Colorectal cancer diagnosis from histology images: A comparative study

Computer-aided diagnosis (CAD) based on histopathological imaging has progressed rapidly in recent years with the rise of machine learning based methodologies. Traditional approaches consist of training a classification model using features extracted from the images, based on textures or morphological properties. Recently, deep-learning based methods have been applied directly to the raw (unprocessed) data. However, their usability is impacted by the paucity of annotated data in the biomedical sector. In order to leverage the learning capabilities of deep Convolutional Neural Nets (CNNs) within the confines of limited labelled data, in this study we shall investigate the transfer learning approaches that aim to apply the knowledge gained from solving a source (e.g., non-medical) problem, to learn better predictive models for the target (e.g., biomedical) task. As an alternative, we shall further propose a new adaptive and compact CNN based architecture that can be trained from scratch even on scarce and low-resolution data. Moreover, we conduct quantitative comparative evaluations among the traditional methods, transfer learning-based methods and the proposed adaptive approach for the particular task of cancer detection and identification from scarce and low-resolution histology images. Over the largest benchmark dataset formed for this purpose, the proposed adaptive approach achieved a higher cancer detection accuracy with a significant gap, whereas the deep CNNs with transfer learning achieved a superior cancer identification.

A Multi-resolution Model for Histopathology Image Classification and Localization with Multiple Instance Learning

Histopathological images provide rich information for disease diagnosis. Large numbers of histopathological images have been digitized into high resolution whole slide images, opening opportunities in developing computational image analysis tools to reduce pathologists' workload and potentially improve inter- and intra- observer agreement. Most previous work on whole slide image analysis has focused on classification or segmentation of small pre-selected regions-of-interest, which requires fine-grained annotation and is non-trivial to extend for large-scale whole slide analysis. In this paper, we proposed a multi-resolution multiple instance learning model that leverages saliency maps to detect suspicious regions for fine-grained grade prediction. Instead of relying on expensive region- or pixel-level annotations, our model can be trained end-to-end with only slide-level labels. The model is developed on a large-scale prostate biopsy dataset containing 20,229 slides from 830 patients. The model achieved 92.7% accuracy, 81.8% Cohen's Kappa for benign, low grade (i.e. Grade group 1) and high grade (i.e. Grade group >= 2) prediction, an area under the receiver operating characteristic curve (AUROC) of 98.2% and an average precision (AP) of 97.4% for differentiating malignant and benign slides. The model obtained an AUROC of 99.4% and an AP of 99.8% for cancer detection on an external dataset.

Machine Learning Applications in Diagnosis, Treatment and Prognosis of Lung Cancer

The recent development of imaging and sequencing technologies enables systematic advances in the clinical study of lung cancer. Meanwhile, the human mind is limited in effectively handling and fully utilizing the accumulation of such enormous amounts of data. Machine learning-based approaches play a critical role in integrating and analyzing these large and complex datasets, which have extensively characterized lung cancer through the use of different perspectives from these accrued data. In this article, we provide an overview of machine learning-based approaches that strengthen the varying aspects of lung cancer diagnosis and therapy, including early detection, auxiliary diagnosis, prognosis prediction and immunotherapy practice. Moreover, we highlight the challenges and opportunities for future applications of machine learning in lung cancer.

Photonic single perceptron at Giga-OP/s speeds with Kerr microcombs for scalable optical neural networks

Optical artificial neural networks (ONNs) have significant potential for ultra-high computing speed and energy efficiency. We report a novel approach to ONNs that uses integrated Kerr optical microcombs. This approach is programmable and scalable and is capable of reaching ultrahigh speeds. We demonstrate the basic building block ONNs, a single neuron perceptron, by mapping synapses onto 49 wavelengths to achieve an operating speed of 11.9 x 109 operations per second, or GigaOPS, at 8 bits per operation, which equates to 95.2 gigabits/s (Gbps). We test the perceptron on handwritten digit recognition and cancer cell detection, achieving over 90% and 85% accuracy, respectively. By scaling the perceptron to a deep learning network using off the shelf telecom technology we can achieve high throughput operation for matrix multiplication for real-time massive data processing.

Detection and Classification of Breast Cancer Metastates Based on U-Net

This paper presents U-net based breast cancer metastases detection and classification in lymph nodes, as well as patient-level classification based on metastases detection. The whole pipeline can be divided into five steps: preprocessing and data argumentation, patch-based segmentation, post processing, slide-level classification, and patient-level classification. In order to reduce overfitting and speedup convergence, we applied batch normalization and dropout into U-Net. The final Kappa score reaches 0.902 on training data.

