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Tissue clearing methods enable the imaging of biological specimens without sectioning. However, reliable and scalable analysis of large imaging datasets in three dimensions remains a challenge. Here we developed a deep learning-based framework to quantify and analyze brain vasculature, named Vessel Segmentation & Analysis Pipeline (VesSAP). Our pipeline uses a convolutional neural network (CNN) with a transfer learning approach for segmentation and achieves human-level accuracy. By using VesSAP, we analyzed the vascular features of whole C57BL/6J, CD1 and BALB/c mouse brains at the micrometer scale after registering them to the Allen mouse brain atlas. We report evidence of secondary intracranial collateral vascularization in CD1 mice and find reduced vascularization of the brainstem in comparison to the cerebrum. Thus, VesSAP enables unbiased and scalable quantifications of the angioarchitecture of cleared mouse brains and yields biological insights into the vascular function of the brain.
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Encéfalo/irrigación sanguínea , Aprendizaje Automático , Animales , Imagenología Tridimensional , RatonesRESUMEN
Accurate detection and quantification of unruptured intracranial aneurysms (UIAs) is important for rupture risk assessment and to allow an informed treatment decision to be made. Currently, 2D manual measures used to assess UIAs on Time-of-Flight magnetic resonance angiographies (TOF-MRAs) lack 3D information and there is substantial inter-observer variability for both aneurysm detection and assessment of aneurysm size and growth. 3D measures could be helpful to improve aneurysm detection and quantification but are time-consuming and would therefore benefit from a reliable automatic UIA detection and segmentation method. The Aneurysm Detection and segMentation (ADAM) challenge was organised in which methods for automatic UIA detection and segmentation were developed and submitted to be evaluated on a diverse clinical TOF-MRA dataset. A training set (113 cases with a total of 129 UIAs) was released, each case including a TOF-MRA, a structural MR image (T1, T2 or FLAIR), annotation of any present UIA(s) and the centre voxel of the UIA(s). A test set of 141 cases (with 153 UIAs) was used for evaluation. Two tasks were proposed: (1) detection and (2) segmentation of UIAs on TOF-MRAs. Teams developed and submitted containerised methods to be evaluated on the test set. Task 1 was evaluated using metrics of sensitivity and false positive count. Task 2 was evaluated using dice similarity coefficient, modified hausdorff distance (95th percentile) and volumetric similarity. For each task, a ranking was made based on the average of the metrics. In total, eleven teams participated in task 1 and nine of those teams participated in task 2. Task 1 was won by a method specifically designed for the detection task (i.e. not participating in task 2). Based on segmentation metrics, the top two methods for task 2 performed statistically significantly better than all other methods. The detection performance of the top-ranking methods was comparable to visual inspection for larger aneurysms. Segmentation performance of the top ranking method, after selection of true UIAs, was similar to interobserver performance. The ADAM challenge remains open for future submissions and improved submissions, with a live leaderboard to provide benchmarking for method developments at https://adam.isi.uu.nl/.
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Angiografía Cerebral/métodos , Aneurisma Intracraneal/diagnóstico por imagen , Angiografía por Resonancia Magnética/métodos , Conjuntos de Datos como Asunto , Evaluación Educacional , Humanos , Imagen por Resonancia Magnética , Distribución Aleatoria , Medición de RiesgoRESUMEN
In the last two decades, neuroscience has produced intriguing evidence for a central role of the claustrum in mammalian forebrain structure and function. However, relatively few in vivo studies of the claustrum exist in humans. A reason for this may be the delicate and sheet-like structure of the claustrum lying between the insular cortex and the putamen, which makes it not amenable to conventional segmentation methods. Recently, Deep Learning (DL) based approaches have been successfully introduced for automated segmentation of complex, subcortical brain structures. In the following, we present a multi-view DL-based approach to segment the claustrum in T1-weighted MRI scans. We trained and evaluated the proposed method in 181 individuals, using bilateral manual claustrum annotations by an expert neuroradiologist as reference standard. Cross-validation experiments yielded median volumetric similarity, robust Hausdorff distance, and Dice score of 93.3%, 1.41 mm, and 71.8%, respectively, representing equal or superior segmentation performance compared to human intra-rater reliability. The leave-one-scanner-out evaluation showed good transferability of the algorithm to images from unseen scanners at slightly inferior performance. Furthermore, we found that DL-based claustrum segmentation benefits from multi-view information and requires a sample size of around 75 MRI scans in the training set. We conclude that the developed algorithm allows for robust automated claustrum segmentation and thus yields considerable potential for facilitating MRI-based research of the human claustrum. The software and models of our method are made publicly available.
