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H. R. Tizhoosh

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Published work

22 published item(s)

preprint2026arXiv

Validation of Whole-Slide Foundation Models for Image Retrieval in TCGA Data

Foundation models are reshaping computational histopathology, yet their value for whole-slide image retrieval relative to strong patch-based and supervised aggregation baselines remains unclear. We benchmarked ten pipelines on 9,387 diagnostic slides spanning 17 organs and 60 diagnoses from The Cancer Genome Atlas (TCGA) using patient-level leave-one-patient-out evaluation. Methods included four pre-trained slide foundation models, a supervised attention-based multiple instance learning (ABMIL) aggregator on patch embeddings, and patch-level retrieval across five sampling densities. Performance varied more across organs and diagnoses than across architectures. Although the slide foundation model TITAN achieved the strongest overall results, its advantage was modest; ABMIL and patch-based methods reached comparable Top-1 and Top-3 accuracy, with no model consistently dominant. Morphologically distinctive entities approached ceiling performance, while rare, heterogeneous, and closely related subtypes remained challenging. Misclassifications aligned with organs exhibiting known inter-observer variability, suggesting an intrinsic ceiling for morphology-only retrieval. Performance was driven primarily by patch-level feature representations, with limited benefit from slide-level aggregation, indicating aggregation may be unnecessary in many settings. These findings argue against a universally optimal architecture and instead support organ-resolved benchmarking, diagnosis-aware or ensemble strategies, stronger feature representations, and multimodal retrieval frameworks. Notably, even the best model achieved only $\approx 68\% \pm 21\%$ retrieval accuracy on TCGA, and some subtypes showed $0\%$ accuracy across all methods, highlighting fundamental limitations of morphology-based representations and the need for substantial progress before reliable clinical deployment.

preprint2022arXiv

Cluster Based Secure Multi-Party Computation in Federated Learning for Histopathology Images

Federated learning (FL) is a decentralized method enabling hospitals to collaboratively learn a model without sharing private patient data for training. In FL, participant hospitals periodically exchange training results rather than training samples with a central server. However, having access to model parameters or gradients can expose private training data samples. To address this challenge, we adopt secure multiparty computation (SMC) to establish a privacy-preserving federated learning framework. In our proposed method, the hospitals are divided into clusters. After local training, each hospital splits its model weights among other hospitals in the same cluster such that no single hospital can retrieve other hospitals' weights on its own. Then, all hospitals sum up the received weights, sending the results to the central server. Finally, the central server aggregates the results, retrieving the average of models' weights and updating the model without having access to individual hospitals' weights. We conduct experiments on a publicly available repository, The Cancer Genome Atlas (TCGA). We compare the performance of the proposed framework with differential privacy and federated averaging as the baseline. The results reveal that compared to differential privacy, our framework can achieve higher accuracy with no privacy leakage risk at a cost of higher communication overhead.

preprint2022arXiv

Hospital-Agnostic Image Representation Learning in Digital Pathology

Whole Slide Images (WSIs) in digital pathology are used to diagnose cancer subtypes. The difference in procedures to acquire WSIs at various trial sites gives rise to variability in the histopathology images, thus making consistent diagnosis challenging. These differences may stem from variability in image acquisition through multi-vendor scanners, variable acquisition parameters, and differences in staining procedure; as well, patient demographics may bias the glass slide batches before image acquisition. These variabilities are assumed to cause a domain shift in the images of different hospitals. It is crucial to overcome this domain shift because an ideal machine-learning model must be able to work on the diverse sources of images, independent of the acquisition center. A domain generalization technique is leveraged in this study to improve the generalization capability of a Deep Neural Network (DNN), to an unseen histopathology image set (i.e., from an unseen hospital/trial site) in the presence of domain shift. According to experimental results, the conventional supervised-learning regime generalizes poorly to data collected from different hospitals. However, the proposed hospital-agnostic learning can improve the generalization considering the low-dimensional latent space representation visualization, and classification accuracy results.

