Aumento de la confianza en la interpretación del PET con 18F-Florbetaben: “machine learning” basado en la aproximación cuantitativa / Increasing the confidence of 18F-florbetaben PET interpretations: Machine learning quantitative approximation

Objetivo: Determinar el valor a-adido de los parámetros semicuantitativos en el análisis visual y estudiar los patrones del depósito cerebral de 18F-Florbetaben. Material y métodos: Análisis retrospectivo de pacientes con deterioro cognitivo leve o demencia de origen incierto procedentes de un estudio multicentrico. Los PET con 18F-Florbetaben fueron interpretados de forma visual por dos observadores independientes, analizando las regiones “diana” con la finalidad de calcular el acuerdo interobservador. Se realizó análisis semicuantitativo de todas las regiones corticales con respecto a tres regiones de referencia para obtener índices de captación (SUVRs). Se analizó la capacidad de los SUVRs para predecir el resultado de la interpretación visual, la posibilidad de depósito preferencial del radiotrazador en algunas regiones “diana” así como las diferencias interhemisféricas. Resultados: Se evaluaron 135 pacientes. En la valoración visual, 72 estudios se clasificaron como positivos. El acuerdo interobservador fue excelente. Todos los SUVRs fueron significativamente superiores en pacientes con PET positivos con respecto a los negativos. Las regiones corticales correspondientes al área prefrontal y al cingulado posterior mostraron la mejor correlación con la evaluación visual, seguidas por la valoración integrada cortical. Usando análisis de ROC, los SUVRs obtenidos en las mismas regiones “diana” mostraron la mejor capacidad diagnóstica. Conclusiones: La información obtenida de las regiones “diana” parece ser de ayuda en la clasificación visual, basado en un depósito preferencial de amiloide, lo que permitiría el “machine learning”. El depósito de amiloide, aunque difuso en todas las regiones corticales, parece no ser uniforme ni simétrico (AU)

Aim: To assess the added value of semiquantitative parameters on the visual assessment and to study the patterns of 18F-Florbetaben brain deposition. Materials and methods: Retrospective analysis of multicenter study performed in patients with mild cognitive impairment or dementia of uncertain origin. 18F-Florbetaben PET scans were visually interpreted by two experienced observers, analyzing target regions in order to calculate the interobserver agreement. Semiquantification of all cortical regions with respect to three reference regions was performed to obtain standardized uptake value ratios (SUVRs). The ability of SUVRs to predict the visual evaluation, the possibility of preferential radiotracer deposition in some target regions and interhemisphere differenceswere analyzed. Results: 135 patients were evaluated. In the visual assessment, 72 were classified as positive. Interobserver agreement was excellent. All SUVRs were significantly higher in positive PET scans than in negative ones. Prefrontal area and posterior cingulate were the cortical regions with the best correlations with the visual evaluation, followed by the composite region. Using ROC analysis, the SUVRs obtained in same target locations showed the best diagnostic performance. Conclusions: The derived information from target regions seems to help the visual classification, based on a preferential amyloid deposit, allowing machine learning. The amyloid deposit, although diffuse in all cortical regions, seems not to be uniform and symmetric (AU)

Metodología de la gammagrafía con leucocitos marcados en el diagnóstico de infección osteoarticular protésica/no protésica: ¿análisis visual o semicuantitativo? ¿Protocolo de uno o 2 días? / Diagnostic methodology in labelled leukocyte scan for prosthetic / non-prosthetic osteoarticular infection: Visual or semi-quantitative analysis? One- or two-day protocol?

