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BACKGROUND: The objective of this comprehensive pan-cancer study is to evaluate the potential of deep learning (DL) for molecular profiling of multi-omic biomarkers directly from hematoxylin and eosin (H&E)-stained whole slide images. METHODS: A total of 12,093 DL models predicting 4031 multi-omic biomarkers across 32 cancer types were trained and validated. The study included a broad range of genetic, transcriptomic, and proteomic biomarkers, as well as established prognostic markers, molecular subtypes, and clinical outcomes. RESULTS: Here we show that 50% of the models achieve an area under the curve (AUC) of 0.644 or higher. The observed AUC for 25% of the models is at least 0.719 and exceeds 0.834 for the top 5%. Molecular profiling with image-based histomorphological features is generally considered feasible for most of the investigated biomarkers and across different cancer types. The performance appears to be independent of tumor purity, sample size, and class ratio (prevalence), suggesting a degree of inherent predictability in histomorphology. CONCLUSIONS: The results demonstrate that DL holds promise to predict a wide range of biomarkers across the omics spectrum using only H&E-stained histological slides of solid tumors. This paves the way for accelerating diagnosis and developing more precise treatments for cancer patients.
Molecular profiling tests are used to check cancers for changes in certain genes, proteins, or other molecules. Results of such tests can be used to identify the most effective treatment for cancer patients. Faster and more accessible alternatives to standard tests are needed to improve cancer care. This study investigates whether deep learning (DL), a series of advanced computer techniques, can perform molecular profiling directly from routinely-collected images of tumor specimens used for diagnostic purposes. Over 12,000 DL models were utilized to evaluate thousands of biomarkers using statistical approaches. The results indicate that DL can effectively detect molecular changes in a tumor from these images, for many biomarkers and tumor types. The study shows that DL-based molecular profiling from images is possible. Introducing this type of approach into routine clinical workflows could potentially accelerate treatment decisions and improve outcomes.
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The macro-connectome elucidates the pathways through which brain regions are structurally connected or functionally coupled to perform a specific cognitive task. It embodies the notion of representing and understanding all connections within the brain as a network, while the subdivision of the brain into interacting functional units is inherent in its architecture. As a result, the definition of network nodes is one of the most critical steps in connectivity network analysis. Although brain atlases obtained from cytoarchitecture or anatomy have long been used for this task, connectivity-driven methods have arisen only recently, aiming to delineate more homogeneous and functionally coherent regions. This study provides a systematic comparison between anatomical, connectivity-driven and random parcellation methods proposed in the thriving field of brain parcellation. Using resting-state functional MRI data from the Human Connectome Project and a plethora of quantitative evaluation techniques investigated in the literature, we evaluate 10 subject-level and 24 groupwise parcellation methods at different resolutions. We assess the accuracy of parcellations from four different aspects: (1) reproducibility across different acquisitions and groups, (2) fidelity to the underlying connectivity data, (3) agreement with fMRI task activation, myelin maps, and cytoarchitectural areas, and (4) network analysis. This extensive evaluation of different parcellations generated at the subject and group level highlights the strengths and shortcomings of the various methods and aims to provide a guideline for the choice of parcellation technique and resolution according to the task at hand. The results obtained in this study suggest that there is no optimal method able to address all the challenges faced in this endeavour simultaneously.
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Mapeamento Encefálico/métodos , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiologia , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Modelos Teóricos , Humanos , Interpretação de Imagem Assistida por ComputadorRESUMO
Advances in neuroimaging have provided a tremendous amount of in-vivo information on the brain's organisation. Its anatomy and cortical organisation can be investigated from the point of view of several imaging modalities, many of which have been studied for mapping functionally specialised cortical areas. There is strong evidence that a single modality is not sufficient to fully identify the brain's cortical organisation. Combining multiple modalities in the same parcellation task has the potential to provide more accurate and robust subdivisions of the cortex. Nonetheless, existing brain parcellation methods are typically developed and tested on single modalities using a specific type of information. In this paper, we propose Graph-based Multi-modal Parcellation (GraMPa), an iterative framework designed to handle the large variety of available input modalities to tackle the multi-modal parcellation task. At each iteration, we compute a set of parcellations from different modalities and fuse them based on their local reliabilities. The fused parcellation is used to initialise the next iteration, forcing the parcellations to converge towards a set of mutually informed modality specific parcellations, where correspondences are established. We explore two different multi-modal configurations for group-wise parcellation using resting-state fMRI, diffusion MRI tractography, myelin maps and task fMRI. Quantitative and qualitative results on the Human Connectome Project database show that integrating multi-modal information yields a stronger agreement with well established atlases and more robust connectivity networks that provide a better representation of the population.
