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We compared different LLMs, notably chatGPT, GPT4, and Google Bard and we tested whether their performance differs in subspeciality domains, in executing examinations from four different courses of the European Society of Neuroradiology (ESNR) notably anatomy/embryology, neuro-oncology, head and neck and pediatrics. Written exams of ESNR were used as input data, related to anatomy/embryology (30 questions), neuro-oncology (50 questions), head and neck (50 questions), and pediatrics (50 questions). All exams together, and each exam separately were introduced to the three LLMs: chatGPT 3.5, GPT4, and Google Bard. Statistical analyses included a group-wise Friedman test followed by a pair-wise Wilcoxon test with multiple comparison corrections. Overall, there was a significant difference between the 3 LLMs (p < 0.0001), with GPT4 having the highest accuracy (70%), followed by chatGPT 3.5 (54%) and Google Bard (36%). The pair-wise comparison showed significant differences between chatGPT vs GPT 4 (p < 0.0001), chatGPT vs Bard (p < 0. 0023), and GPT4 vs Bard (p < 0.0001). Analyses per subspecialty showed the highest difference between the best LLM (GPT4, 70%) versus the worst LLM (Google Bard, 24%) in the head and neck exam, while the difference was least pronounced in neuro-oncology (GPT4, 62% vs Google Bard, 48%). We observed significant differences in the performance of the three different LLMs in the running of official exams organized by ESNR. Overall GPT 4 performed best, and Google Bard performed worst. This difference varied depending on subspeciality and was most pronounced in head and neck subspeciality.
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Sociedades Médicas , Humanos , Europa (Continente) , Evaluación Educacional , Radiología/educación , NeurorradiografíaRESUMEN
Commercial software based on artificial intelligence (AI) is entering clinical practice in neuroradiology. Consequently, medico-legal aspects of using Software as a Medical Device (SaMD) become increasingly important. These medico-legal issues warrant an interdisciplinary approach and may affect the way we work in daily practice. In this article, we seek to address three major topics: medical malpractice liability, regulation of AI-based medical devices, and privacy protection in shared medical imaging data, thereby focusing on the legal frameworks of the European Union and the USA. As many of the presented concepts are very complex and, in part, remain yet unsolved, this article is not meant to be comprehensive but rather thought-provoking. The goal is to engage clinical neuroradiologists in the debate and equip them to actively shape these topics in the future.
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Inteligencia Artificial , Mala Praxis , Humanos , Programas Informáticos , RadiólogosRESUMEN
Artificial intelligence (AI)-based tools are gradually blending into the clinical neuroradiology practice. Due to increasing complexity and diversity of such AI tools, it is not always obvious for the clinical neuroradiologist to capture the technical specifications of these applications, notably as commercial tools very rarely provide full details. The clinical neuroradiologist is thus confronted with the increasing dilemma to base clinical decisions on the output of AI tools without knowing in detail what is happening inside the "black box" of those AI applications. This dilemma is aggravated by the fact that currently, no established and generally accepted rules exist concerning best clinical practice and scientific and clinical validation nor for the medico-legal consequences in cases of wrong diagnoses. The current review article provides a practical checklist of essential points, intended to aid the user to identify and double-check necessary aspects, although we are aware that not all this information may be readily available at this stage, even for certified and commercially available AI tools. Furthermore, we therefore suggest that the developers of AI applications provide this information.
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Inteligencia Artificial , Lista de Verificación , HumanosRESUMEN
The use of standardized imaging protocols is paramount in order to facilitate comparable, reproducible images and, consequently, to optimize patient care. Standardized MR protocols are lacking when studying head and neck pathologies in the pediatric population. We propose an international, multicenter consensus paper focused on providing the best combination of acquisition time/technical requirements and image quality. Distinct protocols for different regions of the head and neck and, in some cases, for specific pathologies or clinical indications are recommended. This white paper is endorsed by several international scientific societies and it is the result of discussion, in consensus, among experts in pediatric head and neck imaging.
