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H. R. Tizhoosh

H. R. Tizhoosh contributes to research discovery and scholarly infrastructure.

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Published work

13 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.