Alexander Krull

Ashesh, Alexander Krull, Moises Di Sante et al.

We present μSplit, a dedicated approach for trained image decomposition in the context of fluorescence microscopy images. We find that best results using regular deep architectures are achieved when large image patches are used during training, making memory consumption the limiting factor to further improving performance. We therefore introduce lateral contextualization (LC), a novel meta-architecture that enables the memory efficient incorporation of large image-context, which we observe is a key ingredient to solving the image decomposition task at hand. We integrate LC with U-Nets, Hierarchical AEs, and Hierarchical VAEs, for which we formulate a modified ELBO loss. Additionally, LC enables training deeper hierarchical models than otherwise possible and, interestingly, helps to reduce tiling artefacts that are inherently impossible to avoid when using tiled VAE predictions. We apply μSplit to five decomposition tasks, one on a synthetic dataset, four others derived from real microscopy data. Our method consistently achieves best results (average improvements to the best baseline of 2.25 dB PSNR), while simultaneously requiring considerably less GPU memory. Our code and datasets can be found at https://github.com/juglab/uSplit.

Xinxing Cheng, Xi Jia, Wenqi Lu et al.

Deep image registration has demonstrated exceptional accuracy and fast inference. Recent advances have adopted either multiple cascades or pyramid architectures to estimate dense deformation fields in a coarse-to-fine manner. However, due to the cascaded nature and repeated composition/warping operations on feature maps, these methods negatively increase memory usage during training and testing. Moreover, such approaches lack explicit constraints on the learning process of small deformations at different scales, thus lacking explainability. In this study, we introduce a model-driven WiNet that incrementally estimates scale-wise wavelet coefficients for the displacement/velocity field across various scales, utilizing the wavelet coefficients derived from the original input image pair. By exploiting the properties of the wavelet transform, these estimated coefficients facilitate the seamless reconstruction of a full-resolution displacement/velocity field via our devised inverse discrete wavelet transform (IDWT) layer. This approach avoids the complexities of cascading networks or composition operations, making our WiNet an explainable and efficient competitor with other coarse-to-fine methods. Extensive experimental results from two 3D datasets show that our WiNet is accurate and GPU efficient. The code is available at https://github.com/x-xc/WiNet .

Alexander Krull, Hector Basevi, Benjamin Salmon et al.

We present a fresh perspective on shot noise corrupted images and noise removal. By viewing image formation as the sequential accumulation of photons on a detector grid, we show that a network trained to predict where the next photon could arrive is in fact solving the minimum mean square error (MMSE) denoising task. This new perspective allows us to make three contributions: We present a new strategy for self-supervised denoising, We present a new method for sampling from the posterior of possible solutions by iteratively sampling and adding small numbers of photons to the image. We derive a full generative model by starting this process from an empty canvas. We call this approach generative accumulation of photons (GAP). We evaluate our method quantitatively and qualitatively on 4 new fluorescence microscopy datasets, which will be made available to the community. We find that it outperforms supervised, self-supervised and unsupervised baselines or performs on-par.

Benjamin Salmon, Alexander Krull

Traditional supervised denoisers are trained using pairs of noisy input and clean target images. They learn to predict a central tendency of the posterior distribution over possible clean images. When, e.g., trained with the popular quadratic loss function, the network's output will correspond to the minimum mean square error (MMSE) estimate. Unsupervised denoisers based on Variational AutoEncoders (VAEs) have succeeded in achieving state-of-the-art results while requiring only unpaired noisy data as training input. In contrast to the traditional supervised approach, unsupervised denoisers do not directly produce a single prediction, such as the MMSE estimate, but allow us to draw samples from the posterior distribution of clean solutions corresponding to the noisy input. To approximate the MMSE estimate during inference, unsupervised methods have to create and draw a large number of samples - a computationally expensive process - rendering the approach inapplicable in many situations. Here, we present an alternative approach that trains a deterministic network alongside the VAE to directly predict a central tendency. Our method achieves results that surpass the results achieved by the unsupervised method at a fraction of the computational cost.

