Tomografía por Emisión de Positrones cuantificada en la evaluación prequirúrgica de la epilepsia

[spa] La epilepsia es una enfermedad con una elevada prevalencia e impacto sociosanitario. Aproximadamente un tercio de los pacientes son resistentes al tratamiento farmacológico y en estos casos debe considerarse la cirugía como la única opción potencialmente curativa. El éxito de la cirugía de la epilepsia está directamente relacionado con la precisa localización y resección del córtex epileptógeno, por lo que es crucial realizar una exhaustiva valoración prequirúrgica considerando varias modalidades diagnósticas. Los estudios de neuroimagen funcional como la PET, analizados visual y objetivamente mediante programas informáticos específicos, pueden desempeñar un papel decisivo en este contexto. Este trabajo de investigación se ha basado en la publicación dos estudios. En el primer estudio se incluyeron retrospectivamente 55 pacientes con epilepsia resistente al tratamiento farmacológico a los que se les realizó una PET con 18F-FDG que se interpretó como normal o con hallazgos muy sutiles o dudosos al análisis visual. De entre los pacientes incluidos, 20 habían sido operados con buenos resultados postquirúrgicos (Engel I-II). Se analizaron todos los estudios PET con SPM. Se usaron como dinteles de segmentación un valor de p corregido de p<0,05 con un tamaño mínimo de cluster k=0 (combinación 1 o C1), y tres valores de p no corregidos que eran gradualmente mayores con tamaños mínimos de cluster que también eran progresivamente de mayor tamaño. Estas tres combinaciones fueron p<0,0001 con k=20 (C2), p<0,001 con k=100 (C3) y p=0,005 con k=200 (C4). SPM evidenció áreas hipometabólicas en los estudios PET dudosos o negativos al análisis visual incluídos con los cuatro dinteles. La localización correcta de la ZE aumentó de forma progresiva desde el dintel con valor de p más restrictivo hasta el más liberal (de C1 a C4). En el grupo de pacientes operados, la proporción máxima de estudios correctamente localizadores se obtuvo con el dintel C4, que fue del 55% (11/20), una proporción ligeramente inferior al 65% (13/20) obtenido con la RM. Sin embargo, no se encontraron diferencias estadísticamente significativas entre estas dos proporciones. C3 fue el segundo dintel con la máxima proporción de estudios correctamente localizadores, acertando en la localización de la ZE en el 40% (8/20) de los pacientes operados. En el análisis global de los 55 pacientes, C4 también obtuvo la máxima proporción con un 40% (22/55) de estudios correctamente localizadores, y C3 obtuvo la segunda máxima proporción con un 29.1% (16/55). El aumento progresivo de estudios positivos de C1 a C4 no conllevó un aumento relevante en la proporción de estudios falsamente localizadores. Hubo tres pacientes operados en los que ni la RM ni la PET con SPM detectaron algun área que potencialmente pudiese ser la ZE. La concordancia entre la ZE y el dintel C1 fue justa y moderada con C2, C3 y C4. Cuando se analizó por separado a los pacientes operados las concordancias aumentaron, siendo substancial para C2 (к = 0,696; 95% IC 0,303–1,000) y C4 (к = 0,607; 95% IC 0,258–0,957), valores similares a los obtenidos con la RM (к = 0,783; 95% IC 0,509–1,000). Cuatro pacientes que tuvieron estudios de RM negativos o falsamente localizadores de la ZE tuvieron estudios PET correctamente localizadores tras el análisis con SPM. En el segundo estudio se incluyeron 30 pacientes con epilepsia refractaria al tratamiento farmacológico a los que se realizó una PET con 18F-FDG y que tuvieron unos resultados posoperatorios óptimos. Los estudios PET se evaluaron visualmente, con SPM y con PET-analysis. Para el análisis con SPM, se usaron los dinteles p corregida 50 y p no corregida 100. Como PET-analysis procesa rápidamente varias combinaciones de dinteles de significación, se usaron múltiples dinteles basados en combinaciones de diferentes desviaciones estándar y tamaños de cluster. PET-analysis obtuvo un 66,7% (20/30) de estudios correctamente localizadores de la ZE, comparable con el 70,0% (21/30) obtenido mediante el análisis visual y significativamente superior (p100, que obtuvo 36,7% (11/30). Sólo un estudio fue positivo, aunque no localizador, con el dintel de SPM p50. En cuanto a la RM, un 16/30 (53,3%) de los estudios fueron correctamente localizadores. La concordancia de la ZE posquirúrgica fue sustancial con PET-analysis (к=0,643, IC95% 0,439-0,847) y la interpretación visual (к=0,622, IC95% 0,367-0,877), pero fue débil con SPM (к=0,242, IC95% 0,028-0,455) y moderada con la RM (к=0,520, IC95% 0,268-0,772). En comparación con SPM, PET-analysis podría ser superior para la localización de la ZE con su procesado rápido y sencillo de diferentes combinaciones de dinteles de significación. Los resultados de este estudio validan el uso clínico de PET-analysis como una herramienta robusta complementaria al análisis visual en la localización de la ZE.