Spatial interplay of tissue hypoxia and T-cell regulation in ductal carcinoma in situ.

Hypoxia promotes aggressive tumor phenotypes and mediates the recruitment of suppressive T cells in invasive breast carcinomas. We investigated the role of hypoxia in relation to T-cell regulation in ductal carcinoma in situ (DCIS). We designed a deep learning system tailored for the tissue architecture complexity of DCIS, and compared pure DCIS cases with the synchronous DCIS and invasive components within invasive ductal carcinoma cases. Single-cell classification was applied in tandem with a new method for DCIS ductal segmentation in dual-stained CA9 and FOXP3, whole-tumor section digital pathology images. Pure DCIS typically has an intermediate level of colocalization of FOXP3+ and CA9+ cells, but in invasive carcinoma cases, the FOXP3+ (T-regulatory) cells may have relocated from the DCIS and into the invasive parts of the tumor, leading to high levels of colocalization in the invasive parts but low levels in the synchronous DCIS component. This may be due to invasive, hypoxic tumors evolving to recruit T-regulatory cells in order to evade immune predation. Our data support the notion that hypoxia promotes immune tolerance through recruitment of T-regulatory cells, and furthermore indicate a spatial pattern of relocalization of T-regulatory cells from DCIS to hypoxic tumor cells. Spatial colocalization of hypoxic and T-regulatory cells may be a key event and useful marker of DCIS progression.

Artificial intelligence and digital pathology: Opportunities and implications for immuno-oncology.

The field of immuno-oncology has expanded rapidly over the past decade, but key questions remain. How does tumour-immune interaction regulate disease progression? How can we prospectively identify patients who will benefit from immunotherapy? Identifying measurable features of the tumour immune-microenvironment which have prognostic or predictive value will be key to making meaningful gains in these areas. Recent developments in deep learning enable big-data analysis of pathological samples. Digital approaches allow data to be acquired, integrated and analysed far beyond what is possible with conventional techniques, and to do so efficiently and at scale. This has the potential to reshape what can be achieved in terms of volume, precision and reliability of output, enabling data for large cohorts to be summarised and compared. This review examines applications of artificial intelligence (AI) to important questions in immuno-oncology (IO). We discuss general considerations that need to be taken into account before AI can be applied in any clinical setting. We describe AI methods that have been applied to the field of IO to date and present several examples of their use.

DeepPod: a convolutional neural network based quantification of fruit number in Arabidopsis.

BACKGROUND: High-throughput phenotyping based on non-destructive imaging has great potential in plant biology and breeding programs. However, efficient feature extraction and quantification from image data remains a bottleneck that needs to be addressed. Advances in sensor technology have led to the increasing use of imaging to monitor and measure a range of plants including the model Arabidopsis thaliana. These extensive datasets contain diverse trait information, but feature extraction is often still implemented using approaches requiring substantial manual input. RESULTS: The computational detection and segmentation of individual fruits from images is a challenging task, for which we have developed DeepPod, a patch-based 2-phase deep learning framework. The associated manual annotation task is simple and cost-effective without the need for detailed segmentation or bounding boxes. Convolutional neural networks (CNNs) are used for classifying different parts of the plant inflorescence, including the tip, base, and body of the siliques and the stem inflorescence. In a post-processing step, different parts of the same silique are joined together for silique detection and localization, whilst taking into account possible overlapping among the siliques. The proposed framework is further validated on a separate test dataset of 2,408 images. Comparisons of the CNN-based prediction with manual counting (R2 = 0.90) showed the desired capability of methods for estimating silique number. CONCLUSIONS: The DeepPod framework provides a rapid and accurate estimate of fruit number in a model system widely used by biologists to investigate many fundemental processes underlying growth and reproduction.

Investigating the Performance of Generative Adversarial Networks for Prostate Tissue Detection and Segmentation.

The manual delineation of region of interest (RoI) in 3D magnetic resonance imaging (MRI) of the prostate is time-consuming and subjective. Correct identification of prostate tissue is helpful to define a precise RoI to be used in CAD systems in clinical practice during diagnostic imaging, radiotherapy and monitoring the progress of disease. Conditional GAN (cGAN), cycleGAN and U-Net models and their performances were studied for the detection and segmentation of prostate tissue in 3D multi-parametric MRI scans. These models were trained and evaluated on MRI data from 40 patients with biopsy-proven prostate cancer. Due to the limited amount of available training data, three augmentation schemes were proposed to artificially increase the training samples. These models were tested on a clinical dataset annotated for this study and on a public dataset (PROMISE12). The cGAN model outperformed the U-Net and cycleGAN predictions owing to the inclusion of paired image supervision. Based on our quantitative results, cGAN gained a Dice score of 0.78 and 0.75 on the private and the PROMISE12 public datasets, respectively.

Deep learning in mammography and breast histology, an overview and future trends.

Recent improvements in biomedical image analysis using deep learning based neural networks could be exploited to enhance the performance of Computer Aided Diagnosis (CAD) systems. Considering the importance of breast cancer worldwide and the promising results reported by deep learning based methods in breast imaging, an overview of the recent state-of-the-art deep learning based CAD systems developed for mammography and breast histopathology images is presented. In this study, the relationship between mammography and histopathology phenotypes is described, which takes biological aspects into account. We propose a computer based breast cancer modelling approach: the Mammography-Histology-Phenotype-Linking-Model, which develops a mapping of features/phenotypes between mammographic abnormalities and their histopathological representation. Challenges are discussed along with the potential contribution of such a system to clinical decision making and treatment management.

Manifold learning based registration algorithms applied to multimodal images.

Manifold learning algorithms are proposed to be used in image processing based on their ability in preserving data structures while reducing the dimension and the exposure of data structure in lower dimension. Multi-modal images have the same structure and can be registered together as monomodal images if only structural information is shown. As a result, manifold learning is able to transform multi-modal images to mono-modal ones and subsequently do the registration using mono-modal methods. Based on this application, in this paper novel similarity measures are proposed for multi-modal images in which Laplacian eigenmaps are employed as manifold learning algorithm and are tested against rigid registration of PET/MR images. Results show the feasibility of using manifold learning as a way of calculating the similarity between multimodal images.