ENFOQUE DIAGNÓSTICO EN PACIENTES CON SOSPECHA DE TUMOR CEREBRAL PRIMARIO RECURRENTE UTILIZANDO 18FDG-PET/RM, RM DE PERFUSIÓN, ANÁLISIS VISUAL Y CUANTITATIVO Y PROYECCIONES ESTEREOTÁxiCAS DE SUPERFICIE TRIDIMENSIONALES. PRIMERA EXPERIENCIA EN MÉxiCO | Revista Española de Medicina Nuclear e Imagen Molecular

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CI: cardiopatía isquémica." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "S Ruiz Solís, M Maure Rico, M Cortés Romera, VM Poblete García, B Rodríguez Alfonso, P Talavera Rubio, A Palomar Muñoz, AM García Vicente, C Martínez Delgado, A Soriano Castrejón" "autores" => array:10 [ 0 => array:2 [ "Iniciales" => "S" "apellidos" => "Ruiz Solís" ] 1 => array:2 [ "Iniciales" => "M" "apellidos" => "Maure Rico" ] 2 => array:2 [ "Iniciales" => "M" "apellidos" => "Cortés Romera" ] 3 => array:2 [ "Iniciales" => "VM" "apellidos" => "Poblete García" ] 4 => array:2 [ "Iniciales" => "B" "apellidos" => "Rodríguez Alfonso" ] 5 => array:2 [ "Iniciales" => "P" "apellidos" => "Talavera Rubio" ] 6 => array:2 [ "Iniciales" => "A" "apellidos" => "Palomar Muñoz" ] 7 => array:2 [ "Iniciales" => "AM" "apellidos" => "García Vicente" ] 8 => array:2 [ "Iniciales" => "C" "apellidos" => "Martínez Delgado" ] 9 => array:2 [ "Iniciales" => "A" "apellidos" => "Soriano Castrejón" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/13126190?idApp=UINPBA00004N" "url" => "/2253654X/0000002700000005/v0_201308011034/13126190/v0_201308011035/es/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "titulo" => "ENFOQUE DIAGNÓSTICO EN PACIENTES CON SOSPECHA DE TUMOR CEREBRAL PRIMARIO RECURRENTE UTILIZANDO 18FDG-PET/RM, RM DE PERFUSIÓN, ANÁLISIS VISUAL Y CUANTITATIVO Y PROYECCIONES ESTEREOTÁxiCAS DE SUPERFICIE TRIDIMENSIONALES. PRIMERA EXPERIENCIA EN MÉxiCO" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "329" "paginaFinal" => "339" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "G Estrada, L González-Maya, MA Celis-López, J Gavito, JM Lárraga-Gutiérrez, P Salgad, J Altamirano" "autores" => array:7 [ 0 => array:3 [ "Iniciales" => "G" "apellidos" => "Estrada" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "affa" ] ] ] 1 => array:3 [ "Iniciales" => "L" "apellidos" => "González-Maya" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "affb" ] ] ] 2 => array:3 [ "Iniciales" => "MA" "apellidos" => "Celis-López" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "affc" ] ] ] 3 => array:3 [ "Iniciales" => "J" "apellidos" => "Gavito" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "affd" ] ] ] 4 => array:3 [ "Iniciales" => "JM" "apellidos" => "Lárraga-Gutiérrez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "affc" ] ] ] 5 => array:3 [ "Iniciales" => "P" "apellidos" => "Salgad" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "affd" ] ] ] 6 => array:3 [ "Iniciales" => "J" "apellidos" => "Altamirano" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "affe" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "PET-Cyclotron Unit, National Autonomous University of Mexico (UNAM). Mexico. Autonomous University of Morelos, Pharmacy School. Mexico." "etiqueta" => "a" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Autonomous University of Morelos, Pharmacy School. Mexico." "etiqueta" => "b" "identificador" => "affb" ] 2 => array:3 [ "entidad" => "Neurosurgery Department, National Institute of Neurology and Neurosurgery. Mexico." "etiqueta" => "c" "identificador" => "affc" ] 3 => array:3 [ "entidad" => "Radiology Department National Institute of Neurology and Neurosurgery. Mexico." "etiqueta" => "d" "identificador" => "affd" ] 4 => array:3 [ "entidad" => "Autonomous University of Morelos, Pharmacy School. Mexico. Nuclear Medicine Department, National Institute of Cancerology. Mexico." "etiqueta" => "e" "identificador" => "affe" ] ] ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Diagnostic approach in suspected recurrent primary brain tumors using 18FDG-PET/MRI, perfusion MRI, visual and quantitative analysis, and three dimensional stereotactic surface projections. First experience in Mexico" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "FIG. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "125v27n05-13126189fig03.jpg" "Alto" => 411 "Ancho" => 505 "Tamanyo" => 44857 ] ] "descripcion" => array:1 [ "en" => "—Receiver operating characteristic (ROC) curves analysis. The ROC curves for detection of recurrent brain tumors by software PET/MRI fusion and PMRI. Analysis showed an area under the curve (AUC) of 0.9627 for PET/MRI and AUC of 0.7584 for PMRI (p = 0.02). There was statistically significant difference between both methods." ] ] ] "textoCompleto" => "INTRODUCTIONThe most recent advances in nuclear medicine technologies in developing countries like Mexico arrived only some years ago. While, there are over 160 sites in the USA and over 120 sites in Europe (80 of these are in Germany) and have access to many tracers, in our country we have only five sites with a positron emission tomography (PET)/computed tomography (CT) and the only tracer for oncologic studies is 2-deoxy-2-fluoro-D-glucose labeled with F-18 (18FDG)1. Gliomas are the most common primary neoplasms of the brain in adults, accounting for 45 % of all brain tumors. The World Health Organization (WHO) classificated the four histopathological grades of gliomas, from I to IV (low grade to high grade), the grade IV is called glioblastoma multiforme (GBM)2,3. High-grade gliomas include WHO grade III and WHO grade IV. Noninvasive evaluation of primary cerebral tumors after treatment is usually done by CT, magnetic resonance imaging (MRI), perfusion magnetic resonance imaging (PMRI) and PET. Treatment options to allow histologic evaluation of cerebral tumors include surgery, stereotactic brain surgery and radiation therapy4-10.After high radiation doses, all patients developed hyperintensity seen on the MRI; stable or progressive enhancement occurred with tumor recurrence, radionecrosis and inflammation11-13, so its important to make the difference between them, from tumor recurrence.PMRI has recently been developed and shows tumor areas vs. radiation necrosis and assesses tumor response to therapy, also it has the ability to provide a preoperative assessment of tumor histology and helping guide tumor biopsy14. Various clinical studies show the efficiency of relative cerebral blood volume (rCBV) measured by PMRI for the evaluation of brain tumours15.18FDG is taken up preferentially by cells actively metabolizing glucose. Most of malignant cells, show increased glucose utilization, caused by an increased number of glucose transporter proteins and increased enzyme levels16,17. The 18FDG uptake by the cell is not affected by the changes in the blood brain barrier (BBB). 18FDG PET in the brain has special application in the differentiation between tumor areas and radiation necrosis12. The radiation necrosis shows decreased 18FDG uptake, whereas the tumor recurrence shows increased metabolism17. But although 18FDG PET is a nonspecific tracer, the 18FDG uptake also continue to be a prognostic marker in brain tumors after treatment and the tracer of choice for noninvasive indicator of histologic grade of gliomas13,18. Other investigators emphasized the complementary use of physiologic and morphologic information from PET and MRI, to optimize the diagnosis between tumor areas and radiation necrosis16. Automated methods of diagnostic image analysis have been developed to facilitate 18FDG PET evaluations of single patient’s scans with respect to a normative database by producing an observer-independent quantitative mapping of regional measurement of the cerebral metabolic rate of glucose (CMRglc) abnormalities19.The aims of this study was to prospectively determine the diagnostic accuracy of 18FDG PET/MRI fusion and perfusion MRI and also to determine whether combined PET/MRI is more accurate than either PET or MRI alone in the assessment of suspected recurrent primary cerebral tumors.MATERIAL AND METHODSThis was a prospective, observational and comparative study conducted from July 2004 to March 2006. The study was approved by the institutional review board. Informed consent was obtained from all patients. Thirty six consecutive patients were eligible for participation, four patients were excluded (three didn’t have the PMRI and one didn’t have the PET) and two patients declined consent, finally thirty patients were included for further analysis (20 men and 10 women; median age for both, 43 years) with histopathologically confirmed diagnosis of primary cerebral tumor WHO III and IV from the Neuroscience and Neurosurgery National Institute and previously treated by surgical resection and/or radiation (13 GBM, 12 anaplastic astrocytoma, 3 anaplastic oligoastrocytoma, 1 gliosarcoma, 1 choroid plexus carcinoma), and now presented with clinical or radiological data suggestive of tumoral recurrence. All patients were examined with MRI, PMRI and PET.Exclusion criteria were also age younger than 15 years old, pregnancy, nursing, blood glucose level higher than 130 mg/dL, history of diabetes and low grade glioma. The patients characteristics are summarized in table 1.<img src="125v27n05-13126189tab01.gif"></img>Table 1 PATIENT DATAPET image acquisitionThe 18FDG PET images were performed 30-40 minutes after the intravenous injection of 185 MBq (5 mCi) of 18FDG and continue for 30 min. The patients were resting in a dimly lit room during this time. Blood glucose levels were measured prior to injection. Patients were scanned using a high resolution full ring dedicated camera, Ecat exact HR (+). The acquisition parameters were 35 cm field of view, 3 dimensional system, 3 mm slice thickness. Transmission scans were acquired to correct for photon attenuation using a Ge-68 source and the acquired images were reconstructed using iterative reconstruction with ordered subset expectation maximization.MRI and perfusion MRI image acquisitionMRI and perfusion weighted MRI was performed by using a 3 Tesla imager that was equipped with high speed gradients. All imaging was performed by using a standard circular-polarized head coil. Sequences were performed parallel to the orbitomeatal line and included a dynamic (transverse T1-and T2-weighted spin-echo planar imaging) tracking of a bolus of 0.2 mmol/kg gadolinium-DTPA, injected at a rate of 5 ml/s, with an 8-s delay prior to imaging, using an MRI-compatible power injector (Spectris Solaris Medrad). This bolus was immediately followed by injection of an equal volume of physiologic saline, also at a rate of 5 ml/s. The acquisition parameters were TR/TE = 1,399/33 ms, flip angle 20°, 96 × 96 resolution, the field of view was 24 cm field of view, 5-mm slice thickness with a 1.5-mm gap, with a 57-s acquisition time. A post-gadolinium T2 and T1-weighted spoiled gradient recall sequence was acquired.MRI analysisAfter data acquisition and processing, two neuroradiologists who were unaware of each patient’s PET image findings independently reviewed MRI data to evaluated the presence of lesions at conventional weighted MRI in each location for each patient. Each neuroradiologists looked for enhancing areas on postcontrast weighted T1 MR images that corresponded