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Neoplasias de Cabeza y Cuello , Cabeza , Niño , Consenso , Cabeza/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodos , Cuello/diagnóstico por imagenRESUMEN
The basal ganglia and thalami are paired deep grey matter structures with extensive metabolic activity that renders them susceptible to injury by various diseases. Most pathological processes lead to bilateral lesions, which may be symmetric or asymmetric, frequently showing characteristic patterns on imaging studies. In this comprehensive pictorial review, the most common and/or typical genetic, acquired metabolic/toxic, infectious, inflammatory, vascular and neoplastic pathologies affecting the central grey matter are subdivided according to the preferential location of the lesions: in the basal ganglia, in the thalami or both. The characteristic imaging findings are described with emphasis on the differential diagnosis and clinical context.
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Ganglios Basales/patología , Encefalopatías/diagnóstico por imagen , Encefalopatías/patología , Sustancia Gris/patología , Tálamo/patología , Diagnóstico Diferencial , HumanosRESUMEN
PURPOSE: The aim of this study is to compare a qualitative and a quantitative assessment of brain diffusion-weighted imaging (DWI) in predicting outcome of comatose patients after cardiac arrest (CA). METHODS: Two observers used a scoring template to analyze the DWI of 75 patients. A total of 13 regions were scored from 0 to 3 (0 = normal, 1 = probably normal, 2 = probably abnormal, 3 = definitely abnormal). The total cerebral cortex (TCC), the total deep grey nuclei (TDGN), the total brain stem, the total cerebellum, and the total brain score were calculated. Intra- and inter-observer variability were tested. The mean whole brain apparent diffusion coefficient (ADC) values and percentage of voxels below a specific ADC value cut-off were calculated. The data were correlated with clinical outcome (cerebral performance category score after 180 days, dichotomized in a score 1-2 with favorable outcome and score 3-5 with unfavorable outcome) using ROC analysis. RESULTS: Intra-observer variability was excellent for the TCC score (ICC 0.95 and 0.86) and the TDGN score (ICC 0.89 and 0.75). Inter-observer variability was good to excellent for total cerebral cortex score and total deep grey nuclei score in both the first (ICC 0.78 and 0.69) and third (ICC 0.86 and 0.83) image assessment. TCC and TDGN score show the best correlation with clinical outcome (highest AUC values 0.87 and 0.87). Quantitative parameters did not show good correlation with clinical outcome (AUC values 0.57 and 0.60). CONCLUSION: A qualitative assessment of brain DWI using a scoring template provides useful data regarding patient outcome while quantitative data appeared less reliable.
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Coma/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Paro Cardíaco , Anciano , Bélgica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Examen Neurológico , Pronóstico , Estudios Prospectivos , Sensibilidad y Especificidad , SobrevivientesRESUMEN
PURPOSE: We aim to illustrate the diagnostic performance of diffusional kurtosis imaging (DKI) in the diagnosis of gliomas. METHODS: A review protocol was developed according to the (PRISMA-P) checklist, registered in the international prospective register of systematic reviews (PROSPERO) and published. A literature search in 4 databases was performed using the keywords 'glioma' and 'diffusional kurtosis'. After applying a robust inclusion/exclusion criteria, included articles were independently evaluated according to the QUADAS-2 tool and data extraction was done. Reported sensitivities and specificities were used to construct 2 × 2 tables and paired forest plots using the Review Manager (RevMan®) software. A random-effect model was pursued using the hierarchical summary receiver operator characteristics. RESULTS: A total of 216 hits were retrieved. Considering duplicates and inclusion criteria, 23 articles were eligible for full-text reading. Ultimately, 19 studies were eligible for final inclusion. The quality assessment revealed 9 studies with low risk of bias in the 4 domains. Using a bivariate random-effect model for data synthesis, summary ROC curve showed a pooled area under the curve (AUC) of 0.92 and estimated sensitivity of 0.87 (95% CI 0.78-0.92) in high-/low-grade gliomas' differentiation. A mean difference in mean kurtosis (MK) value between HGG and LGG of 0.22 (95% CI 0.25-0.19) was illustrated (p value = 0.0014) with moderate heterogeneity (I2 = 73.8%). CONCLUSION: DKI shows good diagnostic accuracy in the differentiation of high- and low-grade gliomas further supporting its potential role in clinical practice. Further exploration of DKI in differentiating IDH status and in characterising non-glioma CNS tumours is however needed.
