44; the first and the last slices of each tumor were not used&#44; to avoid the volume effect&#46; For reference tissue&#44; ROIs were selected at the uninvolved contralateral hemisphere of the same slice of the lesion ROI&#44; including both gray and white matter&#46; The average standardized uptake value &#40;SUV&#41; of all regions was used to calculate the tumor to normal tissue &#40;T&#47;N&#41; ratio&#44; enabling reconstruction of a T&#47;N ratio image&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">All datasets &#40;standard anatomical images and PET data&#41; were exported to in-house software written in MATLAB 7&#46;6 &#40;MathWorks&#44; Natick&#44; MA&#44; USA&#41; for further analysis&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Decoupling score calculation</span><p id="par0055" class="elsevierStylePara elsevierViewall">As illustrated in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#44; a linear relationship between <span class="elsevierStyleSup">13</span>N-ammonia uptake and <span class="elsevierStyleSup">18</span>F-FDG uptake in normal brain was observedas follows&#58;<elsevierMultimedia ident="eq0005"></elsevierMultimedia>where &#40;<span class="elsevierStyleSup">13</span>N-ammonia&#41; and &#40;<span class="elsevierStyleSup">18</span>F-FDG&#41; represent the T&#47;N ratios of <span class="elsevierStyleSup">13</span>N-ammonia and <span class="elsevierStyleSup">18</span>F-FDG PET&#44; respectively&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Subsequently&#44; calculate the deviation of each data point &#40;i&#41; from the expected linear regression fit as follows&#58;<elsevierMultimedia ident="eq0010"></elsevierMultimedia>where &#40;<span class="elsevierStyleSup">13</span>N-ammonia&#41; and &#40;<span class="elsevierStyleSup">18</span>F-FDG&#41; represent the T&#47;N ratios of <span class="elsevierStyleSup">13</span>N-ammonia and <span class="elsevierStyleSup">18</span>F-FDG PET&#44; respectively&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The decoupling score of each data point was defined as follows&#58;<elsevierMultimedia ident="eq0015"></elsevierMultimedia>where &#181; and &#963; represent the mean and standard deviation of deviation &#40;i&#41; for the ROI located in the normal brain&#46; This score &#40;i&#41; could be used to quantify the difference between <span class="elsevierStyleSup">13</span>N-ammonia uptake and <span class="elsevierStyleSup">18</span>F-FDG uptake in brain lesions&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;16</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Statistical analysis</span><p id="par0070" class="elsevierStylePara elsevierViewall">Statistical analysis was conducted on the platform of PASW Statistics 18&#46;0 &#40;IBM&#44; Armonk&#44; NY&#44; USA&#41;&#46; Sensitivity&#44; specificity&#44; negative predictive value &#40;NPV&#41;&#44; and positive predictive value &#40;PPV&#41; with 95&#37; confidence intervals &#40;CI&#41; were calculated for each tracer with T&#47;N ratios&#46; Student&#8217;s t-test was used to compare T&#47;N ratios and decoupling scores of each tracer between LGGs and BILs&#46; Receiver operating characteristic &#40;ROC&#41; analysis was used to establish a cut-off value for the decoupling score&#44; and the area under the curve &#40;AUC&#41; was calculated to evaluate differential efficacy&#46; Results were considered significant at the level of p&#8239;&#60;&#8239;0&#46;05&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Decoupling map reconstruction in LGG and BIL</span><p id="par0075" class="elsevierStylePara elsevierViewall">According to visual analysis&#44; decoupling scores were markedly increased in the tumors&#44; compared to surrounding normal brain tissues&#59; this allowed precise delineation of the extent of tumor &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Conversely&#44; decoupling scores of BILs were similar to or lower than those of surrounding normal brain tissue &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; In <span class="elsevierStyleSup">18</span>F-FDG or <span class="elsevierStyleSup">13</span>N-ammonia T&#47;N ratio maps&#44; LGGs and BILs did not exhibit fixed patterns of expression and were higher or lower than surrounding normal brain tissues&#46; Tumor boundaries were always more clearly delineated in the decoupling map than in the T&#47;N ratio map&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">T&#47;N ratios in LGG and BIL</span><p id="par0080" class="elsevierStylePara elsevierViewall">The T&#47;N ratios of <span class="elsevierStyleSup">18</span>F-FDG were lower than those of <span class="elsevierStyleSup">13</span>N-ammonia in LGGs &#40;mean&#8239;&#177;&#8239;standard deviation&#44; 0&#46;76&#8239;&#177;&#8239;0&#46;23 vs&#46; 1&#46;00&#8239;&#177;&#8239;0&#46;18&#44; t&#8239;&#61;&#8239;&#8722;6&#46;718&#44; p&#8239;&#60;&#8239;0&#46;001&#41;&#46; However&#44; no significant difference was observed between <span class="elsevierStyleSup">18</span>F-FDG and <span class="elsevierStyleSup">13</span>N-ammonia in BILs &#40;0&#46;88&#8239;&#177;&#8239;0&#46;52 vs&#46; 0&#46;84&#8239;&#177;&#8239;0&#46;22&#44; t&#8239;&#61;&#8239;0&#46;330&#44; p&#8239;&#61;&#8239;0&#46;746&#41;&#46; The T&#47;N ratios of <span class="elsevierStyleSup">18</span>F-FDG uptake were not useful for differentiating LGGs from BILs &#40;LGG vs&#46; BIL&#58; 0&#46;76&#8239;&#177;&#8239;0&#46;23 vs&#46; 0&#46;88&#8239;&#177;&#8239;0&#46;52&#44; t&#8239;&#61;&#8239;&#8722;0&#46;836&#44; p&#8239;&#61;&#8239;0&#46;413&#41;&#44; whereas the T&#47;N ratios of <span class="elsevierStyleSup">13</span>N-ammonia &#40;LGG vs&#46; BIL&#58; 1&#46;00&#8239;&#177;&#8239;0&#46;18 vs&#46; 