to regions of recurrence. Images were interpreted as positive or negative. The tumoral volume was assessed using the data from the MRI imaging (on the gadolinium enhancement) using the length of the three axis.Perfusion image analysisThe cerebral blood volume (CBV) was defined as the total volume of blood passing through a certain area of the brain at a given time in ml/100 g brain tissue. The relative CBV (rCBV) (obtained by calculating the area under the concentration-times curves, normalized to a contralateral, uninvolved region). The acquired images were transferred to an offline work station for analysis by using manufacturer-provided software (Functool, version 2.5). Symmetrical regions of interest (ROI) of 5 mm of diameter were placed in the suspected tumoral tissue and in the normal gray matter of the contralateral hemisphere for all patients and rCBV ratios of gray to white matter (GM/WM) were calculated20. According to data reported in the literature, the cut off value for positive studies was equal or greater than 1.221.PET/MRI fusionThe PET image fusion was done with the MRI imaging study (axial T1-weighted or T2-weighted postgadolinium), using the free software for image fusion and registration called Rview22,23, that uses the development of a entropy-based registration criteria for automated 3D multi-modality medical image alignment. This approach does not use geometric landmarks but searches for intensity similarities of voxels instead. After loading the PET and MRI datasets, a rigid transformation that use translations, rotations and voxel scaling was applied to the PET data using this software (Rview). The whole fusion procedure was performed automatically without any manual adjustments. The time required for fusion of a PET and MRI dataset was 0.5-3 min, it depends of image set dimensions. The registration software produced a visually satisfactory registration (that was proven using a phantom study for PET and a phantom study for MRI and then fusion with Rview program).PET image analysis (alone and PET/MRI)PET images were interpreted by 2 nuclear medicine physicians compared with the MRI (side by side and coregistered). Images were interpreted as positive or negative. The degree of 18FDG uptake was assessed by visual inspection and the degree of uptake was scored using a 5-point scale (to try to indicate the tumoral grade): 0, no uptake; 1, less than the contralateral cortex; 2, equal than the contralateral cortex; 3, higher than the contralateral cortex but less than the rest of the normal gray matter; 4, higher than the contralateral cortex and than the rest of the normal gray matter, in a region showing enhancing areas on postcontrast T1-weighted MR images.Lesions with an uptake of 0 were considered negative and an uptake of 1,2, 3, or 4 was considered positive for recurrent tumor. In addition, a ROI of 5 mm of diameter was placed around areas of abnormal uptake an over contralateral gray matter for all patients. The maximum standardized uptake value (SUVmax) was determined and analyzed separately. Also 18FDG PET scans were processed using Neurologic Statistical Image Analysis software (Neurostat; Washington University). Each image was warped to the common stereotactic coordinate system. Gray-matter activities were extracted to predefined surface pixels using a 3-dimensional stereotactic surface projection technique (3D-SSP), which minimized residual anatomic variances across subjects and partial-volume effects, yielding robust voxel-based statistical analysis19-24.18FDG PET and the MRI and PMRI were done with a difference between them of no more than 15 days. 18FDG PET images were read by two board certified nuclear medicine physician and the MRI and the PMRI images by a two board-certified neuroradiologist both with experience in interpretation.Reference standardPatients were followed up for a minimum of 6 months. The follow-up range 6-21 months. Stereotactic biopsy (50 %), imaging follow-up (gadolinium enhanced MRI or PET), and clinical follow-up (new presence of seizures, headaches, nausea, vomiting) were all used as reference standards for determining the presence or absence of a recurrence.STATISTICAL ANALYSISThe accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated by using standard formulas and differences between these parameters were tested with linear regression analyses. Results are presented as the mean ± 1 standard deviation (SD). A receiv-er-operating-characteristic (ROC) analysis was performed on the diagnostic accuracy of PMRI and PET/MRI fusion.Differences in the area under the curve (AUC) were tested with the chi-square statistic. Bivariate correlations (Pearson and Spearman) were done to determine whether a relationship between those variables could be established. All statistical analyses were performed in SPSS (version 12.0; Chicago, IL). For all tests, a p value of 0.05 was considered significant.RESULTS20 men and 10 women; (median age for both, 43 years) with histopathologically confirmed diagnosis of primary cerebral tumor WHO III and IV (13 GBM, 12 anaplastic astrocytoma, 3 anaplastic oligoastrocytoma, 1 gliosarcoma, 1 choroid plexus carcinoma).MRIMRI had a sensitivity of 94 % and a specificity of 25 %. There was 1 false negative MRI finding that was defined by pathology as GBM and 9 false-posi-tive MRI results.Perfusion MRIPMRI had a sensitivity of 63 %, specificity of 82 %, PPV of 86 %, accuracy of 56 % and NPV of 86 %. There were 2 false-positive PMRI results, one was also FP for PET/MRI fusion. The other one was negative in the PET/MRI images and the clinical follow up didn’t show any progression of the tumor in the next 6 months.The rCBV values for GBM were from 0.10 to 6.40 (mean 2.32 ± 2.0) and for anaplastic astrocytomas were from 0.50 to 9.20 (mean 1.99 ± 2.4).PET (alone)PET had a sensitivity of 67 % and a specificity of 82 % (table 2). The 6 false-negative PET findings included four astrocytomas, one GBM and one sarcoma. False-positive PET findings included 2 cases that were defined by pathology as chronic inflammation in one case and foreign body granulomas in the second case (tissue reaction to the metal plate that was surgically removed).<img src="125v27n05-13126189tab02.gif"></img>Table 2 PET, MRI, PET/MRI AND PMRIPET/MRI fusion18FDG PET/MRI fusion had a sensitivity of 100 %, specificity of 82 %, PPV of 90 %, an accuracy of 93 % and NPV of 100 %. There were 2 false-positive PET/MRI result findings that were defined by pathology as chronic inflammation in one case and foreign body granulomas in the second case (tissue reaction to the metal plate that was surgically removed).By semiquantitative analysis, the SUVmax for all positive PET lesions (n = 21) averaged at 4.8 ± 3.2 (range, 1.1-14.3). In the true-positive PET/MRI subgroup (n = 19), the lesion size ranged from 2.3 to 124.4 cm3 (averaged at 45.9 ± 42.9), with a mean SUVmax of 4.9 ± 3.2 (range, 1.8-14.3). The SUVmax in the contralateral gray matter averaged at 7.9 ± 2.0 (range, 5.8-13.2). The SUVmax tumor to gray matter ratio (T/G) in all lesions ranged from 0.1 to 2.2 (mean ± 0.4), in the true-positive PET/MRI subgroup (n = 19), the SUVmax T/G ratio ranged from 0.2 to (mean 0.6± 0.5) (table 1).With 3D-SSP only in two cases the z scores were higher in a focal area, (in the cases that the visual score was 4), no reaching statistical significance. Z scores not yielded significantly discrimination accuracies.PET/MRI fusion had 8 discordant interpretations compared with PMRI, 6 of which were true positive, 1 true negative and 1 false positive for the PET/MRI fusion. PET/MRI had 11 discordant interpretations compared with PET alone. PET-only interpretations missed 6 lesions because there was low 18FDG uptake. PET/MRI had 8 discordant interpretations compared with MRI alone, 7 were false positive for MRI.A ROC analysis was performed for PMRI and PET/MRI, which is shown in figure 1. The additional value of PET/MRI over PMRI is clearly seen and appears to hold over the entire range of sensitivity, PPV and NPV.<img src="125v27n05-13126189fig03.jpg"></img>FIG. 1.—Receiver operating characteristic (ROC) curves analysis. The ROC curves for detection of recurrent brain tumors by software PET/MRI fusion and PMRI. Analysis showed an area under the curve (AUC) of 0.9627 for PET/MRI and AUC of 0.7584 for PMRI (p = 0.02). There was statistically significant difference between both methods.Nine patients had tumor progression. Four patients die, while the rest remained alive during the 21 months of follow up.We had one secondary glioblastoma, upon progression of an anaplastic astrocytoma (diagnosed from a gross total resection and histologically confirmed 1 year previously). Then, another resection of tumor was performed, yielding the diagnosis of glioblastoma.There was statistically significant difference between the recurrent tumors and the visual uptake scale for PET/MRI (p = 0.001).There was no statistically significant difference between tumoral volume (cm3) and the rCBV and the visual uptake scale for PET/MRI, nor as recurrent tumors and the rCBV.DISCUSSIONThe brain uses great amounts of glucose to meet its metabolic energy requirements so the normal PET brain study has high levels of uptake in cerebral cortex, thalamus and basal ganglia that makes that in many cases the brain tumors are similar in metabolism than the rest of the cortex, especially when they were already treated. The clinical utility of 18FDG for the assessment of tumor recurrence depends on selection of the patients. Also it is important to notice that in the assessment of tumor recurrence without anatomical references, it is almost impossible to interpret adequately if a PET study is positive or negative, so anatomic references are very important17,25,26. The use of automated voxel based analysis is used for its convenience in image analysis and in statistical examination of group differences27. Our data indicate that the assessment of recurrent tumors with statistical parametric mappings may not be particularly useful.Hustinx et al25 in the diagnostic value of FDG-PET (alone) for differentiating radiation necrosis from recurrent tumors reported a sensitivity of 73 % and a specificity of 56 % in 31 patients with a pathologyproven final diagnosis. These results were obtained using a visual score. We obtained similar findings. They also reported that the sensitivity of PET alone increased when MRI and PET images were coregistered, while specificity remained unchanged and that, both the specificity and the accuracy were higher with PET than with MRI. We obtained also similar findings in the present study.As shown in table 2, PET/MRI performs better than PET alone in accuracy, sensitivity, PPV and NPV and better than MRI alone in specificity, accuracy, sensitivity, PPV and NPV. The most frequent limitation of 18FDG PET involves detecting small lesions and lesions with low metabolism, this in part because steroids are commonly used in clinical settings and this treatment decrease 18FDG uptake28, but PET/MRI seems to overcome many of the equivocal findings.PET imaging also provides information about heterogeneities within a tumor which might improve diagnostic performance guiding the biopsy or helping planning the treatment with radiotherapy, this heterogeneities some times are not seen in the MRI images and the most of the times the PET images shows areas of uptake different in size than the MRI, this areas with enhancement and 18FDG uptake are the ones that are treated, and before the physiological studies like PET, there were treated all areas of enhancement, with an increase of side effects (fig. 2).