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Mapeamento Encefálico/métodos , Córtex Cerebral/anatomia & histologia , Processamento de Imagem Assistida por Computador/métodos , HumanosRESUMO
The delineation of functionally and structurally distinct regions as well as their connectivity can provide key knowledge towards understanding the brain's behaviour and function. Cytoarchitecture has long been the gold standard for such parcellation tasks, but has poor scalability and cannot be mapped in vivo. Functional and diffusion magnetic resonance imaging allow in vivo mapping of brain's connectivity and the parcellation of the brain based on local connectivity information. Several methods have been developed for single subject connectivity driven parcellation, but very few have tackled the task of group-wise parcellation, which is essential for uncovering group specific behaviours. In this paper, we propose a group-wise connectivity-driven parcellation method based on spectral clustering that captures local connectivity information at multiple scales and directly enforces correspondences between subjects. The method is applied to diffusion Magnetic Resonance Imaging driven parcellation on two independent groups of 50 subjects from the Human Connectome Project. Promising quantitative and qualitative results in terms of information loss, modality comparisons, group consistency and inter-group similarities demonstrate the potential of the method.
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Córtex Cerebral/anatomia & histologia , Córtex Cerebral/fisiologia , Conectoma/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/anatomia & histologia , Rede Nervosa/fisiologia , Algoritmos , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Reconhecimento Automatizado de Padrão/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Técnica de SubtraçãoRESUMO
Identification of functional connections within the human brain has gained a lot of attention due to its potential to reveal neural mechanisms. In a whole-brain connectivity analysis, a critical stage is the computation of a set of network nodes that can effectively represent cortical regions. To address this problem, we present a robust cerebral cortex parcellation method based on spectral graph theory and resting-state fMRI correlations that generates reliable parcellations at the single-subject level and across multiple subjects. Our method models the cortical surface in each hemisphere as a mesh graph represented in the spectral domain with its eigenvectors. We connect cortices of different subjects with each other based on the similarity of their connectivity profiles and construct a multi-layer graph, which effectively captures the fundamental properties of the whole group as well as preserves individual subject characteristics. Spectral decomposition of this joint graph is used to cluster each cortical vertex into a subregion in order to obtain whole-brain parcellations. Using rs-fMRI data collected from 40 healthy subjects, we show that our proposed algorithm computes highly reproducible parcellations across different groups of subjects and at varying levels of detail with an average Dice score of 0.78, achieving up to 9% better reproducibility compared to existing approaches. We also report that our group-wise parcellations are functionally more consistent, thus, can be reliably used to represent the population in network analyses.
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Algoritmos , Córtex Cerebral/fisiologia , Conectoma/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/fisiologia , Adulto , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Reprodutibilidade dos Testes , Descanso/fisiologia , Sensibilidade e Especificidade , Adulto JovemRESUMO
The analysis of the connectome of the human brain provides key insight into the brain's organisation and function, and its evolution in disease or ageing. Parcellation of the cortical surface into distinct regions in terms of structural connectivity is an essential step that can enable such analysis. The estimation of a stable connectome across a population of healthy subjects requires the estimation of a groupwise parcellation that can capture the variability of the connectome across the population. This problem has solely been addressed in the literature via averaging of connectivity profiles or finding correspondences between individual parcellations a posteriori. In this paper, we propose a groupwise parcellation method of the cortex based on diffusion MR images (dMRI). We borrow ideas from the area of cosegmentation in computer vision and directly estimate a consistent parcellation across different subjects and scales through a spectral clustering approach. The parcellation is driven by the tractography connectivity profiles, and information between subjects and across scales. Promising qualitative and quantitative results on a sizeable data-set demonstrate the strong potential of the method.
