Morteza Babaie

Sobhan Hemati, Shivam Kalra, Morteza Babaie et al.

Learning suitable Whole slide images (WSIs) representations for efficient retrieval systems is a non-trivial task. The WSI embeddings obtained from current methods are in Euclidean space not ideal for efficient WSI retrieval. Furthermore, most of the current methods require high GPU memory due to the simultaneous processing of multiple sets of patches. To address these challenges, we propose a novel framework for learning binary and sparse WSI representations utilizing a deep generative modelling and the Fisher Vector. We introduce new loss functions for learning sparse and binary permutation-invariant WSI representations that employ instance-based training achieving better memory efficiency. The learned WSI representations are validated on The Cancer Genomic Atlas (TCGA) and Liver-Kidney-Stomach (LKS) datasets. The proposed method outperforms Yottixel (a recent search engine for histopathology images) both in terms of retrieval accuracy and speed. Further, we achieve competitive performance against SOTA on the public benchmark LKS dataset for WSI classification.

Kimia Hemmatirad, Morteza Babaie, Jeffrey Hodgin et al.

Context: Analyzing digital pathology images is necessary to draw diagnostic conclusions by investigating tissue patterns and cellular morphology. However, manual evaluation can be time-consuming, expensive, and prone to inter- and intra-observer variability. Objective: To assist pathologists using computerized solutions, automated tissue structure detection and segmentation must be proposed. Furthermore, generating pixel-level object annotations for histopathology images is expensive and time-consuming. As a result, detection models with bounding box labels may be a feasible solution. Design: This paper studies. YOLO-v4 (You-Only-Look-Once), a real-time object detector for microscopic images. YOLO uses a single neural network to predict several bounding boxes and class probabilities for objects of interest. YOLO can enhance detection performance by training on whole slide images. YOLO-v4 has been used in this paper. for glomeruli detection in human kidney images. Multiple experiments have been designed and conducted based on different training data of two public datasets and a private dataset from the University of Michigan for fine-tuning the model. The model was tested on the private dataset from the University of Michigan, serving as an external validation of two different stains, namely hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS). Results: Average specificity and sensitivity for all experiments, and comparison of existing segmentation methods on the same datasets are discussed. Conclusions: Automated glomeruli detection in human kidney images is possible using modern AI models. The design and validation for different stains still depends on variability of public multi-stain datasets.

Abubakr Shafique, Morteza Babaie, Ricardo Gonzalez et al.

Medical practitioners use a number of diagnostic tests to make a reliable diagnosis. Traditionally, Haematoxylin and Eosin (H&E) stained glass slides have been used for cancer diagnosis and tumor detection. However, recently a variety of immunohistochemistry (IHC) stained slides can be requested by pathologists to examine and confirm diagnoses for determining the subtype of a tumor when this is difficult using H&E slides only. Deep learning (DL) has received a lot of interest recently for image search engines to extract features from tissue regions, which may or may not be the target region for diagnosis. This approach generally fails to capture high-level patterns corresponding to the malignant or abnormal content of histopathology images. In this work, we are proposing a targeted image search approach, inspired by the pathologists workflow, which may use information from multiple IHC biomarker images when available. These IHC images could be aligned, filtered, and merged together to generate a composite biomarker image (CBI) that could eventually be used to generate an attention map to guide the search engine for localized search. In our experiments, we observed that an IHC-guided image search engine can retrieve relevant data more accurately than a conventional (i.e., H&E-only) search engine without IHC guidance. Moreover, such engines are also able to accurately conclude the subtypes through majority votes.

Benyamin Ghojogh, Morteza Babaie

We propose the concepts of philomatics and psychomatics as hybrid combinations of philosophy and psychology with mathematics. We explain four motivations for this combination which are fulfilling the desire of analytical philosophy, proposing science of philosophy, justifying mathematical algorithms by philosophy, and abstraction in both philosophy and mathematics. We enumerate various examples for philomatics and psychomatics, some of which are explained in more depth. The first example is the analysis of relation between the context principle, semantic holism, and the usage theory of meaning with the attention mechanism in mathematics. The other example is on the relations of Plato's theory of forms in philosophy with the holographic principle in string theory, object-oriented programming, and machine learning. Finally, the relation between Wittgenstein's family resemblance and clustering in mathematics is explained. This paper opens the door of research for combining philosophy and psychology with mathematics.

Abubakr Shafique, Morteza Babaie, Ricardo Gonzalez et al.