0&#46;84&#8239;&#177;&#8239;0&#46;22&#44; t&#8239;&#61;&#8239;2&#46;519&#44; p&#8239;&#61;&#8239;0&#46;018&#41; uptake were better performance than those of <span class="elsevierStyleSup">18</span>F-FDG in differentiating LGGs from BILs&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">ROC analysis yielded optimal T&#47;N cut-off values of 0&#46;73 for <span class="elsevierStyleSup">18</span>F-FDG and 0&#46;97 for <span class="elsevierStyleSup">13</span>N-ammonia for differentiating between LGGs and BILs&#59; the respective AUCs were 0&#46;48 and 0&#46;68&#46; For prediction of LGGs using these optimal cut-off values&#44; the respective sensitivity&#44; specificity&#44; accuracy&#44; PPV&#44; and NPV were 53&#46;6&#37; &#40;15&#47;28&#41;&#44; 62&#46;5&#37; &#40;10&#47;16&#41;&#44; 56&#46;8&#37; &#40;25&#47;44&#41;&#44; 71&#46;4&#37; &#40;15&#47;21&#41;&#44; and 43&#46;5&#37; &#40;10&#47;23&#41; for <span class="elsevierStyleSup">18</span>F-FDG&#59; they were 50&#46;0&#37; &#40;14&#47;28&#41;&#44; 75&#46;0&#37; &#40;12&#47;16&#41;&#44; 59&#46;1&#37; &#40;26&#47;44&#41;&#44; 77&#46;8&#37; &#40;14&#47;18&#41;&#44; and 46&#46;2&#37; &#40;12&#47;26&#41; for <span class="elsevierStyleSup">13</span>N-ammonia&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Decoupling score in LGGs and BILs</span><p id="par0090" class="elsevierStylePara elsevierViewall">The average decoupling scores of <span class="elsevierStyleSup">18</span>F-FDG and <span class="elsevierStyleSup">13</span>N-ammonia were calculated for both LGGs and BILs&#59; these were 2&#46;48&#8239;&#177;&#8239;0&#46;62 and 1&#46;72&#8239;&#177;&#8239;0&#46;61&#44; respectively&#44; demonstrating a significant difference &#40;t&#8239;&#61;&#8239;3&#46;252&#44; p&#8239;&#61;&#8239;0&#46;003&#41;&#46; The optimal T&#47;N cut-off value for the decoupling score to differentiate between LGG and BIL&#44; as determined by ROC curve analysis&#44; was 2&#46;31 &#40;AUC&#44; 0&#46;77&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; For the diagnosis of LGG using the optimal cut-off values&#44; the respective sensitivity&#44; specificity&#44; accuracy&#44; PPV&#44; and NPV were 60&#46;7&#37; &#40;17&#47;28&#41;&#44; 93&#46;8&#37; &#40;15&#47;16&#41;&#44; 72&#46;7&#37; &#40;32&#47;44&#41;&#44; 94&#46;4&#37; &#40;17&#47;18&#41;&#44; and 57&#46;7&#37; &#40;15&#47;26&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> summarizes the PET results of T&#47;N ratios and decoupling scores for <span class="elsevierStyleSup">13</span>N-ammonia and <span class="elsevierStyleSup">18</span>F-FDG PET uptake studies&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0095" class="elsevierStylePara elsevierViewall">Although molecular diagnostics &#40;e&#46;g&#46;&#44; chromosomal and gene array technologies&#41; are becoming increasingly beneficial for understanding tumor genetic heterogeneity&#44; <a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> these approaches always require invasive tissue analysis and therefore cannot fully replace non-invasive diagnostics&#46; MRI&#44; with or without gadolinium&#44; remains the gold standard for noninvasive diagnosis and follow-up of patients with gliomas&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;3&#44;4</span></a> In patients with a suspected brain tumor&#44; anatomic imaging sequences typically include T1- and T2-weighted MR sequences&#44; as well as fluid attenuation inversion recovery MR sequences&#59; T1- weighted imaging is performed after administration of gadolinium-based contrast&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> However&#44; this technique only indirectly reflects the biological activity of the tumor by detecting destruction of the blood-brain barrier&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Therefore&#44; routine MRI lacks accuracy in terms of non-invasive assessment&#44; especially for LGGs and BILs&#46; Although advanced MR techniques &#40;e&#46;g&#46;&#44; perfusion imaging&#44; diffusion-weighted imaging&#44; diffusion tensor imaging&#44; and MR spectroscopy&#41; provide some metabolic and functional information for differentiating gliomas from non-neoplastic brain lesions&#44;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#8211;22</span></a> they also involve some limitations&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> These drawbacks include&#58; partial volume effects&#44; non-standardized acquisition&#44; and a postprocessing protocol that is non-specific for LGGs&#46; Herein&#44; the molecular information provided by PET is valuable in its ability to supplement additional imaging data&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">18</span>F-FDG and amino-acid tracers&#44; such as <span class="elsevierStyleSup">11</span>C-methionine &#40;<span class="elsevierStyleSup">11</span>C-MET&#41;&#44; <span class="elsevierStyleSup">18</span>F-FET&#44; and <span class="elsevierStyleSup">18</span>F-FDOPA&#44; provide corresponding metabolic data that enable precise assessment of glioma extension&#44; detection of anaplastic areas&#44; and postoperative follow-up&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23&#8211;25</span></a> These methods have high sensitivity&#44; as well as positive results&#44; in both acute and chronic inflammation&#46; Previously&#44; we reported that <span class="elsevierStyleSup">13</span>N-ammonia&#44; combined with <span class="elsevierStyleSup">18</span>F-FDG&#44; exhibits great potential for the diagnosis&#44; grading&#44; and postoperative follow-up of intracranial lesions&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#8211;11</span></a> Moreover&#44; we analyzed the application of <span class="elsevierStyleSup">13</span>N-ammonia in the diagnosis of glioma and