[eng] FIRST ARTICLE SUMMARY Seizure onset zone localization by Statistical Parametric Mapping in visually normal 18F-FDG PET studies Introduction and objective: Neuroimaging is crucial in the presurgical evaluation of patients with medically refractory epilepsy. To improve the moderate sensitivity of [18F]fluorodeoxyglucose (18F-FDG) positron emission tomograpghy (PET) our aim was to evaluate the usefulness of Statistical Parametric Mapping (SPM) to localize the seizure onset zone (SOZ) in PET studies deemed normal by visual assessment. Methods: Fifty-five patients with medically refractory epilepsy whose 18F-FDG PET was visually evaluated as normal were retrospectively included. Twenty of these patients were surgically-intervened. PET images were analysed by SPM8 using a corrected p value of p0, k>20, k>100 and k>200, respectively. The SPM-identified potential seizure zone (SZ) was compared to the SOZ, which was determined by consensus during patient management meetings in the Epilepsy Unit, taking into account presurgical tests. Studies in which the SPM-identified potential SZ was concordant with the SOZ were considered “correctly localizing”. Results: The SPM threshold combination with the least restrictive p-value and greatest minimum cluster size achieved the highest rate of correctly localizing studies. When p200 was used, 40% (22/55) of studies were correctly localizing, and the concordance obtained in the surgically-intervened subgroup was substantial (к=0.607, CI95% 0.258,0.957), which was comparable to the concordance obtained by MRI (к=0.783, CI95% 0.509,1.000). Conclusion: SPM offers improved SOZ localization in 18F-FDG PET studies that are negative on visual assessment. For this purpose, statistical parametric maps could be thresholded with liberal p-values and restrictive cluster sizes. SECOND ARTICLE SUMMARY Epileptogenic Zone Localization with 18FDG PET Using a New Dynamic Parametric Analysis Introduction and objective: [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is part of the regular preoperative work-up in medically refractory epilepsy. As a complement to visual evaluation of PET, statistical parametric maps can help in the detection of the epileptogenic zone (EZ). However, software packages currently available are time-consuming and little intuitive for physicians. We develop a user-friendly software (referred as PET-analysis) for EZ localization in PET studies that allows dynamic real-time statistical parametric analysis. To evaluate its performance, the outcome of PET-analysis was compared with the results obtained by visual assessment and Statistical Parametric Mapping (SPM). Methods: Thirty patients with medically refractory epilepsy who underwent presurgical 18F-FDG PET with good postoperative outcomes were included. The 18F-FDG PET studies were evaluated by visual assessment, with SPM8 and PET-analysis. In SPM, parametric T-maps were thresholded at corrected p<0.05 and cluster size k=50 and at uncorrected p<0.001 and k=100 (the most used parameters in the literature). Since PET-analysis rapidly processes different threshold combinations, T-maps were thresholded with multiple p-value and different clusters sizes. The presurgical EZ identified by visual assessment, SPM and PET-analysis was compared to the confirmed EZ according to postsurgical follow-up. Results: PET-analysis obtained 66.7% (20/30) of correctly localizing studies, comparable to the 70.0% (21/30) achieved by visual assessment and significantly higher (p<0.05) than that obtained with the SPM threshold p<0.001/k=100, of 36.7% (11/30). Only one study was positive, albeit non-localizing, with the SPM threshold corrected p<0.05/k=50. Concordance was substantial for PET-analysis (к=0.643) and visual interpretation (к=0.622), being fair for SPM (к=0.242). Conclusion: Compared to SPM with the fixed standard parameters, PET-analysis may be superior in EZ localization with its easy and rapid processing of different threshold combinations. The results of this initial proof-of-concept study validate the clinical use of PET-analysis as a robust objective complementary tool to visual assessment for EZ localization

