Spatial transcriptomics (ST) is a novel technology that enables the observation of gene expression at the resolution of individual spots within pathological tissues. ST quantifies the expression of tens of thousands of genes in a tissue section; however, heavy observational noise is often introduced during measurement. In prior studies, to ensure meaningful assessment, both training and evaluation have been restricted to only a small subset of highly variable genes, and genes outside this subset have also been excluded from the training process. However, since there are likely co-expression relationships between genes, low-expression genes may still contribute to the estimation of the evaluation target. In this paper, we propose Auxiliary Gene Learning (AGL) that utilizes the benefit of the ignored genes by reformulating their expression estimation as auxiliary tasks and training them jointly with the primary tasks. To effectively leverage auxiliary genes, we must select a subset of auxiliary genes that positively influence the prediction of the target genes. However, this is a challenging optimization problem due to the vast number of possible combinations. To overcome this challenge, we propose Prior-Knowledge-Based Differentiable Top-k Gene Selection via Bi-level Optimization (DkGSB), a method that ranks genes by leveraging prior knowledge and relaxes the combinatorial selection problem into a differentiable top-k selection problem. The experiments confirm the effectiveness of incorporating auxiliary genes and show that the proposed method outperforms conventional auxiliary task learning approaches.

Active learning (AL) is a label-efficient machine learning paradigm that focuses on selectively annotating high-value instances to maximize learning efficiency. Its effectiveness can be further enhanced by incorporating weak supervision, which uses rough yet cost-effective annotations instead of exact (i.e., full) but expensive annotations. We introduce a novel AL framework, Instance-wise Supervision-Level Optimization (ISO), which not only selects the instances to annotate but also determines their optimal annotation level within a fixed annotation budget. Its optimization criterion leverages the value-to-cost ratio (VCR) of each instance while ensuring diversity among the selected instances. In classification experiments, ISO consistently outperforms traditional AL methods and surpasses a state-of-the-art AL approach that combines full and weak supervision, achieving higher accuracy at a lower overall cost. This code is available at https://github.com/matsuo-shinnosuke/ISOAL.

Domain shift is a significant challenge in machine learning, particularly in medical applications where data distributions differ across institutions due to variations in data collection practices, equipment, and procedures. This can degrade performance when models trained on source domain data are applied to the target domain. Domain adaptation methods have been widely studied to address this issue, but most struggle when class proportions between the source and target domains differ. In this paper, we propose a weakly-supervised domain adaptation method that leverages class proportion information from the target domain, which is often accessible in medical datasets through prior knowledge or statistical reports. Our method assigns pseudo-labels to the unlabeled target data based on class proportion (called proportion-constrained pseudo-labeling), improving performance without the need for additional annotations. Experiments on two endoscopic datasets demonstrate that our method outperforms semi-supervised domain adaptation techniques, even when 5% of the target domain is labeled. Additionally, the experimental results with noisy proportion labels highlight the robustness of our method, further demonstrating its effectiveness in real-world application scenarios.

Gene expression estimation from pathology images has the potential to reduce the RNA sequencing cost. Point-wise loss functions have been widely used to minimize the discrepancy between predicted and absolute gene expression values. However, due to the complexity of the sequencing techniques and intrinsic variability across cells, the observed gene expression contains stochastic noise and batch effects, and estimating the absolute expression values accurately remains a significant challenge. To mitigate this, we propose a novel objective of learning relative expression patterns rather than absolute levels. We assume that the relative expression levels of genes exhibit consistent patterns across independent experiments, even when absolute expression values are affected by batch effects and stochastic noise in tissue samples. Based on the assumption, we model the relation and propose a novel loss function called STRank that is robust to noise and batch effects. Experiments using synthetic datasets and real datasets demonstrate the effectiveness of the proposed method. The code is available at https://github.com/naivete5656/STRank.

Patient-level diagnosis of severity in ulcerative colitis (UC) is common in clinical practice, where the most severe score for a patient is typically recorded as the diagnosis result. However, previous UC classification methods (i.e., image-level estimation) mainly assumed the input was a single image. Thus, these methods can not utilize severity labels recorded in real clinical settings. In this paper, we propose a patient-level severity estimation method by a transformer with selective aggregator tokens, where a severity label is estimated from multiple images taken from a patient, similar to a clinical setting. Our method can effectively aggregate features of severe parts from a set of images captured in each patient, and it facilitates improving the discriminative ability between adjacent severity classes. Experiments demonstrate the effectiveness of the proposed method on two datasets compared with the state-of-the-art MIL methods. Moreover, we evaluated our method using real clinical data and confirmed that our method outperformed the previous image-level methods. The code is publicly available at https://github.com/Shiku-Kaito/Ordinal-Multiple-instance-Learning-for-Ulcerative-Colitis-Severity-Estimation.