<img src="125v27n05-13126189fig04.jpg"></img>FIG. 2.—Concordant results between PET/MRI fusion and perfusion MRI. Fifty years old male with a GBM. A: 3T Magnetic resonance imaging, postcontrast T1-weighted sequence; B: 18FDG-PET; C: PET/MRI fusion that shows over the hyperintensity on the MRI, 18FDG uptake less than the contralateral cortex (grade 1) and reported as positive; D: CBV map shows elevated blood volume within the lesion; E: Time-signal curve. The green line is the normal cortex and the purple line the suspected area, with a calculated rCBV of 6.4 and reported as positive. Both studies were consistent with high-grade neoplasm. The reader should note that there is a pretty big discrepancy between the gadolinium enhanced MRI and the 18FDG uptake. The MRI report was positive for tumour in all areas of enhancement (because of disruption of the blood brain barrier), while noticing that only some areas show 18FDG uptake (areas with viable cells). Before the physiological studies appear, all areas of enhancement were treated, and now, there are treated only the areas with 18FDG uptake. F and G. Predefined anatomic surface ROIs (in yellow) are superimposed onto (from left to right) right and left lateral, superior, inferior and right and left medial views of standardized brain template showing surface projection maps of statistical abnormalities as compared with normals, z scores are represented on color coded scale ranging from 0 (black) to 7 (red), for decreased and increased respectively.Like other authors16 we found areas of hypometabolism adjacent to the tumor site that in the most of our cases correspond to edema on MRI images. This areas were perfectly identified with the 3D-SSP.The diagnosis of tumoral recurrence was independent of the tumor size (cm3).The ROI were visually analyzed and described as recurrent tumors when any uptake (1 to 4) was present on the enhancing areas on post contrast T1 weighted MRI (figs. 3 and 4).<img src="125v27n05-13126189fig05.jpg"></img>FIG. 3.—Discordant results between PET/MRI fusion and perfusion MRI. Thirty years old male with an anaplastic astrocytoma. A: 3T Magnetic resonance imaging, postcontrast T1-weighted sequence. B: 18FDG-PET. C: PET/MRI fusion that shows over the hyperintensity on the MRI, 18FDG uptake less than the contralateral cortex (grade 1) and reported as positive. D: CBV map shows similar blood volume within the lesion than in the uninvolved region. E: Time-signal curve. The green line is the normal cortex and the purple line the suspected area, with a calculated rCBV of 0.5 and reported as negative. It was a true positive study for the PET/MRI fusion and a false negative study for the perfusion MRI. F and G. Predefined anatomic surface ROIs (in yellow) are superimposed onto (from left to right) right and left lateral, superior, inferior and right and left medial views of standardized brain template showing surface projection maps of statistical abnormalities as compared with normals, z scores are represented on color coded scale ranging from 0 (black) to 7 (red), for decreased and increased respectively.<img src="125v27n05-13126189fig06.jpg"></img>FIG. 4.—Concordant results between fusion PET/MRI and perfusion MRI. Twenty eight years old female with a choroidal plexus carcinoma. A) 3T Magnetic resonance imaging, postcontrast T1-weighted sequence. B: 18FDG-PET. C: PET/MRI fusion that shows over the hyperintensity on the MRI, 18FDG uptake greater than the contralateral cortex and grater than the rest of the normal gray matter (grade 4) and reported as positive. D: Time-signal curve. The green line is the normal cortex and the purple line the suspected area, with a calculated rCBV of 5.1 and reported as positive. E: CBV map shows elevated blood volume within the lesion, consistent with high-grade neoplasm. F and G. Predefined anatomic surface ROIs (in yellow) are superimposed onto (from left to right) right and left lateral, superior, inferior and right and left medial views of standardized brain template showing surface projection maps of statistical abnormalities as compared with normals, z scores are represented on color coded scale ranging from 0 (black) to 7 (red), for decrease and increased respectively.Although 18FDG SUVmax in whole body is used as a routine. It was shown previously that 18FDG SUVmax in brain tumors were not a reliable measure for evaluating recurrent tumors17,28; we obtained similar findings in the present study, with a large overlap of 18FDG uptake between recurrent tumors and normal gray matter, so as with the T/G ratio’s. SUVs and T/G ratio’s appear to be of limited value in characterizing recurrent primary brain tumors. We agreed with Hustinx et al25 that reported that no study has proved that quantitative methods are better than visual interpretation by the physician. Visual assessment by an experienced nuclear medicine specialist with the criterion that any uptake on the enhancing areas on post contrast T1 MRI should be considered abnormal provided a higher sensitivity.In the current study, we found two PET/MRI that were false positive confirmed by biopsy (chronic inflammation in one case and foreign body granulomas in the second case). It is well known that infection and inflammatory cells using glucose as a main source of energy have increased uptake of the 18FDG29 and frequently cause false positive results. There are few references in the literature about the 18FDG uptake in the brain for chronic inflammation and encephalitis30,31, but to our knowledge this is the first report about a patient with a foreign body in the skull and 18FDG uptake. Both patients remain alive and with good clinical conditions. Table 3 shows the physiological targets of the 3 methods32.<img src="125v27n05-13126189tab07.gif"></img>Table 3 METHODS AND THEIR PHYSIOLOGICAL TARGETSThe literature refers that the PET study can be used also to monitoring the histological changes in patients with brain tumors for evidence of degeneration into a malignancy of higher grade33, like in our patient with secondary GBM. Both the primary and the secondary GBM share some genetic abnormalities34. The uptake was lower than we expected for a GBM, this in part because the zone was recently treated and also be-cause the patient was taking corticosteroids, that decreased 18FDG uptake28.The PMRI sensitivity was low (63 %), which may be explained by the inherent glioma heterogeneity, as observed previously15 that are more evident after the treatment. Weber et al21 reported that a threshold value of 1.2 provided sensitivity 97 %, specificity 80 %, PPV 94 %, and NPV 89 % (first detection of a brain neoplasm, without treatment), and our group of patients were already treated. He also reported that for discrimination of glioblastomas from grade III gliomas, sensitivity was 97 %, specificity was 50 %, PPV was 84 %, and NPV was 86 %. However, we observed a significant overlap in the rCBV values of grade III astrocytomas from glioblastomas21,35. This functional MRI technique has limited utility when the glioma was already treated. In a study by Leimgruber et al36, PMRI used in follow-up after chemoradiation for glioblastomas was not shown to be useful for predicting tumor progression.In general the survival for GBM is longer now with the new therapeutics and interdisciplinary cancer therapy trials can significantly prolong survival and allows a small subgroup of patients to survive 3 to 5 years37-40.The first images for small animals from the complete system PET/MRI have been successfully acquired and reconstructed, demonstrating that simultaneous PET and MRI studies are feasible41, but until this systems is available for clinical use, the software Rview could be an excellent option for PET/MRI fusion. PET-MRI coregistration accuracy was widely discussed by Stuldhome et al23, Kiebel et al42 and García et al43. They find that PET-MRI coregistration using automated image techniques are feasible within the size of a PET pixel.A limitation of our study was that we don’t have availability of other more specific tracers for brain tumours, like the amino acid PET tracers 11C-methion-ine and 18FDOPA18,26,28 angiogenesis markers, like 18F-Fluorocholine and 18F-FET44, markers for receptors like F-FLT45, among other tracers for protein and DNA synthesis32. Also that only half of the lesions suspicious for recurrent brain tumour were confirmed by biopsy. As seen in some reports histopathologic proof, is not always available. Patients with negative PET findings are less likely to undergo surgical confirmation of their status and the clinical follow up appear to be enough in these patients28. The highest reported incidence of pathology-proven radiation necrosis is only 24 %25. Therefore, further studies involving a bigger number of cases and the validation of the visual scale proposed by the authors is needed to introduce this technique (PET/MRI fusion) for routine clinical practice.CONCLUSIONSThe combination of anatomic and metabolic imaging (PET/MRI) performs better than PMRI in accuracy, sensitivity, PPV and NPV.18FDG SUVmax in brain tumours were not a reliable measure for evaluating recurrent tumours. No additional information was provided by performing semiquantitative analysis, including the use of the automated program 3D stereotactic surface projections. Visual inspection of PET/MRI images with the criterion that any uptake on the enhancing areas on post contrast T1 MRI should be considered abnormal, provided a higher sensitivity. Hence, PET/MRI images allow us to readily appreciate tumor extension. The MRI alone has the lowest specificity. The PMRI has the lowest value of sensitivity.ACKNOWLEDGMENTSThe work described in this paper was undertaken with the financial support of UNAM’s PET-cyclotron unit. The authors thanks Satoshi Minoshima, PhD, for the support of 3D-SSP Neurostat program, René Drucker Colin, MD, PhD, Alfonso Dueñas MD, PhD, and Luis Alberto Medina V, PhD, for their help in the manuscript. Dr. Héctor Carrillo for statistical evaluation of the results, Claudia M. Segura and Patricia Miranda for technical assistance, Dr Alexanderson, TMN Antonio Manzo, TMN Ricardo Cárdenas, Fis. Armando Flores and M. C. Adolfo Zárate from UNAM PET-Cyclotron unit.Received: 11-02-08. Accepted: 13-06-08.Correspondencia:G. ESTRADA-SÁNCHEZ CT Scanner del Sur Rafael Checa No. 3, col. San Ángel 01000 San Ángel. México, D.F. E-mail: dragiselaus@yahoo.com" "pdfFichero" => "125v27n05a13126189pdf001.