preprint2022arXiv

Learning to Predict RNA Sequence Expressions from Whole Slide Images with Applications for Search and Classification

Deep learning methods are widely applied in digital pathology to address clinical challenges such as prognosis and diagnosis. As one of the most recent applications, deep models have also been used to extract molecular features from whole slide images. Although molecular tests carry rich information, they are often expensive, time-consuming, and require additional tissue to sample. In this paper, we propose tRNAsfomer, an attention-based topology that can learn both to predict the bulk RNA-seq from an image and represent the whole slide image of a glass slide simultaneously. The tRNAsfomer uses multiple instance learning to solve a weakly supervised problem while the pixel-level annotation is not available for an image. We conducted several experiments and achieved better performance and faster convergence in comparison to the state-of-the-art algorithms. The proposed tRNAsfomer can assist as a computational pathology tool to facilitate a new generation of search and classification methods by combining the tissue morphology and the molecular fingerprint of the biopsy samples.

preprint2022arXiv

Monitoring Shortcut Learning using Mutual Information

The failure of deep neural networks to generalize to out-of-distribution data is a well-known problem and raises concerns about the deployment of trained networks in safety-critical domains such as healthcare, finance and autonomous vehicles. We study a particular kind of distribution shift $\unicode{x2013}$ shortcuts or spurious correlations in the training data. Shortcut learning is often only exposed when models are evaluated on real-world data that does not contain the same spurious correlations, posing a serious dilemma for AI practitioners to properly assess the effectiveness of a trained model for real-world applications. In this work, we propose to use the mutual information (MI) between the learned representation and the input as a metric to find where in training, the network latches onto shortcuts. Experiments demonstrate that MI can be used as a domain-agnostic metric for monitoring shortcut learning.

preprint2022arXiv

Offline versus Online Triplet Mining based on Extreme Distances of Histopathology Patches

We analyze the effect of offline and online triplet mining for colorectal cancer (CRC) histopathology dataset containing 100,000 patches. We consider the extreme, i.e., farthest and nearest patches to a given anchor, both in online and offline mining. While many works focus solely on selecting the triplets online (batch-wise), we also study the effect of extreme distances and neighbor patches before training in an offline fashion. We analyze extreme cases' impacts in terms of embedding distance for offline versus online mining, including easy positive, batch semi-hard, batch hard triplet mining, neighborhood component analysis loss, its proxy version, and distance weighted sampling. We also investigate online approaches based on extreme distance and comprehensively compare offline, and online mining performance based on the data patterns and explain offline mining as a tractable generalization of the online mining with large mini-batch size. As well, we discuss the relations of different colorectal tissue types in terms of extreme distances. We found that offline and online mining approaches have comparable performances for a specific architecture, such as ResNet-18 in this study. Moreover, we found the assorted case, including different extreme distances, is promising, especially in the online approach.

preprint2021arXiv

Automatic Multi-Stain Registration of Whole Slide Images in Histopathology

Joint analysis of multiple biomarker images and tissue morphology is important for disease diagnosis, treatment planning and drug development. It requires cross-staining comparison among Whole Slide Images (WSIs) of immuno-histochemical and hematoxylin and eosin (H&E) microscopic slides. However, automatic, and fast cross-staining alignment of enormous gigapixel WSIs at single-cell precision is challenging. In addition to morphological deformations introduced during slide preparation, there are large variations in cell appearance and tissue morphology across different staining. In this paper, we propose a two-step automatic feature-based cross-staining WSI alignment to assist localization of even tiny metastatic foci in the assessment of lymph node. Image pairs were aligned allowing for translation, rotation, and scaling. The registration was performed automatically by first detecting landmarks in both images, using the scale-invariant image transform (SIFT), followed by the fast sample consensus (FSC) protocol for finding point correspondences and finally aligned the images. The Registration results were evaluated using both visual and quantitative criteria using the Jaccard index. The average Jaccard similarity index of the results produced by the proposed system is 0.942 when compared with the manual registration.