Objetivo: Como hay poca literatura sobre el tema, nos propusimos comparar la utilidad diagnóstica del análisis semicuantitativo versus el análisis visual en la escintigrafía de glóbulos blancos etiquetados (WBCS) para la infección osteoarticular. Se evaluaron protocolos de uno y dos días, en particular en los dispositivos ortopédicos.Material y métodos: Estudio prospectivo de 79 pacientes consecutivos con sospecha de infección osteoarticular. En todos los pacientes, la SCBM se realizó a los 30 min, 4 h, 8 h y 24 h. Las imágenes se analizaron agrupándolas en dos protocolos: protocolo de un día (los expertos evaluaron imágenes planas de 30 min, 4 h y 8 h) y protocolo de dos días (los expertos evaluaron imágenes planas de 30 min, 4 h y 24 h). Las imágenes planas se interpretaron cualitativa y semicuantitativamente y también se compararon agrupando a los pacientes con y sin dispositivos ortopédicos. Para determinar qué valor de corte de la variación porcentual podía predecir la infección osteoarticular, se calcularon múltiples valores de corte en ambos protocolos a partir del índice de Youden. Tres lectores ciegos analizaron las imágenes.Resultados: Comparando el diagnóstico final, el análisis visual del protocolo de un día proporcionó mejores resultados con una sensibilidad del 95,5%, una especificidad del 93% y una precisión diagnóstica del 93,7% (p < 0,01) que el protocolo de dos días con valores del 86,4%, 94,7% y 92,4%, respectivamente (p < 0,01). Para el análisis semicuantitativo, el protocolo de un día también obtuvo mejores resultados con una sensibilidad del 72,7%, una especificidad del 78,9% y una precisión del 77,2% (p < 0,01) que el protocolo de dos días (sin resultados significativos; p = 0,14), especialmente en el grupo de pacientes con aparatos ortopédicos (sensibilidad del 100%, especificidad del 79,5% y precisión del 82,7%; p < 0,01)

Objective: As scarce literature on the topic is available, we aimed to compare diagnostic utility of semi-quantitative versus visual analysis in labelled white blood cell scintigraphy (WBCS) for osteoarticular infection. One-day and two-day protocols were assessed, particularly in orthopaedic devices.Material and methods: Prospective study of 79 consecutive patients with suspected osteoarticular infection. In all patients, WBCS were performed at 30min, 4h, 8h and 24h. Images were analysed by grouping in two protocols: one-day-protocol (experts evaluated 30min, 4h and 8h planar images) and two-day-protocol (experts evaluated 30min, 4h and 24h planar images). Planar images were interpreted qualitative and semiquantitatively and also were compared grouping patients with and without orthopaedic devices. To find which cut-off value of the percentage variation could predict of osteoarticular infection, multiple cut-off values were calculated in both protocols from the Youden index. Three blinded readers analysed the images.Results: Comparing final diagnosis visual analysis of the one-day-protocol provided better results with sensitivity of 95.5%, specificity of 93% and diagnostic accuracy of 93.7% (P<.01) than the two-day-protocol with values of 86.4%, 94.7% and 92.4%, respectively (P<.01). For semi-quantitative analysis, the one-day-protocol also obtained better results with sensitivity of 72.7%, specificity of 78.9% and accuracy of 77.2% (P<.01) than two-day-protocol (no significant results; P=.14), especially in the group of patients with orthopaedic devices (sensitivity of 100%, specificity of 79.5% and accuracy of 82.7%; P<.01).Conclusions: Most accurate approach in the diagnosis of osteoarticular infection corresponded to visual analysis in one-day-protocol that showed greater sensitivity and specificity than semi-quantitative analysis. Semi-quantitative analysis only could be useful when visual analysis is doubtful

Diagnostic methodology in labelled leukocyte scan for prosthetic / non-prosthetic osteoarticular infection: Visual or semi-quantitative analysis? One- or two-day protocol? / Metodología de la gammagrafía con leucocitos marcados en el diagnóstico de infección osteoarticular protésica/no protésica: ¿análisis visual o semicuantitativo? ¿Protocolo de uno o 2 días?