inflammatory lesions&#44; concluding that <span class="elsevierStyleSup">13</span>N-ammonia could distinguish high-grade gliomas from low-grade gliomas and inflammations&#44; but could not distinguish low-grade gliomas from inflammatory lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Therefore&#44; we used a new voxel-wise analysis to process <span class="elsevierStyleSup">13</span>N-ammonia and <span class="elsevierStyleSup">18</span>F-FDG uptake in both LGGs and inflammatory lesions&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Our previous reports showed that <span class="elsevierStyleSup">13</span>N-ammonia uptake was higher than <span class="elsevierStyleSup">18</span>F-FDG uptake in high-grade gliomas and meningiomas&#44;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;26</span></a> while <span class="elsevierStyleSup">13</span>N-ammonia uptake was lower than <span class="elsevierStyleSup">18</span>F-FDG uptake in brain abscesses and primary central nervous system lymphomas&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;27</span></a> However&#44; LGGs and BILs showed heterogeneous uptake in both <span class="elsevierStyleSup">13</span>N-ammonia and <span class="elsevierStyleSup">18</span>F-FDG&#46; As shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>b&#44; lesions &#40;WHO grade &#8545; oligodendroglioma&#41; showed lower <span class="elsevierStyleSup">18</span>F-FDG and <span class="elsevierStyleSup">13</span>N-ammonia uptake than normal brain tissues&#46; The average T&#47;N ratios of <span class="elsevierStyleSup">18</span>F-FDG and <span class="elsevierStyleSup">13</span>N-ammonia uptake&#44; obtained from 16 layers of lesions&#44; were 0&#46;55 and 0&#46;93&#44; respectively&#46; These results were not helpful in the diagnosis of the lesions&#46; Conversely&#44; a remarkably high decoupling score was observed in the lesions in the decoupling map&#44; which could be helpful for diagnosis&#46; Similarly&#44; as shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>a&#44; lesions &#40;WHO grade &#8545; astrocytoma&#41; showed lower <span class="elsevierStyleSup">18</span>F-FDG uptake&#44; but higher <span class="elsevierStyleSup">13</span>N-ammonia uptake and decoupling score&#44; compared to normal brain tissues&#46; Furthermore&#44; as shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#44; lesions &#40;inflammation&#41; showed higher <span class="elsevierStyleSup">18</span>F-FDG uptake&#44; but lower <span class="elsevierStyleSup">13</span>N-ammonia uptake and decoupling score&#44; compared to normal brain tissues&#46; ROC analysis revealed the optimal performance of the decoupling score at a cut-off value of 2&#46;31 &#40;sensitivity&#44; 60&#46;7&#37;&#59; specificity&#44; 93&#46;8&#37;&#41;&#44; with an AUC of 0&#46;77&#46; This result indicated that the decoupling score is a better surrogate indicator for discriminating between LGGs and BILs&#44; compared to <span class="elsevierStyleSup">13</span>N-ammonia and <span class="elsevierStyleSup">18</span>F-FDG PET alone&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Many studies have shown that amino acid tracers were used in the management of patients with low-grade gliomas&#44; but few have directly compared their differential efficacy to differentiate LGGs and inflammation&#46; Kracht et al&#46; reported <span class="elsevierStyleSup">11</span>C-MET PET in 13 LGGs and 3 nontumor lesions patients with 87&#37; sensitivity and 89&#37; specificity of 1&#46;3-fold <span class="elsevierStyleSup">11</span>C-MET uptake relative to normal brain tissue&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">18</span>F-FET PET also appeared to be superior to FDG-PET for biopsy planning in non-contrast-enhancing brain tumurs&#44; 69&#37; LGGs &#40;49&#47;71&#41; had been found increased <span class="elsevierStyleSup">18</span>F-FET uptake in Jansen NL study&#44; 8&#47;9 LGGs had increased 18F-FET uptake in Plotkin M study&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23&#44;24</span></a><span class="elsevierStyleSup">18</span>F-DOPA was also useful to discriminate low-grade gliomas from high-grade gliomas in 2&#46;16 SUVmax with 60&#37; sensitivity and 100&#37; specificity&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Compared with the above amino acid tracers&#44; the decoupling score of <span class="elsevierStyleSup">18</span>F-FDG and <span class="elsevierStyleSup">13</span>N-ammonia method has higher specificity &#40;93&#46;8&#37;&#41; to differentiate LGGs and BILs&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Some previous studies<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;16</span></a> have reported that <span class="elsevierStyleSup">18</span>F-FDG-<span class="elsevierStyleSup">11</span>C-methionine uptake decoupling score reflects glioma cell infiltration to assess glioma invasion&#46; Similarly&#44; a linear relationship could be inferred between <span class="elsevierStyleSup">13</span>N-ammonia uptake and <span class="elsevierStyleSup">18</span>F-FDG uptake in the normal brain&#44; such that <span class="elsevierStyleSup">18</span>F-FDG can be used as a reference index for <span class="elsevierStyleSup">13</span>N-ammonia uptake in normal brain tissues&#46; The decoupling score calculated at each voxel represents the magnitude of the disrupted correlation of <span class="elsevierStyleSup">18</span>F-FDG and <span class="elsevierStyleSup">13</span>N-ammonia at each location of the brain&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">According to Cooper&#44;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> ammonia can act as a source of glutamine in the glutamine cycle&#46; Although inactive neovasculature