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec232361" "palabras" => array:1 [ 0 => "18FDG PET,tumores cerebrales,perfusión por RM, fusión PET/RM, 3D-SSP" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec232360" "palabras" => array:1 [ 0 => "18FDG PET, brain tumors, perfusion MRI, PET/MRI fusion, 3D SSP" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:1 [ "resumen" => "Thirty patients with primary cerebral tumors WHO III and IV previously treated, undergoing evaluation for tumoral recurrence, they underwent 18FDG-PET study, MRI and PMRI. PET uptake was determined by visual inspection and was quantified by use of standard uptake values, the ratio of tumor uptake to normal tissue and were z scored using automated voxel-based comparison. PMRI was quantified by use of ratios of cerebral blood volume (rCBV). The accuracies were determined by comparing imaging data with histologic findings and clinical follow up of up to 21 mo. Results. Sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and accuracy were 100 %, 82 %, 90 %, 100 % and 93 % respectively for the PET/MRI fusion and 68 %, 82 %, 87 %, 60 % and 73 % respectively for PMRI. There were two false positive cases for PET/MRI fusion that were confirmed by biopsy: chronic inflammation; and foreign body granulomas. The receiver operating characteristic (ROC) curve analysis showed statistically significant difference (p = 0.0225). Conclusions. 18FDG SUVs, glucose uptake ratios and 3D stereotactic surface projections in brain tumors were not a reliable measure for evaluating recurrent tumors. PET/MRI fusion was more sensitive and accurate than PMRI for imaging recurrent primary brain tumors. The region of interest can be visually analyzed on the PET/MRI fusion images and described as recurrent tumor when any activity (lower, equal or greater than the contralateral cortex) is presented in the zone of hyperintensity seen on the post-gadolinium T1-weighted MRI." ] "es" => array:1 [ "resumen" => "Se ha hecho un estudio con 18FDG-PET, RM y perfusión por resonancia magnética en 30 pacientes con tumores cerebrales primarios grado OMS III y IV, previamente tratados y a los que se les iba a hacer el seguimiento de recurrencia tumoral. La captación de la PET estuvo determinada por la inspección visual y se cuantificó utilizando los valores de captación estándar, la proporción de captación tumoral/tejido normal y la desviación estándar z mediante comparación automatizada con vóxeles. La perfusión por resonancia magnética se cuantificó mediante la utilización de las proporciones del volumen sanguíneo cerebral. La exactitud diagnóstica se determinó comparando los datos de las imágenes con los hallazgos histológicos y el seguimiento clínico durante un período de hasta 21 meses. Resultados. La sensibilidad (Se), la especificidad (Sp), el valor predictivo positivo (VPP), el valor predictivo negativo (VPN) y la exactitud diagnóstica fueron del 100, 82, 90, 100 y 93 %, respectivamente, para la fusión PET/RM; y del 68, 82, 87, 60 y 73%, respectivamente, para la perfusión por resonancia magnética. Hubo dos casos falsos positivos para la fusión PET/RM que se confirmaron mediante biopsia: inflamación crónica y granulomas por cuerpo extraño. El análisis de las curvas características operativas del receptor (ROC) demostró una diferencia estadísticamente significativa (p = 0,0225). Conclusiones. Los valores de captación estandarizados de 18FDG (SUV), las proporciones de captación de glucosa y las proyecciones estereotáxicas de superficie en 3D (3D-SSP) de los tumores cerebrales no demostraron ser mediciones útiles para evaluar tumores recurrentes. La fusión PET/RM resultó ser más sensible y con mayor exactitud diagnóstica que la perfusión por resonancia magnética como diagnóstico de imagen de los tumores cerebrales primarios recurrentes. En las imágenes de fusión PET/RM puede analizarse la región de interés y reportarse como tumor recurrente cuando aparece cualquier actividad (menor, igual o mayor que en la corteza contralateral) en la zona de hiperintensidad observada en la RM con gadolinio y ponderada en T1." ] ] "multimedia" => array:10 [ 0 => array:8 [ "identificador" => "tbl1" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tablaImagen" => array:1 [ 0 => array:4 [ "imagenFichero" => "125v27n05-13126189tab01.gif" "imagenAlto" => 721 "imagenAncho" => 892 "imagenTamanyo" => 55698 ] ] ] ] ] "descripcion" => array:1 [ "en" => "PATIENT DATA" ] ] 1 => array:8 [ "identificador" => "tbl2" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tablaImagen" => array:1 [ 0 => array:4 [ "imagenFichero" => "125v27n05-13126189tab02.gif" "imagenAlto" => 207 "imagenAncho" => 889 "imagenTamanyo" => 9829 ] ] ] ] ] "descripcion" => array:1 [ "en" => "PET, MRI, PET/MRI AND PMRI" ] ] 2 => array:8 [ "identificador" => "fig1" "etiqueta" => "FIG. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "125v27n05-13126189fig03.jpg" "Alto" => 411 "Ancho" => 505 "Tamanyo" => 44857 ] ] "descripcion" => array:1 [ "en" => "—Receiver operating characteristic (ROC) curves analysis. The ROC curves for detection of recurrent brain tumors by software PET/MRI fusion and PMRI. Analysis showed an area under the curve (AUC) of 0.9627 for PET/MRI and AUC of 0.7584 for PMRI (p = 0.02). There was statistically significant difference between both methods." ] ] 3 => array:8 [ "identificador" => "fig2" "etiqueta" => "FIG. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "125v27n05-13126189fig04.jpg" "Alto" => 626 "Ancho" => 1039 "Tamanyo" => 203192 ] ] "descripcion" => array:1 [ "en" => "—Concordant results between PET/MRI fusion and perfusion MRI. Fifty years old male with a GBM. A: 3T Magnetic resonance imaging, postcontrast T1-weighted sequence; B: 18FDG-PET; C: PET/MRI fusion that shows over the hyperintensity on the MRI, 18FDG uptake less than the contralateral cortex (grade 1) and reported as positive; D: CBV map shows elevated blood volume within the lesion; E: Time-signal curve. The green line is the normal cortex and the purple line the suspected area, with a calculated rCBV of 6.4 and reported as positive. Both studies were consistent with high-grade neoplasm. The reader should note that there is a pretty big discrepancy between the gadolinium enhanced MRI and the 18FDG uptake. The MRI report was positive for tumour in all areas of enhancement (because of disruption of the blood brain barrier), while noticing that only some areas show 18FDG uptake (areas with viable cells). Before the physiological studies appear, all areas of enhancement were treated, and now, there are treated only the areas with 18FDG uptake. F and G. Predefined anatomic surface ROIs (in yellow) are superimposed onto (from left to right) right and left lateral, superior, inferior and right and left medial views of standardized brain template showing surface projection maps of statistical abnormalities as compared with normals, z scores are represented on color coded scale ranging from 0 (black) to 7 (red), for decreased and increased respectively." ] ] 4 => array:8 [ "identificador" => "fig3" "etiqueta" => "FIG. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "125v27n05-13126189fig05.jpg" "Alto" => 602 "Ancho" => 1035 "Tamanyo" => 198297 ] ] "descripcion" => array:1 [ "en" => "—Discordant results between PET/MRI fusion and perfusion MRI. Thirty years old male with an anaplastic astrocytoma. A: 3T Magnetic resonance imaging, postcontrast T1-weighted sequence. B: 18FDG-PET. C: PET/MRI fusion that shows over the hyperintensity on the MRI, 18FDG uptake less than the contralateral cortex (grade 1) and reported as positive. D: CBV map shows similar blood volume within the lesion than in the uninvolved region. E: Time-signal curve. The green line is the normal cortex and the purple line the suspected area, with a calculated rCBV of 0.5 and reported as negative. It was a true positive study for the PET/MRI fusion and a false negative study for the perfusion MRI. F and G. Predefined anatomic surface ROIs (in yellow) are superimposed onto (from left to right) right and left lateral, superior, inferior and right and left medial views of standardized brain template showing surface projection maps of statistical abnormalities as compared with normals, z scores are represented on color coded scale ranging from 0 (black) to 7 (red), for decreased and increased respectively." ] ] 5 => array:8 [ "identificador" => "fig4" "etiqueta" => "FIG. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "125v27n05-13126189fig06.jpg" "Alto" => 597 "Ancho" => 1029 "Tamanyo" => 192768 ] ] "descripcion" => array:1 [ "en" => "—Concordant results between fusion PET/MRI and perfusion MRI. Twenty eight years old female with a choroidal plexus carcinoma. A) 3T Magnetic resonance imaging, postcontrast T1-weighted sequence. B: 18FDG-PET. C: PET/MRI fusion that shows over the hyperintensity on the MRI, 18FDG uptake greater than the contralateral cortex and grater than the rest of the normal gray matter (grade 4) and reported as positive. D: Time-signal curve. The green line is the normal cortex and the purple line the suspected area, with a calculated rCBV of 5.1 and reported as positive. E: CBV map shows elevated blood volume within the lesion, consistent with high-grade neoplasm. F and G. Predefined anatomic surface ROIs (in yellow) are superimposed onto (from left to right) right and left lateral, superior, inferior and right and left medial views of standardized brain template showing surface projection maps of statistical abnormalities as compared with normals, z scores are represented on color coded scale ranging from 0 (black) to 7 (red), for decrease and increased respectively." ] ] 6 => array:8 [ "identificador" => "tbl3" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tablaImagen" => array:1 [ 0 => array:4 [ "imagenFichero" => "125v27n05-13126189tab07.gif" "imagenAlto" => 245 "imagenAncho" => 446 "imagenTamanyo" => 10396 ] ] ] ] ] "descripcion" => array:1 [ "en" => "METHODS AND THEIR PHYSIOLOGICAL TARGETS" ] ] 7 => array:5 [ "identificador" => "tbl4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" ] 8 => array:5 [ "identificador" => "tbl5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" ] 9 => array:5 [ "identificador" => "tbl6" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:45 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "referenciaCompleta" => "Positron emission Tomography: A strategy for provision in the UK. 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ENFOQUE DIAGNÓSTICO EN PACIENTES CON SOSPECHA DE TUMOR CEREBRAL PRIMARIO RECURRENTE UTILIZANDO 18FDG-PET/RM, RM DE PERFUSIÓN, ANÁLISIS VISUAL Y CUANTITATIVO Y PROYECCIONES ESTEREOTÁxiCAS DE SUPERFICIE TRIDIMENSIONALES. PRIMERA EXPERIENCIA EN MÉxiCO

Diagnostic approach in suspected recurrent primary brain tumors using 18FDG-PET/MRI, perfusion MRI, visual and quantitative analysis, and three dimensional stereotactic surface projections. First experience in Mexico

G. Estradaa, L. González-Mayab, MA. Celis-Lópezc, J. Gavitod, JM. Lárraga-Gutiérrezc, P. Salgadd, J. Altamiranoe

a PET-Cyclotron Unit, National Autonomous University of Mexico (UNAM). Mexico. Autonomous University of Morelos, Pharmacy School. Mexico.

b Autonomous University of Morelos, Pharmacy School. Mexico.

c Neurosurgery Department, National Institute of Neurology and Neurosurgery. Mexico.

d Radiology Department National Institute of Neurology and Neurosurgery. Mexico.

e Autonomous University of Morelos, Pharmacy School. Mexico. Nuclear Medicine Department, National Institute of Cancerology. Mexico.