preprint2021arXiv

Colored Kimia Path24 Dataset: Configurations and Benchmarks with Deep Embeddings

The Kimia Path24 dataset has been introduced as a classification and retrieval dataset for digital pathology. Although it provides multi-class data, the color information has been neglected in the process of extracting patches. The staining information plays a major role in the recognition of tissue patterns. To address this drawback, we introduce the color version of Kimia Path24 by recreating sample patches from all 24 scans to propose Kimia Path24C. We run extensive experiments to determine the best configuration for selected patches. To provide preliminary results for setting a benchmark for the new dataset, we utilize VGG16, InceptionV3 and DenseNet-121 model as feature extractors. Then, we use these feature vectors to retrieve test patches. The accuracy of image retrieval using DenseNet was 95.92% while the highest accuracy using InceptionV3 and VGG16 reached 92.45% and 92%, respectively. We also experimented with "deep barcodes" and established that with a small loss in accuracy (e.g., 93.43% for binarized features for DenseNet instead of 95.92% when the features themselves are used), the search operations can be significantly accelerated.

preprint2021arXiv

Fine-Tuning and Training of DenseNet for Histopathology Image Representation Using TCGA Diagnostic Slides

Feature vectors provided by pre-trained deep artificial neural networks have become a dominant source for image representation in recent literature. Their contribution to the performance of image analysis can be improved through finetuning. As an ultimate solution, one might even train a deep network from scratch with the domain-relevant images, a highly desirable option which is generally impeded in pathology by lack of labeled images and the computational expense. In this study, we propose a new network, namely KimiaNet, that employs the topology of the DenseNet with four dense blocks, fine-tuned and trained with histopathology images in different configurations. We used more than 240,000 image patches with 1000x1000 pixels acquired at 20x magnification through our proposed "highcellularity mosaic" approach to enable the usage of weak labels of 7,126 whole slide images of formalin-fixed paraffin-embedded human pathology samples publicly available through the The Cancer Genome Atlas (TCGA) repository. We tested KimiaNet using three public datasets, namely TCGA, endometrial cancer images, and colorectal cancer images by evaluating the performance of search and classification when corresponding features of different networks are used for image representation. As well, we designed and trained multiple convolutional batch-normalized ReLU (CBR) networks. The results show that KimiaNet provides superior results compared to the original DenseNet and smaller CBR networks when used as feature extractor to represent histopathology images.

preprint2020arXiv

A Comparative Study of U-Net Topologies for Background Removal in Histopathology Images

During the last decade, the digitization of pathology has gained considerable momentum. Digital pathology offers many advantages including more efficient workflows, easier collaboration as well as a powerful venue for telepathology. At the same time, applying Computer-Aided Diagnosis (CAD) on Whole Slide Images (WSIs) has received substantial attention as a direct result of the digitization. The first step in any image analysis is to extract the tissue. Hence, background removal is an essential prerequisite for efficient and accurate results for many algorithms. In spite of the obvious discrimination for human operators, the identification of tissue regions in WSIs could be challenging for computers, mainly due to the existence of color variations and artifacts. Moreover, some cases such as alveolar tissue types, fatty tissues, and tissues with poor staining are difficult to detect. In this paper, we perform experiments on U-Net architecture with different network backbones (different topologies) to remove the background as well as artifacts from WSIs in order to extract the tissue regions. We compare a wide range of backbone networks including MobileNet, VGG16, EfficientNet-B3, ResNet50, ResNext101 and DenseNet121. We trained and evaluated the network on a manually labeled subset of The Cancer Genome Atlas (TCGA) Dataset. EfficientNet-B3 and MobileNet by almost 99% sensitivity and specificity reached the best results.