provides a limited quantity of glutamine for trapping in LGGs&#44;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> deviation between <span class="elsevierStyleSup">18</span>F-FDG and <span class="elsevierStyleSup">13</span>N-ammonia uptake will be markedly evident in reconstructed images&#44; in the event of tumor infiltration&#46; Extreme decoupling of <span class="elsevierStyleSup">18</span>F-FDG and <span class="elsevierStyleSup">13</span>N-ammonia uptake was observed in LGGs&#44; suggesting that the difference in <span class="elsevierStyleSup">18</span>F-FDG and <span class="elsevierStyleSup">13</span>N-ammonia uptake could be expressed as the decoupling score&#46; This difference implies that the decoupling score is based on tumor infiltration into brain tissue&#44; although the relationship between inflammation and gliomas is rather complex&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> As reported in some literature&#44; tumor was usually accompanied by inflammation&#44; but the microenvironment of glioma contains many coordination mechanisms that are different from inflammation&#44; include various glioma-secreted signaling factors such as cytokines&#44; chemokines&#44; and growth factors&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> As also&#44; <span class="elsevierStyleSup">13</span>N-ammonia is involved in the glioma cells glutamine cycle&#44; <span class="elsevierStyleSup">18</span>F-FDG is involved in the glioma cells glucose cycle&#46; It may be due to the difference in the intracellular metabolic patterns of the two imaging agents in inflammation and glioma&#44; which ultimately leads to the difference in the decoupling scores&#44; and the mechanism needs further research&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">When <span class="elsevierStyleSup">11</span>C-MET coupled with <span class="elsevierStyleSup">18</span>F-FDG is used to diagnose gliomas&#44; patients are required to visit the hospital 2 times&#46; In the current one-day protocol&#44; after <span class="elsevierStyleSup">13</span>N-ammonia PET is acquired&#44; intravenous injection of <span class="elsevierStyleSup">18</span>F-FDG is administered after a 3-h interval&#46; Notably&#44; because of the short half-life of <span class="elsevierStyleSup">13</span>N and the urine excretion mechanism&#44; <span class="elsevierStyleSup">13</span>N-ammonia is already cleared from the body&#46; Therefore&#44; it would not affect the two PET tracers&#59; this enables same-day evaluation of <span class="elsevierStyleSup">13</span>N-ammonia and <span class="elsevierStyleSup">18</span>F-FDG PET&#46; Finally&#44; this approach was beneficial to the patients&#44; who were not required to travel to our PET center 2 times&#46; In addition&#44; according to the present study&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> the patient effective dose for <span class="elsevierStyleSup">13</span>N-ammonia brain PET&#47;CT &#40;active from 555 to 740&#8239;MBq&#41; was 4&#46;35&#8211;5&#46;57 mSv&#44; which is below the 5&#46;2&#8239;&#177;&#8239;0&#46;5&#8239;mSv dose for <span class="elsevierStyleSup">11</span>C-MET&#46; This radiation dose is below the threshold established by the International Commission on Radiological Protection &#40;ICRP&#41;&#59; therefore&#44; excess radiation dose caused by <span class="elsevierStyleSup">13</span>N-ammonia is not a concern with our new approach&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In this study&#44; we have presented decoupling score as a new voxel-wise method for evaluating <span class="elsevierStyleSup">18</span>F-FDG and <span class="elsevierStyleSup">13</span>N-ammonia uptake in LGGs&#46; Although registration-based voxel-by-voxel analysis has shown promising results and comprises a new analytical method for the prediction of LGGs and inflammatory lesions&#44; there are some inherent limitations in this study&#46; First&#44; the present study used small sample sizes of patients with LGGs or BILs&#59; thus&#44; these results should be further validated in prospective studies with a larger sample size&#46; Second&#44; clinical follow-up&#44; rather than histopathology&#44; was used in some patients with BILs&#46; Finally&#44; <span class="elsevierStyleSup">13</span>N-ammonia had an extremely short half-life &#40;approximately 10&#8239;min&#41;&#59; thus&#44; a cyclotron is needed on-site for clinical use of <span class="elsevierStyleSup">13</span>N-ammonia&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusions</span><p id="par0130" class="elsevierStylePara elsevierViewall">In conclusion&#44; a one-day protocol for <span class="elsevierStyleSup">18</span>F-FDG and <span class="elsevierStyleSup">13</span>N-ammonia PET&#47;CT with uptake decoupling score was implemented to analyze deviation of <span class="elsevierStyleSup">18</span>F-FDG and <span class="elsevierStyleSup">13</span>N-ammonia uptake in treatment-na&#239;ve LGGs and BILs&#46; The present results showed that the <span class="elsevierStyleSup">18</span>F-FDG&#8211;<span class="elsevierStyleSup">13</span>N-ammonia decoupling score was superior for detecting LGGs&#44; compared to <span class="elsevierStyleSup">18</span>F-FDG or <span class="elsevierStyleSup">13</span>N-ammonia uptake alone&#46; Thus&#44; this method seems feasible&#44; and may constitute an analytical approach for semi-quantitative image analysis to discriminate between LGGs and BILs&#46;</p></span></span>"
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          "titulo" => "Resumen"
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              "titulo" => "Prop&#243;sito"
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              "titulo" => "PET data acquisition"
