Gozde N. Gunesli

Arwa Al-Rubaian, Gozde N. Gunesli, Wajd A. Althakfi et al.

Lung adenocarcinoma is a morphologically heterogeneous disease, characterized by five primary histologic growth patterns. The quantity of these patterns can be related to tumor behavior and has a significant impact on patient prognosis. In this work, we propose a novel machine learning pipeline capable of classifying tissue tiles into one of the five patterns or as non-tumor, with an Area Under the Receiver Operating Characteristic Curve (AUCROC) score of 0.97. Our model's strength lies in its comprehensive consideration of cellular spatial patterns, where it first generates cell maps from Hematoxylin and Eosin (H&E) whole slide images (WSIs), which are then fed into a convolutional neural network classification model. Exploiting these cell maps provides the model with robust generalizability to new data, achieving approximately 30% higher accuracy on unseen test-sets compared to current state of the art approaches. The insights derived from our model can be used to predict prognosis, enhancing patient outcomes.

Arwa Al-Rubaian, Gozde N. Gunesli, Wajd A. Althakfi et al.

Lung adenocarcinoma (LUAD) is a morphologically heterogeneous disease, characterized by five primary histological growth patterns. The classification of such patterns is crucial due to their direct relation to prognosis but the high subjectivity and observer variability pose a major challenge. Although several studies have developed machine learning methods for growth pattern classification, they either only report the predominant pattern per slide or lack proper evaluation. We propose a generalizable machine learning pipeline capable of classifying lung tissue into one of the five patterns or as non-tumor. The proposed pipeline's strength lies in a novel compact Cell Organization Maps (cellOMaps) representation that captures the cellular spatial patterns from Hematoxylin and Eosin whole slide images (WSIs). The proposed pipeline provides state-of-the-art performance on LUAD growth pattern classification when evaluated on both internal unseen slides and external datasets, significantly outperforming the current approaches. In addition, our preliminary results show that the model's outputs can be used to predict patients Tumor Mutational Burden (TMB) levels.

Gozde N. Gunesli, Mohsin Bilal, Shan E Ahmed Raza et al.

Federated learning (FL) enables collaborative learning of a deep learning model without sharing the data of participating sites. FL in medical image analysis tasks is relatively new and open for enhancements. In this study, we propose FedDropoutAvg, a new federated learning approach for training a generalizable model. The proposed method takes advantage of randomness, both in client selection and also in federated averaging process. We compare FedDropoutAvg to several algorithms in an FL scenario for real-world multi-site histopathology image classification task. We show that with FedDropoutAvg, the final model can achieve performance better than other FL approaches and closer to a classical deep learning model that requires all data to be shared for centralized training. We test the trained models on a large dataset consisting of 1.2 million image tiles from 21 different centers. To evaluate the generalization ability of the proposed approach, we use held-out test sets from centers whose data was used in the FL and for unseen data from other independent centers whose data was not used in the federated training. We show that the proposed approach is more generalizable than other state-of-the-art federated training approaches. To the best of our knowledge, ours is the first study to use a randomized client and local model parameter selection procedure in a federated setting for a medical image analysis task.

Can Fahrettin Koyuncu, Gozde Nur Gunesli, Rengul Cetin-Atalay et al.

This paper presents a new deep regression model, which we call DeepDistance, for cell detection in images acquired with inverted microscopy. This model considers cell detection as a task of finding most probable locations that suggest cell centers in an image. It represents this main task with a regression task of learning an inner distance metric. However, different than the previously reported regression based methods, the DeepDistance model proposes to approach its learning as a multi-task regression problem where multiple tasks are learned by using shared feature representations. To this end, it defines a secondary metric, normalized outer distance, to represent a different aspect of the problem and proposes to define its learning as complementary to the main cell detection task. In order to learn these two complementary tasks more effectively, the DeepDistance model designs a fully convolutional network (FCN) with a shared encoder path and end-to-end trains this FCN to concurrently learn the tasks in parallel. DeepDistance uses the inner distances estimated by this FCN in a detection algorithm to locate individual cells in a given image. For further performance improvement on the main task, this paper also presents an extended version of the DeepDistance model. This extended model includes an auxiliary classification task and learns it in parallel to the two regression tasks by sharing feature representations with them. Our experiments on three different human cell lines reveal that the proposed multi-task learning models, the DeepDistance model and its extended version, successfully identify cell locations, even for the cell line that was not used in training, and improve the results of the previous deep learning methods.

Gozde Nur Gunesli, Cenk Sokmensuer, Cigdem Gunduz-Demir

Dense prediction models are widely used for image segmentation. One important challenge is to sufficiently train these models to yield good generalizations for hard-to-learn pixels. A typical group of such hard-to-learn pixels are boundaries between instances. Many studies have proposed to give specific attention to learning the boundary pixels. They include designing multi-task networks with an additional task of boundary prediction and increasing the weights of boundary pixels' predictions in the loss function. Such strategies require defining what to attend beforehand and incorporating this defined attention to the learning model. However, there may exist other groups of hard-to-learn pixels and manually defining and incorporating the appropriate attention for each group may not be feasible. In order to provide a more attainable and scalable solution, this paper proposes AttentionBoost, which is a new multi-attention learning model based on adaptive boosting. AttentionBoost designs a multi-stage network and introduces a new loss adjustment mechanism for a dense prediction model to adaptively learn what to attend at each stage directly on image data without necessitating any prior definition about what to attend. This mechanism modulates the attention of each stage to correct the mistakes of previous stages, by adjusting the loss weight of each pixel prediction separately with respect to how accurate the previous stages are on this pixel. This mechanism enables AttentionBoost to learn different attentions for different pixels at the same stage, according to difficulty of learning these pixels, as well as multiple attentions for the same pixel at different stages, according to confidence of these stages on their predictions for this pixel. Using gland segmentation as a showcase application, our experiments demonstrate that AttentionBoost improves the results of its counterparts.