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Claustro/anatomía & histología , Claustro/diagnóstico por imagen , Aprendizaje Profundo , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodos , HumanosRESUMEN
Ultra-wideband raster-scan optoacoustic mesoscopy (RSOM) is a novel modality that has demonstrated unprecedented ability to visualize epidermal and dermal structures in-vivo. However, an automatic and quantitative analysis of three-dimensional RSOM datasets remains unexplored. In this work we present our framework: Deep Learning RSOM Analysis Pipeline (DeepRAP), to analyze and quantify morphological skin features recorded by RSOM and extract imaging biomarkers for disease characterization. DeepRAP uses a multi-network segmentation strategy based on convolutional neural networks with transfer learning. This strategy enabled the automatic recognition of skin layers and subsequent segmentation of dermal microvasculature with an accuracy equivalent to human assessment. DeepRAP was validated against manual segmentation on 25 psoriasis patients under treatment and our biomarker extraction was shown to characterize disease severity and progression well with a strong correlation to physician evaluation and histology. In a unique validation experiment, we applied DeepRAP in a time series sequence of occlusion-induced hyperemia from 10 healthy volunteers. We observe how the biomarkers decrease and recover during the occlusion and release process, demonstrating accurate performance and reproducibility of DeepRAP. Furthermore, we analyzed a cohort of 75 volunteers and defined a relationship between aging and microvascular features in-vivo. More precisely, this study revealed that fine microvascular features in the dermal layer have the strongest correlation to age. The ability of our newly developed framework to enable the rapid study of human skin morphology and microvasculature in-vivo promises to replace biopsy studies, increasing the translational potential of RSOM.
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Biomarcadores , Técnicas Fotoacústicas , Psoriasis , Piel , Humanos , Psoriasis/diagnóstico por imagen , Técnicas Fotoacústicas/métodos , Piel/diagnóstico por imagen , Piel/irrigación sanguínea , Aprendizaje Profundo , Aprendizaje Automático , Adulto , Envejecimiento de la Piel/fisiología , Femenino , Persona de Mediana Edad , MasculinoRESUMEN
The Circle of Willis (CoW) is an important network of arteries connecting major circulations of the brain. Its vascular architecture is believed to affect the risk, severity, and clinical outcome of serious neuro-vascular diseases. However, characterizing the highly variable CoW anatomy is still a manual and time-consuming expert task. The CoW is usually imaged by two angiographic imaging modalities, magnetic resonance angiography (MRA) and computed tomography angiography (CTA), but there exist limited public datasets with annotations on CoW anatomy, especially for CTA. Therefore we organized the TopCoW Challenge in 2023 with the release of an annotated CoW dataset. The TopCoW dataset was the first public dataset with voxel-level annotations for thirteen possible CoW vessel components, enabled by virtual-reality (VR) technology. It was also the first large dataset with paired MRA and CTA from the same patients. TopCoW challenge formalized the CoW characterization problem as a multiclass anatomical segmentation task with an emphasis on topological metrics. We invited submissions worldwide for the CoW segmentation task, which attracted over 140 registered participants from four continents. The top performing teams managed to segment many CoW components to Dice scores around 90%, but with lower scores for communicating arteries and rare variants. There were also topological mistakes for predictions with high Dice scores. Additional topological analysis revealed further areas for improvement in detecting certain CoW components and matching CoW variant topology accurately. TopCoW represented a first attempt at benchmarking the CoW anatomical segmentation task for MRA and CTA, both morphologically and topologically.
