Universal in vivo Textural Model for Human Skin based on Optical Coherence Tomograms

Currently, diagnosis of skin diseases is based primarily on visual pattern recognition skills and expertise of the physician observing the lesion. Even though dermatologists are trained to recognize patterns of morphology, it is still a subjective visual assessment. Tools for automated pattern recognition can provide objective information to support clinical decision-making. Noninvasive skin imaging techniques provide complementary information to the clinician. In recent years, optical coherence tomography has become a powerful skin imaging technique. According to specific functional needs, skin architecture varies across different parts of the body, as do the textural characteristics in OCT images. There is, therefore, a critical need to systematically analyze OCT images from different body sites, to identify their significant qualitative and quantitative differences. Sixty-three optical and textural features extracted from OCT images of healthy and diseased skin are analyzed and in conjunction with decision-theoretic approaches used to create computational models of the diseases. We demonstrate that these models provide objective information to the clinician to assist in the diagnosis of abnormalities of cutaneous microstructure, and hence, aid in the determination of treatment. Specifically, we demonstrate the performance of this methodology on differentiating basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) from healthy tissue

Machine learning in oral squamous cell carcinoma: current status, clinical concerns and prospects for future-A systematic review

Background: Oral cancer can show heterogenous patterns of behavior. For proper and effective management of oral cancer, early diagnosis and accurate prediction of prognosis are important. To achieve this, artificial intelligence (AI) or its subfield, machine learning, has been touted for its potential to revolutionize cancer management through improved diagnostic precision and prediction of outcomes. Yet, to date, it has made only few contributions to actual medical practice or patient care. Objectives: This study provides a systematic review of diagnostic and prognostic application of machine learning in oral squamous cell carcinoma (OSCC) and also highlights some of the limitations and concerns of clinicians towards the implementation of machine learning-based models for daily clinical practice. Data sources: We searched OvidMedline, PubMed, Scopus, Web of Science, and Institute of Electrical and Electronics Engineers (IEEE) databases from inception until February 2020 for articles that used machine learning for diagnostic or prognostic purposes of OSCC. Eligibility criteria: Only original studies that examined the application of machine learning models for prognostic and/or diagnostic purposes were considered. Data extraction: Independent extraction of articles was done by two researchers (A.R. & O.Y) using predefine study selection criteria. We used the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) in the searching and screening processes. We also used Prediction model Risk of Bias Assessment Tool (PROBAST) for assessing the risk of bias (ROB) and quality of included studies. Results: A total of 41 studies were published to have used machine learning to aid in the diagnosis/or prognosis of OSCC. The majority of these studies used the support vector machine (SVM) and artificial neural network (ANN) algorithms as machine learning techniques. Their specificity ranged from 0.57 to 1.00, sensitivity from 0.70 to 1.00, and accuracy from 63.4 % to 100.0 % in these studies. The main limitations and concerns can be grouped as either the challenges inherent to the science of machine learning or relating to the clinical implementations. Conclusion: Machine learning models have been reported to show promising performances for diagnostic and prognostic analyses in studies of oral cancer. These models should be developed to further enhance explainability, interpretability, and externally validated for generalizability in order to be safely integrated into daily clinical practices. Also, regulatory frameworks for the adoption of these models in clinical practices are necessary.Peer reviewe

Deep learning for digitized histology image analysis

“Cervical cancer is the fourth most frequent cancer that affects women worldwide. Assessment of cervical intraepithelial neoplasia (CIN) through histopathology remains as the standard for absolute determination of cancer. The examination of tissue samples under a microscope requires considerable time and effort from expert pathologists. There is a need to design an automated tool to assist pathologists for digitized histology slide analysis. Pre-cervical cancer is generally determined by examining the CIN which is the growth of atypical cells from the basement membrane (bottom) to the top of the epithelium. It has four grades, including: Normal, CIN1, CIN2, and CIN3. In this research, different facets of an automated digitized histology epithelium assessment pipeline have been explored to mimic the pathologist diagnostic approach. The entire pipeline from slide to epithelium CIN grade has been designed and developed using deep learning models and imaging techniques to analyze the whole slide image (WSI). The process is as follows: 1) identification of epithelium by filtering the regions extracted from a low-resolution image with a binary classifier network; 2) epithelium segmentation; 3) deep regression for pixel-wise segmentation of epithelium by patch-based image analysis; 4) attention-based CIN classification with localized sequential feature modeling. Deep learning-based nuclei detection by superpixels was performed as an extension of our research. Results from this research indicate an improved performance of CIN assessment over state-of-the-art methods for nuclei segmentation, epithelium segmentation, and CIN classification, as well as the development of a prototype WSI-level tool”--Abstract, page iv

Texture-based Deep Neural Network for Histopathology Cancer Whole Slide Image (WSI) Classification

Automatic histopathological Whole Slide Image (WSI) analysis for cancer classification has been highlighted along with the advancements in microscopic imaging techniques. However, manual examination and diagnosis with WSIs is time-consuming and tiresome. Recently, deep convolutional neural networks have succeeded in histopathological image analysis. In this paper, we propose a novel cancer texture-based deep neural network (CAT-Net) that learns scalable texture features from histopathological WSIs. The innovation of CAT-Net is twofold: (1) capturing invariant spatial patterns by dilated convolutional layers and (2) Reducing model complexity while improving performance. Moreover, CAT-Net can provide discriminative texture patterns formed on cancerous regions of histopathological images compared to normal regions. The proposed method outperformed the current state-of-the-art benchmark methods on accuracy, precision, recall, and F1 score

Multi-omic biomarker discovery and network analyses to elucidate the molecular mechanisms of lung cancer premalignancy