Learning from label proportions (LLP) is a kind of weakly supervised learning that trains an instance-level classifier from label proportions of bags, which consist of sets of instances without using instance labels. A challenge in LLP arises when the number of instances in a bag (bag size) is numerous, making the traditional LLP methods difficult due to GPU memory limitations. This study aims to develop an LLP method capable of learning from bags with large sizes. In our method, smaller bags (mini-bags) are generated by sampling instances from large-sized bags (original bags), and these mini-bags are used in place of the original bags. However, the proportion of a mini-bag is unknown and differs from that of the original bag, leading to overfitting. To address this issue, we propose a perturbation method for the proportion labels of sampled mini-bags to mitigate overfitting to noisy label proportions. This perturbation is added based on the multivariate hypergeometric distribution, which is statistically modeled. Additionally, loss weighting is implemented to reduce the negative impact of proportions sampled from the tail of the distribution. Experimental results demonstrate that the proportion label perturbation and loss weighting achieve classification accuracy comparable to that obtained without sampling. Our codes are available at https://github.com/stainlessnight/LLP-LargeBags.

The paper proposes a novel problem in multi-class Multiple-Instance Learning (MIL) called Learning from the Majority Label (LML). In LML, the majority class of instances in a bag is assigned as the bag’s label. LML aims to classify instances using bag-level majority classes. This problem is valuable in various applications. Existing MIL methods are unsuitable for LML due to aggregating confidences, which may lead to inconsistency between the bag-level label and the label obtained by counting the number of instances for each class. This may lead to incorrect instance-level classification. We propose a counting network trained to produce the bag-level majority labels estimated by counting the number of instances for each class. This led to the consistency of the majority class between the network outputs and one obtained by counting the number of instances. Experimental results show that our counting network outperforms conventional MIL methods on four datasets1.

Medical image segmentation is an important task in medical imaging and diagnosis. Data augmentation can substantially improve the accuracy of medical image segmentation when the dataset has a small amount of medical images. However, the data augmentation methods for medical image are usually based on big models that require extensive search space. Furthermore, excessively complex models often have a heavy burden for the general healthcare organization or researcher. To address this problem, we propose a method of data augmentation that is simple to implement even for the general researcher and simple to transplant across various models. Here we introduce our new methods called KeepMask and KeepMix, which can be simply ported to a variety of models and provide high performance. These methods allow data augmentation without any effect on the target organ or lesion and can also be adapted to multi-class segmentation. KeepMask and KeepMix can not only perturb the background of an existing medical image but also add target organs that are not present to it and generate new images based on the image. In this paper, we performed our methods on both binary class datasets and multi-class datasets and obtained better performance. We conducted numerous experiments showing the predicted segmentation images using our proposed methods obtained more accurate boundaries.

This paper proposes a novel and efficient method for Learning from Label Proportions (LLP), whose goal is to train a classifier only by using the class label proportions of instance sets, called bags. We propose a novel LLP method based on an online pseudo-labeling method with regret minimization. As opposed to the previous LLP methods, the proposed method effectively works even if the bag sizes are large. We demonstrate the effectiveness of the proposed method using some benchmark datasets.

Learning from label proportions (LLP) is a promising weakly supervised learning problem. In LLP, a set of instances (bag) has label proportions, but no instance-level labels are given. LLP aims to train an instance-level classifier by using the label proportions of the bag. In this paper, we propose a bag-level data augmentation method for LLP called MixBag, based on the key observation from our preliminary experiments; that the instance-level classification accuracy improves as the number of labeled bags increases even though the total number of instances is fixed. We also propose a confidence interval loss designed based on statistical theory to use the augmented bags effectively. To the best of our knowledge, this is the first attempt to propose bag-level data augmentation for LLP. The advantage of MixBag is that it can be applied to instance-level data augmentation techniques and any LLP method that uses the proportion loss. Experimental results demonstrate this advantage and the effectiveness of our method.

Drone crowd tracking has various applications such as crowd management and video surveillance. Unlike in general multi-object tracking, the size of the objects to be tracked are small, and the ground truth is given by a point-level annotation, which has no region information. This causes the lack of discriminative features for finding the same objects from many similar objects. Thus, similarity-based tracking techniques, which are widely used for multi-object tracking with bounding-box, are difficult to use. To deal with this problem, we take into account the temporal context of the local area. To aggregate temporal context in a local area, we propose a multi-frame attention with feature-level warping. The feature-level warping can align the features of the same object in multiple frames, and then multi-frame attention can effectively aggregate the temporal context from the warped features. The experimental results show the effectiveness of our method. Our method outperformed the state-of-the-art method in DroneCrowd dataset. The code is publicly available in https://github.com/asanomitakanori/mfa-feature-warping.