Immunohistochemistry (IHC) biomarkers are essential tools for reliable cancer diagnosis and subtyping. It requires cross-staining comparison among Whole Slide Images (WSIs) of IHCs and hematoxylin and eosin (H&E) slides. Currently, pathologists examine the visually co-localized areas across IHC and H&E glass slides for a final diagnosis, which is a tedious and challenging task. Moreover, visually inspecting different IHC slides back and forth to analyze local co-expressions is inherently subjective and prone to error, even when carried out by experienced pathologists. Relying on digital pathology, we propose Composite Biomarker Image (CBI) in this work. CBI is a single image that can be composed using different filtered IHC biomarker images for better visualization. We present a CBI image produced in two steps by the proposed solution for better visualization and hence more efficient clinical workflow. In the first step, IHC biomarker images are aligned with the H&E images using one coordinate system and orientation. In the second step, the positive or negative IHC regions from each biomarker image (based on the pathologists recommendation) are filtered and combined into one image using a fuzzy inference system. For evaluation, the resulting CBI images, from the proposed system, were evaluated qualitatively by the expert pathologists. The CBI concept helps the pathologists to identify the suspected target tissues more easily, which could be further assessed by examining the actual WSIs at the same suspected regions.

Abubakr Shafique, Morteza Babaie, Mahjabin Sajadi et al.

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.

Sobhan Shafiei, Morteza Babaie, Shivam Kalra et al.

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.

Danial Maleki, Mehdi Afshari, Morteza Babaie et al.

Due to the recent advancements in machine vision, digital pathology has gained significant attention. Histopathology images are distinctly rich in visual information. The tissue glass slide images are utilized for disease diagnosis. Researchers study many methods to process histopathology images and facilitate fast and reliable diagnosis; therefore, the availability of high-quality slides becomes paramount. The quality of the images can be negatively affected when the glass slides are ink-marked by pathologists to delineate regions of interest. As an example, in one of the largest public histopathology datasets, The Cancer Genome Atlas (TCGA), approximately $12\%$ of the digitized slides are affected by manual delineations through ink markings. To process these open-access slide images and other repositories for the design and validation of new methods, an algorithm to detect the marked regions of the images is essential to avoid confusing tissue pixels with ink-colored pixels for computer methods. In this study, we propose to segment the ink-marked areas of pathology patches through a deep network. A dataset from $79$ whole slide images with $4,305$ patches was created and different networks were trained. Finally, the results showed an FPN model with the EffiecentNet-B3 as the backbone was found to be the superior configuration with an F1 score of $94.53\%$.

Aditya Sriram, Shivam Kalra, Morteza Babaie et al.

In this paper, we propose a novel image descriptor called Forming Local Intersections of Projections (FLIP) and its multi-resolution version (mFLIP) for representing histopathology images. The descriptor is based on the Radon transform wherein we apply parallel projections in small local neighborhoods of gray-level images. Using equidistant projection directions in each window, we extract unique and invariant characteristics of the neighborhood by taking the intersection of adjacent projections. Thereafter, we construct a histogram for each image, which we call the FLIP histogram. Various resolutions provide different FLIP histograms which are then concatenated to form the mFLIP descriptor. Our experiments included training common networks from scratch and fine-tuning pre-trained networks to benchmark our proposed descriptor. Experiments are conducted on the publicly available dataset KIMIA Path24 and KIMIA Path960. For both of these datasets, FLIP and mFLIP descriptors show promising results in all experiments.Using KIMIA Path24 data, FLIP outperformed non-fine-tuned Inception-v3 and fine-tuned VGG16 and mFLIP outperformed fine-tuned Inception-v3 in feature extracting.

Morteza Babaie, Hany Kashani, Meghana D. Kumar et al.

Content-based image retrieval (CBIR) is an essential part of computer vision research, especially in medical expert systems. Having a discriminative image descriptor with the least number of parameters for tuning is desirable in CBIR systems. In this paper, we introduce a new simple descriptor based on the histogram of local Radon projections. We also propose a very fast convolution-based local Radon estimator to overcome the slow process of Radon projections. We performed our experiments using pathology images (KimiaPath24) and lung CT patches and test our proposed solution for medical image processing. We achieved superior results compared with other histogram-based descriptors such as LBP and HoG as well as some pre-trained CNNs.

Manit Zaveri, Shivam Kalra, Morteza Babaie et al.

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.

Shivam Kalra, H. R. Tizhoosh, Sultaan Shah et al.

