Balancing Privacy and Progress in Artificial Intelligence: Anonymization in Histopathology for Biomedical Research and Education

The advancement of biomedical research heavily relies on access to large amounts of medical data. In the case of histopathology, Whole Slide Images (WSI) and clinicopathological information are valuable for developing Artificial Intelligence (AI) algorithms for Digital Pathology (DP). Transferring medical data "as open as possible" enhances the usability of the data for secondary purposes but poses a risk to patient privacy. At the same time, existing regulations push towards keeping medical data "as closed as necessary" to avoid re-identification risks. Generally, these legal regulations require the removal of sensitive data but do not consider the possibility of data linkage attacks due to modern image-matching algorithms. In addition, the lack of standardization in DP makes it harder to establish a single solution for all formats of WSIs. These challenges raise problems for bio-informatics researchers in balancing privacy and progress while developing AI algorithms. This paper explores the legal regulations and terminologies for medical data-sharing. We review existing approaches and highlight challenges from the histopathological perspective. We also present a data-sharing guideline for histological data to foster multidisciplinary research and education.

Vision Transformers for Small Histological Datasets Learned through Knowledge Distillation

Computational Pathology (CPATH) systems have the potential to automate diagnostic tasks. However, the artifacts on the digitized histological glass slides, known as Whole Slide Images (WSIs), may hamper the overall performance of CPATH systems. Deep Learning (DL) models such as Vision Transformers (ViTs) may detect and exclude artifacts before running the diagnostic algorithm. A simple way to develop robust and generalized ViTs is to train them on massive datasets. Unfortunately, acquiring large medical datasets is expensive and inconvenient, prompting the need for a generalized artifact detection method for WSIs. In this paper, we present a student-teacher recipe to improve the classification performance of ViT for the air bubbles detection task. ViT, trained under the student-teacher framework, boosts its performance by distilling existing knowledge from the high-capacity teacher model. Our best-performing ViT yields 0.961 and 0.911 F1-score and MCC, respectively, observing a 7% gain in MCC against stand-alone training. The proposed method presents a new perspective of leveraging knowledge distillation over transfer learning to encourage the use of customized transformers for efficient preprocessing pipelines in the CPATH systems.

Self-supervised learning of a tailored Convolutional Auto Encoder for histopathological prostate grading

According to GLOBOCAN 2020, prostate cancer is the second most common cancer in men worldwide and the fourth most prevalent cancer overall. For pathologists, grading prostate cancer is challenging, especially when discriminating between Grade 3 (G3) and Grade 4 (G4). This paper proposes a Self-Supervised Learning (SSL) framework to classify prostate histopathological images when labeled images are scarce. In particular, a tailored Convolutional Auto Encoder (CAE) is trained to reconstruct 128x128x3 patches of prostate cancer Whole Slide Images (WSIs) as a pretext task. The downstream task of the proposed SSL paradigm is the automatic grading of histopathological patches of prostate cancer. The presented framework reports promising results on the validation set, obtaining an overall accuracy of 83% and on the test set, achieving an overall accuracy value of 76% with F1-score of 77% in G4.

Self-Supervised Few-Shot Learning for Ischemic Stroke Lesion Segmentation

Precise ischemic lesion segmentation plays an essential role in improving diagnosis and treatment planning for ischemic stroke, one of the prevalent diseases with the highest mortality rate. While numerous deep neural network approaches have recently been proposed to tackle this problem, these methods require large amounts of annotated regions during training, which can be impractical in the medical domain where annotated data is scarce. As a remedy, we present a prototypical few-shot segmentation approach for ischemic lesion segmentation using only one annotated sample during training. The proposed approach leverages a novel self-supervised training mechanism that is tailored to the task of ischemic stroke lesion segmentation by exploiting color-coded parametric maps generated from Computed Tomography Perfusion scans. We illustrate the benefits of our proposed training mechanism, leading to considerable improvements in performance in the few-shot setting. Given a single annotated patient, an average Dice score of 0.58 is achieved for the segmentation of ischemic lesions.

Exploiting 4D CT Perfusion for segmenting infarcted areas in patients with suspected acute ischemic stroke

Precise and fast prediction methods for ischemic areas (core and penumbra) in acute ischemic stroke (AIS) patients are of significant clinical interest: they play an essential role in improving diagnosis and treatment planning. Computed Tomography (CT) scan is one of the primary modalities for early assessment in patients with suspected AIS. CT Perfusion (CTP) is often used as a primary assessment to determine stroke location, severity, and volume of ischemic lesions. Current automatic segmentation methods for CTP mostly use already processed 3D color maps conventionally used for visual assessment by radiologists as input. Alternatively, the raw CTP data is used on a slice-by-slice basis as 2D+time input, where the spatial information over the volume is ignored. In this paper, we investigate different methods to utilize the entire 4D CTP as input to fully exploit the spatio-temporal information. This leads us to propose a novel 4D convolution layer. Our comprehensive experiments on a local dataset comprised of 152 patients divided into three groups show that our proposed models generate more precise results than other methods explored. A Dice Coefficient of 0.70 and 0.45 is achieved for penumbra and core areas, respectively. The code is available on https://github.com/Biomedical-Data-Analysis-Laboratory/4D-mJ-Net.git.