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Current treatment planning of patients diagnosed with a brain tumor, such as glioma, could significantly benefit by accessing the spatial distribution of tumor cell concentration. Existing diagnostic modalities, e.g. magnetic resonance imaging (MRI), contrast sufficiently well areas of high cell density. In gliomas, however, they do not portray areas of low cell concentration, which can often serve as a source for the secondary appearance of the tumor after treatment. To estimate tumor cell densities beyond the visible boundaries of the lesion, numerical simulations of tumor growth could complement imaging information by providing estimates of full spatial distributions of tumor cells. Over recent years a corpus of literature on medical image-based tumor modeling was published. It includes different mathematical formalisms describing the forward tumor growth model. Alongside, various parametric inference schemes were developed to perform an efficient tumor model personalization, i.e. solving the inverse problem. However, the unifying drawback of all existing approaches is the time complexity of the model personalization which prohibits a potential integration of the modeling into clinical settings. In this work, we introduce a deep learning based methodology for inferring the patient-specific spatial distribution of brain tumors from T1Gd and FLAIR MRI medical scans. Coined as Learn-Morph-Infer, the method achieves real-time performance in the order of minutes on widely available hardware and the compute time is stable across tumor models of different complexity, such as reaction-diffusion and reaction-advection-diffusion models. We believe the proposed inverse solution approach not only bridges the way for clinical translation of brain tumor personalization but can also be adopted to other scientific and engineering domains.
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Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/diagnóstico por imagenRESUMEN
BACKGROUND: Contrast-enhancing (CE) lesions are an important finding on brain magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) but can be missed easily. Automated solutions for reliable CE lesion detection are emerging; however, independent validation of artificial intelligence (AI) tools in the clinical routine is still rare. METHODS: A three-dimensional convolutional neural network for CE lesion segmentation was trained externally on 1488 datasets of 934 MS patients from 81 scanners using concatenated information from FLAIR and T1-weighted post-contrast imaging. This externally trained model was tested on an independent dataset comprising 504 T1-weighted post-contrast and FLAIR image datasets of MS patients from clinical routine. Two neuroradiologists (R1, R2) labeled CE lesions for gold standard definition in the clinical test dataset. The algorithmic output was evaluated on both patient- and lesion-level. RESULTS: On a patient-level, recall, specificity, precision, and accuracy of the AI tool to predict patients with CE lesions were 0.75, 0.99, 0.91, and 0.96. The agreement between the AI tool and both readers was within the range of inter-rater agreement (Cohen's kappa; AI vs. R1: 0.69; AI vs. R2: 0.76; R1 vs. R2: 0.76). On a lesion-level, false negative lesions were predominately found in infratentorial location, significantly smaller, and at lower contrast than true positive lesions (p < 0.05). CONCLUSIONS: AI-based identification of CE lesions on brain MRI is feasible, approaching human reader performance in independent clinical data and might be of help as a second reader in the neuroradiological assessment of active inflammation in MS patients. CRITICAL RELEVANCE STATEMENT: Al-based detection of contrast-enhancing multiple sclerosis lesions approaches human reader performance, but careful visual inspection is still needed, especially for infratentorial, small and low-contrast lesions.
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In this work, we report the set-up and results of the Liver Tumor Segmentation Benchmark (LiTS), which was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI) 2017 and the International Conferences on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2017 and 2018. The image dataset is diverse and contains primary and secondary tumors with varied sizes and appearances with various lesion-to-background levels (hyper-/hypo-dense), created in collaboration with seven hospitals and research institutions. Seventy-five submitted liver and liver tumor segmentation algorithms were trained on a set of 131 computed tomography (CT) volumes and were tested on 70 unseen test images acquired from different patients. We found that not a single algorithm performed best for both liver and liver tumors in the three events. The best liver segmentation algorithm achieved a Dice score of 0.963, whereas, for tumor segmentation, the best algorithms achieved Dices scores of 0.674 (ISBI 2017), 0.702 (MICCAI 2017), and 0.739 (MICCAI 2018). Retrospectively, we performed additional analysis on liver tumor detection and revealed that not all top-performing segmentation algorithms worked well for tumor detection. The best liver tumor detection method achieved a lesion-wise recall of 0.458 (ISBI 2017), 0.515 (MICCAI 2017), and 0.554 (MICCAI 2018), indicating the need for further research. LiTS remains an active benchmark and resource for research, e.g., contributing the liver-related segmentation tasks in http://medicaldecathlon.com/. In addition, both data and online evaluation are accessible via https://competitions.codalab.org/competitions/17094.