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Córtex Cerebral/anatomia & histologia , Conectoma/métodos , Imagem de Tensor de Difusão/métodos , Interpretação de Imagem Assistida por Computador/métodos , Fibras Nervosas Mielinizadas/ultraestrutura , Reconhecimento Automatizado de Padrão/métodos , Adulto , Idoso , Algoritmos , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
Computer-based imaging systems are becoming important tools for quantitative assessment of peripheral blood and bone marrow samples to help experts diagnose blood disorders such as acute leukemia. These systems generally initiate a segmentation stage where white blood cells are separated from the background and other nonsalient objects. As the success of such imaging systems mainly depends on the accuracy of this stage, studies attach great importance for developing accurate segmentation algorithms. Although previous studies give promising results for segmentation of sparsely distributed normal white blood cells, only a few of them focus on segmenting touching and overlapping cell clusters, which is usually the case when leukemic cells are present. In this article, we present a new algorithm for segmentation of both normal and leukemic cells in peripheral blood and bone marrow images. In this algorithm, we propose to model color and shape characteristics of white blood cells by defining two transformations and introduce an efficient use of these transformations in a marker-controlled watershed algorithm. Particularly, these domain specific characteristics are used to identify markers and define the marking function of the watershed algorithm as well as to eliminate false white blood cells in a postprocessing step. Working on 650 white blood cells in peripheral blood and bone marrow images, our experiments reveal that the proposed algorithm improves the segmentation performance compared with its counterparts, leading to high accuracies for both sparsely distributed normal white blood cells and dense leukemic cell clusters.
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Células da Medula Óssea/patologia , Processamento de Imagem Assistida por Computador/métodos , Leucemia Aguda Bifenotípica/diagnóstico , Reconhecimento Automatizado de Padrão/métodos , Algoritmos , Humanos , Aumento da Imagem/métodos , Leucemia Aguda Bifenotípica/patologia , Leucócitos/patologia , MicroscopiaRESUMO
More rapid and accurate high-throughput screening in molecular cellular biology research has become possible with the development of automated microscopy imaging, for which cell nucleus segmentation commonly constitutes the core step. Although several promising methods exist for segmenting the nuclei of monolayer isolated and less-confluent cells, it still remains an open problem to segment the nuclei of more-confluent cells, which tend to grow in overlayers. To address this problem, we propose a new model-based nucleus segmentation algorithm. This algorithm models how a human locates a nucleus by identifying the nucleus boundaries and piecing them together. In this algorithm, we define four types of primitives to represent nucleus boundaries at different orientations and construct an attributed relational graph on the primitives to represent their spatial relations. Then, we reduce the nucleus identification problem to finding predefined structural patterns in the constructed graph and also use the primitives in region growing to delineate the nucleus borders. Working with fluorescence microscopy images, our experiments demonstrate that the proposed algorithm identifies nuclei better than previous nucleus segmentation algorithms.
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Núcleo Celular/química , Processamento de Imagem Assistida por Computador/métodos , Microscopia de Fluorescência/métodos , Algoritmos , Células Hep G2 , HumanosRESUMO
Automated cell imaging systems facilitate fast and reliable analysis of biological events at the cellular level. In these systems, the first step is usually cell segmentation that greatly affects the success of the subsequent system steps. On the other hand, similar to other image segmentation problems, cell segmentation is an ill-posed problem that typically necessitates the use of domain-specific knowledge to obtain successful segmentations even by human subjects. The approaches that can incorporate this knowledge into their segmentation algorithms have potential to greatly improve segmentation results. In this work, we propose a new approach for the effective segmentation of live cells from phase contrast microscopy. This approach introduces a new set of "smart markers" for a marker-controlled watershed algorithm, for which the identification of its markers is critical. The proposed approach relies on using domain-specific knowledge, in the form of visual characteristics of the cells, to define the markers. We evaluate our approach on a total of 1,954 cells. The experimental results demonstrate that this approach, which uses the proposed definition of smart markers, is quite effective in identifying better markers compared to its counterparts. This will, in turn, be effective in improving the segmentation performance of a marker-controlled watershed algorithm.