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    "textoCompleto" => "<span class="elsevierStyleSectionTitle">INTRODUCTION</span><p class="elsevierStylePara">The most recent advances in nuclear medicine technologies in developing countries like Mexico arrived only some years ago&#46; While&#44; there are over 160 sites in the USA and over 120 sites in Europe &#40;80 of these are in Germany&#41; and have access to many tracers&#44; in our country we have only five sites with a positron emission tomography &#40;PET&#41;&#47;computed tomography &#40;CT&#41; and the only tracer for oncologic studies is 2-deoxy-2-fluoro-D-glucose labeled with F-18 &#40;<span class="elsevierStyleSup">18</span>FDG&#41;<span class="elsevierStyleSup">1</span>&#46; Gliomas are the most common primary neoplasms of the brain in adults&#44; accounting for 45 &#37; of all brain tumors&#46; The World Health Organization &#40;WHO&#41; classificated the four histopathological grades of gliomas&#44; from I to IV &#40;low grade to high grade&#41;&#44; the grade IV is called glioblastoma multiforme &#40;GBM&#41;<span class="elsevierStyleSup">2&#44;3</span>&#46; High-grade gliomas include WHO grade III and WHO grade IV&#46; Noninvasive evaluation of primary cerebral tumors after treatment is usually done by CT&#44; magnetic resonance imaging &#40;MRI&#41;&#44; perfusion magnetic resonance imaging &#40;PMRI&#41; and PET&#46; Treatment options to allow histologic evaluation of cerebral tumors include surgery&#44; stereotactic brain surgery and radiation therapy<span class="elsevierStyleSup">4-10</span>&#46;</p><p class="elsevierStylePara">After high radiation doses&#44; all patients developed hyperintensity seen on the MRI&#59; stable or progressive enhancement occurred with tumor recurrence&#44; radionecrosis and inflammation<span class="elsevierStyleSup">11-13</span>&#44; so its important to make the difference between them&#44; from tumor recurrence&#46;</p><p class="elsevierStylePara">PMRI has recently been developed and shows tumor areas vs&#46; radiation necrosis and assesses tumor response to therapy&#44; also it has the ability to provide a preoperative assessment of tumor histology and helping guide tumor biopsy<span class="elsevierStyleSup">14</span>&#46; Various clinical studies show the efficiency of relative cerebral blood volume &#40;rCBV&#41; measured by PMRI for the evaluation of brain tumours<span class="elsevierStyleSup">15</span>&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleSup">18</span>FDG is taken up preferentially by cells actively metabolizing glucose&#46; Most of malignant cells&#44; show increased glucose utilization&#44; caused by an increased number of glucose transporter proteins and increased enzyme levels<span class="elsevierStyleSup">16&#44;17</span>&#46; The <span class="elsevierStyleSup">18</span>FDG uptake by the cell is not affected by the changes in the blood brain barrier &#40;BBB&#41;&#46; <span class="elsevierStyleSup">18</span>FDG PET in the brain has special application in the differentiation between tumor areas and radiation necrosis<span class="elsevierStyleSup">12</span>&#46; The radiation necrosis shows decreased <span class="elsevierStyleSup">18</span>FDG uptake&#44; whereas the tumor recurrence shows increased metabolism<span class="elsevierStyleSup">17</span>&#46; But although <span class="elsevierStyleSup">18</span>FDG PET is a nonspecific tracer&#44; the <span class="elsevierStyleSup">18</span>FDG uptake also continue to be a prognostic marker in brain tumors after treatment and the tracer of choice for noninvasive indicator of histologic grade of gliomas<span class="elsevierStyleSup">13&#44;18</span>&#46; Other investigators emphasized the complementary use of physiologic and morphologic information from PET and MRI&#44; to optimize the diagnosis between tumor areas and radiation necrosis<span class="elsevierStyleSup">16</span>&#46; Automated methods of diagnostic image analysis have been developed to facilitate <span class="elsevierStyleSup">18</span>FDG PET evaluations of single patient&#8217;s scans with respect to a normative database by producing an observer-independent quantitative mapping of regional measurement of the cerebral metabolic rate of glucose &#40;CMRglc&#41; abnormalities<span class="elsevierStyleSup">19</span>&#46;</p><p class="elsevierStylePara">The aims of this study was to prospectively determine the diagnostic accuracy of <span class="elsevierStyleSup">18</span>FDG PET&#47;MRI fusion and perfusion MRI and also to determine whether combined PET&#47;MRI is more accurate than either PET or MRI alone in the assessment of suspected recurrent primary cerebral tumors&#46;</p><span class="elsevierStyleSectionTitle">MATERIAL AND METHODS</span><p class="elsevierStylePara">This was a prospective&#44; observational and comparative study conducted from July 2004 to March 2006&#46; The study was approved by the institutional review board&#46; Informed consent was obtained from all patients&#46; Thirty six consecutive patients were eligible for participation&#44; four patients were excluded &#40;three didn&#8217;t have the PMRI and one didn&#8217;t have the PET&#41; and two patients declined consent&#44; finally thirty patients were included for further analysis &#40;20 men and 10 women&#59; median age for both&#44; 43 years&#41; with histopathologically confirmed diagnosis of primary cerebral tumor WHO III and IV from the Neuroscience and Neurosurgery National Institute and previously treated by surgical resection and&#47;or radiation &#40;13 GBM&#44; 12 anaplastic astrocytoma&#44; 3 anaplastic oligoastrocytoma&#44; 1 gliosarcoma&#44; 1 choroid plexus carcinoma&#41;&#44; and now presented with clinical or radiological data suggestive of tumoral recurrence&#46; All patients were examined with MRI&#44; PMRI and PET&#46;</p><p class="elsevierStylePara">Exclusion criteria were also age younger than 15 years old&#44; pregnancy&#44; nursing&#44; blood glucose level higher than 130 mg&#47;dL&#44; history of diabetes and low grade glioma&#46; The patients characteristics are summarized in table 1&#46;</p><p class="elsevierStylePara"><img src="125v27n05-13126189tab01.gif"></img></p><p class="elsevierStylePara">Table 1 PATIENT DATA</p><span class="elsevierStyleSectionTitle">PET image acquisition</span><p class="elsevierStylePara">The <span class="elsevierStyleSup">18</span>FDG PET images were performed 30-40 minutes after the intravenous injection of 185 MBq &#40;5 mCi&#41; of <span class="elsevierStyleSup"> 18</span>FDG and continue for 30 min&#46; The patients were resting in a dimly lit room during this time&#46; Blood glucose levels were measured prior to injection&#46; Patients were scanned using a high resolution full ring dedicated camera&#44; Ecat exact HR &#40;&#43;&#41;&#46; The acquisition parameters were 35 cm field of view&#44; 3 dimensional system&#44; 3 mm slice thickness&#46; Transmission scans were acquired to correct for photon attenuation using a Ge-68 source and the acquired images were reconstructed using iterative reconstruction with ordered subset expectation maximization&#46;</p><span class="elsevierStyleSectionTitle">MRI and perfusion MRI image acquisition</span><p class="elsevierStylePara">MRI and perfusion weighted MRI was performed by using a 3 Tesla imager that was equipped with high speed gradients&#46; All imaging was performed by using a standard circular-polarized head coil&#46; Sequences were performed parallel to the orbitomeatal line and included a dynamic &#40;transverse T1-and T2-weighted spin-echo planar imaging&#41; tracking of a bolus of 0&#46;2 mmol&#47;kg gadolinium-DTPA&#44; injected at a rate of 5 ml&#47;s&#44; with an 8-s delay prior to imaging&#44; using an MRI-compatible power injector &#40;Spectris Solaris Medrad&#41;&#46; This bolus was immediately followed by injection of an equal volume of physiologic saline&#44; also at a rate of 5 ml&#47;s&#46; The acquisition parameters were TR&#47;TE &#61; 1&#44;399&#47;33 ms&#44; flip angle 20&#176;&#44; 96 &#215; 96 resolution&#44; the field of view was 24 cm field of view&#44; 5-mm slice thickness with a 1&#46;5-mm gap&#44; with a 57-s acquisition time&#46; A post-gadolinium T2 and T1-weighted spoiled gradient recall sequence was acquired&#46;</p><span class="elsevierStyleSectionTitle">MRI analysis</span><p class="elsevierStylePara">After data acquisition and processing&#44; two neuroradiologists who were unaware of each patient&#8217;s PET image findings independently reviewed MRI data to evaluated the presence of lesions at conventional weighted MRI in each location for each patient&#46; Each neuroradiologists looked for enhancing areas on postcontrast weighted T1 MR images that corresponded to regions of recurrence&#46; Images were interpreted as positive or negative&#46; The tumoral volume was assessed using the data from the MRI imaging &#40;on the gadolinium enhancement&#41; using the length of the three axis&#46;</p><span class="elsevierStyleSectionTitle">Perfusion image analysis</span><p class="elsevierStylePara">The cerebral blood volume &#40;CBV&#41; was defined as the total volume of blood passing through a certain area of the brain at a given time in ml&#47;100 g brain tissue&#46; The relative CBV &#40;rCBV&#41; &#40;obtained by calculating the area under the concentration-times curves&#44; normalized to a contralateral&#44; uninvolved region&#41;&#46; The acquired images were transferred to an offline work station for analysis by using manufacturer-provided software &#40;Functool&#44; version 2&#46;5&#41;&#46; Symmetrical regions of interest &#40;ROI&#41; of 5 mm of diameter were placed in the suspected tumoral tissue and in the normal gray matter of the contralateral hemisphere for all patients and rCBV ratios of gray to white matter &#40;GM&#47;WM&#41; were calculated<span class="elsevierStyleSup">20</span>&#46; According to data reported in the literature&#44; the cut off value for positive studies was equal or greater than 1&#46;2<span class="elsevierStyleSup">21</span>&#46;</p><span class="elsevierStyleSectionTitle">PET&#47;MRI fusion</span><p class="elsevierStylePara">The PET image fusion was done with the MRI imaging study &#40;axial T1-weighted or T2-weighted postgadolinium&#41;&#44; using the free software for image fusion and registration called Rview<span class="elsevierStyleSup">22&#44;23</span>&#44; that uses the development of a entropy-based registration criteria for automated 3D multi-modality medical image alignment&#46; This approach does not use geometric landmarks but searches for intensity similarities of voxels instead&#46; After loading the PET and MRI datasets&#44; a rigid transformation that use translations&#44; rotations and voxel scaling was applied to the PET data using this software &#40;Rview&#41;&#46; The whole fusion procedure was performed automatically without any manual adjustments&#46; The time required for fusion of a PET and MRI dataset was 0&#46;5-3 min&#44; it depends of image set dimensions&#46; The registration software produced a visually satisfactory registration &#40;that was proven using a phantom study for PET and a phantom study for MRI and then fusion with Rview program&#41;&#46;</p><span class="elsevierStyleSectionTitle">PET image analysis &#40;alone and PET&#47;MRI&#41;</span><p class="elsevierStylePara">PET images were interpreted by 2 nuclear medicine physicians compared with the MRI &#40;side by side and coregistered&#41;&#46; Images were interpreted as positive or negative&#46; The degree of <span class="elsevierStyleSup">18</span>FDG uptake was assessed by