Machine Intelligence-Driven Classification of Cancer Patients-Derived Extracellular Vesicles using Fluorescence Correlation Spectroscopy: Results from a Pilot Study

Patient-derived extracellular vesicles (EVs) that contains a complex biological cargo is a valuable source of liquid biopsy diagnostics to aid in early detection, cancer screening, and precision nanotherapeutics. In this study, we predicted that coupling cancer patient blood-derived EVs to time-resolved spectroscopy and artificial intelligence (AI) could provide a robust cancer screening and follow-up tools. Methods: Fluorescence correlation spectroscopy (FCS) measurements were performed on 24 blood samples-derived EVs. Blood samples were obtained from 15 cancer patients (presenting 5 different types of cancers), and 9 healthy controls (including patients with benign lesions). The obtained FCS autocorrelation spectra were processed into power spectra using the Fast-Fourier Transform algorithm and subjected to various machine learning algorithms to distinguish cancer spectra from healthy control spectra. Results and Applications: The performance of AdaBoost Random Forest (RF) classifier, support vector machine, and multilayer perceptron, were tested on selected frequencies in the N=118 power spectra. The RF classifier exhibited a 90% classification accuracy and high sensitivity and specificity in distinguishing the FCS power spectra of cancer patients from those of healthy controls. Further, an image convolutional neural network (CNN), ResNet network, and a quantum CNN were assessed on the power spectral images as additional validation tools. All image-based CNNs exhibited a nearly equal classification performance with an accuracy of roughly 82% and reasonably high sensitivity and specificity scores. Our pilot study demonstrates that AI-algorithms coupled to time-resolved FCS power spectra can accurately and differentially classify the complex patient-derived EVs from different cancer samples of distinct tissue subtypes.

Multi-level colonoscopy malignant tissue detection with adversarial CAC-UNet

The automatic and objective medical diagnostic model can be valuable to achieve early cancer detection, and thus reducing the mortality rate. In this paper, we propose a highly efficient multi-level malignant tissue detection through the designed adversarial CAC-UNet. A patch-level model with a pre-prediction strategy and a malignancy area guided label smoothing is adopted to remove the negative WSIs, with which to lower the risk of false positive detection. For the selected key patches by multi-model ensemble, an adversarial context-aware and appearance consistency UNet (CAC-UNet) is designed to achieve robust segmentation. In CAC-UNet, mirror designed discriminators are able to seamlessly fuse the whole feature maps of the skillfully designed powerful backbone network without any information loss. Besides, a mask prior is further added to guide the accurate segmentation mask prediction through an extra mask-domain discriminator. The proposed scheme achieves the best results in MICCAI DigestPath2019 challenge on colonoscopy tissue segmentation and classification task. The full implementation details and the trained models are available at https://github.com/Raykoooo/CAC-UNet.

End-to-end Prostate Cancer Detection in bpMRI via 3D CNNs: Effect of Attention Mechanisms, Clinical Priori and Decoupled False Positive Reduction

We present a novel multi-stage 3D computer-aided detection and diagnosis (CAD) model for automated localization of clinically significant prostate cancer (csPCa) in bi-parametric MR imaging (bpMRI). Deep attention mechanisms drive its detection network, targeting multi-resolution, salient structures and highly discriminative feature dimensions, in order to accurately identify csPCa lesions from indolent cancer and the wide range of benign pathology that can afflict the prostate gland. In parallel, a decoupled residual classifier is used to achieve consistent false positive reduction, without sacrificing high sensitivity or computational efficiency. Furthermore, a probabilistic anatomical prior, which captures the spatial prevalence of csPCa as well as its zonal distinction, is computed and encoded into the CNN architecture to guide model generalization with domain-specific clinical knowledge. For 486 institutional testing scans, the 3D CAD system achieves $83.69\pm5.22\%$ and $93.19\pm2.96\%$ detection sensitivity at 0.50 and 1.46 false positive(s) per patient, respectively, along with $0.882$ AUROC in patient-based diagnosis $-$significantly outperforming four state-of-the-art baseline architectures (U-SEResNet, UNet++, nnU-Net, Attention U-Net) from recent literature. For 296 external testing scans, the ensembled CAD system shares moderate agreement with a consensus of expert radiologists ($76.69\%$; $kappa=0.511$) and independent pathologists ($81.08\%$; $kappa=0.559$); demonstrating strong generalization to histologically-confirmed malignancies, despite using 1950 training-validation cases with radiologically-estimated annotations only.

Computational Enhancement of Molecularly Targeted Contrast-Enhanced Ultrasound: Application to Human Breast Tumor Imaging

Molecularly targeted contrast enhanced ultrasound (mCEUS) is a clinically promising approach for early cancer detection through targeted imaging of VEGFR2 (KDR) receptors. We have developed computational enhancement techniques for mCEUS tailored to address the unique challenges of imaging contrast accumulation in humans. These techniques utilize dynamic analysis to distinguish molecularly bound contrast agent from other contrast-mode signal sources, enabling analysis of contrast agent accumulation to be performed during contrast bolus arrival when the signal due to molecular binding is strongest. Applied to the 18 human patient examinations of the first-in-human molecular ultrasound breast lesion study, computational enhancement improved the ability to differentiate between pathology-proven lesion and pathology-proven normal tissue in real-world human examination conditions that involved both patient and probe motion, with improvements in contrast ratio between lesion and normal tissue that in most cases exceed an order of magnitude (10x). Notably, computational enhancement eliminated a false positive result in which tissue leakage signal was misinterpreted by radiologists to be contrast agent accumulation.