Benjamin Salmon, Alexander Krull

Accurate analysis of microscopy images is hindered by the presence of noise. This noise is usually signal-dependent and often additionally correlated along rows or columns of pixels. Current self- and unsupervised denoisers can address signal-dependent noise, but none can reliably remove noise that is also row- or column-correlated. Here, we present the first fully unsupervised deep learning-based denoiser capable of handling imaging noise that is row-correlated as well as signal-dependent. Our approach uses a Variational Autoencoder (VAE) with a specially designed autoregressive decoder. This decoder is capable of modeling row-correlated and signal-dependent noise but is incapable of independently modeling underlying clean signal. The VAE therefore produces latent variables containing only clean signal information, and these are mapped back into image space using a proposed second decoder network. Our method does not require a pre-trained noise model and can be trained from scratch using unpaired noisy data. We benchmark our approach on microscopy datatsets from a range of imaging modalities and sensor types, each with row- or column-correlated, signal-dependent noise, and show that it outperforms existing self- and unsupervised denoisers.

Samuel Tonks, Cuong Nguyen, Steve Hood et al.

The large volume and variety of imaging data from high-throughput screening (HTS) in the pharmaceutical industry present an excellent resource for training virtual staining models. However, the potential of models trained under one set of experimental conditions to generalize to other conditions remains underexplored. This study systematically investigates whether data from three cell types (lung, ovarian, and breast) and two phenotypes (toxic and non-toxic conditions) commonly found in HTS can effectively train virtual staining models to generalize across three typical HTS distribution shifts: unseen phenotypes, unseen cell types, and the combination of both. Utilizing a dataset of 772,416 paired bright-field, cytoplasm, nuclei, and DNA-damage stain images, we evaluate the generalization capabilities of models across pixel-based, instance-wise, and biological-feature-based levels. Our findings indicate that training virtual nuclei and cytoplasm models on non-toxic condition samples not only generalizes to toxic condition samples but leads to improved performance across all evaluation levels compared to training on toxic condition samples. Generalization to unseen cell types shows variability depending on the cell type; models trained on ovarian or lung cell samples often perform well under other conditions, while those trained on breast cell samples consistently show poor generalization. Generalization to unseen cell types and phenotypes shows good generalization across all levels of evaluation compared to addressing unseen cell types alone. This study represents the first large-scale, data-centric analysis of the generalization capability of virtual staining models trained on diverse HTS datasets, providing valuable strategies for experimental training data generation.

Samuel Tonks, Steve Hood, Ryan Musso et al.

Generative virtual staining (VS) models for high-throughput screening (HTS) can provide an estimated posterior distribution of possible biological feature values for each input and cell. However, when evaluating a VS model, the true posterior is unavailable. Existing evaluation protocols only check the accuracy of the marginal distribution over the dataset rather than the predicted posteriors. We introduce information gain (IG) as a cell-wise evaluation framework that enables direct assessment of predicted posteriors. IG is a strictly proper scoring rule and comes with a sound theoretical motivation allowing for interpretability, and for comparing results across models and features. We evaluate diffusion- and GAN-based models on an extensive HTS dataset using IG and other metrics and show that IG can reveal substantial performance differences other metrics cannot.

Anna Foix Romero, Craig Russell, Alexander Krull et al.

The shape of objects is an important source of visual information in a wide range of applications. One of the core challenges of shape quantification is to ensure that the extracted measurements remain invariant to transformations that preserve an object's intrinsic geometry, such as changing its size, orientation, and position in the image. In this work, we introduce ShapeEmbed, a self-supervised representation learning framework designed to encode the contour of objects in 2D images, represented as a Euclidean distance matrix, into a shape descriptor that is invariant to translation, scaling, rotation, reflection, and point indexing. Our approach overcomes the limitations of traditional shape descriptors while improving upon existing state-of-the-art autoencoder-based approaches. We demonstrate that the descriptors learned by our framework outperform their competitors in shape classification tasks on natural and biological images. We envision our approach to be of particular relevance to biological imaging applications.

Yehe Liu, Alexander Krull, Hector Basevi et al.

