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This review paper presents the practical development of imaging biomarkers in the scope of the PRIMAGE (PRedictive In silico Multiscale Analytics to support cancer personalized diaGnosis and prognosis, Empowered by imaging biomarkers) project, as a noninvasive and reliable way to improve the diagnosis and prognosis in pediatric oncology. The PRIMAGE project is a European multi-center research initiative that focuses on developing medical imaging-derived artificial intelligence (AI) solutions designed to enhance overall management and decision-making for two types of pediatric cancer: neuroblastoma and diffuse intrinsic pontine glioma. To allow this, the PRIMAGE project has created an open-cloud platform that combines imaging, clinical, and molecular data together with AI models developed from this data, creating a comprehensive decision support environment for clinicians managing patients with these two cancers. In order to achieve this, a standardized data processing and analysis workflow was implemented to generate robust and reliable predictions for different clinical endpoints. Magnetic resonance (MR) image harmonization and registration was performed as part of the workflow. Subsequently, an automated tool for the detection and segmentation of tumors was trained and internally validated. The Dice similarity coefficient obtained for the independent validation dataset was 0.997, indicating compatibility with the manual segmentation variability. Following this, radiomics and deep features were extracted and correlated with clinical endpoints. Finally, reproducible and relevant imaging quantitative features were integrated with clinical and molecular data to enrich both the predictive models and a set of visual analytics tools, making the PRIMAGE platform a complete clinical decision aid system. In order to ensure the advancement of research in this field and to foster engagement with the wider research community, the PRIMAGE data repository and platform are currently being integrated into the European Federation for Cancer Images (EUCAIM), which is the largest European cancer imaging research infrastructure created to date.
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Inteligência Artificial , Neoplasias , Criança , Humanos , Radiômica , Prognóstico , Neoplasias/diagnóstico por imagem , BiomarcadoresRESUMO
Several noise sources, such as the Johnson-Nyquist noise, affect MR images disturbing the visualization of structures and affecting the subsequent extraction of radiomic data. We evaluate the performance of 5 denoising filters (anisotropic diffusion filter (ADF), curvature flow filter (CFF), Gaussian filter (GF), non-local means filter (NLMF), and unbiased non-local means (UNLMF)), with 33 different settings, in T2-weighted MR images of phantoms (N = 112) and neuroblastoma patients (N = 25). Filters were discarded until the most optimal solutions were obtained according to 3 image quality metrics: peak signal-to-noise ratio (PSNR), edge-strength similarity-based image quality metric (ESSIM), and noise (standard deviation of the signal intensity of a region in the background area). The selected filters were ADFs and UNLMs. From them, 107 radiomics features preservation at 4 progressively added noise levels were studied. The ADF with a conductance of 1 and 2 iterations standardized the radiomic features, improving reproducibility and quality metrics.
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Algoritmos , Diagnóstico por Imagem , Biomarcadores , Humanos , Reprodutibilidade dos Testes , Razão Sinal-RuídoRESUMO
Purpose To evaluate the reproducibility of radiomics features extracted from T2-weighted MR images in patients with neuroblastoma. Materials and Methods A retrospective study included 419 patients (mean age, 29 months ± 34 [SD]; 220 male, 199 female) with neuroblastic tumors diagnosed between 2002 and 2023, within the scope of the PRedictive In-silico Multiscale Analytics to support cancer personalized diaGnosis and prognosis, Empowered by imaging biomarkers (ie, PRIMAGE) project, involving 746 T2/T2*-weighted MRI sequences at diagnosis and/or after initial chemotherapy. Images underwent processing steps (denoising, inhomogeneity bias field correction, normalization, and resampling). Tumors were automatically segmented, and 107 shape, first-order, and second-order radiomics features were extracted, considered as the reference standard. Subsequently, the previous image processing settings were modified, and volumetric masks were applied. New radiomics features were extracted and compared with the reference standard. Reproducibility was assessed using the concordance correlation coefficient (CCC); intrasubject repeatability was measured using the coefficient of variation (CoV). Results When normalization was omitted, only 5% of the radiomics features demonstrated high reproducibility. Statistical analysis revealed significant changes in the normalization and resampling processes (P < .001). Inhomogeneities removal had the least impact on radiomics (83% of parameters remained stable). Shape features remained stable after mask modifications, with a CCC greater than 0.90. Mask modifications were the most favorable changes for achieving high CCC values, with a radiomics features stability of 70%. Only 7% of second-order radiomics features showed an excellent CoV of less than 0.10. Conclusion Modifications in the T2-weighted MRI preparation process in patients with neuroblastoma resulted in changes in radiomics features, with normalization identified as the most influential factor for reproducibility. Inhomogeneities removal had the least impact on radiomics features. Keywords: Pediatrics, MR Imaging, Oncology, Radiomics, Reproducibility, Repeatability, Neuroblastic Tumors Supplemental material is available for this article. © RSNA, 2024 See also the commentary by Safdar and Galaria in this issue.