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Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Imagen de Difusión Tensora/métodos , Glioma/diagnóstico por imagen , Glioma/patología , Diagnóstico Diferencial , Humanos , Interpretación de Imagen Asistida por Computador , Clasificación del TumorRESUMEN
Tissue characterization in brain tumors and, in particular, in high-grade gliomas is challenging as a result of the co-existence of several intra-tumoral tissue types within the same region and the high spatial heterogeneity. This study presents a method for the detection of the relevant tumor substructures (i.e. viable tumor, necrosis and edema), which could be of added value for the diagnosis, treatment planning and follow-up of individual patients. Twenty-four patients with glioma [10 low-grade gliomas (LGGs), 14 high-grade gliomas (HGGs)] underwent a multi-parametric MRI (MP-MRI) scheme, including conventional MRI (cMRI), perfusion-weighted imaging (PWI), diffusion kurtosis imaging (DKI) and short-TE (1)H MRSI. MP-MRI parameters were derived: T2, T1 + contrast, fluid-attenuated inversion recovery (FLAIR), relative cerebral blood volume (rCBV), mean diffusivity (MD), fractional anisotropy (FA), mean kurtosis (MK) and the principal metabolites lipids (Lip), lactate (Lac), N-acetyl-aspartate (NAA), total choline (Cho), etc. Hierarchical non-negative matrix factorization (hNMF) was applied to the MP-MRI parameters, providing tissue characterization on a patient-by-patient and voxel-by-voxel basis. Tissue-specific patterns were obtained and the spatial distribution of each tissue type was visualized by means of abundance maps. Dice scores were calculated by comparing tissue segmentation derived from hNMF with the manual segmentation by a radiologist. Correlation coefficients were calculated between each pathologic tissue source and the average feature vector within the corresponding tissue region. For the patients with HGG, mean Dice scores of 78%, 85% and 83% were obtained for viable tumor, the tumor core and the complete tumor region. The mean correlation coefficients were 0.91 for tumor, 0.97 for necrosis and 0.96 for edema. For the patients with LGG, a mean Dice score of 85% and mean correlation coefficient of 0.95 were found for the tumor region. hNMF was also applied to reduced MRI datasets, showing the added value of individual MRI modalities.
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Neoplasias Encefálicas/patología , Imagen de Difusión por Resonancia Magnética/métodos , Imagen Eco-Planar/métodos , Glioma/patología , Imagen por Resonancia Magnética/métodos , Imagen Multimodal/métodos , Adulto , Anciano , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
PURPOSE: The authors hypothesise that the trochlear dysplastic distal femur is not only characterised by morphological changes to the trochlea. The purpose of this study is to describe the morphological characteristics of the trochlear dysplastic femur in and outside the trochlear region with a landmark-based 3D analysis. METHODS: Arthro-CT scans of 20 trochlear dysplastic and 20 normal knees were used to generate 3D models including the cartilage. To rule out size differences, a set of landmarks were defined on the distal femur to isotropically scale the 3D models to a standard size. A predefined series of landmark-based reference planes were applied on the distal femur. With these landmarks and reference planes, a series of previously described characteristics associated with trochlear dysplasia as well as a series of morphometric characteristics were measured. RESULTS: For the previously described characteristics, the analysis replicated highly significant differences between trochlear dysplastic and normal knees. Furthermore, the analysis showed that, when knee size is taken into account, the cut-off values of the trochlear bump and depth would be 1 mm larger in the largest knees compared to the smallest knees. For the morphometric characteristics, the analysis revealed that the trochlear dysplastic femur is also characterised by a 10% smaller intercondylar notch, 6-8% larger posterior condyles (lateral-medial) in the anteroposterior direction and a 6% larger medial condyle in the proximodistal direction compared to a normal femur. CONCLUSIONS: This study shows that knee size is important in the application of absolute metric cut-off values and that the posterior femur also shows a significantly different morphology.