visual inspection and the degree of uptake was scored using a 5-point scale &#40;to try to indicate the tumoral grade&#41;&#58; 0&#44; no uptake&#59; 1&#44; less than the contralateral cortex&#59; 2&#44; equal than the contralateral cortex&#59; 3&#44; higher than the contralateral cortex but less than the rest of the normal gray matter&#59; 4&#44; higher than the contralateral cortex and than the rest of the normal gray matter&#44; in a region showing enhancing areas on postcontrast T1-weighted MR images&#46;</p><p class="elsevierStylePara">Lesions with an uptake of 0 were considered negative and an uptake of 1&#44;2&#44; 3&#44; or 4 was considered positive for recurrent tumor&#46; In addition&#44; a ROI of 5 mm of diameter was placed around areas of abnormal uptake an over contralateral gray matter for all patients&#46; The maximum standardized uptake value &#40;SUVmax&#41; was determined and analyzed separately&#46; Also <span class="elsevierStyleSup">18</span>FDG PET scans were processed using Neurologic Statistical Image Analysis software &#40;Neurostat&#59; Washington University&#41;&#46; Each image was warped to the common stereotactic coordinate system&#46; Gray-matter activities were extracted to predefined surface pixels using a 3-dimensional stereotactic surface projection technique &#40;3D-SSP&#41;&#44; which minimized residual anatomic variances across subjects and partial-volume effects&#44; yielding robust voxel-based statistical analysis<span class="elsevierStyleSup">19-24</span>&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleSup">18</span>FDG PET and the MRI and PMRI were done with a difference between them of no more than 15 days&#46; <span class="elsevierStyleSup">18</span>FDG PET images were read by two board certified nuclear medicine physician and the MRI and the PMRI images by a two board-certified neuroradiologist both with experience in interpretation&#46;</p><span class="elsevierStyleSectionTitle">Reference standard</span><p class="elsevierStylePara">Patients were followed up for a minimum of 6 months&#46; The follow-up range 6-21 months&#46; Stereotactic biopsy &#40;50 &#37;&#41;&#44; imaging follow-up &#40;gadolinium enhanced MRI or PET&#41;&#44; and clinical follow-up &#40;new presence of seizures&#44; headaches&#44; nausea&#44; vomiting&#41; were all used as reference standards for determining the presence or absence of a recurrence&#46;</p><span class="elsevierStyleSectionTitle">STATISTICAL ANALYSIS</span><p class="elsevierStylePara">The accuracy&#44; sensitivity&#44; specificity&#44; positive predictive value &#40;PPV&#41; and negative predictive value &#40;NPV&#41; were calculated by using standard formulas and differences between these parameters were tested with linear regression analyses&#46; Results are presented as the mean &#177; 1 standard deviation &#40;SD&#41;&#46; A receiv-er-operating-characteristic &#40;ROC&#41; analysis was performed on the diagnostic accuracy of PMRI and PET&#47;MRI fusion&#46;</p><p class="elsevierStylePara">Differences in the area under the curve &#40;AUC&#41; were tested with the chi-square statistic&#46; Bivariate correlations &#40;Pearson and Spearman&#41; were done to determine whether a relationship between those variables could be established&#46; All statistical analyses were performed in SPSS &#40;version 12&#46;0&#59; Chicago&#44; IL&#41;&#46; For all tests&#44; a p value of 0&#46;05 was considered significant&#46;</p><span class="elsevierStyleSectionTitle">RESULTS</span><p class="elsevierStylePara">20 men and 10 women&#59; &#40;median age for both&#44; 43 years&#41; with histopathologically confirmed diagnosis of primary cerebral tumor WHO III and IV &#40;13 GBM&#44; 12 anaplastic astrocytoma&#44; 3 anaplastic oligoastrocytoma&#44; 1 gliosarcoma&#44; 1 choroid plexus carcinoma&#41;&#46;</p><span class="elsevierStyleSectionTitle">MRI</span><p class="elsevierStylePara">MRI had a sensitivity of 94 &#37; and a specificity of 25 &#37;&#46; There was 1 false negative MRI finding that was defined by pathology as GBM and 9 false-posi-tive MRI results&#46;</p><span class="elsevierStyleSectionTitle">Perfusion MRI</span><p class="elsevierStylePara">PMRI had a sensitivity of 63 &#37;&#44; specificity of 82 &#37;&#44; PPV of 86 &#37;&#44; accuracy of 56 &#37; and NPV of 86 &#37;&#46; There were 2 false-positive PMRI results&#44; one was also FP for PET&#47;MRI fusion&#46; The other one was negative in the PET&#47;MRI images and the clinical follow up didn&#8217;t show any progression of the tumor in the next 6 months&#46;</p><p class="elsevierStylePara">The rCBV values for GBM were from 0&#46;10 to 6&#46;40 &#40;mean 2&#46;32 &#177; 2&#46;0&#41; and for anaplastic astrocytomas were from 0&#46;50 to 9&#46;20 &#40;mean 1&#46;99 &#177; 2&#46;4&#41;&#46;</p><span class="elsevierStyleSectionTitle">PET &#40;alone&#41;</span><p class="elsevierStylePara">PET had a sensitivity of 67 &#37; and a specificity of 82 &#37; &#40;table 2&#41;&#46; The 6 false-negative PET findings included four astrocytomas&#44; one GBM and one sarcoma&#46; False-positive PET findings included 2 cases that were defined by pathology as chronic inflammation in one case and foreign body granulomas in the second case &#40;tissue reaction to the metal plate that was surgically removed&#41;&#46;</p><p class="elsevierStylePara"><img src="125v27n05-13126189tab02.gif"></img></p><p class="elsevierStylePara">Table 2 PET&#44; MRI&#44; PET&#47;MRI AND PMRI</p><span class="elsevierStyleSectionTitle">PET&#47;MRI fusion</span><p class="elsevierStylePara"><span class="elsevierStyleSup">18</span>FDG PET&#47;MRI fusion had a sensitivity of 100 &#37;&#44; specificity of 82 &#37;&#44; PPV of 90 &#37;&#44; an accuracy of 93 &#37; and NPV of 100 &#37;&#46; There were 2 false-positive PET&#47;MRI result findings that were defined by pathology as chronic inflammation in one case and foreign body granulomas in the second case &#40;tissue reaction to the metal plate that was surgically removed&#41;&#46;</p><p class="elsevierStylePara">By semiquantitative analysis&#44; the SUVmax for all positive PET lesions &#40;n &#61; 21&#41; averaged at 4&#46;8 &#177; 3&#46;2 &#40;range&#44; 1&#46;1-14&#46;3&#41;&#46; In the true-positive PET&#47;MRI subgroup &#40;n &#61; 19&#41;&#44; the lesion size ranged from 2&#46;3 to 124&#46;4 cm<span class="elsevierStyleSup">3</span> &#40;averaged at 45&#46;9 &#177; 42&#46;9&#41;&#44; with a mean SUVmax of 4&#46;9 &#177; 3&#46;2 &#40;range&#44; 1&#46;8-14&#46;3&#41;&#46; The SUVmax in the contralateral gray matter averaged at 7&#46;9 &#177; 2&#46;0 &#40;range&#44; 5&#46;8-13&#46;2&#41;&#46; The SUVmax tumor to gray matter ratio &#40;T&#47;G&#41; in all lesions ranged from 0&#46;1 to 2&#46;2 &#40;mean &#177; 0&#46;4&#41;&#44; in the true-positive PET&#47;MRI subgroup &#40;n &#61; 19&#41;&#44; the SUVmax T&#47;G ratio ranged from 0&#46;2 to &#40;mean 0&#46;6&#177; 0&#46;5&#41; &#40;table 1&#41;&#46;</p><p class="elsevierStylePara">With 3D-SSP only in two cases the z scores were higher in a focal area&#44; &#40;in the cases that the visual score was 4&#41;&#44; no reaching statistical significance&#46; Z scores not yielded significantly discrimination accuracies&#46;</p><p class="elsevierStylePara">PET&#47;MRI fusion had 8 discordant interpretations compared with PMRI&#44; 6 of which were true positive&#44; 1 true negative and 1 false positive for the PET&#47;MRI fusion&#46; PET&#47;MRI had 11 discordant interpretations compared with PET alone&#46; PET-only interpretations missed 6 lesions because there was low <span class="elsevierStyleSup">18</span>FDG uptake&#46; PET&#47;MRI had 8 discordant interpretations compared with MRI alone&#44; 7 were false positive for MRI&#46;</p><p class="elsevierStylePara">A ROC analysis was performed for PMRI and PET&#47;MRI&#44; which is shown in figure 1&#46; The additional value of PET&#47;MRI over PMRI is clearly seen and appears to hold over the entire range of sensitivity&#44; PPV and NPV&#46;</p><p class="elsevierStylePara"><img src="125v27n05-13126189fig03.jpg"></img></p><p class="elsevierStylePara">FIG&#46; 1&#46;&#8212;Receiver operating characteristic &#40;ROC&#41; curves analysis&#46; The ROC curves for detection of recurrent brain tumors by software PET&#47;MRI fusion and PMRI&#46; Analysis showed an area under the curve &#40;AUC&#41; of 0&#46;9627 for PET&#47;MRI and AUC of 0&#46;7584 for PMRI &#40;p &#61; 0&#46;02&#41;&#46; There was statistically significant difference between both methods&#46;</p><p class="elsevierStylePara">Nine patients had tumor progression&#46; Four patients die&#44; while the rest remained alive during the 21 months of follow up&#46;</p><p class="elsevierStylePara">We had one secondary glioblastoma&#44; upon progression of an anaplastic astrocytoma &#40;diagnosed from a gross total resection and histologically confirmed 1 year previously&#41;&#46; Then&#44; another resection of tumor was performed&#44; yielding the diagnosis of glioblastoma&#46;</p><p class="elsevierStylePara">There was statistically significant difference between the recurrent tumors and the visual uptake scale for PET&#47;MRI &#40;p &#61; 0&#46;001&#41;&#46;There was no statistically significant difference between tumoral volume &#40;cm<span class="elsevierStyleSup">3</span>&#41; and the rCBV and the visual uptake scale for PET&#47;MRI&#44; nor as recurrent tumors and the rCBV&#46;</p><span class="elsevierStyleSectionTitle">DISCUSSION</span><p class="elsevierStylePara">The brain uses great amounts of glucose to meet its metabolic energy requirements so the normal PET brain study has high levels of uptake in cerebral cortex&#44; thalamus and basal ganglia that makes that in many cases the brain tumors are similar in metabolism than the rest of the cortex&#44; especially when they were already treated&#46; The clinical utility of <span class="elsevierStyleSup">18</span>FDG for the assessment of tumor recurrence depends on selection of the patients&#46; Also it is important to notice that in the assessment of tumor recurrence without anatomical references&#44; it is almost impossible to interpret adequately if a PET study is positive or negative&#44; so anatomic references are very important<span class="elsevierStyleSup">17&#44;25&#44;26</span>&#46; The use of automated voxel based analysis is used for its convenience in image analysis and in statistical examination of group differences<span class="elsevierStyleSup">27</span>&#46; Our data indicate that the assessment of recurrent tumors with statistical parametric mappings may not be particularly useful&#46;</p><p class="elsevierStylePara">Hustinx et al<span class="elsevierStyleSup">25</span> in the diagnostic value of FDG-PET &#40;alone&#41; for differentiating radiation necrosis from recurrent tumors reported a sensitivity of 73 &#37; and a specificity of 56 &#37; in 31 patients with a pathologyproven final diagnosis&#46; These results were obtained using a visual score&#46; We obtained similar findings&#46; They also reported that the sensitivity of PET alone increased when MRI and PET images were coregistered&#44; while specificity remained unchanged and that&#44; both the specificity and the accuracy were higher with PET than with MRI&#46; We obtained also similar findings in the present study&#46;</p><p class="elsevierStylePara">As shown in table 2&#44; PET&#47;MRI performs better than PET alone in accuracy&#44; sensitivity&#44; PPV and NPV and better than MRI alone in specificity&#44; accuracy&#44; sensitivity&#44; PPV and NPV&#46; The most frequent limitation of <span class="elsevierStyleSup">18</span>FDG PET involves detecting