preprint2020arXiv

Recognizing Magnification Levels in Microscopic Snapshots

Recent advances in digital imaging has transformed computer vision and machine learning to new tools for analyzing pathology images. This trend could automate some of the tasks in the diagnostic pathology and elevate the pathologist workload. The final step of any cancer diagnosis procedure is performed by the expert pathologist. These experts use microscopes with high level of optical magnification to observe minute characteristics of the tissue acquired through biopsy and fixed on glass slides. Switching between different magnifications, and finding the magnification level at which they identify the presence or absence of malignant tissues is important. As the majority of pathologists still use light microscopy, compared to digital scanners, in many instance a mounted camera on the microscope is used to capture snapshots from significant field-of-views. Repositories of such snapshots usually do not contain the magnification information. In this paper, we extract deep features of the images available on TCGA dataset with known magnification to train a classifier for magnification recognition. We compared the results with LBP, a well-known handcrafted feature extraction method. The proposed approach achieved a mean accuracy of 96% when a multi-layer perceptron was trained as a classifier.

preprint2020arXiv

Supervision and Source Domain Impact on Representation Learning: A Histopathology Case Study

As many algorithms depend on a suitable representation of data, learning unique features is considered a crucial task. Although supervised techniques using deep neural networks have boosted the performance of representation learning, the need for a large set of labeled data limits the application of such methods. As an example, high-quality delineations of regions of interest in the field of pathology is a tedious and time-consuming task due to the large image dimensions. In this work, we explored the performance of a deep neural network and triplet loss in the area of representation learning. We investigated the notion of similarity and dissimilarity in pathology whole-slide images and compared different setups from unsupervised and semi-supervised to supervised learning in our experiments. Additionally, different approaches were tested, applying few-shot learning on two publicly available pathology image datasets. We achieved high accuracy and generalization when the learned representations were applied to two different pathology datasets.

preprint2020arXiv

Weighted Fisher Discriminant Analysis in the Input and Feature Spaces

Fisher Discriminant Analysis (FDA) is a subspace learning method which minimizes and maximizes the intra- and inter-class scatters of data, respectively. Although, in FDA, all the pairs of classes are treated the same way, some classes are closer than the others. Weighted FDA assigns weights to the pairs of classes to address this shortcoming of FDA. In this paper, we propose a cosine-weighted FDA as well as an automatically weighted FDA in which weights are found automatically. We also propose a weighted FDA in the feature space to establish a weighted kernel FDA for both existing and newly proposed weights. Our experiments on the ORL face recognition dataset show the effectiveness of the proposed weighting schemes.

preprint2017arXiv

Retrieving Similar X-Ray Images from Big Image Data Using Radon Barcodes with Single Projections

The idea of Radon barcodes (RBC) has been introduced recently. In this paper, we propose a content-based image retrieval approach for big datasets based on Radon barcodes. Our method (Single Projection Radon Barcode, or SP-RBC) uses only a few Radon single projections for each image as global features that can serve as a basis for weak learners. This is our most important contribution in this work, which improves the results of the RBC considerably. As a matter of fact, only one projection of an image, as short as a single SURF feature vector, can already achieve acceptable results. Nevertheless, using multiple projections in a long vector will not deliver anticipated improvements. To exploit the information inherent in each projection, our method uses the outcome of each projection separately and then applies more precise local search on the small subset of retrieved images. We have tested our method using IRMA 2009 dataset a with 14,400 x-ray images as part of imageCLEF initiative. Our approach leads to a substantial decrease in the error rate in comparison with other non-learning methods.

