Cascaded Diffusion Models for 2D and 3D Microscopy Image Synthesis to Enhance Cell Segmentation

Automated cell segmentation in microscopy images is essential for biomedical research, yet conventional methods are labor-intensive and prone to error. While deep learning-based approaches have proven effective, they often require large annotated datasets, which are scarce due to the challenges of manual annotation. To overcome this, we propose a novel framework for synthesizing densely annotated 2D and 3D cell microscopy images using cascaded diffusion models. Our method synthesizes 2D and 3D cell masks from sparse 2D annotations using multi-level diffusion models and NeuS, a 3D surface reconstruction approach. Following that, a pretrained 2D Stable Diffusion model is finetuned to generate realistic cell textures and the final outputs are combined to form cell populations. We show that training a segmentation model with a combination of our synthetic data and real data improves cell segmentation performance by up to 9\% across multiple datasets. Additionally, the FID scores indicate that the synthetic data closely resembles real data. The code for our proposed approach will be available at https://github.com/ruveydayilmaz0/cascaded_diffusion.

Visual Fixation-Based Retinal Prosthetic Simulation

This study proposes a retinal prosthetic simulation framework driven by visual fixations, inspired by the saccade mechanism, and assesses performance improvements through end-to-end optimization in a classification task. Salient patches are predicted from input images using the self-attention map of a vision transformer to mimic visual fixations. These patches are then encoded by a trainable U-Net and simulated using the pulse2percept framework to predict visual percepts. By incorporating a learnable encoder, we aim to optimize the visual information transmitted to the retinal implant, addressing both the limited resolution of the electrode array and the distortion between the input stimuli and resulting phosphenes. The predicted percepts are evaluated using the self-supervised DINOv2 foundation model, with an optional learnable linear layer for classification accuracy. On a subset of the ImageNet validation set, the fixation-based framework achieves a classification accuracy of 87.72%, using computational parameters based on a real subject's physiological data, significantly outperforming the downsampling-based accuracy of 40.59% and approaching the healthy upper bound of 92.76%. Our approach shows promising potential for producing more semantically understandable percepts with the limited resolution available in retinal prosthetics.

Optimizing Retinal Prosthetic Stimuli with Conditional Invertible Neural Networks

Implantable retinal prostheses offer a promising solution to restore partial vision by circumventing damaged photoreceptor cells in the retina and directly stimulating the remaining functional retinal cells. However, the information transmission between the camera and retinal cells is often limited by the low resolution of the electrode array and the lack of specificity for different ganglion cell types, resulting in suboptimal stimulations. In this work, we propose to utilize normalizing flow-based conditional invertible neural networks to optimize retinal implant stimulation in an unsupervised manner. The invertibility of these networks allows us to use them as a surrogate for the computational model of the visual system, while also encoding input camera signals into optimized electrical stimuli on the electrode array. Compared to other methods, such as trivial downsampling, linear models, and feed-forward convolutional neural networks, the flow-based invertible neural network and its conditional extension yield better visual reconstruction qualities w.r.t. various metrics using a physiologically validated simulation tool.

Loss Functions in the Era of Semantic Segmentation: A Survey and Outlook

Semantic image segmentation, the process of classifying each pixel in an image into a particular class, plays an important role in many visual understanding systems. As the predominant criterion for evaluating the performance of statistical models, loss functions are crucial for shaping the development of deep learning-based segmentation algorithms and improving their overall performance. To aid researchers in identifying the optimal loss function for their particular application, this survey provides a comprehensive and unified review of $25$ loss functions utilized in image segmentation. We provide a novel taxonomy and thorough review of how these loss functions are customized and leveraged in image segmentation, with a systematic categorization emphasizing their significant features and applications. Furthermore, to evaluate the efficacy of these methods in real-world scenarios, we propose unbiased evaluations of some distinct and renowned loss functions on established medical and natural image datasets. We conclude this review by identifying current challenges and unveiling future research opportunities. Finally, we have compiled the reviewed studies that have open-source implementations on our GitHub page.

Retinal OCT Synthesis with Denoising Diffusion Probabilistic Models for Layer Segmentation

Modern biomedical image analysis using deep learning often encounters the challenge of limited annotated data. To overcome this issue, deep generative models can be employed to synthesize realistic biomedical images. In this regard, we propose an image synthesis method that utilizes denoising diffusion probabilistic models (DDPMs) to automatically generate retinal optical coherence tomography (OCT) images. By providing rough layer sketches, the trained DDPMs can generate realistic circumpapillary OCT images. We further find that more accurate pseudo labels can be obtained through knowledge adaptation, which greatly benefits the segmentation task. Through this, we observe a consistent improvement in layer segmentation accuracy, which is validated using various neural networks. Furthermore, we have discovered that a layer segmentation model trained solely with synthesized images can achieve comparable results to a model trained exclusively with real images. These findings demonstrate the promising potential of DDPMs in reducing the need for manual annotations of retinal OCT images.