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              "identificador" => "sec0025"
              "titulo" => "Data analysis"
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              "identificador" => "sec0030"
              "titulo" => "Decoupling score calculation"
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              "titulo" => "Statistical analysis"
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          "titulo" => "Results"
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            0 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Decoupling map reconstruction in LGG and BIL"
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            1 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "T&#47;N ratios in LGG and BIL"
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              "identificador" => "sec0055"
              "titulo" => "Decoupling score in LGGs and BILs"
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          "titulo" => "Discussion"
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            0 => "One-Day protocol"
            1 => "<span class="elsevierStyleSup">13</span>N-ammonia"
            2 => "<span class="elsevierStyleSup">18</span>F-FDG"
            3 => "Voxel-Wise analysis"
            4 => "Low-Grade gliomas"
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          "titulo" => "Palabras clave"
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          "palabras" => array:5 [
            0 => "protocolo de un d&#237;a"
            1 => "13N-amonio"
            2 => "18F-FDG"
            3 => "an&#225;lisis de voxel"
            4 => "gliomas de bajo grado"
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0011">Purpose</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Accurate identification of low-grade gliomas &#40;LGGs&#59; World Health Organization grades I and II&#41; and their differentiation from brain inflammation lesions &#40;BILs&#41; remains difficult&#59; however&#44; it is essential for treatment&#46; This study assessed whether a one-day protocol for voxel-wise <span class="elsevierStyleSup">18</span>F-FDG and <span class="elsevierStyleSup">13</span>N-ammonia PET&#47;CT with uptake decoupling analysis could differentiate LGGs from BILs&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Twenty-eight patients with LGGs and 16 patients with BILs underwent <span class="elsevierStyleSup">18</span>F-FDG and <span class="elsevierStyleSup">13</span>N-ammonia PET&#47;CT on the same day before any type of therapy&#46; The decoupling score and tumor-to-normal tissue &#40;T&#47;N&#41; ratio of <span class="elsevierStyleSup">18</span>F-FDG and <span class="elsevierStyleSup">13</span>N-ammonia were calculated at each location&#46; Student&#8217;s t-test was used to compare values&#44; and ROC curve analysis was used to establish a cut-off value for the T&#47;N ratio and decoupling score&#46; Area under the curve &#40;AUC&#41; was calculated to evaluate differential efficacy&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Significant differences were observed in <span class="elsevierStyleSup">13</span>N-ammonia T&#47;N ratio &#40;p&#8239;&#61;&#8239;0&#46;018&#41; and decoupling score &#40;p&#8239;&#61;&#8239;0&#46;003&#41; between LGGs and BILs&#59; however&#44; the <span class="elsevierStyleSup">18</span>F-FDG T&#47;N ratio did not show any differences &#40;p&#8239;&#61;&#8239;0&#46;413&#41;&#46; Optimal cut-off values for <span class="elsevierStyleSup">18</span>F-FDG T&#47;N ratio&#44; <span class="elsevierStyleSup">13</span>N-ammonia T&#47;N ratio&#44; and decoupling score were 0&#46;73&#44; 0&#46;97&#44; and 2&#46;31&#44; respectively&#44; with corresponding AUCs of 0&#46;48&#44; 0&#46;68&#44; and 0&#46;77&#46; The respective sensitivity&#44; specificity&#44; and accuracy parameters using these cut-off values were 53&#46;6&#37;&#44; 62&#46;5&#37;&#44; and 56&#46;8&#37;&#44; respectively&#44; for <span class="elsevierStyleSup">18</span>F-FDG&#59; 50&#46;0&#37;&#44; 75&#46;0&#37;&#44; and 59&#46;1&#37;&#44; respectively&#44; for <span class="elsevierStyleSup">13</span>N-ammonia&#59; and 60&#46;7&#37;&#44; 93&#46;8&#37;&#44; and 72&#46;7&#37;&#44; respectively&#44; for decoupling score&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">18</span>F-FDG&#47;<span class="elsevierStyleSup">13</span>N-ammonia uptake decoupling score can be used to discriminate between LGGs and BILs&#46; Use of a decoupling map of these two tracers can improve visual analysis and diagnostic accuracy&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Purpose"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Materials and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0012">Prop&#243;sito</span><p id="spar0031" class="elsevierStyleSimplePara elsevierViewall">La identificaci&#243;n precisa de los gliomas de bajo grado &#40;LGGs&#59; grados I y II de la Organizaci&#243;n Mundial de la Salud&#41; y su diferenciaci&#243;n de las lesiones por inflamaci&#243;n cerebral &#40;BILs&#41; sigue siendo dif&#237;cil&#59; sin embargo&#44; es esencial para el tratamiento&#46; Este estudio evalu&#243; si un protocolo de un d&#237;a para la TEP&#47;TC con amon&#237;aco 18F-FDG y 13Namon&#237;aco con an&#225;lisis de desacoplamiento de la captaci&#243;n podr&#237;a diferenciar los LGG de los BIL&#46;</p></span> <span id="abst0013" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0016">Materiales y m&#233;todos</span><p id="spar0036" class="elsevierStyleSimplePara elsevierViewall">Veintiocho pacientes con GLG y 16 pacientes con BIL se sometieron a TEP&#47;TC con 18F-FDG y 13N-amon&#237;aco el mismo d&#237;a antes de cualquier