Clinical role of subtraction ictal SPECT coregistered to MR Imaging and 18F-FDG PET in pediatric epilepsy

A precise assessment of the drug-resistant epileptic pediatric population for surgical candidacy is often challenging, and to date there are no evidence-based guidelines for presurgical identification of the epileptogenic zone. To evaluate the usefulness of radionuclide imaging techniques for presurgical evaluation of epileptic pediatric patients, we compared the results of video-electroencephalography (EEG), brain MR imaging, interictal SPECT, ictal SPECT, subtraction ictal SPECT coregistered to MR imaging (SISCOM), and interictal PET with (18)F-FDG. METHODS: Fifty-four children with drug-resistant epilepsy who had undergone video-EEG monitoring, brain MR imaging, interictal and ictal brain perfusion SPECT, SISCOM, and (18)F-FDG PET were included in this study. All abnormal findings revealed by these neuroimaging techniques were compared with the presumed location of the epileptogenic zone (PEZ) as determined by video-EEG and clinical data. The proportion of localizing studies for each technique was statistically compared. In the 18 patients who underwent resective brain surgery, neuroimaging results were compared with histopathology results and surgical outcome. RESULTS: SISCOM and (18)F-FDG PET concordance with the PEZ was significantly higher than MR imaging (P < 0.05). MR imaging showed localizing results in 21 of 54 cases (39%), SISCOM in 36 of 54 cases (67%), and (18)F-FDG PET in 31 of 54 cases (57%). If we consider SISCOM and (18)F-FDG PET results together, nuclear medicine imaging techniques showed coinciding video-EEG results in 76% of patients (41/54). In those cases in which MR imaging failed to identify any epileptogenic lesion (61% [33/54]), SISCOM or (18)F-FDG PET findings matched PEZ in 67% (22/33) of cases. CONCLUSION: SISCOM and (18)F-FDG PET provide complementary presurgical information that matched video-EEG results and clinical data in three fourths of our sample. SISCOM was particularly useful in those cases in which MR imaging findings were abnormal but no epileptogenic lesion was identified. Radionuclide imaging techniques are both useful and reliable, extending the possibility of surgical treatment to patients who may have been discouraged without a nuclear medicine approach

Epileptogenic zone localization with (18)FDG PET using a new dynamic parametric analysis

Introduction: [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is part of the regular preoperative work-up in medically refractory epilepsy. As a complement to visual evaluation of PET, statistical parametric maps can help in the detection of the epileptogenic zone (EZ). However, software packages currently available are time-consuming and little intuitive for physicians. We develop a user-friendly software (referred as PET-analysis) for EZ localization in PET studies that allows dynamic real-time statistical parametric analysis. To evaluate its performance, the outcome of PET-analysis was compared with the results obtained by visual assessment and Statistical Parametric Mapping (SPM). Methods: Thirty patients with medically refractory epilepsy who underwent presurgical 18F-FDG PET with good post-operative outcomes were included. The 18F-FDG PET studies were evaluated by visual assessment, with SPM8 and PET-analysis. In SPM, parametric T-maps were thresholded at corrected p < 0.05 and cluster size k = 50 and at uncorrected p < 0.001 and k = 100 (the most used parameters in the literature). Since PET-analysis rapidly processes different threshold combinations, T-maps were thresholded with multiple p-value and different clusters sizes. The presurgical EZ identified by visual assessment, SPM and PET-analysis was compared to the confirmed EZ according to post-surgical follow-up. Results: PET-analysis obtained 66.7% (20/30) of correctly localizing studies, comparable to the 70.0% (21/30) achieved by visual assessment and significantly higher (p < 0.05) than that obtained with the SPM threshold p < 0.001/k = 100, of 36.7% (11/30). Only one study was positive, albeit non-localizing, with the SPM threshold corrected p < 0.05/k = 50. Concordance was substantial for PET-analysis (κ = 0.643) and visual interpretation (κ = 0.622), being fair for SPM (κ = 0.242). Conclusion: Compared to SPM with the fixed standard parameters, PET-analysis may be superior in EZ localization with its easy and rapid processing of different threshold combinations. The results of this initial proof-of-concept study validate the clinical use of PET-analysis as a robust objective complementary tool to visual assessment for EZ localization