The emergence of digital pathology has opened new horizons for histopathology and cytology. Artificial-intelligence algorithms are able to operate on digitized slides to assist pathologists with diagnostic tasks. Whereas machine learning involving classification and segmentation methods have obvious benefits for image analysis in pathology, image search represents a fundamental shift in computational pathology. Matching the pathology of new patients with already diagnosed and curated cases offers pathologist a novel approach to improve diagnostic accuracy through visual inspection of similar cases and computational majority vote for consensus building. In this study, we report the results from searching the largest public repository (The Cancer Genome Atlas [TCGA] program by National Cancer Institute, USA) of whole slide images from almost 11,000 patients depicting different types of malignancies. For the first time, we successfully indexed and searched almost 30,000 high-resolution digitized slides constituting 16 terabytes of data comprised of 20 million 1000x1000 pixels image patches. The TCGA image database covers 25 anatomic sites and contains 32 cancer subtypes. High-performance storage and GPU power were employed for experimentation. The results were assessed with conservative "majority voting" to build consensus for subtype diagnosis through vertical search and demonstrated high accuracy values for both frozen sections slides (e.g., bladder urothelial carcinoma 93%, kidney renal clear cell carcinoma 97%, and ovarian serous cystadenocarcinoma 99%) and permanent histopathology slides (e.g., prostate adenocarcinoma 98%, skin cutaneous melanoma 99%, and thymoma 100%). The key finding of this validation study was that computational consensus appears to be possible for rendering diagnoses if a sufficiently large number of searchable cases are available for each cancer subtype.

H. R. Tizhoosh, Shivam Kalra, Shalev Lifshitz et al.

In recent years, artificial neural networks have achieved tremendous success for many vision-based tasks. However, this success remains within the paradigm of \emph{weak AI} where networks, among others, are specialized for just one given task. The path toward \emph{strong AI}, or Artificial General Intelligence, remains rather obscure. One factor, however, is clear, namely that the feed-forward structure of current networks is not a realistic abstraction of the human brain. In this preliminary work, some ideas are proposed to define a \textit{subtractive Perceptron} (s-Perceptron), a graph-based neural network that delivers a more compact topology to learn one specific task. In this preliminary study, we test the s-Perceptron with the MNIST dataset, a commonly used image archive for digit recognition. The proposed network achieves excellent results compared to the benchmark networks that rely on more complex topologies.

Wafa Chenni, Habib Herbi, Morteza Babaie et al.

Whole Slide Imaging (WSI) has become an important topic during the last decade. Even though significant progress in both medical image processing and computational resources has been achieved, there are still problems in WSI that need to be solved. A major challenge is the scan size. The dimensions of digitized tissue samples may exceed 100,000 by 100,000 pixels causing memory and efficiency obstacles for real-time processing. The main contribution of this work is representing a WSI by selecting a small number of patches for algorithmic processing (e.g., indexing and search). As a result, we reduced the search time and storage by various factors between ($50\% - 90\%$), while losing only a few percentages in the patch retrieval accuracy. A self-organizing map (SOM) has been applied on local binary patterns (LBP) and deep features of the KimiaPath24 dataset in order to cluster patches that share the same characteristics. We used a Gaussian mixture model (GMM) to represent each class with a rather small ($10\%-50\%$) portion of patches. The results showed that LBP features can outperform deep features. By selecting only $50\%$ of all patches after SOM clustering and GMM patch selection, we received $65\%$ accuracy for retrieval of the best match, while the maximum accuracy (using all patches) was $69\%$.

Morteza Babaie, H. R. Tizhoosh

Whole slide imaging (WSI) refers to the digitization of a tissue specimen which enables pathologists to explore high-resolution images on a monitor rather than through a microscope. The formation of tissue folds occur during tissue processing. Their presence may not only cause out-of-focus digitization but can also negatively affect the diagnosis in some cases. In this paper, we have compared five pre-trained convolutional neural networks (CNNs) of different depths as feature extractors to characterize tissue folds. We have also explored common classifiers to discriminate folded tissue against the normal tissue in hematoxylin and eosin (H\&E) stained biopsy samples. In our experiments, we manually select the folded area in roughly 2.5mm $\times$ 2.5mm patches at $20$x magnification level as the training data. The ``DenseNet'' with 201 layers alongside an SVM classifier outperformed all other configurations. Based on the leave-one-out validation strategy, we achieved $96.3\%$ accuracy, whereas with augmentation the accuracy increased to $97.2\%$. We have tested the generalization of our method with five unseen WSIs from the NIH (National Cancer Institute) dataset. The accuracy for patch-wise detection was $81\%$. One folded patch within an image suffices to flag the entire specimen for visual inspection.

Dhruv Sharma, Sarim Zafar, Morteza Babaie et al.