small lesions and lesions with low metabolism&#44; this in part because steroids are commonly used in clinical settings and this treatment decrease <span class="elsevierStyleSup">18</span>FDG uptake<span class="elsevierStyleSup">28</span>&#44; but PET&#47;MRI seems to overcome many of the equivocal findings&#46;</p><p class="elsevierStylePara">PET imaging also provides information about heterogeneities within a tumor which might improve diagnostic performance guiding the biopsy or helping planning the treatment with radiotherapy&#44; this heterogeneities some times are not seen in the MRI images and the most of the times the PET images shows areas of uptake different in size than the MRI&#44; this areas with enhancement and <span class="elsevierStyleSup">18</span>FDG uptake are the ones that are treated&#44; and before the physiological studies like PET&#44; there were treated all areas of enhancement&#44; with an increase of side effects &#40;fig&#46; 2&#41;&#46;</p><p class="elsevierStylePara"><img src="125v27n05-13126189fig04.jpg"></img></p><p class="elsevierStylePara">FIG&#46; 2&#46;&#8212;Concordant results between PET&#47;MRI fusion and perfusion MRI&#46; Fifty years old male with a GBM&#46; A&#58; 3T Magnetic resonance imaging&#44; postcontrast T1-weighted sequence&#59; B&#58; 18FDG-PET&#59; C&#58; PET&#47;MRI fusion that shows over the hyperintensity on the MRI&#44; 18FDG uptake less than the contralateral cortex &#40;grade 1&#41; and reported as positive&#59; D&#58; CBV map shows elevated blood volume within the lesion&#59; E&#58; Time-signal curve&#46; The green line is the normal cortex and the purple line the suspected area&#44; with a calculated rCBV of 6&#46;4 and reported as positive&#46; Both studies were consistent with high-grade neoplasm&#46; The reader should note that there is a pretty big discrepancy between the gadolinium enhanced MRI and the 18FDG uptake&#46; The MRI report was positive for tumour in all areas of enhancement &#40;because of disruption of the blood brain barrier&#41;&#44; while noticing that only some areas show 18FDG uptake &#40;areas with viable cells&#41;&#46; Before the physiological studies appear&#44; all areas of enhancement were treated&#44; and now&#44; there are treated only the areas with 18FDG uptake&#46; F and G&#46; Predefined anatomic surface ROIs &#40;in yellow&#41; are superimposed onto &#40;from left to right&#41; right and left lateral&#44; superior&#44; inferior and right and left medial views of standardized brain template showing surface projection maps of statistical abnormalities as compared with normals&#44; z scores are represented on color coded scale ranging from 0 &#40;black&#41; to 7 &#40;red&#41;&#44; for decreased and increased respectively&#46;</p><p class="elsevierStylePara">Like other authors<span class="elsevierStyleSup">16</span> we found areas of hypometabolism adjacent to the tumor site that in the most of our cases correspond to edema on MRI images&#46; This areas were perfectly identified with the 3D-SSP&#46;</p><p class="elsevierStylePara">The diagnosis of tumoral recurrence was independent of the tumor size &#40;cm<span class="elsevierStyleSup">3</span>&#41;&#46;</p><p class="elsevierStylePara">The ROI were visually analyzed and described as recurrent tumors when any uptake &#40;1 to 4&#41; was present on the enhancing areas on post contrast T1 weighted MRI &#40;figs&#46; 3 and 4&#41;&#46;</p><p class="elsevierStylePara"><img src="125v27n05-13126189fig05.jpg"></img></p><p class="elsevierStylePara">FIG&#46; 3&#46;&#8212;Discordant results between PET&#47;MRI fusion and perfusion MRI&#46; Thirty years old male with an anaplastic astrocytoma&#46; A&#58; 3T Magnetic resonance imaging&#44; postcontrast T1-weighted sequence&#46; B&#58; 18FDG-PET&#46; C&#58; PET&#47;MRI fusion that shows over the hyperintensity on the MRI&#44; 18FDG uptake less than the contralateral cortex &#40;grade 1&#41; and reported as positive&#46; D&#58; CBV map shows similar blood volume within the lesion than in the uninvolved region&#46; E&#58; Time-signal curve&#46; The green line is the normal cortex and the purple line the suspected area&#44; with a calculated rCBV of 0&#46;5 and reported as negative&#46; It was a true positive study for the PET&#47;MRI fusion and a false negative study for the perfusion MRI&#46; F and G&#46; Predefined anatomic surface ROIs &#40;in yellow&#41; are superimposed onto &#40;from left to right&#41; right and left lateral&#44; superior&#44; inferior and right and left medial views of standardized brain template showing surface projection maps of statistical abnormalities as compared with normals&#44; z scores are represented on color coded scale ranging from 0 &#40;black&#41; to 7 &#40;red&#41;&#44; for decreased and increased respectively&#46;</p><p class="elsevierStylePara"><img src="125v27n05-13126189fig06.jpg"></img></p><p class="elsevierStylePara">FIG&#46; 4&#46;&#8212;Concordant results between fusion PET&#47;MRI and perfusion MRI&#46; Twenty eight years old female with a choroidal plexus carcinoma&#46; A&#41; 3T Magnetic resonance imaging&#44; postcontrast T1-weighted sequence&#46; B&#58; 18FDG-PET&#46; C&#58; PET&#47;MRI fusion that shows over the hyperintensity on the MRI&#44; 18FDG uptake greater than the contralateral cortex and grater than the rest of the normal gray matter &#40;grade 4&#41; and reported as positive&#46; D&#58; Time-signal curve&#46; The green line is the normal cortex and the purple line the suspected area&#44; with a calculated rCBV of 5&#46;1 and reported as positive&#46; E&#58; CBV map shows elevated blood volume within the lesion&#44; consistent with high-grade neoplasm&#46; F and G&#46; Predefined anatomic surface ROIs &#40;in yellow&#41; are superimposed onto &#40;from left to right&#41; right and left lateral&#44; superior&#44; inferior and right and left medial views of standardized brain template showing surface projection maps of statistical abnormalities as compared with normals&#44; z scores are represented on color coded scale ranging from 0 &#40;black&#41; to 7 &#40;red&#41;&#44; for decrease and increased respectively&#46;</p><p class="elsevierStylePara">Although <span class="elsevierStyleSup">18</span>FDG SUVmax in whole body is used as a routine&#46; It was shown previously that <span class="elsevierStyleSup">18</span>FDG SUVmax in brain tumors were not a reliable measure for evaluating recurrent tumors<span class="elsevierStyleSup">17&#44;28</span>&#59; we obtained similar findings in the present study&#44; with a large overlap of <span class="elsevierStyleSup">18</span>FDG uptake between recurrent tumors and normal gray matter&#44; so as with the T&#47;G ratio&#8217;s&#46; SUVs and T&#47;G ratio&#8217;s appear to be of limited value in characterizing recurrent primary brain tumors&#46; We agreed with Hustinx et al<span class="elsevierStyleSup">25</span> that reported that no study has proved that quantitative methods are better than visual interpretation by the physician&#46; Visual assessment by an experienced nuclear medicine specialist with the criterion that any uptake on the enhancing areas on post contrast T1 MRI should be considered abnormal provided a higher sensitivity&#46;</p><p class="elsevierStylePara">In the current study&#44; we found two PET&#47;MRI that were false positive confirmed by biopsy &#40;chronic inflammation in one case and foreign body granulomas in the second case&#41;&#46; It is well known that infection and inflammatory cells using glucose as a main source of energy have increased uptake of the <span class="elsevierStyleSup">18</span>FDG<span class="elsevierStyleSup">29</span> and frequently cause false positive results&#46; There are few references in the literature about the <span class="elsevierStyleSup">18</span>FDG uptake in the brain for chronic inflammation and encephalitis<span class="elsevierStyleSup">30&#44;31</span>&#44; but to our knowledge this is the first report about a patient with a foreign body in the skull and <span class="elsevierStyleSup">18</span>FDG uptake&#46; Both patients remain alive and with good clinical conditions&#46; Table 3 shows the physiological targets of the 3 methods<span class="elsevierStyleSup">32</span>&#46;</p><p class="elsevierStylePara"><img src="125v27n05-13126189tab07.gif"></img></p><p class="elsevierStylePara">Table 3 METHODS AND THEIR PHYSIOLOGICAL TARGETS</p><p class="elsevierStylePara">The literature refers that the PET study can be used also to monitoring the histological changes in patients with brain tumors for evidence of degeneration into a malignancy of higher grade<span class="elsevierStyleSup">33</span>&#44; like in our patient with secondary GBM&#46; Both the primary and the secondary GBM share some genetic abnormalities<span class="elsevierStyleSup">34</span>&#46; The uptake was lower than we expected for a GBM&#44; this in part because the zone was recently treated and also be-cause the patient was taking corticosteroids&#44; that decreased <span class="elsevierStyleSup">18</span>FDG uptake<span class="elsevierStyleSup">28</span>&#46;</p><p class="elsevierStylePara">The PMRI sensitivity was low &#40;63 &#37;&#41;&#44; which may be explained by the inherent glioma heterogeneity&#44; as observed previously<span class="elsevierStyleSup">15</span> that are more evident after the treatment&#46; Weber et al<span class="elsevierStyleSup">21</span> reported that a threshold value of 1&#46;2 provided sensitivity 97 &#37;&#44; specificity 80 &#37;&#44; PPV 94 &#37;&#44; and NPV 89 &#37; &#40;first detection of a brain neoplasm&#44; without treatment&#41;&#44; and our group of patients were already treated&#46; He also reported that for discrimination of glioblastomas from grade III gliomas&#44; sensitivity was 97 &#37;&#44; specificity was 50 &#37;&#44; PPV was 84 &#37;&#44; and NPV was 86 &#37;&#46; However&#44; we observed a significant overlap in the rCBV values of grade III astrocytomas from glioblastomas<span class="elsevierStyleSup">21&#44;35</span>&#46; This functional MRI technique has limited utility when the glioma was already treated&#46; In a study by Leimgruber et al<span class="elsevierStyleSup">36</span>&#44; PMRI used in follow-up after chemoradiation for glioblastomas was not shown to be useful for predicting tumor progression&#46;</p><p class="elsevierStylePara">In general the survival for GBM is longer now with the new therapeutics and interdisciplinary cancer therapy trials can significantly prolong survival and allows a small subgroup of patients to survive 3 to 5 years<span class="elsevierStyleSup">37-40</span>&#46;</p><p class="elsevierStylePara">The first images for small animals from the complete system PET&#47;MRI have been successfully acquired and reconstructed&#44; demonstrating that simultaneous PET and MRI studies are feasible<span class="elsevierStyleSup">41</span>&#44; but until this systems is available for clinical use&#44; the software Rview could be an excellent option for PET&#47;MRI fusion&#46; PET-MRI coregistration accuracy was widely discussed by Stuldhome et al<span class="elsevierStyleSup">23</span>&#44; Kiebel et al<span class="elsevierStyleSup">42</span> and Garc&#237;a et al<span class="elsevierStyleSup">43</span>&#46; They find that PET-MRI coregistration using automated image techniques are feasible within the size of a PET pixel&#46;</p><p class="elsevierStylePara">A limitation of our study was that we don&#8217;t have availability of other more specific tracers for brain tumours&#44; like the amino acid PET tracers <span class="elsevierStyleSup">11</span>C-methion-ine and <span