OBJECTIVE: As scarce literature on the topic is available, we aimed to compare diagnostic utility of semi-quantitative versus visual analysis in labelled white blood cell scintigraphy (WBCS) for osteoarticular infection. One-day and two-day protocols were assessed, particularly in orthopaedic devices. MATERIAL AND METHODS: Prospective study of 79 consecutive patients with suspected osteoarticular infection. In all patients, WBCS were performed at 30min, 4h, 8h and 24h. Images were analysed by grouping in two protocols: one-day-protocol (experts evaluated 30min, 4h and 8h planar images) and two-day-protocol (experts evaluated 30min, 4h and 24h planar images). Planar images were interpreted qualitative and semiquantitatively and also were compared grouping patients with and without orthopaedic devices. To find which cut-off value of the percentage variation could predict of osteoarticular infection, multiple cut-off values were calculated in both protocols from the Youden index. Three blinded readers analysed the images. RESULTS: Comparing final diagnosis visual analysis of the one-day-protocol provided better results with sensitivity of 95.5%, specificity of 93% and diagnostic accuracy of 93.7% (P<.01) than the two-day-protocol with values of 86.4%, 94.7% and 92.4%, respectively (P<.01). For semi-quantitative analysis, the one-day-protocol also obtained better results with sensitivity of 72.7%, specificity of 78.9% and accuracy of 77.2% (P<.01) than two-day-protocol (no significant results; P=.14), especially in the group of patients with orthopaedic devices (sensitivity of 100%, specificity of 79.5% and accuracy of 82.7%; P<.01). CONCLUSIONS: Most accurate approach in the diagnosis of osteoarticular infection corresponded to visual analysis in one-day-protocol that showed greater sensitivity and specificity than semi-quantitative analysis. Semi-quantitative analysis only could be useful when visual analysis is doubtful. In patients with joint prostheses, an increase in percentage variation above 9% obtained maximum sensitivity and negative predictive value.

Segmentation of gliomas in 18F-fluorocholine PET/CT. A multiapproach study. / Segmentación de gliomas con PET/TC con 18F-fluorocolina. Estudio multiaproximación.

AIM: Our aim was two-fold, to study the interobserver agreement in tumour segmentation and to search for a reliable methodology to segment gliomas using 18F-fluorocholine PET/CT. METHODS: 25 patients with glioma, from a prospective and non-randomized study (Functional and Metabolic Glioma Analysis), were included.Interobserver variability in tumour segmentation was assessed using fixed thresholds. Different strategies were used to segment the tumours. First, a semi-automatic tumour segmentation was performed, selecting the best SUVmax-% threshold for each lesion. Next we determined a variable SUVmax-% depending on the SUVmax. Finally a segmentation using a fixed SUVmax threshold was performed. To do so, a sampling of 10 regions of interest (ROI of 2.8cm2) located in the normal brain was performed. The upper value of the sample mean SUVmax±3 SD was used as cut-off. All procedures were tested and classified as effective or not for tumour segmentation by two observer's consensus. RESULTS: In the pilot segmentation, the mean±SD of SUVmax, SUVmean and optimal SUVmax-% threshold were: 3.64±1.77, 1.32±0.57 and 21.32±8.39, respectively. Optimal SUVmax-% threshold showed a significant association with the SUVmax (Pearson=-0.653, p=.002). However, the linear regression model for the total sample was not good, that supported the division in two homogeneous groups, defining two formulas for predicting the optimal SUVmax-% threshold. As to the third procedure, the obtained value for the mean SUVmax background+3 SD was 0.33. This value allowed segmenting correctly a significant fraction of tumours, although not all. CONCLUSION: A great interobserver variability in the tumour segmentation was found. None of the methods was able to segment correctly all the gliomas, probably explained by the wide tumour heterogeneity on 18F-fluorocholine PET/CT.

Global heterogeneity assessed with 18F-FDG PET/CT. Relation with biological variables and prognosis in locally advanced breast cancer. / Medidas de heterogeneidad global y esfericidad con 18F-FDG PET/TC en el cáncer de mama: relación con la biología tumoral, valor predictivo y pronóstico.