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Imageamento por Ressonância Magnética , Neuroblastoma , Humanos , Neuroblastoma/diagnóstico por imagem , Neuroblastoma/patologia , Masculino , Feminino , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Reprodutibilidade dos Testes , Pré-Escolar , Criança , Lactente , Interpretação de Imagem Assistida por Computador/métodos , RadiômicaRESUMO
OBJECTIVES: To externally validate and assess the accuracy of a previously trained fully automatic nnU-Net CNN algorithm to identify and segment primary neuroblastoma tumors in MR images in a large children cohort. METHODS: An international multicenter, multivendor imaging repository of patients with neuroblastic tumors was used to validate the performance of a trained Machine Learning (ML) tool to identify and delineate primary neuroblastoma tumors. The dataset was heterogeneous and completely independent from the one used to train and tune the model, consisting of 300 children with neuroblastic tumors having 535 MR T2-weighted sequences (486 sequences at diagnosis and 49 after finalization of the first phase of chemotherapy). The automatic segmentation algorithm was based on a nnU-Net architecture developed within the PRIMAGE project. For comparison, the segmentation masks were manually edited by an expert radiologist, and the time for the manual editing was recorded. Different overlaps and spatial metrics were calculated to compare both masks. RESULTS: The median Dice Similarity Coefficient (DSC) was high 0.997; 0.944-1.000 (median; Q1-Q3). In 18 MR sequences (6%), the net was not able neither to identify nor segment the tumor. No differences were found regarding the MR magnetic field, type of T2 sequence, or tumor location. No significant differences in the performance of the net were found in patients with an MR performed after chemotherapy. The time for visual inspection of the generated masks was 7.9 ± 7.5 (mean ± Standard Deviation (SD)) seconds. Those cases where manual editing was needed (136 masks) required 124 ± 120 s. CONCLUSIONS: The automatic CNN was able to locate and segment the primary tumor on the T2-weighted images in 94% of cases. There was an extremely high agreement between the automatic tool and the manually edited masks. This is the first study to validate an automatic segmentation model for neuroblastic tumor identification and segmentation with body MR images. The semi-automatic approach with minor manual editing of the deep learning segmentation increases the radiologist's confidence in the solution with a minor workload for the radiologist.
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Tumor segmentation is one of the key steps in imaging processing. The goals of this study were to assess the inter-observer variability in manual segmentation of neuroblastic tumors and to analyze whether the state-of-the-art deep learning architecture nnU-Net can provide a robust solution to detect and segment tumors on MR images. A retrospective multicenter study of 132 patients with neuroblastic tumors was performed. Dice Similarity Coefficient (DSC) and Area Under the Receiver Operating Characteristic Curve (AUC ROC) were used to compare segmentation sets. Two more metrics were elaborated to understand the direction of the errors: the modified version of False Positive (FPRm) and False Negative (FNR) rates. Two radiologists manually segmented 46 tumors and a comparative study was performed. nnU-Net was trained-tuned with 106 cases divided into five balanced folds to perform cross-validation. The five resulting models were used as an ensemble solution to measure training (n = 106) and validation (n = 26) performance, independently. The time needed by the model to automatically segment 20 cases was compared to the time required for manual segmentation. The median DSC for manual segmentation sets was 0.969 (±0.032 IQR). The median DSC for the automatic tool was 0.965 (±0.018 IQR). The automatic segmentation model achieved a better performance regarding the FPRm. MR images segmentation variability is similar between radiologists and nnU-Net. Time leverage when using the automatic model with posterior visual validation and manual adjustment corresponds to 92.8%.