Cell instance segmentation that recognizes each cell boundary is an important task in cell image analysis. While deep learning-based methods have shown promising performances with a certain amount of training data, most of them require full annotations that show the boundary of each cell. Generating the annotation for cell segmentation is time-consuming and human labor. To reduce the annotation cost, we propose a weakly supervised segmentation method using two types of weak labels (one for cell type and one for nuclei position). Unlike general images, these two labels are easily obtained in phase-contrast images. The intercellular boundary, which is necessary for cell instance segmentation, cannot be directly obtained from these two weak labels, so to generate the boundary information, we propose a single instance pasting based on the copy-and-paste technique. First, we locate single-cell regions by counting cells and store them in a pool. Then, we generate the intercel-lular boundary by pasting the stored single-cell regions to the original image. Finally, we train a boundary estimation network with the generated labels and perform instance segmentation with the network. Our evaluation on a public dataset demonstrated that the proposed method achieves the best performance among the several weakly supervised methods we compared.

Multi-object tracking is essential in biomedical image analysis. Most methods follow a tracking-by-detection approach that involves using object detectors and learning the appearance feature models of the detected regions for association. Although these methods can learn the appearance similarity features to identify the same objects among frames, they have difficulties identifying the same cells because cells have a similar appearance and their shapes change as they migrate. In addition, cells often partially overlap for several frames. In this case, even an expert biologist would require knowledge of the spatial-temporal context in order to identify individual cells. To tackle such difficult situations, we propose a cell-tracking method that can effectively use the spatial-temporal context in multiple frames by using long-term motion estimation and an object-level warping loss. We conducted experiments showing that the proposed method outperformed state-of-the-art methods under various conditions on real biological images.

Recognizing wet surfaces and their degrees of wetness is essential for many computer vision applications. Surface wetness can inform us slippery spots on a road to autonomous vehicles, muddy areas of a trail to humanoid robots, and the freshness of groceries to us. The fact that surfaces darken when wet, i.e., monochromatic appearance change, has been modeled to recognize wet surfaces in the past. In this paper, we show that color change, particularly in its spectral behavior, carries rich information about surface wetness. We first derive an analytical spectral appearance model of wet surfaces that expresses the characteristic spectral sharpening due to multiple scattering and absorption in the surface. We present a novel method for estimating key parameters of this spectral appearance model, which enables the recovery of the original surface color and the degree of wetness from a single multispectral image. Applied to a multispectral image, the method estimates the spatial map of wetness together with the dry spectral distribution of the surface. To our knowledge, this is the first work to model and leverage the spectral characteristics of wet surfaces to decipher its appearance. We conduct comprehensive experimental validation with a number of wet real surfaces. The results demonstrate the accuracy of our model and the effectiveness of our method for surface wetness and color estimation.

Conventional cell tracking methods detect multiple cells in each frame (detection) and then associate the detection results in successive time-frames (association). Most cell tracking methods perform the association task independently from the detection task. However, there is no guarantee of preserving coherence between these tasks, and lack of coherence may adversely affect tracking performance. In this paper, we propose the Motion and Position Map (MPM) that jointly represents both detection and association for not only migration but also cell division. It guarantees coherence such that if a cell is detected, the corresponding motion flow can always be obtained. It is a simple but powerful method for multi-object tracking in dense environments. We compared the proposed method with current tracking methods under various conditions in real biological images and found that it outperformed the state-of-the-art (+5.2% improvement compared to the second-best).

Automated digital histopathology image segmentation is an important task to help pathologists diagnose tumors and cancer subtypes. For pathological diagnosis of cancer subtypes, pathologists usually change the magnification of whole-slide images (WSI) viewers. A key assumption is that the importance of the magnifications depends on the characteristics of the input image, such as cancer subtypes. In this paper, we propose a novel semantic segmentation method, called Adaptive-Weighting-Multi-Field-of-View-CNN (AWMF-CNN), that can adaptively use image features from images with different magnifications to segment multiple cancer subtype regions in the input image. The proposed method aggregates several expert CNNs for images of different magnifications by adaptively changing the weight of each expert depending on the input image. It leverages information in the images with different magnifications that might be useful for identifying the subtypes. It outperformed other state-of-the-art methods in experiments.