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Fémur/anomalías , Fémur/diagnóstico por imagen , Articulación de la Rodilla/diagnóstico por imagen , Tibia/diagnóstico por imagen , Adolescente , Adulto , Simulación por Computador , Femenino , Humanos , Imagenología Tridimensional , Masculino , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
ABSTRACT: In this case report, we describe a 76-year-old woman, presenting with dizziness for the past 2 months, without other focal neurological signs. A magnetic resonance imaging of the brain was ordered by her GP. The MRI demonstrated multiple ring-enhancing lesions, both supratentorial and infratentorial. Lumbar puncture showed normal findings, in particular a normal cell count and culture. Because of the radiologic appearance, initially thought to be suggestive of cerebral abscesses, antibiotics were started. However, further workup revealed a new diagnosis of a stage IV (metastatic) small cell lung carcinoma, making diffuse brain metastases more likely. The patient was transferred to oncology/pneumology, where she was started on whole-brain radiotherapy, after which systemic therapy would start. However, because of further clinical deterioration, she was admitted at the palliative ward, where she died only 3 months after the initial presentation. In this case report, we emphasize the importance of keeping a broad differential diagnosis and briefly review the various possible pathologies causing ring-enhancing lesions.
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Neoplasias Encefálicas , Toxoplasmosis Cerebral , Femenino , Humanos , Anciano , Toxoplasmosis Cerebral/diagnóstico por imagen , Encéfalo/patología , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Diagnóstico DiferencialRESUMEN
Teaching point: Meningovascular neurosyphilis is a cause of stroke in the young, and the diagnosis could be aided by black-blood MRI sequences.
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PURPOSE: To validate the reproducibility of a chemical shift imaging (CSI) acquisition protocol with parallel imaging, using automated repositioning software. MATERIALS AND METHODS: Ten volunteers were imaged three times on two different 3 Tesla (T) MRI scanners, receiving anatomical imaging and two identical CSI measurements, using automated repositioning software for consistent repositioning of the CSI grid. Offcenter parameters of the CSI plane were analyzed. Coefficients of variation (CoV), Cramér-Rao lower bounds (CRLB), intraclass correlation coefficients (ICC), and coefficients of repeatability (CoR) for immediate repetition and between scanners were calculated for N-acetylaspartate, total choline, creatine, myo-inositol (Myo) and glutamine+glutamate (Glx). Proportions of variance reflecting the effect of voxel location, volunteer, repetition, time instance and scanner were calculated from an analysis of variance analysis. RESULTS: The offcenter vector and angulations of the CSI grid differed less than 1 mm and 2° between all measurements. The mean CoV and CRLB were less than 30% for all metabolites, except for Myo. The variance due to voxel location in the volume of interest and the error represent the largest contributions in variability. The ICC is the lowest for Myo and Glx. CoR for immediate repetition and between scanners display values between 22 and 83%. CONCLUSION: We propose a CSI protocol with acceptable reproducibility, applicable in clinical routine.
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Algoritmos , Química Encefálica , Encéfalo/anatomía & histología , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Adulto , Femenino , Humanos , Aumento de la Imagen/métodos , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
ABSTRACT: In this case report we describe the case of a 66-year old man with subacute gait difficulties, with a progression to confusion coma with multiple generalised epileptic seizures during the following days. Biochemical analysis showed hyperglycaemia, cerebrospinal fluid (CSF) testing showed a mild lymphocytic pleocytosis and an elevated protein and lactate. Broad-spectrum antibiotics and antiviral therapy where initiated. However, all other CSF testing remained negative. Magnetic resonance imaging of the brain showed remarkably symmetric hyperintense T2 white matter lesions most noticable in the corpus callosum. The lesion pattern was suggestive of a metabolic or toxic encephalopathy, the preponderance for the corpus callosum was furthermore suggestive for Marchiafava-Bignami disease (MDB), as was the clinical course since admission of the patient. A high dose IV substitution of vitamin B1, B6 and B12 was started and antibiotic and antiviral therapy was discontinued. After one day the patient showed progressive regaining of consciousness and he returned to premorbid functioning in a matter of 1-2 weeks. MRI of the brain after 1 week showed notable improvement of the white matter lesions. At routine follow-up two weeks later he presented with icterus and a diagnosis of Epstein-Barr virus (EBV) hepatitis was made, lymph node biopsies showed an EBV positive diffuse large cell B-cell lymphoma (DLCBL). MDB is mostly associated with severe alcoholism, with malnourishment being the second leading cause, however there are case reports describing MDB in patients with chronically poorly controlled diabetes mellitus. We hypothesize that his condition may have been precipitated by his poorly controlled diabetes mellitus. However it is also possible that weight loss (probably related to the DLCBL diagnosis) might have contributed to a state of malnourishment and therefore played a role in the aetiology as well.