Quanta image sensors, such as SPAD arrays, are an emerging sensor technology, producing 1-bit arrays representing photon detection events over exposures as short as a few nanoseconds. In practice, raw data are post-processed using heavy spatiotemporal binning to create more useful and interpretable images at the cost of degrading spatiotemporal resolution. In this work, we propose bit2bit, a new method for reconstructing high-quality image stacks at the original spatiotemporal resolution from sparse binary quanta image data. Inspired by recent work on Poisson denoising, we developed an algorithm that creates a dense image sequence from sparse binary photon data by predicting the photon arrival location probability distribution. However, due to the binary nature of the data, we show that the assumption of a Poisson distribution is inadequate. Instead, we model the process with a Bernoulli lattice process from the truncated Poisson. This leads to the proposal of a novel self-supervised solution based on a masked loss function. We evaluate our method using both simulated and real data. On simulated data from a conventional video, we achieve 34.35 mean PSNR with extremely photon-sparse binary input (<0.06 photons per pixel per frame). We also present a novel dataset containing a wide range of real SPAD high-speed videos under various challenging imaging conditions. The scenes cover strong/weak ambient light, strong motion, ultra-fast events, etc., which will be made available to the community, on which we demonstrate the promise of our approach. Both reconstruction quality and throughput substantially surpass the state-of-the-art methods (e.g., Quanta Burst Photography (QBP)). Our approach significantly enhances the visualization and usability of the data, enabling the application of existing analysis techniques.

Anna S. Goncharova, Alf Honigmann, Florian Jug et al.

Many microscopy applications are limited by the total amount of usable light and are consequently challenged by the resulting levels of noise in the acquired images. This problem is often addressed via (supervised) deep learning based denoising. Recently, by making assumptions about the noise statistics, self-supervised methods have emerged. Such methods are trained directly on the images that are to be denoised and do not require additional paired training data. While achieving remarkable results, self-supervised methods can produce high-frequency artifacts and achieve inferior results compared to supervised approaches. Here we present a novel way to improve the quality of self-supervised denoising. Considering that light microscopy images are usually diffraction-limited, we propose to include this knowledge in the denoising process. We assume the clean image to be the result of a convolution with a point spread function (PSF) and explicitly include this operation at the end of our neural network. As a consequence, we are able to eliminate high-frequency artifacts and achieve self-supervised results that are very close to the ones achieved with traditional supervised methods.

Mangal Prakash, Alexander Krull, Florian Jug

Deep Learning based methods have emerged as the indisputable leaders for virtually all image restoration tasks. Especially in the domain of microscopy images, various content-aware image restoration (CARE) approaches are now used to improve the interpretability of acquired data. Naturally, there are limitations to what can be restored in corrupted images, and like for all inverse problems, many potential solutions exist, and one of them must be chosen. Here, we propose DivNoising, a denoising approach based on fully convolutional variational autoencoders (VAEs), overcoming the problem of having to choose a single solution by predicting a whole distribution of denoised images. First we introduce a principled way of formulating the unsupervised denoising problem within the VAE framework by explicitly incorporating imaging noise models into the decoder. Our approach is fully unsupervised, only requiring noisy images and a suitable description of the imaging noise distribution. We show that such a noise model can either be measured, bootstrapped from noisy data, or co-learned during training. If desired, consensus predictions can be inferred from a set of DivNoising predictions, leading to competitive results with other unsupervised methods and, on occasion, even with the supervised state-of-the-art. DivNoising samples from the posterior enable a plethora of useful applications. We are (i) showing denoising results for 13 datasets, (ii) discussing how optical character recognition (OCR) applications can benefit from diverse predictions, and are (iii) demonstrating how instance cell segmentation improves when using diverse DivNoising predictions.

Tim-Oliver Buchholz, Mangal Prakash, Alexander Krull et al.

Microscopy image analysis often requires the segmentation of objects, but training data for this task is typically scarce and hard to obtain. Here we propose DenoiSeg, a new method that can be trained end-to-end on only a few annotated ground truth segmentations. We achieve this by extending Noise2Void, a self-supervised denoising scheme that can be trained on noisy images alone, to also predict dense 3-class segmentations. The reason for the success of our method is that segmentation can profit from denoising, especially when performed jointly within the same network. The network becomes a denoising expert by seeing all available raw data, while co-learning to segment, even if only a few segmentation labels are available. This hypothesis is additionally fueled by our observation that the best segmentation results on high quality (very low noise) raw data are obtained when moderate amounts of synthetic noise are added. This renders the denoising-task non-trivial and unleashes the desired co-learning effect. We believe that DenoiSeg offers a viable way to circumvent the tremendous hunger for high quality training data and effectively enables few-shot learning of dense segmentations.