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Benchmarking , Neoplasias Hepáticas , Humanos , Estudios Retrospectivos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Hígado/diagnóstico por imagen , Hígado/patología , Algoritmos , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
Exploiting 4D-flow magnetic resonance imaging (MRI) data to quantify hemodynamics requires an adequate spatio-temporal vector field resolution at a low noise level. To address this challenge, we provide a learned solution to super-resolve in vivo 4D-flow MRI data at a post-processing level. We propose a deep convolutional neural network (CNN) that learns the inter-scale relationship of the velocity vector map and leverages an efficient residual learning scheme to make it computationally feasible. A novel, direction-sensitive, and robust loss function is crucial to learning vector-field data. We present a detailed comparative study between the proposed super-resolution and the conventional cubic B-spline based vector-field super-resolution. Our method improves the peak-velocity to noise ratio of the flow field by 10 and 30% for in vivo cardiovascular and cerebrovascular data, respectively, for 4 × super-resolution over the state-of-the-art cubic B-spline. Significantly, our method offers 10x faster inference over the cubic B-spline. The proposed approach for super-resolution of 4D-flow data would potentially improve the subsequent calculation of hemodynamic quantities.
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Self-supervised pretext tasks have been introduced as an effective strategy when learning target tasks on small annotated data sets. However, while current research focuses on exploring novel pretext tasks for meaningful and reusable representation learning for the target task, the study of its robustness and generalizability has remained relatively under-explored. Specifically, it is crucial in medical imaging to proactively investigate performance under different perturbations for reliable deployment of clinical applications. In this work, we revisit medical imaging networks pre-trained with self-supervised learnings and categorically evaluate robustness and generalizability compared to vanilla supervised learning. Our experiments on pneumonia detection in X-rays and multi-organ segmentation in CT yield conclusive results exposing the hidden benefits of self-supervision pre-training for learning robust feature representations.
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Diagnóstico por Imagen , RadiografíaRESUMEN
Automatic localization and segmentation of organs-at-risk (OAR) in CT are essential pre-processing steps in medical image analysis tasks, such as radiation therapy planning. For instance, the segmentation of OAR surrounding tumors enables the maximization of radiation to the tumor area without compromising the healthy tissues. However, the current medical workflow requires manual delineation of OAR, which is prone to errors and is annotator-dependent. In this work, we aim to introduce a unified 3D pipeline for OAR localization-segmentation rather than novel localization or segmentation architectures. To the best of our knowledge, our proposed framework fully enables the exploitation of 3D context information inherent in medical imaging. In the first step, a 3D multi-variate regression network predicts organs' centroids and bounding boxes. Secondly, 3D organ-specific segmentation networks are leveraged to generate a multi-organ segmentation map. Our method achieved an overall Dice score of 0.9260 ± 0.18% on the VISCERAL dataset containing CT scans with varying fields of view and multiple organs.
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Órganos en Riesgo , Tomografía Computarizada por Rayos X , Tomografía Computarizada por Rayos X/métodosRESUMEN
Modeling of brain tumor dynamics has the potential to advance therapeutic planning. Current modeling approaches resort to numerical solvers that simulate the tumor progression according to a given differential equation. Using highly-efficient numerical solvers, a single forward simulation takes up to a few minutes of compute. At the same time, clinical applications of tumor modeling often imply solving an inverse problem, requiring up to tens of thousands of forward model evaluations when used for a Bayesian model personalization via sampling. This results in a total inference time prohibitively expensive for clinical translation. While recent data-driven approaches become capable of emulating physics simulation, they tend to fail in generalizing over the variability of the boundary conditions imposed by the patient-specific anatomy. In this paper, we propose a learnable surrogate for simulating tumor growth which maps the biophysical model parameters directly to simulation outputs, i.e. the local tumor cell densities, whilst respecting patient geometry. We test the neural solver in a Bayesian model personalization task for a cohort of glioma patients. Bayesian inference using the proposed surrogate yields estimates analogous to those obtained by solving the forward model with a regular numerical solver. The near real-time computation cost renders the proposed method suitable for clinical settings. The code is available at https://github.com/IvanEz/tumor-surrogate.