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BACKGROUND/AIM: In recent years, the apparent diffusion coefficient (ADC) has been used in many oncology applications as a surrogate marker of tumor cellularity and aggressiveness, although several factors may introduce bias when calculating this coefficient. The goal of this study was to develop a novel methodology (Fit-Cluster-Fit) based on confidence habitats that could be applied to quantitative diffusion-weighted magnetic resonance images (DWIs) to enhance the power of ADC values to discriminate between benign and malignant neuroblastic tumor profiles in children. METHODS: Histogram analysis and clustering-based algorithms were applied to DWIs from 33 patients to perform tumor voxel discrimination into two classes. Voxel uncertainties were quantified and incorporated to obtain a more reproducible and meaningful estimate of ADC values within a tumor habitat. Computational experiments were performed by smearing the ADC values in order to obtain confidence maps that help identify and remove noise from low-quality voxels within high-signal clustered regions. The proposed Fit-Cluster-Fit methodology was compared with two other methods: conventional voxel-based and a cluster-based strategy. RESULTS: The cluster-based and Fit-Cluster-Fit models successfully differentiated benign and malignant neuroblastic tumor profiles when using values from the lower ADC habitat. In particular, the best sensitivity (91%) and specificity (89%) of all the combinations and methods explored was achieved by removing uncertainties at a 70% confidence threshold, improving standard voxel-based sensitivity and negative predictive values by 4% and 10%, respectively. CONCLUSIONS: The Fit-Cluster-Fit method improves the performance of imaging biomarkers in classifying pediatric solid tumor cancers and it can probably be adapted to dynamic signal evaluation for any tumor.
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Xanthogranulomatous pyelonephritis (XPN) is an unusual and severe form of chronic inflammatory lesion of the kidney, characterised by the destruction of the renal parenchyma and the presence of multinucleated giant cells and lipid-laden macrophages, inflammatory infiltration and intensive renal fibrosis. There are a few cases in the literature which describe the disease in children. The pathomechanism of XPN is poorly understood. Renal obstruction with concomitant urinary tract infection is the most commonly associated pathological finding. The process is typically unilateral and may be focal or diffuse. In both cases, the perirenal infiltration is possible and can be mistaken for common renal neoplasm or inflammatory process. The symptoms are non-specific. Diagnostic imaging techniques with clinical suspicion have enabled XPN to be diagnosed and differentiated from malignancy with a high degree of confidence. Computed tomography (CT) is the mainstay of diagnostic imaging. The definitive diagnosis of XPN is based on pathological assessment after nephrectomy. We review and illustrate the clinical, radiological, surgical and pathological characteristics of XPN in children. All cases shown are surgically and histopathologically proven. TEACHING POINTS: ⢠XPN can present different clinical manifestations. ⢠CT is the mainstay of diagnostic imaging in XPN. ⢠Focal type of XPN should be included in the differential diagnosis of children with a renal mass. ⢠There are no clear guidelines on the management of XPN. ⢠Conservative and surgical treatments should be considered for each individual case. ⢠Histopathological examination confirms the diagnosis and excludes other benign and malign diseases.
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Enteric duplication cysts (EDCs) are rare congenital malformations formed during the embryonic development of the digestive tract. They are usually detected prenatally or in the first years of life. The size, location, type, mucosal pattern and presence of complications produce a varied clinical presentation and different imaging findings. Ultrasonography (US) is the most used imaging method for diagnosis. Magnetic resonance (MR) and computed tomography (CT) are less frequently used, but can be helpful in cases of difficult surgical approach. Conservative surgery is the treatment of choice. Pathology confirms the intestinal origin of the cyst, showing a layer of smooth muscle in the wall and an epithelial lining inside, resembling some part of the gastrointestinal tract (GT). We review the different forms of presentation of the EDCs, showing both the typical and atypical imaging findings with the different imaging techniques. We correlate the imaging findings with the surgical results and the final pathological features. TEACHING POINTS: ⢠EDCs are rare congenital anomalies from the digestive tract with uncertain pathogenesis. ⢠More frequently, diagnosis is antenatal, with most EDCs occurring in the distal ileum. ⢠Ultrasonography is the method of choice for diagnosis of EDCs. ⢠Complicated EDCs can show atypical imaging findings. ⢠Surgery is necessary to avoid complications.