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Infecciones por Virus de Epstein-Barr , Desnutrición , Enfermedad de Marchiafava-Bignami , Masculino , Humanos , Anciano , Enfermedad de Marchiafava-Bignami/complicaciones , Enfermedad de Marchiafava-Bignami/patología , Coma/complicaciones , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4 , Imagen por Resonancia Magnética , Desnutrición/complicaciones , AntiviralesRESUMEN
Thanks to its non-invasive nature and high-resolution imaging capabilities, magnetic resonance imaging (MRI) is a valuable diagnostic tool for pediatric patients. However, the fear and anxiety experienced by young children during MRI scans often result in suboptimal image quality and the need for sedation/anesthesia. This study aimed to evaluate the effect of a smartphone application called COSMO@home to prepare children for MRI scans to reduce the need for sedation or general anesthesia. The COSMO@home app was developed incorporating mini-games and an engaging storyline to prepare children for learning goals related to the MRI procedure. A multicenter study was conducted involving four hospitals in Belgium. Eligible children aged 4-10 years were prepared with the COSMO@home app at home. Baseline, pre-scan, and post-scan questionnaires measured anxiety evolution in two age groups (4-6 years and 7-10 years). Eighty-two children participated in the study, with 95% obtaining high-quality MRI images. The app was well-received by children and parents, with minimal technical difficulties reported. In the 4-6-year-old group (N = 33), there was a significant difference between baseline and pre-scan parent-reported anxiety scores, indicating an increase in anxiety levels prior to the scan. In the 7-10-year-old group (N = 49), no significant differences were observed between baseline and pre-scan parent-reported anxiety scores. Overall, the COSMO@home app proved to be useful in preparing children for MRI scans, with high satisfaction rates and successful image outcomes across different hospitals. The app, combined with minimal face-to-face guidance on the day of the scan, showed the potential to replace or assist traditional face-to-face training methods. This innovative approach has the potential to reduce the need for sedation or general anesthesia during pediatric MRI scans and its associated risks and improve patient experience.
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PURPOSE: To assess the diagnostic accuracy of diffusion kurtosis magnetic resonance imaging parameters in grading gliomas. MATERIALS AND METHODS: The institutional review board approved this prospective study, and informed consent was obtained from all patients. Diffusion parameters-mean diffusivity (MD), fractional anisotropy (FA), mean kurtosis, and radial and axial kurtosis-were compared in the solid parts of 17 high-grade gliomas and 11 low-grade gliomas (P<.05 significance level, Mann-Whitney-Wilcoxon test, Bonferroni correction). MD, FA, mean kurtosis, radial kurtosis, and axial kurtosis in solid tumors were also normalized to the corresponding values in contralateral normal-appearing white matter (NAWM) and the contralateral posterior limb of the internal capsule (PLIC) after age correction and were compared among tumor grades. RESULTS: Mean, radial, and axial kurtosis were significantly higher in high-grade gliomas than in low-grade gliomas (P = .02, P = .015, and P = .01, respectively). FA and MD did not significantly differ between glioma grades. All values, except for axial kurtosis, that were normalized to the values in the contralateral NAWM were significantly different between high-grade and low-grade gliomas (mean kurtosis, P = .02; radial kurtosis, P = .03; FA, P = .025; and MD, P = .03). When values were normalized to those in the contralateral PLIC, none of the considered parameters showed significant differences between high-grade and low-grade gliomas. The highest sensitivity and specificity for discriminating between high-grade and low-grade gliomas were found for mean kurtosis (71% and 82%, respectively) and mean kurtosis normalized to the value in the contralateral NAWM (100% and 73%, respectively). Optimal thresholds for mean kurtosis and mean kurtosis normalized to the value in the contralateral NAWM for differentiating high-grade from low-grade gliomas were 0.52 and 0.51, respectively. CONCLUSION: There were significant differences in kurtosis parameters between high-grade and low-grade gliomas; hence, better separation was achieved with these parameters than with conventional diffusion imaging parameters.
