Dataset Information

Probabilistic spatial analysis in quantitative microscopy with uncertainty-aware cell detection using deep Bayesian regression.

ABSTRACT: The investigation of biological systems with three-dimensional microscopy demands automatic cell identification methods that not only are accurate but also can imply the uncertainty in their predictions. The use of deep learning to regress density maps is a popular successful approach for extracting cell coordinates from local peaks in a postprocessing step, which then, however, hinders any meaningful probabilistic output. We propose a framework that can operate on large microscopy images and output probabilistic predictions (i) by integrating deep Bayesian learning for the regression of uncertainty-aware density maps, where peak detection algorithms generate cell proposals, and (ii) by learning a mapping from prediction proposals to a probabilistic space that accurately represents the chances of a successful prediction. Using these calibrated predictions, we propose a probabilistic spatial analysis with Monte Carlo sampling. We demonstrate this in a bone marrow dataset, where our proposed methods reveal spatial patterns that are otherwise undetectable.

SUBMITTER: Gomariz A

PROVIDER: S-EPMC8816343 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Probabilistic spatial analysis in quantitative microscopy with uncertainty-aware cell detection using deep Bayesian regression.

Gomariz Alvaro A Portenier Tiziano T Nombela-Arrieta César C Goksel Orcun O

Science advances 20220204 5

The investigation of biological systems with three-dimensional microscopy demands automatic cell identification methods that not only are accurate but also can imply the uncertainty in their predictions. The use of deep learning to regress density maps is a popular successful approach for extracting cell coordinates from local peaks in a postprocessing step, which then, however, hinders any meaningful probabilistic output. We propose a framework that can operate on large microscopy images and ou ...[more]

PMID: 35119934

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Project description:Mistrust is a major barrier to implementing deep learning in healthcare settings. Entrustment could be earned by conveying model certainty, or the probability that a given model output is accurate, but the use of uncertainty estimation for deep learning entrustment is largely unexplored, and there is no consensus regarding optimal methods for quantifying uncertainty. Our purpose is to critically evaluate methods for quantifying uncertainty in deep learning for healthcare applications and propose a conceptual framework for specifying certainty of deep learning predictions. We searched Embase, MEDLINE, and PubMed databases for articles relevant to study objectives, complying with PRISMA guidelines, rated study quality using validated tools, and extracted data according to modified CHARMS criteria. Among 30 included studies, 24 described medical imaging applications. All imaging model architectures used convolutional neural networks or a variation thereof. The predominant method for quantifying uncertainty was Monte Carlo dropout, producing predictions from multiple networks for which different neurons have dropped out and measuring variance across the distribution of resulting predictions. Conformal prediction offered similar strong performance in estimating uncertainty, along with ease of interpretation and application not only to deep learning but also to other machine learning approaches. Among the six articles describing non-imaging applications, model architectures and uncertainty estimation methods were heterogeneous, but predictive performance was generally strong, and uncertainty estimation was effective in comparing modeling methods. Overall, the use of model learning curves to quantify epistemic uncertainty (attributable to model parameters) was sparse. Heterogeneity in reporting methods precluded the performance of a meta-analysis. Uncertainty estimation methods have the potential to identify rare but important misclassifications made by deep learning models and compare modeling methods, which could build patient and clinician trust in deep learning applications in healthcare. Efficient maturation of this field will require standardized guidelines for reporting performance and uncertainty metrics.

Project description:SignificanceLensless digital inline holographic microscopy (LDIHM) is an emerging quantitative phase imaging modality that uses advanced computational methods for phase retrieval from the interference pattern. The existing end-to-end deep networks require a large training dataset with sufficient diversity to achieve high-fidelity hologram reconstruction. To mitigate this data requirement problem, physics-aware deep networks integrate the physics of holography in the loss function to reconstruct complex objects without needing prior training. However, the data fidelity term measures the data consistency with a single low-resolution hologram without any external regularization, which results in a low performance on complex biological data.AimWe aim to mitigate the challenges with trained and physics-aware untrained deep networks separately and combine the benefits of both methods for high-resolution phase recovery from a single low-resolution hologram in LDIHM.ApproachWe propose a hybrid deep framework (HDPhysNet) using a plug-and-play method that blends the benefits of trained and untrained deep models for phase recovery in LDIHM. The high-resolution phase is generated by a pre-trained high-definition generative adversarial network (HDGAN) from a single low-resolution hologram. The generated phase is then plugged into the loss function of a physics-aware untrained deep network to regulate the complex object reconstruction process.ResultsSimulation results show that the SSIM of the proposed method is increased by 0.07 over the trained and 0.04 over the untrained deep networks. The average phase-SNR is elevated by 8.2 dB over trained deep models and 9.8 dB over untrained deep networks on the experimental biological cells (cervical cells and red blood cells).ConclusionsWe showed improved performance of the HDPhysNet against the unknown perturbation in the imaging parameters such as the propagation distance, the wavelength of the illuminating source, and the imaging sample compared with the trained network (HDGAN). LDIHM, combined with HDPhysNet, is a portable and technology-driven microscopy best suited for point-of-care cytology applications.

Dataset Information

Probabilistic spatial analysis in quantitative microscopy with uncertainty-aware cell detection using deep Bayesian regression.

Publications

Probabilistic spatial analysis in quantitative microscopy with uncertainty-aware cell detection using deep Bayesian regression.

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