Object Detection During Newborn Resuscitation Activities

Birth asphyxia is a major newborn mortality problem in low-resource countries. International guideline provides treatment recommendations; however, the importance and effect of the different treatments are not fully explored. The available data is collected in Tanzania, during newborn resuscitation, for analysis of the resuscitation activities and the response of the newborn. An important step in the analysis is to create activity timelines of the episodes, where activities include ventilation, suction, stimulation etc. Methods: The available recordings are noisy real-world videos with large variations. We propose a two-step process in order to detect activities possibly overlapping in time. The first step is to detect and track the relevant objects, like bag-mask resuscitator, heart rate sensors etc., and the second step is to use this information to recognize the resuscitation activities. The topic of this paper is the first step, and the object detection and tracking are based on convolutional neural networks followed by post processing. Results: The performance of the object detection during activities were 96.97 % (ventilations), 100 % (attaching/removing heart rate sensor) and 75 % (suction) on a test set of 20 videos. The system also estimate the number of health care providers present with a performance of 71.16 %. Conclusion: The proposed object detection and tracking system provides promising results in noisy newborn resuscitation videos. Significance: This is the first step in a thorough analysis of newborn resuscitation episodes, which could provide important insight about the importance and effect of different newborn resuscitation activities

Activity Recognition From Newborn Resuscitation Videos

Objective: Birth asphyxia is one of the leading causes of neonatal deaths. A key for survival is performing immediate and continuous quality newborn resuscitation. A dataset of recorded signals during newborn resuscitation, including videos, has been collected in Haydom, Tanzania, and the aim is to analyze the treatment and its effect on the newborn outcome. An important step is to generate timelines of relevant resuscitation activities, including ventilation, stimulation, suction, etc., during the resuscitation episodes. Methods: We propose a two-step deep neural network system, ORAA-net, utilizing low-quality video recordings of resuscitation episodes to do activity recognition during newborn resuscitation. The first step is to detect and track relevant objects using Convolutional Neural Networks (CNN) and post-processing, and the second step is to analyze the proposed activity regions from step 1 to do activity recognition using 3D CNNs. Results: The system recognized the activities newborn uncovered, stimulation, ventilation and suction with a mean precision of 77.67 %, a mean recall of 77,64 %, and a mean accuracy of 92.40 %. Moreover, the accuracy of the estimated number of Health Care Providers (HCPs) present during the resuscitation episodes was 68.32 %. Conclusion: The results indicate that the proposed CNN-based two-step ORAAnet could be used for object detection and activity recognition in noisy low-quality newborn resuscitation videos. Significance: A thorough analysis of the effect the different resuscitation activities have on the newborn outcome could potentially allow us to optimize treatment guidelines, training, debriefing, and local quality improvement in newborn resuscitation.

Deep Learning for Predicting Metastasis on Melanoma WSIs

Northern Europe has the second highest mortality rate of melanoma globally. In 2020, the mortality rate of melanoma rose to 1.9 per 100 000 habitants. Melanoma prognosis is based on a pathologist's subjective visual analysis of the patient's tumor. This methodology is heavily time-consuming, and the prognosis variability among experts is notable, drastically jeopardizing its reproducibility. Thus, the need for faster and more reproducible methods arises. Machine learning has paved its way into digital pathology, but so far, most contributions are on localization, segmentation, and diagnostics, with little emphasis on prognostics. This paper presents a convolutional neural network (CNN) method based on VGG16 to predict melanoma prognosis as the presence of metastasis within five years. Patches are extracted from regions of interest from Whole Slide Images (WSIs) at different magnification levels used in model training and validation. Results infer that utilizing WSI patches at 20x magnification level has the best performance, with an F1 score of 0.7667 and an AUC of 0.81.

Active Learning Based Domain Adaptation for Tissue Segmentation of Histopathological Images

Accurate segmentation of tissue in histopathological images can be very beneficial for defining regions of interest (ROI) for streamline of diagnostic and prognostic tasks. Still, adapting to different domains is essential for histopathology image analysis, as the visual characteristics of tissues can vary significantly across datasets. Yet, acquiring sufficient annotated data in the medical domain is cumbersome and time-consuming. The labeling effort can be significantly reduced by leveraging active learning, which enables the selective annotation of the most informative samples. Our proposed method allows for fine-tuning a pre-trained deep neural network using a small set of labeled data from the target domain, while also actively selecting the most informative samples to label next. We demonstrate that our approach performs with significantly fewer labeled samples compared to traditional supervised learning approaches for similar F1-scores, using barely a 59\% of the training set. We also investigate the distribution of class balance to establish annotation guidelines.

Detection and Localization of Melanoma Skin Cancer in Histopathological Whole Slide Images

Melanoma diagnosed and treated in its early stages can increase the survival rate. A projected increase in skin cancer incidents and a dearth of dermatopathologists have emphasized the need for computational pathology (CPATH) systems. CPATH systems with deep learning (DL) models have the potential to identify the presence of melanoma by exploiting underlying morphological and cellular features. This paper proposes a DL method to detect melanoma and distinguish between normal skin and benign/malignant melanocytic lesions in Whole Slide Images (WSI). Our method detects lesions with high accuracy and localizes them on a WSI to identify potential regions of interest for pathologists. Interestingly, our DL method relies on using a single CNN network to create localization maps first and use them to perform slide-level predictions to determine patients who have melanoma. Our best model provides favorable patch-wise classification results with a 0.992 F1 score and 0.99 sensitivity on unseen data. The source code is https://github.com/RogerAmundsen/Melanoma-Diagnosis-and-Localization-from-Whole-Slide-Images-using-Convolutional-Neural-Networks.