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Neoplasias Encefálicas/patología , Imagen de Difusión por Resonancia Magnética/métodos , Glioma/patología , Adulto , Anciano , Anisotropía , Área Bajo la Curva , Medios de Contraste , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Imagenología Tridimensional , Masculino , Meglumina , Persona de Mediana Edad , Clasificación del Tumor , Compuestos Organometálicos , Estudios Prospectivos , Curva ROC , Sensibilidad y Especificidad , Estadísticas no ParamétricasRESUMEN
INTRODUCTION: This study aims to determine the potential value of MR-PWI and MR-DWI to differentiate immune therapy-induced inflammatory response from recurrent glioblastoma tumour growth. Both can present as contrast-enhancing lesions on conventional magnetic resonance imaging (MRI). METHODS: Patients with recurrent glioblastoma who could obtain a total or near-total resection were treated with dendritic cell immune therapy according to the HGG-IMMUNO-2003 trial. A retrospective analysis of 32 follow-up MRI examinations (mean follow-up time 21 months) in eight patients was performed for this pilot study. For the statistical analysis, the 32 examinations were divided into three groups: 0-obtained in patients that remained stable during the follow-up period, 1a-obtained in progressive-tumour patients at time points before definite progression and 1b-obtained in patients at or after progression. RESULTS: Maximum lesional rCBV ratios were highest in group 1b (Student t test, 9.25 ± 2.68; p < 0.001) and were higher in group 1a (4.87 ± 1.61, p < 0.001) compared to group 0 (1.22 ± 0.47). The minimum apparent diffusion coefficients (ADCs) in the contrast-enhancing regions were lower in group 1a (0.62 ± 0.06 × 10(-3) mm(2)/s) than in group 0 (1.03 ± 0.43 × 10(-3) mm(2)/s, p = 0.01) and higher in group 1b (0.76 ± 0.08) compared to 1a (p = 0.02). The minimum ADCs in the FLAIR-hyperintense region were lower in group 1a (0.62 ± 0.06, p = 0.02) compared to group 0 (0.76 ± 0.16) but not significantly different in group 1b (0.68 ± 0.07) from groups 0 and 1a (p = 0.33, p = 0.10). The mean ADCs of the FLAIR-hyperintense region and the mean ADCs of the contrast-enhancing lesion were not significantly different. CONCLUSION: The maximum lesional rCBV ratios and minimum ADC values in the contrast-enhancing area are potential radiological markers to differentiate between immune therapy-induced inflammatory response and recurrent glioblastoma tumour growth in glioblastoma patients treated with immune therapy.
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Neoplasias Encefálicas/terapia , Encéfalo/patología , Células Dendríticas , Imagen de Difusión por Resonancia Magnética , Glioblastoma/terapia , Inmunoterapia/métodos , Adulto , Neoplasias Encefálicas/patología , Medios de Contraste , Femenino , Estudios de Seguimiento , Glioblastoma/patología , Humanos , Aumento de la Imagen , Masculino , Persona de Mediana Edad , Perfusión , Proyectos Piloto , Resultado del TratamientoRESUMEN
Subacute combined degeneration of the spinal cord is a neurologic complication of vitamin B12 deficiency. It presents as a potentially reversible demyelination of the posterior and lateral columns of the cervical and dorsal spinal cord. We present the case of a 40-year-old male with progressive sensory and motor deficit from the lower extremities ascending to the mid-thoracic region. A combination of laboratory tests and magnetic resonance imaging confirmed the diagnosis of subacute degeneration of the spinal cord due to vitamin B12 deficiency.