Mangal Prakash, Manan Lalit, Pavel Tomancak et al.

Image denoising is the first step in many biomedical image analysis pipelines and Deep Learning (DL) based methods are currently best performing. A new category of DL methods such as Noise2Void or Noise2Self can be used fully unsupervised, requiring nothing but the noisy data. However, this comes at the price of reduced reconstruction quality. The recently proposed Probabilistic Noise2Void (PN2V) improves results, but requires an additional noise model for which calibration data needs to be acquired. Here, we present improvements to PN2V that (i) replace histogram based noise models by parametric noise models, and (ii) show how suitable noise models can be created even in the absence of calibration data. This is a major step since it actually renders PN2V fully unsupervised. We demonstrate that all proposed improvements are not only academic but indeed relevant.

Mangal Prakash, Tim-Oliver Buchholz, Manan Lalit et al.

Deep learning (DL) has arguably emerged as the method of choice for the detection and segmentation of biological structures in microscopy images. However, DL typically needs copious amounts of annotated training data that is for biomedical projects typically not available and excessively expensive to generate. Additionally, tasks become harder in the presence of noise, requiring even more high-quality training data. Hence, we propose to use denoising networks to improve the performance of other DL-based image segmentation methods. More specifically, we present ideas on how state-of-the-art self-supervised CARE networks can improve cell/nuclei segmentation in microscopy data. Using two state-of-the-art baseline methods, U-Net and StarDist, we show that our ideas consistently improve the quality of resulting segmentations, especially when only limited training data for noisy micrographs are available.

Alexander Krull, Tomas Vicar, Florian Jug

Today, Convolutional Neural Networks (CNNs) are the leading method for image denoising. They are traditionally trained on pairs of images, which are often hard to obtain for practical applications. This motivates self-supervised training methods such as Noise2Void~(N2V) that operate on single noisy images. Self-supervised methods are, unfortunately, not competitive with models trained on image pairs. Here, we present 'Probabilistic Noise2Void' (PN2V), a method to train CNNs to predict per-pixel intensity distributions. Combining these with a suitable description of the noise, we obtain a complete probabilistic model for the noisy observations and true signal in every pixel. We evaluate PN2V on publicly available microscopy datasets, under a broad range of noise regimes, and achieve competitive results with respect to supervised state-of-the-art methods.

Alexander Krull, Tim-Oliver Buchholz, Florian Jug

The field of image denoising is currently dominated by discriminative deep learning methods that are trained on pairs of noisy input and clean target images. Recently it has been shown that such methods can also be trained without clean targets. Instead, independent pairs of noisy images can be used, in an approach known as Noise2Noise (N2N). Here, we introduce Noise2Void (N2V), a training scheme that takes this idea one step further. It does not require noisy image pairs, nor clean target images. Consequently, N2V allows us to train directly on the body of data to be denoised and can therefore be applied when other methods cannot. Especially interesting is the application to biomedical image data, where the acquisition of training targets, clean or noisy, is frequently not possible. We compare the performance of N2V to approaches that have either clean target images and/or noisy image pairs available. Intuitively, N2V cannot be expected to outperform methods that have more information available during training. Still, we observe that the denoising performance of Noise2Void drops in moderation and compares favorably to training-free denoising methods.

Alexander Krull, Eric Brachmann, Sebastian Nowozin et al.

State-of-the-art computer vision algorithms often achieve efficiency by making discrete choices about which hypotheses to explore next. This allows allocation of computational resources to promising candidates, however, such decisions are non-differentiable. As a result, these algorithms are hard to train in an end-to-end fashion. In this work we propose to learn an efficient algorithm for the task of 6D object pose estimation. Our system optimizes the parameters of an existing state-of-the art pose estimation system using reinforcement learning, where the pose estimation system now becomes the stochastic policy, parametrized by a CNN. Additionally, we present an efficient training algorithm that dramatically reduces computation time. We show empirically that our learned pose estimation procedure makes better use of limited resources and improves upon the state-of-the-art on a challenging dataset. Our approach enables differentiable end-to-end training of complex algorithmic pipelines and learns to make optimal use of a given computational budget.