AIM: To analyze the relationship between measurements of global heterogeneity, obtained from 18F-FDG PET/CT, with biological variables, and their predictive and prognostic role in patients with locally advanced breast cancer (LABC). MATERIAL AND METHODS: 68 patients from a multicenter and prospective study, with LABC and a baseline 18F-FDG PET/CT were included. Immunohistochemical profile [estrogen receptors (ER) and progesterone receptors (PR), expression of the HER-2 oncogene, Ki-67 proliferation index and tumor histological grade], response to neoadjuvant chemotherapy (NC), overall survival (OS) and disease-free survival (DFS) were obtained as clinical variables. Three-dimensional segmentation of the lesions, providing SUV, volumetric [metabolic tumor volume (MTV) and total lesion glycolysis (TLG)] and global heterogeneity variables [coefficient of variation (COV) and SUVmean/SUVmax ratio], as well as sphericity was performed. The correlation between the results obtained with the immunohistochemical profile, the response to NC and survival was also analyzed. RESULTS: Of the patients included, 62 received NC. Only 18 responded. 13 patients relapsed and 11 died during follow-up. ER negative tumors had a lower COV (p=0.018) as well as those with high Ki-67 (p=0.001) and high risk phenotype (p=0.033) compared to the rest. No PET variable showed association with the response to NC nor OS. There was an inverse relationship between sphericity with DFS (p=0.041), so, for every tenth that sphericity increases, the risk of recurrence decreases by 37%. CONCLUSIONS: Breast tumors in our LABC dataset behaved as homogeneous and spherical lesions. Larger volumes were associated with a lower sphericity. Global heterogeneity variables and sphericity do not seem to have a predictive role in response to NC nor in OS. More spherical tumors with less variation in gray intensity between voxels showed a lower risk of recurrence.

Predictive and prognostic potential of volume-based metabolic variables obtained by a baseline 18F-FDG PET/CT in breast cancer with neoadjuvant chemotherapy indication. / Papel predictivo y pronóstico de las variables volumétricas metabólicas obtenidas en la 18F-FDG PET/TC en el cáncer de mama con indicación de quimioterapia neoadyuvante.

AIM: To investigate the usefulness of metabolic variables using 18F-FDG PET/CT in the prediction of neoadjuvant chemotherapy (NC) response and the prognosis in locally advanced breast cancer (LABC). MATERIAL AND METHODS: Prospective study including 67 patients with LABC, NC indication and a baseline 18F-FDG PET/CT. After breast tumor segmentation, SUV variables (SUVmax, SUVmean and SUVpeak) and volume-based variables, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), were obtained. Tumors were grouped into molecular phenotypes, and classified as responders or non-responders after completion of NC. Disease-free status (DFs), disease-free survival (DFS), and overall survival (OS) were assessed. A univariate and multivariate analysis was performed to study the potential of all variables to predict DFs, DFS, and OS. RESULTS: Fourteen patients were classified as responders. Median±SD of DFS and OS was 43±15 and 46±13 months, respectively. SUV and TLG showed a significant correlation (p<0.005) with the histological response, with higher values in responders compared to non-responders. MTV and TLG showed a significant association with DFs (p=0.015 and p=0.038 respectively). Median, mean and SD of MTV and TLG for patients with DFs were: 8.90, 13.73, 15.10 and 33.78, and 90.54 and 144.64, respectively. Median, mean and SD of MTV and TLG for patients with non-DFs were: 16.72, 29.70 and 31.09 and 90.89, 210.98 and 382.80, respectively. No significant relationships were observed with SUV variables and DFs. Volume-based variables were significantly associated with OS and DFS, although in multivariate analysis only MTV was related to OS. No SUV variables showed an association with the prognosis. CONCLUSION: Volume-based metabolic variables obtained with 18F-FDG PET/CT, unlike SUV based variables, were good predictors of both neoadjuvant chemotherapy response and prognosis.