SortedAP: Rethinking evaluation metrics for instance segmentation

Designing metrics for evaluating instance segmentation revolves around comprehensively considering object detection and segmentation accuracy. However, other important properties, such as sensitivity, continuity, and equality, are overlooked in the current study. In this paper, we reveal that most existing metrics have a limited resolution of segmentation quality. They are only conditionally sensitive to the change of masks or false predictions. For certain metrics, the score can change drastically in a narrow range which could provide a misleading indication of the quality gap between results. Therefore, we propose a new metric called sortedAP, which strictly decreases with both object- and pixel-level imperfections and has an uninterrupted penalization scale over the entire domain. We provide the evaluation toolkit and experiment code at https://www.github.com/looooongChen/sortedAP.

Semi-supervised Instance Segmentation with a Learned Shape Prior

To date, most instance segmentation approaches are based on supervised learning that requires a considerable amount of annotated object contours as training ground truth. Here, we propose a framework that searches for the target object based on a shape prior. The shape prior model is learned with a variational autoencoder that requires only a very limited amount of training data: In our experiments, a few dozens of object shape patches from the target dataset, as well as purely synthetic shapes, were sufficient to achieve results en par with supervised methods with full access to training data on two out of three cell segmentation datasets. Our method with a synthetic shape prior was superior to pre-trained supervised models with access to limited domain-specific training data on all three datasets. Since the learning of prior models requires shape patches, whether real or synthetic data, we call this framework semi-supervised learning.

A Deep Learning-based in silico Framework for Optimization on Retinal Prosthetic Stimulation

We propose a neural network-based framework to optimize the perceptions simulated by the in silico retinal implant model pulse2percept. The overall pipeline consists of a trainable encoder, a pre-trained retinal implant model and a pre-trained evaluator. The encoder is a U-Net, which takes the original image and outputs the stimulus. The pre-trained retinal implant model is also a U-Net, which is trained to mimic the biomimetic perceptual model implemented in pulse2percept. The evaluator is a shallow VGG classifier, which is trained with original images. Based on 10,000 test images from the MNIST dataset, we show that the convolutional neural network-based encoder performs significantly better than the trivial downsampling approach, yielding a boost in the weighted F1-Score by 36.17% in the pre-trained classifier with 6x10 electrodes. With this fully neural network-based encoder, the quality of the downstream perceptions can be fine-tuned using gradient descent in an end-to-end fashion.

Instance Segmentation of Dense and Overlapping Objects via Layering

Instance segmentation aims to delineate each individual object of interest in an image. State-of-the-art approaches achieve this goal by either partitioning semantic segmentations or refining coarse representations of detected objects. In this work, we propose a novel approach to solve the problem via object layering, i.e. by distributing crowded, even overlapping objects into different layers. By grouping spatially separated objects in the same layer, instances can be effortlessly isolated by extracting connected components in each layer. In comparison to previous methods, our approach is not affected by complex object shapes or object overlaps. With minimal post-processing, our method yields very competitive results on a diverse line of datasets: C. elegans (BBBC), Overlapping Cervical Cells (OCC) and cultured neuroblastoma cells (CCDB). The source code is publicly available.

Contextual Attention Network: Transformer Meets U-Net

Currently, convolutional neural networks (CNN) (e.g., U-Net) have become the de facto standard and attained immense success in medical image segmentation. However, as a downside, CNN based methods are a double-edged sword as they fail to build long-range dependencies and global context connections due to the limited receptive field that stems from the intrinsic characteristics of the convolution operation. Hence, recent articles have exploited Transformer variants for medical image segmentation tasks which open up great opportunities due to their innate capability of capturing long-range correlations through the attention mechanism. Although being feasibly designed, most of the cohort studies incur prohibitive performance in capturing local information, thereby resulting in less lucidness of boundary areas. In this paper, we propose a contextual attention network to tackle the aforementioned limitations. The proposed method uses the strength of the Transformer module to model the long-range contextual dependency. Simultaneously, it utilizes the CNN encoder to capture local semantic information. In addition, an object-level representation is included to model the regional interaction map. The extracted hierarchical features are then fed to the contextual attention module to adaptively recalibrate the representation space using the local information. Then, they emphasize the informative regions while taking into account the long-range contextual dependency derived by the Transformer module. We validate our method on several large-scale public medical image segmentation datasets and achieve state-of-the-art performance. We have provided the implementation code in https://github.com/rezazad68/TMUnet.