tipo de terapia&#46; La puntuaci&#243;n de desacoplamiento y la relaci&#243;n tumor&#47;tejido normal &#40;T&#47;N&#41; de 18F-FDG y 13N-amon&#237;aco se calcularon en cada localizaci&#243;n&#46; Se utiliz&#243; la prueba t de Student para comparar valores&#44; y el an&#225;lisis de la curva ROC para establecer un valor de corte para la relaci&#243;n T&#47;N y la puntuaci&#243;n de desacoplamiento&#46; Se calcul&#243; la CUA para evaluar la eficacia diferencial&#46;</p></span> <span id="abst0014" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0017">Resultados</span><p id="spar0038" class="elsevierStyleSimplePara elsevierViewall">Se observaron diferencias significativas en la relaci&#243;n T&#47;N de 13N-amon&#237;aco &#40;p&#61;0&#44;018&#41; y en la puntuaci&#243;n de desacoplamiento &#40;p&#61;0&#44;003&#41; entre los LGG y los BIL&#59; sin embargo&#44; la relaci&#243;n T&#47;N de 18F-FDG no mostr&#243; ninguna diferencia &#40;p&#61;0&#44;413&#41;&#46; Los valores de corte &#243;ptimos para la relaci&#243;n T&#47;N de 18F-FDG&#44; la relaci&#243;n T&#47;N de 13N-amon&#237;aco y la puntuaci&#243;n de desacoplamiento fueron 0&#44;73&#44; 0&#44;97 y 2&#44;31&#44; respectivamente&#44; con AUC correspondientes de 0&#44;48&#44; 0&#44;68 y 0&#44;77&#46; Los respectivos par&#225;metros de sensibilidad&#44; especificidad y precisi&#243;n que utilizan estos valores de corte fueron 53&#44;6&#37;&#44; 62&#44;5&#37; y 56&#44;8&#37;&#44; respectivamente&#44; para 18F-FDG&#59; 50&#44;0&#37;&#44; 75&#44;0&#37; y 59&#44;1&#37;&#44; respectivamente&#44; para la amon&#237;aco 13N&#59; y 60&#44;7&#37;&#44; 93&#44;8&#37; y 72&#44;7&#37;&#44; respectivamente&#44; para la puntuaci&#243;n de desacoplamiento&#46;</p></span> <span id="abst0018" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0021">Conclusiones</span><p id="spar0041" class="elsevierStyleSimplePara elsevierViewall">La puntuaci&#243;n de desacoplamiento de la captaci&#243;n de amon&#237;aco 18FFDG&#47; 13N se puede utilizar para discriminar entre LGG y BIL&#46; El uso de un mapa de desacoplamiento de estos dos trazadores puede mejorar el an&#225;lisis visual y la precisi&#243;n del diagn&#243;stico&#46;</p></span>"
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            "titulo" => "Materiales y m&#233;todos"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Yi C&#44; Quirce R&#44; Yu D&#44; Shi X&#44; Luo G&#44; Zhang B&#44; Lu Y&#44; Zeng R&#44; He Q&#44; Zhang X&#46; Protocolo de un d&#237;a para la TEP&#47;TC con amon&#237;aco 18F-FDG y 13N con puntuaci&#243;n de desacoplamiento de la captaci&#243;n para diferenciar el glioma de bajo grado no tratado de la inflamaci&#243;n&#46; Rev Esp Med Nucl Imagen Mol&#46; 2020&#59;39&#58;68&#8211;74&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar9005">Chang Yi and Donglan Yu contributed equally to this work&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patient examples&#58; region of interest &#40;ROI&#41; near the midline of the brain shows the lesion&#44; ROI in the cerebral cortex shows normal tissue&#46; a&#46; A 30-year-old woman with grade II astrocytoma in the thalamus&#46; <a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>F-FDG tumor-to-normal tissue &#40;T&#47;N&#41; ratio map shows decreased uptake of <a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>F-FDG in the lesion&#44; while <a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>N-ammonia T&#47;N ratio map shows increased uptake of <a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>N-ammonia in the same lesion&#46; Decoupling score map shows high decoupling scores in this lesion&#46; Decoupling scores in each voxel were calculated using the expected linear regression line of <a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>F-FDG and <a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>N-ammonia within normal brain&#46; b&#46; A 45-year-old woman with grade II oligodendrogliomas in the right frontal lobe next to the longitudinal fissure&#46; Decreased uptake of both <a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>F-FDG and <a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>N-ammonia was observed for this lesion in T&#47;N ratio maps&#44; which were not helpful for the diagnosis of the lesions&#46; The decoupling score map showed high decoupling scores in the lesion&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1855
            "Ancho" => 2925
            "Tamanyo" => 491248
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0010"
            "detalle" => "Fig&#46; "
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        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Representative case of a 54-year-old man with a brain inflammation lesion&#46; a&#46; The region of interest shows the lesion in computed tomography images&#46; b and c&#46; Markedly increased uptake of <a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>F-FDG &#40;b&#41; and decreased uptake of <a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>N-ammonia &#40;c&#41; were present in tumor-to-normal tissue &#40;T&#47;N&#41; ratio maps&#46; d&#46; Correlation was determined between <a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>F-FDG and <a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>N-ammonia uptake within normal brain&#46; e&#46; The lesion in the decoupling map appears lower than surrounding normal brain tissue&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "fig0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 1288
            "Ancho" => 1508
            "Tamanyo" => 112433