Frank Michel, Alexander Kirillov, Eric Brachmann et al.

This paper addresses the task of estimating the 6D pose of a known 3D object from a single RGB-D image. Most modern approaches solve this task in three steps: i) Compute local features; ii) Generate a pool of pose-hypotheses; iii) Select and refine a pose from the pool. This work focuses on the second step. While all existing approaches generate the hypotheses pool via local reasoning, e.g. RANSAC or Hough-voting, we are the first to show that global reasoning is beneficial at this stage. In particular, we formulate a novel fully-connected Conditional Random Field (CRF) that outputs a very small number of pose-hypotheses. Despite the potential functions of the CRF being non-Gaussian, we give a new and efficient two-step optimization procedure, with some guarantees for optimality. We utilize our global hypotheses generation procedure to produce results that exceed state-of-the-art for the challenging "Occluded Object Dataset".

Eric Brachmann, Alexander Krull, Sebastian Nowozin et al.

RANSAC is an important algorithm in robust optimization and a central building block for many computer vision applications. In recent years, traditionally hand-crafted pipelines have been replaced by deep learning pipelines, which can be trained in an end-to-end fashion. However, RANSAC has so far not been used as part of such deep learning pipelines, because its hypothesis selection procedure is non-differentiable. In this work, we present two different ways to overcome this limitation. The most promising approach is inspired by reinforcement learning, namely to replace the deterministic hypothesis selection by a probabilistic selection for which we can derive the expected loss w.r.t. to all learnable parameters. We call this approach DSAC, the differentiable counterpart of RANSAC. We apply DSAC to the problem of camera localization, where deep learning has so far failed to improve on traditional approaches. We demonstrate that by directly minimizing the expected loss of the output camera poses, robustly estimated by RANSAC, we achieve an increase in accuracy. In the future, any deep learning pipeline can use DSAC as a robust optimization component.

Daniela Massiceti, Alexander Krull, Eric Brachmann et al.

This work addresses the task of camera localization in a known 3D scene given a single input RGB image. State-of-the-art approaches accomplish this in two steps: firstly, regressing for every pixel in the image its 3D scene coordinate and subsequently, using these coordinates to estimate the final 6D camera pose via RANSAC. To solve the first step, Random Forests (RFs) are typically used. On the other hand, Neural Networks (NNs) reign in many dense regression tasks, but are not test-time efficient. We ask the question: which of the two is best for camera localization? To address this, we make two method contributions: (1) a test-time efficient NN architecture which we term a ForestNet that is derived and initialized from a RF, and (2) a new fully-differentiable robust averaging technique for regression ensembles which can be trained end-to-end with a NN. Our experimental findings show that for scene coordinate regression, traditional NN architectures are superior to test-time efficient RFs and ForestNets, however, this does not translate to final 6D camera pose accuracy where RFs and ForestNets perform slightly better. To summarize, our best method, a ForestNet with a robust average, which has an equivalent fast and lightweight RF, improves over the state-of-the-art for camera localization on the 7-Scenes dataset. While this work focuses on scene coordinate regression for camera localization, our innovations may also be applied to other continuous regression tasks.

Alexander Krull, Eric Brachmann, Frank Michel et al.

Analysis-by-synthesis has been a successful approach for many tasks in computer vision, such as 6D pose estimation of an object in an RGB-D image which is the topic of this work. The idea is to compare the observation with the output of a forward process, such as a rendered image of the object of interest in a particular pose. Due to occlusion or complicated sensor noise, it can be difficult to perform this comparison in a meaningful way. We propose an approach that "learns to compare", while taking these difficulties into account. This is done by describing the posterior density of a particular object pose with a convolutional neural network (CNN) that compares an observed and rendered image. The network is trained with the maximum likelihood paradigm. We observe empirically that the CNN does not specialize to the geometry or appearance of specific objects, and it can be used with objects of vastly different shapes and appearances, and in different backgrounds. Compared to state-of-the-art, we demonstrate a significant improvement on two different datasets which include a total of eleven objects, cluttered background, and heavy occlusion.