18F-FDG PET/CT as predictor of tumour biology and prognosis in epithelial ovarian carcinoma. / PET/TC con 18F-FDG como predictor de la biología tumoral y del pronóstico en el cáncer epitelial ovárico.

OBJECTIVE: To investigate the relationship between maximum standardised uptake value (SUVmax) of ovarian lesions and histopathology subtypes, and their involvement in the response and prognosis of patients with epithelial ovarian carcinoma (EOC). MATERIAL AND METHODS: A retrospective analysis of 31 patients with EOC and 18F-FDG-PET/CT before treatment, including an assessment of the SUVmax of ovarian lesion. Histopathological diagnosis and follow-up was performed. A study was made on the relationship between the SUVmax and histological type (type I and II) and tumour stage, as well as the role of various parameters (SUVmax, histology, stage) on the patient outcomes (complete response [CR], overall survival [OS], disease-free survival [DFS], and disease-free [DF] status, at 12 and 24 months). RESULTS: The medium SUVmax in type I lesions was lower than in type II (6.3 and 9.3, respectively; P=.03). A 7.1 cut-off was set for SUVmax in order to identify type II EOC (sensitivity: 77.8%, specificity: 69.2%; AUC=0.748; P=.02). No significant relationship was found between tumour stage and SUVmax. CR was more common in early stages; relative risk (RR) of 1.64; P=.003, as well as in type I tumours and a lower SUVmax. Tumour stage was decisive in DFS (P=.04), LE24m (0.07) and OS (P=.08). Longer DFS and a higher percentage of DF 24m were observed in type I tumours (RR: 1.32; P=.26). CONCLUSIONS: SUVmax was related to EOC histology, so could predict the response and prognosis of these patients. No association was found between glycolytic activity of the primary tumor with the response and prognosis.

Utility of 18F-FDG-PET/CT in patients suspected of paraneoplastic neurological syndrome: importance of risk classification.

PURPOSE: To assess the diagnostic impact of 18F-FDG-PET/CT in patients suspected of paraneoplastic neurological syndrome (PNS) based on our own pre-test risk classification (PRC). METHODS: A multicenter retrospective longitudinal study was conducted from 2006 to 2014. We designed a seven-point scoring system using the clinical syndrome characteristics [classical (CS) and non-classical syndromes (NCS)] and its location (central, peripheral, in the neuromuscular junction or combined), onconeural antibodies and tumor markers. Patients were classified as low (score 0-2), intermediate (3-4) and high (5-7) pre-test risk of PNS. FDG-PET/CT was classified as negative or positive. Final diagnosis according Graus' criteria (definite, possible or no PNS) was established. Relations between clinical and metabolic variables with the final diagnosis were studied. RESULTS: 73 patients were included, with a follow-up time of 33 months. Eleven (15 %) patients were finally diagnosed with neoplasm (8 invasive cancers). Ultimately, 13 (18 %) and 24 (33 %) subjects were diagnosed as definite or possible PNS. All the patients with final diagnosis of neoplasm had a CS (p = 0.005). PET/CT was helpful to diagnose 6/8 (75 %) invasive cancers. PET/CT findings were associated with the final diagnosis of neoplasm (p = 0.003) and the diagnosis of PNS attending to Graus' criteria (p = 0.019). PRC showed significant association with the final diagnosis of neoplasm and PET/CT results. A majority of patients (10/11) diagnosed of neoplasm had intermediate/high-risk. CONCLUSIONS: Our PRC seems to be a valid tool to select candidates for PET/CT imaging in this setting. PET/CT detected malignancy in a significant proportion of patients with invasive cancer.

[(18)F-FDG PET/CT in the evaluation of patients suspected of paraneoplastic neurological syndrome]. / PET/TC con (18)F-FDG en la valoración de pacientes con sospecha de síndrome paraneoplásico neurológico.

