Histologic examination of tissues is central to the diagnosis and management of neoplasms and many other diseases, and is a foundational technique for preclinical and basic research. However, commonly used bright-field microscopy requires prior preparation of micrometre-thick tissue sections mounted on glass slides, a process that can require hours or days, that contributes to cost, and that delays access to critical information. Here, we introduce a simple, non-destructive slidefree technique that within minutes provides high-resolution diagnostic histological images resembling those obtained from conventional haematoxylin-and-eosin-histology. The approach, which we named microscopy with ultraviolet surface excitation (MUSE), can also generate shape and colour-contrast information. MUSE relies on ~280-nm ultraviolet light to restrict the excitation of conventional fluorescent stains to tissue surfaces, and it has no significant effects on downstream molecular assays (including fluorescence in situ hybridization and RNA-seq). MUSE promises to improve the speed and efficiency of patient care in both state-of-the-art and lowresource settings, and to provide opportunities for rapid histology in research. High-quality tissue microscopy is central to the diagnosis and management of neoplasms as well as other diseases. However, the bright-field (transmission) design of clinical Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Observations in many applications consist of counts of discrete events, such as photons hitting a detector, which cannot be effectively modeled using an additive bounded or Gaussian noise model, and instead require a Poisson noise model. As a result, accurate reconstruction of a spatially or temporally distributed phenomenon (f*) from Poisson data (y) cannot be effectively accomplished by minimizing a conventional penalized least-squares objective function. The problem addressed in this paper is the estimation of f* from y in an inverse problem setting, where the number of unknowns may potentially be larger than the number of observations and f* admits sparse approximation. The optimization formulation considered in this paper uses a penalized negative Poisson log-likelihood objective function with nonnegativity constraints (since Poisson intensities are naturally nonnegative). In particular, the proposed approach incorporates key ideas of using separable quadratic approximations to the objective function at each iteration and penalization terms related to l1 norms of coefficient vectors, total variation seminorms, and partition-based multiscale estimation methods.

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Abstract-This paper describes performance bounds for compressed sensing (CS) where the underlying sparse or compressible (sparsely approximable) signal is a vector of nonnegative intensities whose measurements are corrupted by Poisson noise. In this setting, standard CS techniques cannot be applied directly for several reasons. First, the usual signal-independent and/or bounded noise models do not apply to Poisson noise, which is non-additive and signal-dependent. Second, the CS matrices typically considered are not feasible in real optical systems because they do not adhere to important constraints, such as nonnegativity and photon flux preservation. Third, the typical 2-1 minimization leads to overfitting in the high-intensity regions and oversmoothing in the low-intensity areas. In this paper, we describe how a feasible positivity-and flux-preserving sensing matrix can be constructed, and then analyze the performance of a CS reconstruction approach for Poisson data that minimizes an objective function consisting of a negative Poisson log likelihood term and a penalty term which measures signal sparsity. We show that, as the overall intensity of the underlying signal increases, an upper bound on the reconstruction error decays at an appropriate rate (depending on the compressibility of the signal), but that for a fixed signal intensity, the signal-dependent part of the error bound actually grows with the number of measurements or sensors. This surprising fact is both proved theoretically and justified based on physical intuition.

Photon limitations arise in spectral imaging, nuclear medicine, astronomy and night vision. The Poisson distribution used to model this noise has variance equal to its mean so blind application of standard noise removals methods yields significant artifacts. Recently, overcomplete dictionaries combined with sparse learning techniques have become extremely popular in image reconstruction. The aim of the present work is to demonstrate that for the task of image denoising, nearly state-of-the-art results can be achieved using small dictionaries only, provided that they are learned directly from the noisy image. To this end, we introduce patch-based denoising algorithms which perform an adaptation of PCA (Principal Component Analysis) for Poisson noise. We carry out a comprehensive empirical evaluation of the performance of our algorithms in terms of accuracy when the photon count is really low. The results reveal that, despite its simplicity, PCA-flavored denoising appears to be competitive with other state-of-the-art denoising algorithms.