class="elsevierStyleSup"> 18</span>FDOPA<span class="elsevierStyleSup">18&#44;26&#44;28</span> angiogenesis markers&#44; like <span class="elsevierStyleSup"> 18</span>F-Fluorocholine and <span class="elsevierStyleSup">18</span>F-FET<span class="elsevierStyleSup">44</span>&#44; markers for receptors like F-FLT<span class="elsevierStyleSup">45</span>&#44; among other tracers for protein and DNA synthesis<span class="elsevierStyleSup">32</span>&#46; Also that only half of the lesions suspicious for recurrent brain tumour were confirmed by biopsy&#46; As seen in some reports histopathologic proof&#44; is not always available&#46; Patients with negative PET findings are less likely to undergo surgical confirmation of their status and the clinical follow up appear to be enough in these patients<span class="elsevierStyleSup">28</span>&#46; The highest reported incidence of pathology-proven radiation necrosis is only 24 &#37;<span class="elsevierStyleSup">25</span>&#46; Therefore&#44; further studies involving a bigger number of cases and the validation of the visual scale proposed by the authors is needed to introduce this technique &#40;PET&#47;MRI fusion&#41; for routine clinical practice&#46;</p><span class="elsevierStyleSectionTitle">CONCLUSIONS</span><p class="elsevierStylePara">The combination of anatomic and metabolic imaging &#40;PET&#47;MRI&#41; performs better than PMRI in accuracy&#44; sensitivity&#44; PPV and NPV&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleSup">18</span>FDG SUVmax in brain tumours were not a reliable measure for evaluating recurrent tumours&#46; No additional information was provided by performing semiquantitative analysis&#44; including the use of the automated program 3D stereotactic surface projections&#46; Visual inspection of PET&#47;MRI images with the criterion that any uptake on the enhancing areas on post contrast T1 MRI should be considered abnormal&#44; provided a higher sensitivity&#46; Hence&#44; PET&#47;MRI images allow us to readily appreciate tumor extension&#46; The MRI alone has the lowest specificity&#46; The PMRI has the lowest value of sensitivity&#46;</p><span class="elsevierStyleSectionTitle">ACKNOWLEDGMENTS</span><p class="elsevierStylePara">The work described in this paper was undertaken with the financial support of UNAM&#8217;s PET-cyclotron unit&#46; The authors thanks Satoshi Minoshima&#44; PhD&#44; for the support of 3D-SSP Neurostat program&#44; Ren&#233; Drucker Colin&#44; MD&#44; PhD&#44; Alfonso Due&#241;as MD&#44; PhD&#44; and Luis Alberto Medina V&#44; PhD&#44; for their help in the manuscript&#46; Dr&#46; H&#233;ctor Carrillo for statistical evaluation of the results&#44; Claudia M&#46; Segura and Patricia Miranda for technical assistance&#44; Dr Alexanderson&#44; TMN Antonio Manzo&#44; TMN Ricardo C&#225;rdenas&#44; Fis&#46; Armando Flores and M&#46; C&#46; Adolfo Z&#225;rate from UNAM PET-Cyclotron unit&#46;</p><p class="elsevierStylePara">Received&#58; 11-02-08&#46; Accepted&#58; 13-06-08&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic">Correspondencia&#58;</span></p><p class="elsevierStylePara">G&#46; ESTRADA-S&#193;NCHEZ CT Scanner del Sur Rafael Checa No&#46; 3&#44; col&#46; San &#193;ngel 01000 San &#193;ngel&#46; M&#233;xico&#44; D&#46;F&#46; E-mail&#58; dragiselaus&#64;yahoo&#46;com</p>"
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        "resumen" => "Thirty patients with primary cerebral tumors WHO III and IV previously treated&#44; undergoing evaluation for tumoral recurrence&#44; they underwent 18FDG-PET study&#44; MRI and PMRI&#46; PET uptake was determined by visual inspection and was quantified by use of standard uptake values&#44; the ratio of tumor uptake to normal tissue and were z scored using automated voxel-based comparison&#46; PMRI was quantified by use of ratios of cerebral blood volume &#40;rCBV&#41;&#46; The accuracies were determined by comparing imaging data with histologic findings and clinical follow up of up to 21 mo&#46; Results&#46; Sensitivity &#40;Se&#41;&#44; specificity &#40;Sp&#41;&#44; positive predictive value &#40;PPV&#41;&#44; negative predictive value &#40;NPV&#41; and accuracy were 100 &#37;&#44; 82 &#37;&#44; 90 &#37;&#44; 100 &#37; and 93 &#37; respectively for the PET&#47;MRI fusion and 68 &#37;&#44; 82 &#37;&#44; 87 &#37;&#44; 60 &#37; and 73 &#37; respectively for PMRI&#46; There were two false positive cases for PET&#47;MRI fusion that were confirmed by biopsy&#58; chronic inflammation&#59; and foreign body granulomas&#46; The receiver operating characteristic &#40;ROC&#41; curve analysis showed statistically significant difference &#40;p &#61; 0&#46;0225&#41;&#46; Conclusions&#46; 18FDG SUVs&#44; glucose uptake ratios and 3D stereotactic surface projections in brain tumors were not a reliable measure for evaluating recurrent tumors&#46; PET&#47;MRI fusion was more sensitive and accurate than PMRI for imaging recurrent primary brain tumors&#46; The region of interest can be visually analyzed on the PET&#47;MRI fusion images and described as recurrent tumor when any activity &#40;lower&#44; equal or greater than the contralateral cortex&#41; is presented in the zone of hyperintensity seen on the post-gadolinium T1-weighted MRI&#46;"
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        "resumen" => "Se ha hecho un estudio con 18FDG-PET&#44; RM y perfusi&#243;n por resonancia magn&#233;tica en 30 pacientes con tumores cerebrales primarios grado OMS III y IV&#44; previamente tratados y a los que se les iba a hacer el seguimiento de recurrencia tumoral&#46; La captaci&#243;n de la PET estuvo determinada por la inspecci&#243;n visual y se cuantific&#243; utilizando los valores de captaci&#243;n est&#225;ndar&#44; la proporci&#243;n de captaci&#243;n tumoral&#47;tejido normal y la desviaci&#243;n est&#225;ndar z mediante comparaci&#243;n automatizada con v&#243;xeles&#46; La perfusi&#243;n por resonancia magn&#233;tica se cuantific&#243; mediante la utilizaci&#243;n de las proporciones del volumen sangu&#237;neo cerebral&#46; La exactitud diagn&#243;stica se determin&#243; comparando los datos de las im&#225;genes con los hallazgos histol&#243;gicos y el seguimiento cl&#237;nico durante un per&#237;odo de hasta 21 meses&#46; Resultados&#46; La sensibilidad &#40;Se&#41;&#44; la especificidad &#40;Sp&#41;&#44; el valor predictivo positivo &#40;VPP&#41;&#44; el valor predictivo negativo &#40;VPN&#41; y la exactitud diagn&#243;stica fueron del 100&#44; 82&#44; 90&#44; 100 y 93 &#37;&#44; respectivamente&#44; para la fusi&#243;n PET&#47;RM&#59; y del 68&#44; 82&#44; 87&#44; 60 y 73&#37;&#44; respectivamente&#44; para la perfusi&#243;n por resonancia magn&#233;tica&#46; Hubo dos casos falsos positivos para la fusi&#243;n PET&#47;RM que se confirmaron mediante biopsia&#58; inflamaci&#243;n cr&#243;nica y granulomas por cuerpo extra&#241;o&#46; El an&#225;lisis de las curvas caracter&#237;sticas operativas del receptor &#40;ROC&#41; demostr&#243; una diferencia estad&#237;sticamente significativa &#40;p &#61; 0&#44;0225&#41;&#46; Conclusiones&#46; Los valores de captaci&#243;n estandarizados de 18FDG &#40;SUV&#41;&#44; las proporciones de captaci&#243;n de glucosa y las proyecciones estereot&#225;xicas de superficie en 3D &#40;3D-SSP&#41; de los tumores cerebrales no demostraron ser mediciones &#250;tiles para evaluar tumores recurrentes&#46; La fusi&#243;n PET&#47;RM result&#243; ser m&#225;s sensible y con mayor exactitud diagn&#243;stica que la perfusi&#243;n por resonancia magn&#233;tica como diagn&#243;stico de imagen de los tumores cerebrales primarios recurrentes&#46; En las im&#225;genes de fusi&#243;n PET&#47;RM puede analizarse la regi&#243;n de inter&#233;s y reportarse como tumor recurrente cuando aparece cualquier actividad &#40;menor&#44; igual o mayor que en la corteza contralateral&#41; en la zona de hiperintensidad observada en la RM con gadolinio y ponderada en T1&#46;"
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          "en" => "&#8212;Receiver operating characteristic &#40;ROC&#41; curves analysis&#46; The ROC curves for detection of recurrent brain tumors by software PET&#47;MRI fusion and PMRI&#46; Analysis showed an area under the curve &#40;AUC&#41; of 0&#46;9627 for PET&#47;MRI and AUC of 0&#46;7584 for PMRI &#40;p &#61; 0&#46;02&#41;&#46; There was statistically significant difference between both methods&#46;"
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          "en" => "&#8212;Concordant results between PET&#47;MRI fusion and perfusion MRI&#46; Fifty years old male with a GBM&#46; A&#58; 3T Magnetic resonance imaging&#44; postcontrast T1-weighted sequence&#59; B&#58; 18FDG-PET&#59; C&#58; PET&#47;MRI fusion that shows over the hyperintensity on the MRI&#44; 18FDG uptake less than the contralateral cortex &#40;grade 1&#41; and reported as positive&#59; D&#58; CBV map shows elevated blood volume within the lesion&#59; E&#58; Time-signal curve&#46; The green line is the normal cortex and the purple line the suspected area&#44; with a calculated rCBV of 6&#46;4 and reported as positive&#46; Both studies were consistent with high-grade neoplasm&#46; The reader should note that there is a pretty big discrepancy between the gadolinium enhanced MRI and the 18FDG uptake&#46; The MRI report was positive for tumour in all areas of enhancement &#40;because of disruption of the blood brain barrier&#41;&#44; while noticing that only some areas show 18FDG uptake &#40;areas with viable cells&#41;&#46; Before the physiological studies appear&#44; all areas of enhancement were treated&#44; and now&#44; there are treated only the areas with 18FDG uptake&#46; F and G&#46; Predefined anatomic surface ROIs &#40;in yellow&#41; are superimposed onto &#40;from left to right&#41; right and left lateral&#44; superior&#44; inferior and right and left medial views of standardized brain template showing surface projection maps of statistical abnormalities as compared with normals&#44; z scores are represented on color coded scale ranging from 0 &#40;black&#41; to 7 &#40;red&#41;&#44; for decreased and increased respectively&#46;"
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Article information

ISSN: 2253654X
Original language: English

DOI:10.1157/13126189

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Year/Month	Html	Pdf	Total

2022 October	1	0	1
2020 January	1	2	3
2019 March	1	2	3
2018 March	2	0	2
2018 February	8	3	11
2018 January	21	4	25
2017 December	5	4	9
2017 November	21	4	25
2017 October	14	3	17
2017 September	17	1	18
2017 August	14	12	26
2017 July	13	0	13
2017 June	19	5	24
2017 May	25	0	25
2017 April	26	16	42
2017 March	37	18	55
2017 February	74	5	79
2017 January	23	4	27
2016 December	22	6	28
2016 November	35	6	41
2016 October	34	4	38
2016 September	43	7	50
2016 August	13	8	21
2016 July	41	3	44
2016 June	53	8	61
2016 May	26	17	43
2016 April	21	6	27
2016 March	28	12	40
2016 February	19	9	28
2016 January	30	14	44
2015 December	44	10	54
2015 November	38	11	49
2015 October	53	6	59
2015 September	40	3	43
2015 August	50	6	56
2015 July	74	0	74
2015 June	30	1	31
2015 May	27	12	39
2015 April	28	7	35
2015 March	38	11	49
2015 February	42	3	45
2015 January	39	4	43
2014 December	31	4	35
2014 November	21	0	21
2014 October	28	1	29
2014 September	18	3	21
2014 August	25	2	27
2014 July	43	1	44
2014 June	28	3	31
2014 May	16	1	17
2014 April	6	1	7
2014 March	11	1	12
2014 February	11	3	14
2014 January	16	1	17
2013 December	22	3	25
2013 November	34	2	36
2013 October	79	4	83
2013 September	30	5	35
2013 August	16	2	18
2013 July	5	1	6
2008 August	1456	0	1456

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