Better Research Software Tools to Elevate the Rate of Scientific Discovery -- or why we need to invest in research software engineering

In the past decade, enormous progress has been made in advancing the state-of-the-art in bioimage analysis - a young computational field that works in close collaboration with the life sciences on the quantitative analysis of scientific image data. In many cases, tremendous effort has been spent to package these new advances into usable software tools and, as a result, users can nowadays routinely apply cutting-edge methods to their analysis problems using software tools such as ilastik [1], cellprofiler [2], Fiji/ImageJ2 [3,4] and its many modern plugins that build on the BigDataViewer ecosystem [5], and many others. Such software tools have now become part of a critical infrastructure for science [6]. Unfortunately, overshadowed by the few exceptions that have had long-lasting impact, many other potentially useful tools fail to find their way into the hands of users. While there are many reasons for this, we believe that at least some of the underlying problems, which we discuss in more detail below, can be mitigated. In this opinion piece, we specifically argue that embedding teams of research software engineers (RSEs) within imaging and image analysis core facilities would be a major step towards sustainable bioimage analysis software.Comment: 8 pages, 0 figure

DeepContrast: Deep Tissue Contrast Enhancement using Synthetic Data Degradations and OOD Model Predictions

Microscopy images are crucial for life science research, allowing detailed inspection and characterization of cellular and tissue-level structures and functions. However, microscopy data are unavoidably affected by image degradations, such as noise, blur, or others. Many such degradations also contribute to a loss of image contrast, which becomes especially pronounced in deeper regions of thick samples. Today, best performing methods to increase the quality of images are based on Deep Learning approaches, which typically require ground truth (GT) data during training. Our inability to counteract blurring and contrast loss when imaging deep into samples prevents the acquisition of such clean GT data. The fact that the forward process of blurring and contrast loss deep into tissue can be modeled, allowed us to propose a new method that can circumvent the problem of unobtainable GT data. To this end, we first synthetically degraded the quality of microscopy images even further by using an approximate forward model for deep tissue image degradations. Then we trained a neural network that learned the inverse of this degradation function from our generated pairs of raw and degraded images. We demonstrated that networks trained in this way can be used out-of-distribution (OOD) to improve the quality of less severely degraded images, e.g. the raw data imaged in a microscope. Since the absolute level of degradation in such microscopy images can be stronger than the additional degradation introduced by our forward model, we also explored the effect of iterative predictions. Here, we observed that in each iteration the measured image contrast kept improving while detailed structures in the images got increasingly removed. Therefore, dependent on the desired downstream analysis, a balance between contrast improvement and retention of image details has to be found.Comment: 8 pages, 7 figures, 1 tabl

Efficient Algorithms for Moral Lineage Tracing

Lineage tracing, the joint segmentation and tracking of living cells as they move and divide in a sequence of light microscopy images, is a challenging task. Jug et al. have proposed a mathematical abstraction of this task, the moral lineage tracing problem (MLTP), whose feasible solutions define both a segmentation of every image and a lineage forest of cells. Their branch-and-cut algorithm, however, is prone to many cuts and slow convergence for large instances. To address this problem, we make three contributions: (i) we devise the first efficient primal feasible local search algorithms for the MLTP, (ii) we improve the branch-and-cut algorithm by separating tighter cutting planes and by incorporating our primal algorithms, (iii) we show in experiments that our algorithms find accurate solutions on the problem instances of Jug et al. and scale to larger instances, leveraging moral lineage tracing to practical significance.Comment: Accepted at ICCV 201

A model of functional recovery after significant loss of neural tissue: biofeedback based healing of vestibular dysfunction

ISSN:1471-220

Fully Unsupervised Probabilistic Noise2Void

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.Comment: Accepted at ISBI 202

{\mu}Split: efficient image decomposition for microscopy data

We present {\mu}Split, 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 memory efficient way to train powerful networks and show that LC leads to consistent and significant improvements on the 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 {\mu}Split to five decomposition tasks, one on a synthetic dataset, four others derived from real microscopy data. LC achieves SOTA results (average improvements to the best baseline of 2.36 dB PSNR), while simultaneously requiring considerably less GPU memory.Comment: Published at ICCV 2023. 10 pages, 7 figures, 9 pages supplement, 8 supplementary figure

DenoiSeg: Joint Denoising and Segmentation

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.Comment: 10 pages, 4 figures, 2 pages supplement (4 figures