preprint2016arXiv

Learning Opposites Using Neural Networks

Many research works have successfully extended algorithms such as evolutionary algorithms, reinforcement agents and neural networks using "opposition-based learning" (OBL). Two types of the "opposites" have been defined in the literature, namely \textit{type-I} and \textit{type-II}. The former are linear in nature and applicable to the variable space, hence easy to calculate. On the other hand, type-II opposites capture the "oppositeness" in the output space. In fact, type-I opposites are considered a special case of type-II opposites where inputs and outputs have a linear relationship. However, in many real-world problems, inputs and outputs do in fact exhibit a nonlinear relationship. Therefore, type-II opposites are expected to be better in capturing the sense of "opposition" in terms of the input-output relation. In the absence of any knowledge about the problem at hand, there seems to be no intuitive way to calculate the type-II opposites. In this paper, we introduce an approach to learn type-II opposites from the given inputs and their outputs using the artificial neural networks (ANNs). We first perform \emph{opposition mining} on the sample data, and then use the mined data to learn the relationship between input $x$ and its opposite $\breve{x}$. We have validated our algorithm using various benchmark functions to compare it against an evolving fuzzy inference approach that has been recently introduced. The results show the better performance of a neural approach to learn the opposites. This will create new possibilities for integrating oppositional schemes within existing algorithms promising a potential increase in convergence speed and/or accuracy.

preprint2016arXiv

MinMax Radon Barcodes for Medical Image Retrieval

Content-based medical image retrieval can support diagnostic decisions by clinical experts. Examining similar images may provide clues to the expert to remove uncertainties in his/her final diagnosis. Beyond conventional feature descriptors, binary features in different ways have been recently proposed to encode the image content. A recent proposal is "Radon barcodes" that employ binarized Radon projections to tag/annotate medical images with content-based binary vectors, called barcodes. In this paper, MinMax Radon barcodes are introduced which are superior to "local thresholding" scheme suggested in the literature. Using IRMA dataset with 14,410 x-ray images from 193 different classes, the advantage of using MinMax Radon barcodes over \emph{thresholded} Radon barcodes are demonstrated. The retrieval error for direct search drops by more than 15\%. As well, SURF, as a well-established non-binary approach, and BRISK, as a recent binary method are examined to compare their results with MinMax Radon barcodes when retrieving images from IRMA dataset. The results demonstrate that MinMax Radon barcodes are faster and more accurate when applied on IRMA images.

preprint2016arXiv

Radon Features and Barcodes for Medical Image Retrieval via SVM

For more than two decades, research has been performed on content-based image retrieval (CBIR). By combining Radon projections and the support vector machines (SVM), a content-based medical image retrieval method is presented in this work. The proposed approach employs the normalized Radon projections with corresponding image category labels to build an SVM classifier, and the Radon barcode database which encodes every image in a binary format is also generated simultaneously to tag all images. To retrieve similar images when a query image is given, Radon projections and the barcode of the query image are generated. Subsequently, the k-nearest neighbor search method is applied to find the images with minimum Hamming distance of the Radon barcode within the same class predicted by the trained SVM classifier that uses Radon features. The performance of the proposed method is validated by using the IRMA 2009 dataset with 14,410 x-ray images in 57 categories. The results demonstrate that our method has the capacity to retrieve similar responses for the correctly identified query image and even for those mistakenly classified by SVM. The approach further is very fast and has low memory requirement.

preprint2016arXiv

Radon-Gabor Barcodes for Medical Image Retrieval

In recent years, with the explosion of digital images on the Web, content-based retrieval has emerged as a significant research area. Shapes, textures, edges and segments may play a key role in describing the content of an image. Radon and Gabor transforms are both powerful techniques that have been widely studied to extract shape-texture-based information. The combined Radon-Gabor features may be more robust against scale/rotation variations, presence of noise, and illumination changes. The objective of this paper is to harness the potentials of both Gabor and Radon transforms in order to introduce expressive binary features, called barcodes, for image annotation/tagging tasks. We propose two different techniques: Gabor-of-Radon-Image Barcodes (GRIBCs), and Guided-Radon-of-Gabor Barcodes (GRGBCs). For validation, we employ the IRMA x-ray dataset with 193 classes, containing 12,677 training images and 1,733 test images. A total error score as low as 322 and 330 were achieved for GRGBCs and GRIBCs, respectively. This corresponds to $\approx 81\%$ retrieval accuracy for the first hit.