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0015"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Receiver operating characteristic analysis for detecting lesions with <a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>F-FDG tumor-to-normal tissue &#40;T&#47;N&#41; ratio&#44; <a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>N-ammonia T&#47;N ratio&#44; and decoupling score&#46; The decoupling score showed the best performance&#44; with a cutoff value of 2&#46;31 &#40;area under the curve&#44; AUC&#58; 0&#46;77&#41;&#44; whereas the cutoff values for T&#47;N ratio of <a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>F-FDG and <a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>N-ammonia uptake were 0&#46;73 &#40;AUC&#58; 0&#46;48&#41; and 0&#46;97 &#40;AUC&#58; 0&#46;68&#41;&#44; respectively&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0020"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "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"><th 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" scope="col" style="border-bottom: 2px solid black">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">No&#46; of patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Age &#40;Years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">No&#46; of Sex &#40;M&#47;F&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">No&#46; of diagnoses&#40;histologic&#47;follow-up&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total&nbsp;\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">44&nbsp;\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">40&#46;11&#8239;&#177;&#8239;15&#46;86&nbsp;\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">23&#47;21&nbsp;\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">34&#47;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inflammation&nbsp;\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">16&nbsp;\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">46&#46;38&#8239;&#177;&#8239;16&#46;49&nbsp;\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">8&#47;8&nbsp;\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">6&#47;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Encephalitis&nbsp;\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">4&nbsp;\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">38&#46;00&#8239;&#177;&#8239;13&#46;74&nbsp;\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">2&#47;2&nbsp;\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">&#8722;&#47;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Brain abscess&nbsp;\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">3&nbsp;\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">62&#46;67&#8239;&#177;&#8239;12&#46;34&nbsp;\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">2&#47;1&nbsp;\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">3&#47;&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Demyelination&nbsp;\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">8&nbsp;\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">41&#46;25&#8239;&#177;&#8239;13&#46;44&nbsp;\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">3&#47;5&nbsp;\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">2&#47;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Fungal infection&nbsp;\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">1&nbsp;\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">72&nbsp;\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">1&#47;-&nbsp;\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">1&#47;&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LGGs&nbsp;\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">28&nbsp;\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">36&#46;53&#8239;&#177;&#8239;14&#46;59&nbsp;\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">15&#47;13&nbsp;\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">28&#47;&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Grade I&nbsp;\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">4&nbsp;\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">20&#46;00&#8239;&#177;&#8239;3&#46;16&nbsp;\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">3&#47;1&nbsp;\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">4&#47;&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Grade II&nbsp;\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">24&nbsp;\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">39&#46;30&#8239;&#177;&#8239;13&#46;9&nbsp;\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">12&#47;12&nbsp;\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">24&#47;&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Astrocytoma&nbsp;\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">19&nbsp;\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">39&#46;30&#8239;&#177;&#8239;15&#46;1&nbsp;\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">11&#47;8&nbsp;\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">19&#47;&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oligodendrogliomas&nbsp;\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">4&nbsp;\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">37&#46;50&#8239;&#177;&#8239;9&#46;68&nbsp;\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">1&#47;3&nbsp;\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">4&#47;&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oligoastrocytomas&nbsp;\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">1&nbsp;\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">46&nbsp;\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">-&#47;1&nbsp;\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">1&#47;&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2248631.