Visual recognition of wet surfaces and their degrees of wetness is important for many computer vision applications. It can inform slippery spots on a road to autonomous vehicles, muddy areas of a trail to humanoid robots, and the freshness of groceries to us. In the past, monochromatic appearance change, the fact that surfaces darken when wet, has been modeled to recognize wet surfaces. In this paper, we show that color change, particularly in its spectral behavior, carries rich information about a wet surface. We derive an analytical spectral appearance model of wet surfaces that expresses the characteristic spectral sharpening due to multiple scattering and absorption in the surface. We derive a novel method for estimating key parameters of this spectral appearance model, which enables the recovery of the original surface color and the degree of wetness from a single observation. Applied to a multispectral image, the method estimates the spatial map of wetness together with the dry spectral distribution of the surface. To our knowledge, this work is the first to model and leverage the spectral characteristics of wet surfaces to revert its appearance. We conduct comprehensive experimental validation with a number of wet real surfaces. The results demonstrate the accuracy of our model and the effectiveness of our method for surface wetness and color estimation.

Photoacoustic (PA) imaging has been gaining attention as a new imaging modality that can non-invasively visualize blood vessels inside biological tissues. In the process of imaging large body parts through multi-scan fusion, alignment turns out to be an important issue, since body motion degrades image quality. In this paper, we carefully examine the characteristics of PA images and propose a novel registration method that achieves better alignment while effectively decomposing the shot volumes into low-rank foreground (blood vessels), dense background (noise), and sparse complement (corruption) components on the basis of the PA characteristics. The results of experiments using a challenging real data-set demonstrate the efficacy of the proposed method, which significantly improved image quality, and had the best alignment accuracy among the state-of-the-art methods tested. These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Cell detection in microscopy images is essential for automated cell behavior analysis including cell shape analysis and cell tracking. Robust cell detection in high-density and low-contrast images is still challenging since cells often touch and partially overlap, forming a cell cluster with blurry intercellular boundaries. In such cases, current methods tend to detect multiple cells as a cluster. If the control parameters are adjusted to separate the touching cells, other problems often occur: a single cell may be segmented into several regions, and cells in low-intensity regions may not be detected. To solve these problems, we first detect redundant candidate regions, which include many false positives but in turn very few false negatives, by allowing candidate regions to overlap with each other. Next, the score for how likely the candidate region contains the main part of a single cell is computed for each cell candidate using supervised learning. Then we select an optimal set of cell regions from the redundant regions under nonoverlapping constraints, where each selected region looks like a single cell and the selected regions do not overlap. We formulate this problem of optimal region selection as a binary linear programming problem under nonoverlapping constraints. We demonstrated the effectiveness of our method for several types of cells in microscopy images. Our method performed better than five representative methods, achieving an F-measure of over 0.9 for all data sets. Experimental application of the proposed method to 3-D images demonstrated that also works well for 3-D cell detection.

We present several algorithms for cell image analysis including microscopy image restoration, cell event detection and cell tracking in a large population. The algorithms are integrated into an automated system capable of quantifying cell proliferation metrics in vitro in real-time. This offers unique opportunities for biological applications such as efficient cell behavior discovery in response to different cell culturing conditions and adaptive experiment control. We quantitatively evaluated our system's performance on 16 microscopy image sequences with satisfactory accuracy for biologists' need. We have also developed a public website compatible to the system's local user interface, thereby allowing biologists to conveniently check their experiment progress online. The website will serve as a community resource that allows other research groups to upload their cell images for analysis and comparison.

Due to the enormous potential and impact that stem cells may have on regenerative medicine, there has been a rapidly growing interest for tools to analyze and characterize the behaviors of these cells in vitro in an automated and high throughput fashion. Among these behaviors, mitosis, or cell division, is important since stem cells proliferate and renew themselves through mitosis. However, current automated systems for measuring cell proliferation often require destructive or sacrificial methods of cell manipulation such as cell lysis or in vitro staining. In this paper, we propose an effective approach for automated mitosis detection using phase-contrast time-lapse microscopy, which is a nondestructive imaging modality, thereby allowing continuous monitoring of cells in culture. In our approach, we present a probabilistic model for event detection, which can simultaneously 1) identify spatio-temporal patch sequences that contain a mitotic event and 2) localize a birth event, defined as the time and location at which cell division is completed and two daughter cells are born. Our approach significantly outperforms previous approaches in terms of both detection accuracy and computational efficiency, when applied to multipotent C3H10T1/2 mesenchymal and C2C12 myoblastic stem cell populations.