preprint2016arXiv

Stacked Autoencoders for Medical Image Search

Medical images can be a valuable resource for reliable information to support medical diagnosis. However, the large volume of medical images makes it challenging to retrieve relevant information given a particular scenario. To solve this challenge, content-based image retrieval (CBIR) attempts to characterize images (or image regions) with invariant content information in order to facilitate image search. This work presents a feature extraction technique for medical images using stacked autoencoders, which encode images to binary vectors. The technique is applied to the IRMA dataset, a collection of 14,410 x-ray images in order to demonstrate the ability of autoencoders to retrieve similar x-rays given test queries. Using IRMA dataset as a benchmark, it was found that stacked autoencoders gave excellent results with a retrieval error of 376 for 1,733 test images with a compression of 74.61%.

preprint2015arXiv

Autoencoding the Retrieval Relevance of Medical Images

Content-based image retrieval (CBIR) of medical images is a crucial task that can contribute to a more reliable diagnosis if applied to big data. Recent advances in feature extraction and classification have enormously improved CBIR results for digital images. However, considering the increasing accessibility of big data in medical imaging, we are still in need of reducing both memory requirements and computational expenses of image retrieval systems. This work proposes to exclude the features of image blocks that exhibit a low encoding error when learned by a $n/p/n$ autoencoder ($p\!<\!n$). We examine the histogram of autoendcoding errors of image blocks for each image class to facilitate the decision which image regions, or roughly what percentage of an image perhaps, shall be declared relevant for the retrieval task. This leads to reduction of feature dimensionality and speeds up the retrieval process. To validate the proposed scheme, we employ local binary patterns (LBP) and support vector machines (SVM) which are both well-established approaches in CBIR research community. As well, we use IRMA dataset with 14,410 x-ray images as test data. The results show that the dimensionality of annotated feature vectors can be reduced by up to 50% resulting in speedups greater than 27% at expense of less than 1% decrease in the accuracy of retrieval when validating the precision and recall of the top 20 hits.

preprint2015arXiv

Medical Image Classification via SVM using LBP Features from Saliency-Based Folded Data

Good results on image classification and retrieval using support vector machines (SVM) with local binary patterns (LBPs) as features have been extensively reported in the literature where an entire image is retrieved or classified. In contrast, in medical imaging, not all parts of the image may be equally significant or relevant to the image retrieval application at hand. For instance, in lung x-ray image, the lung region may contain a tumour, hence being highly significant whereas the surrounding area does not contain significant information from medical diagnosis perspective. In this paper, we propose to detect salient regions of images during training and fold the data to reduce the effect of irrelevant regions. As a result, smaller image areas will be used for LBP features calculation and consequently classification by SVM. We use IRMA 2009 dataset with 14,410 x-ray images to verify the performance of the proposed approach. The results demonstrate the benefits of saliency-based folding approach that delivers comparable classification accuracies with state-of-the-art but exhibits lower computational cost and storage requirements, factors highly important for big data analytics.

preprint2015arXiv

Self-Configuring and Evolving Fuzzy Image Thresholding

Every segmentation algorithm has parameters that need to be adjusted in order to achieve good results. Evolving fuzzy systems for adjustment of segmentation parameters have been proposed recently (Evolving fuzzy image segmentation -- EFIS [1]. However, similar to any other algorithm, EFIS too suffers from a few limitations when used in practice. As a major drawback, EFIS depends on detection of the object of interest for feature calculation, a task that is highly application-dependent. In this paper, a new version of EFIS is proposed to overcome these limitations. The new EFIS, called self-configuring EFIS (SC-EFIS), uses available training data to auto-configure the parameters that are fixed in EFIS. As well, the proposed SC-EFIS relies on a feature selection process that does not require the detection of a region of interest (ROI).