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Patient characteristics&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0025"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "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"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Diagnosis</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FDG T&#47;N ratio &#40;average&#41;</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">NH3 T&#47;N ratio &#40;average&#41;</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Decoupling score &#40;average&#41;</th></tr><tr title="table-row"><th 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" scope="col" style="border-bottom: 2px solid black">Mean&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Range&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Mean&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Range&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Mean&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Range&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total&nbsp;\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">0&#46;80&#8239;&#177;&#8239;0&#46;36&nbsp;\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">0&#46;02&#732;3&#46;94&nbsp;\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">0&#46;94&#8239;&#177;&#8239;0&#46;20&nbsp;\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">0&#46;07&#732;3&#46;20&nbsp;\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">2&#46;20&#8239;&#177;&#8239;0&#46;71&nbsp;\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">&#8722;8&#46;82&#732;9&#46;38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inflammation&nbsp;\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">0&#46;88&#8239;&#177;&#8239;0&#46;52&nbsp;\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">0&#46;02&#732;3&#46;94&nbsp;\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">0&#46;84&#8239;&#177;&#8239;0&#46;22&nbsp;\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">0&#46;07&#732;3&#46;20&nbsp;\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">1&#46;72&#8239;&#177;&#8239;0&#46;61&nbsp;\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">&#8722;8&#46;82&#732;5&#46;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Encephalitis&nbsp;\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">0&#46;64&#8239;&#177;&#8239;0&#46;09&nbsp;\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">0&#46;24&#732;1&#46;10&nbsp;\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">0&#46;75&#8239;&#177;&#8239;0&#46;23&nbsp;\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">0&#46;20&#732;1&#46;38&nbsp;\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">1&#46;58&#8239;&#177;&#8239;0&#46;76&nbsp;\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">&#8722;4&#46;51&#732;4&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Brain abscess&nbsp;\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">0&#46;95&#8239;&#177;&#8239;0&#46;32&nbsp;\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">0&#46;02&#732;2&#46;16&nbsp;\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">0&#46;83&#8239;&#177;&#8239;0&#46;26&nbsp;\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">0&#46;07&#732;1&#46;50&nbsp;\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">1&#46;37&#8239;&#177;&#8239;0&#46;76&nbsp;\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">&#8722;1&#46;39&#732;4&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Demyelination&nbsp;\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">1&#46;05&#8239;&#177;&#8239;0&#46;75&nbsp;\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">0&#46;04&#732;3&#46;94&nbsp;\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">0&#46;93&#8239;&#177;&#8239;0&#46;24&nbsp;\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">0&#46;11&#732;3&#46;20&nbsp;\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">1&#46;98&#8239;&#177;&#8239;0&#46;55&nbsp;\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">&#8722;8&#46;82&#732;5&#46;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Fungal infection&nbsp;\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">0&#46;67&nbsp;\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">0&#46;13&#732;1&#46;21&nbsp;\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">0&#46;73&nbsp;\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">0&#46;16&#732;1&#46;26&nbsp;\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">1&#46;52&nbsp;\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">&#8722;0&#46;62&#732;3&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LGGs&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Oligodendrogliomas&nbsp;\t\t\t\t\t\t\n
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        "texto" => "<p id="par0135" class="elsevierStylePara elsevierViewall">This work was supported by the <span class="elsevierStyleGrantSponsor" id="gs0005">Science and Technology Planning Project of Guangdong Province</span> &#91;<span class="elsevierStyleGrantNumber" refid="gs0005">2017B020210001</span>&#93;&#59; the <span class="elsevierStyleGrantSponsor" id="gs0010">Medical Science and Technique Foundation of Guangdong Province</span> &#91;<span class="elsevierStyleGrantNumber" refid="gs0010">A2019516</span>&#93;&#59; the <span class="elsevierStyleGrantSponsor" id="gs0015">Science and Technology Program of Guangzhou</span> &#91;<span class="elsevierStyleGrantNumber" refid="gs0015">201607010353</span>&#93;&#46; We thank Professor Ganghua Tang for advice and suggestions regarding the production of <span class="elsevierStyleSup">13</span>N-ammonia&#46; We also appreciate the technical assistance and commitment of our staff&#46;</p>"
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