Encoded Local Projections (ELP) is a recently introduced dense sampling image descriptor which uses projections in small neighbourhoods to construct a histogram/descriptor for the entire image. ELP has shown to be as accurate as other state-of-the-art features in searching medical images while being time and resource efficient. This paper attempts for the first time to utilize ELP descriptor as primary features for facial recognition and compare the results with LBP histogram on the Labeled Faces in the Wild dataset. We have evaluated descriptors by comparing the chi-squared distance of each image descriptor versus all others as well as training Support Vector Machines (SVM) with each feature vector. In both cases, the results of ELP were better than LBP in the same sub-image configuration.

Meghana Dinesh Kumar, Morteza Babaie, Hamid Tizhoosh

We investigate the concept of deep barcodes and propose two methods to generate them in order to expedite the process of classification and retrieval of histopathology images. Since binary search is computationally less expensive, in terms of both speed and storage, deep barcodes could be useful when dealing with big data retrieval. Our experiments use the dataset Kimia Path24 to test three pre-trained networks for image retrieval. The dataset consists of 27,055 training images in 24 different classes with large variability, and 1,325 test images for testing. Apart from the high-speed and efficiency, results show a surprising retrieval accuracy of 71.62% for deep barcodes, as compared to 68.91% for deep features and 68.53% for compressed deep features.

Morteza Babaie, H. R. Tizhoosh, Amin Khatami et al.

Radon transform and its inverse operation are important techniques in medical imaging tasks. Recently, there has been renewed interest in Radon transform for applications such as content-based medical image retrieval. However, all studies so far have used Radon transform as a global or quasi-global image descriptor by extracting projections of the whole image or large sub-images. This paper attempts to show that the dense sampling to generate the histogram of local Radon projections has a much higher discrimination capability than the global one. In this paper, we introduce Local Radon Descriptor (LRD) and apply it to the IRMA dataset, which contains 14,410 x-ray images as well as to the INRIA Holidays dataset with 1,990 images. Our results show significant improvement in retrieval performance by using LRD versus its global version. We also demonstrate that LRD can deliver results comparable to well-established descriptors like LBP and HOG.

Brady Kieffer, Morteza Babaie, Shivam Kalra et al.

We explore the problem of classification within a medical image data-set based on a feature vector extracted from the deepest layer of pre-trained Convolution Neural Networks. We have used feature vectors from several pre-trained structures, including networks with/without transfer learning to evaluate the performance of pre-trained deep features versus CNNs which have been trained by that specific dataset as well as the impact of transfer learning with a small number of samples. All experiments are done on Kimia Path24 dataset which consists of 27,055 histopathology training patches in 24 tissue texture classes along with 1,325 test patches for evaluation. The result shows that pre-trained networks are quite competitive against training from scratch. As well, fine-tuning does not seem to add any tangible improvement for VGG16 to justify additional training while we observed considerable improvement in retrieval and classification accuracy when we fine-tuned the Inception structure.

Meghana Dinesh Kumar, Morteza Babaie, Shujin Zhu et al.

Despite the progress made in the field of medical imaging, it remains a large area of open research, especially due to the variety of imaging modalities and disease-specific characteristics. This paper is a comparative study describing the potential of using local binary patterns (LBP), deep features and the bag-of-visual words (BoVW) scheme for the classification of histopathological images. We introduce a new dataset, \emph{KIMIA Path960}, that contains 960 histopathology images belonging to 20 different classes (different tissue types). We make this dataset publicly available. The small size of the dataset and its inter- and intra-class variability makes it ideal for initial investigations when comparing image descriptors for search and classification in complex medical imaging cases like histopathology. We investigate deep features, LBP histograms and BoVW to classify the images via leave-one-out validation. The accuracy of image classification obtained using LBP was 90.62\% while the highest accuracy using deep features reached 94.72\%. The dictionary approach (BoVW) achieved 96.50\%. Deep solutions may be able to deliver higher accuracies but they need extensive training with a large number of (balanced) image datasets.

Morteza Babaie, Shivam Kalra, Aditya Sriram et al.

In this paper, we introduce a new dataset, \textbf{Kimia Path24}, for image classification and retrieval in digital pathology. We use the whole scan images of 24 different tissue textures to generate 1,325 test patches of size 1000$\times$1000 (0.5mm$\times$0.5mm). Training data can be generated according to preferences of algorithm designer and can range from approximately 27,000 to over 50,000 patches if the preset parameters are adopted. We propose a compound patch-and-scan accuracy measurement that makes achieving high accuracies quite challenging. In addition, we set the benchmarking line by applying LBP, dictionary approach and convolutional neural nets (CNNs) and report their results. The highest accuracy was 41.80\% for CNN.

Morteza Babaie, H. R. Tizhoosh, Shujin Zhu et al.

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.