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Neoplasias Encefálicas , Glioma , Teorema de Bayes , Neoplasias Encefálicas/diagnóstico por imagen , Calibración , Simulación por Computador , Glioma/diagnóstico por imagen , HumanosRESUMEN
The Cerebral Aneurysm Detection and Analysis (CADA) challenge was organized to support the development and benchmarking of algorithms for detecting, analyzing, and risk assessment of cerebral aneurysms in X-ray rotational angiography (3DRA) images. 109 anonymized 3DRA datasets were provided for training, and 22 additional datasets were used to test the algorithmic solutions. Cerebral aneurysm detection was assessed using the F2 score based on recall and precision, and the fit of the delivered bounding box was assessed using the distance to the aneurysm. The segmentation quality was measured using the Jaccard index and a combination of different surface distance measures. Systematic errors were analyzed using volume correlation and bias. Rupture risk assessment was evaluated using the F2 score. 158 participants from 22 countries registered for the CADA challenge. The U-Net-based detection solutions presented by the community show similar accuracy compared to experts (F2 score 0.92), with a small number of missed aneurysms with diameters smaller than 3.5 mm. In addition, the delineation of these structures, based on U-Net variations, is excellent, with a Jaccard score of 0.92. The rupture risk estimation methods achieved an F2 score of 0.71. The performance of the detection and segmentation solutions is equivalent to that of human experts. The best results are obtained in rupture risk estimation by combining different image-based, morphological, and computational fluid dynamic parameters using machine learning methods. Furthermore, we evaluated the best methods pipeline, from detecting and delineating the vessel dilations to estimating the risk of rupture. The chain of these methods achieves an F2-score of 0.70, which is comparable to applying the risk prediction to the ground-truth delineation (0.71).
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Aneurisma Intracraneal , Algoritmos , Angiografía Cerebral/métodos , Humanos , Imagenología Tridimensional/métodos , Aneurisma Intracraneal/diagnóstico por imagen , Rayos XRESUMEN
A multitude of image-based machine learning segmentation and classification algorithms has recently been proposed, offering diagnostic decision support for the identification and characterization of glioma, Covid-19 and many other diseases. Even though these algorithms often outperform human experts in segmentation tasks, their limited reliability, and in particular the inability to detect failure cases, has hindered translation into clinical practice. To address this major shortcoming, we propose an unsupervised quality estimation method for segmentation ensembles. Our primitive solution examines discord in binary segmentation maps to automatically flag segmentation results that are particularly error-prone and therefore require special assessment by human readers. We validate our method both on segmentation of brain glioma in multi-modal magnetic resonance - and of lung lesions in computer tomography images. Additionally, our method provides an adaptive prioritization mechanism to maximize efficacy in use of human expert time by enabling radiologists to focus on the most difficult, yet important cases while maintaining full diagnostic autonomy. Our method offers an intuitive and reliable uncertainty estimation from segmentation ensembles and thereby closes an important gap toward successful translation of automatic segmentation into clinical routine.
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It is critical to quantitatively analyse the developing human fetal brain in order to fully understand neurodevelopment in both normal fetuses and those with congenital disorders. To facilitate this analysis, automatic multi-tissue fetal brain segmentation algorithms are needed, which in turn requires open datasets of segmented fetal brains. Here we introduce a publicly available dataset of 50 manually segmented pathological and non-pathological fetal magnetic resonance brain volume reconstructions across a range of gestational ages (20 to 33 weeks) into 7 different tissue categories (external cerebrospinal fluid, grey matter, white matter, ventricles, cerebellum, deep grey matter, brainstem/spinal cord). In addition, we quantitatively evaluate the accuracy of several automatic multi-tissue segmentation algorithms of the developing human fetal brain. Four research groups participated, submitting a total of 10 algorithms, demonstrating the benefits the dataset for the development of automatic algorithms.
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Encéfalo/embriología , Feto , Neurogénesis , Algoritmos , Benchmarking , Encéfalo/diagnóstico por imagen , Anomalías Congénitas/diagnóstico por imagen , Curaduría de Datos , Humanos , Imagen por Resonancia Magnética , Tamaño de los ÓrganosRESUMEN
The aim of this paper is to provide a comprehensive overview of the MICCAI 2020 AutoImplant Challenge. The approaches and publications submitted and accepted within the challenge will be summarized and reported, highlighting common algorithmic trends and algorithmic diversity. Furthermore, the evaluation results will be presented, compared and discussed in regard to the challenge aim: seeking for low cost, fast and fully automated solutions for cranial implant design. Based on feedback from collaborating neurosurgeons, this paper concludes by stating open issues and post-challenge requirements for intra-operative use. The codes can be found at https://github.com/Jianningli/tmi.