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BACKGROUND: Histologically classified glioblastomas (GBM) can have different clinical behavior and response to therapy, for which molecular subclassifications have been proposed. We evaluated the relationship of epigenetic GBM subgroups with immune cell infiltrations, systemic immune changes during radiochemotherapy, and clinical outcome. METHODS: 450K genome-wide DNA methylation was assessed on tumor tissue from 93 patients with newly diagnosed GBM, treated with standard radiochemotherapy and experimental immunotherapy. Tumor infiltration of T cells, myeloid cells, and Programmed cell death protein 1 (PD-1) expression were evaluated. Circulating immune cell populations and selected cytokines were assessed on blood samples taken before and after radiochemotherapy. RESULTS: Forty-two tumors had a mesenchymal, 27 a receptor tyrosine kinase (RTK) II, 17 RTK I, and 7 an isocitrate dehydrogenase (IDH) DNA methylation pattern. Mesenchymal tumors had the highest amount of tumor-infiltrating CD3+ and CD8+ T cells and IDH tumors the lowest. There were no significant differences for CD68+ cells, FoxP3+ cells, and PD-1 expression between groups. Systemically, there was a relative increase of CD8+ T cells and CD8+ PD-1 expression and a relative decrease of CD4+ T cells after radiochemotherapy in all subgroups except IDH tumors. Overall survival was the longest in the IDH group (median 36 mo), intermediate in RTK II tumors (27 mo), and significantly lower in mesenchymal and RTK I groups (15.5 and 16 mo, respectively). CONCLUSIONS: Methylation based stratification of GBM is related to T-cell infiltration and survival, with IDH and mesenchymal tumors representing both ends of a spectrum. DNA methylation profiles could be useful in stratifying patients for immunotherapy trials.
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Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Metilación de ADN , Glioblastoma/genética , Glioblastoma/terapia , Humanos , Isocitrato Deshidrogenasa/genética , Regiones Promotoras GenéticasRESUMEN
Background and Purpose: The CT-DRAGON score was developed to predict long-term functional outcome after acute stroke in the anterior circulation treated by thrombolysis. Its implementation in clinical practice may be hampered by its plethora of variables. The current study was designed to develop and evaluate an alternative score, as a reduced set of features, derived from the original CT-DRAGON score. Methods: This single-center retrospective study included 564 patients treated for stroke, in the anterior and the posterior circulation. At 90 days, favorable [modified Rankin Scale score (mRS) of 0-2] and miserable outcome (mRS of 5-6) were predicted by the CT-DRAGON in 427 patients. Bootstrap forests selected the most relevant parameters of the CT-DRAGON, in order to develop a reduced set of features. Discrimination, calibration and misclassification of both models were tested. Results: The area under the receiver operating characteristic curve (AUROC) for the CT-DRAGON was 0.78 (95% CI 0.74-0.81) for favorable and 0.78 (95% CI 0.72-0.83) for miserable outcome. Misclassification was 29% for favorable and 13.5% for miserable outcome, with a 100% specificity for the latter. National Institutes of Health Stroke Scale (NIHSS), pre-stroke mRS and age were identified as the strongest contributors to favorable and miserable outcome and named the reduced features set. While CT-DRAGON was only available in 323 patients (57%), the reduced features set could be calculated in 515 patients (91%) (p < 0.001). Misclassification was 25.8% for favorable and 14.4% for miserable outcome, with a 97% specificity for miserable outcome. The reduced features set had better discriminative power than CT-DRAGON for both outcomes (both p < 0.005), with an AUROC of 0.82 (95% CI 0.79-0.86) and 0.83 (95% CI 0.77-0.87) for favorable and miserable outcome, respectively. Conclusions: The CT-DRAGON score revealed acceptable discrimination in our cohort of both anterior and posterior circulation strokes, receiving all treatment modalities. The reduced features set could be measured in a larger cohort and with better discrimination. However, the reduced features set needs further validation in a prospective, multicentre study. Clinical Trial Registration: http://www.clinicaltrials.gov. Identifiers: NCT03355690, NCT04092543.