OBJECTIVE: This study aimed to determine the diagnostic impact of (18)F-FDG PET/CT based on the clinical features of paraneoplastic neurological syndrome (PNS). MATERIAL AND METHODS: Multicenter retrospective and longitudinal study of patients with suspicion of PNS. The clinical picture was classified into classic (CS) and non-classic syndrome (NCS). After the follow-up, the definitive or possible diagnosis of PNS was established. The pictures that did not match any of the previous criteria were categorized as non-classifiable. The state of the onco-neural antibodies was studied. The PET/CT was classified as positive or negative for the detection of malignancy. The relationship between PET/CT findings and the final diagnosis was determined. The differences between variables (Pearson test X(2)) and the relationship between the results of the PET/CT and the final diagnosis were analyzed. RESULTS: A total of 64 patients were analyzed, classifying 30% as CS and 42% as NCS. After the follow-up, 20% and 16% of subjects were diagnosed as possible and definitive PNS, respectively. Positive onco-neural antibodies were found in 13% of the patients. A definitive diagnosis of PNS was associated with a positive PET/CT (P=.08). A significant relation between antibodies expression and final diagnosis of neoplasia (P=.04) was demonstrated. The PET/CT correctly localized malignancy in 5/7 cases of invasive cancer. CONCLUSIONS: The PET/CT showed a higher percentage of positive results in patients with definitive diagnosis of PNS. Despite the low prevalence of malignancy in our series, the PET/CT detected malignancy in a significant proportion of patients with invasive cancer.

[Lung hot spot as pitfall in PET-CT interpretation: focal lung uptake of 18F-fluorodeoxyglucose]. / Foco pulmonar facticio con (18)F-FDG: posible error en la interpretación de la PET-CT.

(18)F-FDG PET-CT has become an essential tool in oncology patient management. The normal distribution of the FDG and the possible artifacts (pitfalls), including those from CT-based attenuation correction, have already been described in several reviews. However, only a few cases of FDG focal lung uptake have been reported recently. We present two cases of oncology patients during a routine follow-up with this type of pitfall, without morphological correlation in the CT scan. We repeated the study in one of them, which made it possible to verify normalization of the hyperuptake, orienting us towards a possible pitfall.

Solitary focus in the liver in a thyroid cancer patient after a whole body scan with 131 iodine.

A 51-year-old woman diagnosed with follicular variant of papillary thyroid carcinoma underwent a total thyroidectomy followed four weeks later by an ablative dose of 3.7 GBq of 131I. A whole body scan 5 days after ablation showed an intense uptake within the thyroid bed and a focal uptake located in the right lung base or liver dome. Computed tomography examination revealed a hypodense hepatic node in segment VII resembling a liver metastasis. Histological examination after ultrasound-guided fine-needle aspiration characterized the lesion as a liver abscess. The abscess regressed after antibiotic therapy. Liver metastases from papillary thyroid carcinoma are uncommon. On the other hand, false positive findings of 131I whole body scans have been described. A focal hepatic uptake might represent a metastasis (rare in papillary carcinomas) or be related to other causes (cysts, inflammation or infection, non-thyroidal neoplasms, etc.).

[Bone scintigraphy in Erdheim-Chester disease]. / Gammagrafía ósea en la enfermedad de Erdheim-Chester.

Erdheim-Chester disease (ECD) is a rare disorder with fewer than 80 cases reported in the world. It consists of a non-Langerhans' cell histiocytosis that usually presents as pain due to bone involvement; however, the prognosis is marked by extraskeletal involvement. Although the final diagnosis needs an anatomophatologic study (normally through a bone biopsy), radiologic and scintigraphic findings are quasi pathognomonic. In this work, we report 2 ECD cases and their respective bone scans showing typical findings described in the literature. We found bilateral and symmetrical increased uptake of diaphyses and metaphyses of long bones, mainly in lower limbs. The mid-diaphyses and the epiphyses (partially in the first case) as well as the axial skeleton are spared.