Lung cancer (LC) is the leading cause of cancer death in the US, claiming over 160,000 lives annually. Although CT screening has been shown to be efficacious in reducing mortality, the limited access to screening programs among high-risk individuals and the high number of false positives contribute to low survival rates and increased healthcare costs. As a result, there is an urgent need for preventative therapeutics and novel interception biomarkers that would enhance current methods for detection of early-stage LC. This thesis addresses this challenge by examining the hypothesis that transcriptomic changes preceding the onset of LC can be identified by studying bronchial premalignant lesions (PMLs) and the normal-appearing airway epithelial cells altered in their presence (i.e., the PML-associated airway field of injury). PMLs are the presumed precursors of lung squamous cell carcinoma (SCC) whose presence indicates an increased risk of developing SCC and other subtypes of LC. Here, I leverage high-throughput mRNA and miRNA sequencing data from bronchial brushings and lesion biopsies to develop biomarkers of PML presence and progression, and to understand regulatory mechanisms driving early carcinogenesis. First, I utilized mRNA sequencing data from normal-appearing airway brushings to build a biomarker predictive of PML presence. After verifying the power of the 200-gene biomarker to detect the presence of PMLs, I evaluated its capacity to predict PML progression and detect presence of LC (Aim 1). Next, I identified likely regulatory mechanisms associated with PML severity and progression, by evaluating miRNA expression and gene coexpression modules containing their targets in bronchial lesion biopsies (Aim2). Lastly, I investigated the preservation of the PML-associated miRNAs and gene modules in the airway field of injury, highlighting an emergent link between the airway field and the PMLs (Aim 3). Overall, this thesis suggests a multi-faceted utility of PML-associated genomic signatures as markers for stratification of high-risk smokers in chemoprevention trials, markers for early detection of lung cancer, and novel chemopreventive targets, and yields valuable insights into early lung carcinogenesis by characterizing mRNA and miRNA expression alterations that contribute to premalignant disease progression towards LC.2020-01-2

Radiomics in the evaluation of ovarian masses — a systematic review

Objectives The study aim was to conduct a systematic review of the literature reporting the application of radiomics to imaging techniques in patients with ovarian lesions. Methods MEDLINE/PubMed, Web of Science, Scopus, EMBASE, Ovid and ClinicalTrials.gov were searched for relevant articles. Using PRISMA criteria, data were extracted from short-listed studies. Validity and bias were assessed independently by 2 researchers in consensus using the Quality in Prognosis Studies (QUIPS) tool. Radiomic Quality Score (RQS) was utilised to assess radiomic methodology. Results After duplicate removal, 63 articles were identified, of which 33 were eligible. Fifteen assessed lesion classifications, 10 treatment outcomes, 5 outcome predictions, 2 metastatic disease predictions and 1 classification/outcome prediction. The sample size ranged from 28 to 501 patients. Twelve studies investigated CT, 11 MRI, 4 ultrasound and 1 FDG PET-CT. Twenty-three studies (70%) incorporated 3D segmentation. Various modelling methods were used, most commonly LASSO (least absolute shrinkage and selection operator) (10/33). Five studies (15%) compared radiomic models to radiologist interpretation, all demonstrating superior performance. Only 6 studies (18%) included external validation. Five studies (15%) had a low overall risk of bias, 9 (27%) moderate, and 19 (58%) high risk of bias. The highest RQS achieved was 61.1%, and the lowest was − 16.7%. Conclusion Radiomics has the potential as a clinical diagnostic tool in patients with ovarian masses and may allow better lesion stratification, guiding more personalised patient care in the future. Standardisation of the feature extraction methodology, larger and more diverse patient cohorts and real-world evaluation is required before clinical translation. Clinical relevance statement Radiomics shows promising results in improving lesion stratification, treatment selection and outcome prediction. Modelling with larger cohorts and real-world evaluation is required before clinical translation. Key points • Radiomics is emerging as a tool for enhancing clinical decisions in patients with ovarian masses. • Radiomics shows promising results in improving lesion stratification, treatment selection and outcome prediction. • Modelling with larger cohorts and real-world evaluation is required before clinical translation

Tissue Phenomics for prognostic biomarker discovery in low- and intermediate-risk prostate cancer

Tissue Phenomics is the discipline of mining tissue images to identify patterns that are related to clinical outcome providing potential prognostic and predictive value. This involves the discovery process from assay development, image analysis, and data mining to the final interpretation and validation of the findings. Importantly, this process is not linear but allows backward steps and optimization loops over multiple sub-processes. We provide a detailed description of the Tissue Phenomics methodology while exemplifying each step on the application of prostate cancer recurrence prediction. In particular, we automatically identified tissue-based biomarkers having significant prognostic value for low-and intermediate-risk prostate cancer patients (Gleason scores 6-7b) after radical prostatectomy. We found that promising phenes were related to CD8(+) and CD68(+) cells in the microenvironment of cancerous glands in combination with the local micro-vascularization. Recurrence prediction based on the selected phenes yielded accuracies up to 83% thereby clearly outperforming prediction based on the Gleason score. Moreover, we compared different machine learning algorithms to combine the most relevant phenes resulting in increased accuracies of 88% for tumor progression prediction. These findings will be of potential use for future prognostic tests for prostate cancer patients and provide a proof-of-principle of the Tissue Phenomics approach

Development of deep learning methods for head and neck cancer detection in hyperspectral imaging and digital pathology for surgical guidance

Surgeons performing routine cancer resections utilize palpation and visual inspection, along with time-consuming microscopic tissue analysis, to ensure removal of cancer. Despite this, inadequate surgical cancer margins are reported for up to 10-20% of head and neck squamous cell carcinoma (SCC) operations. There exists a need for surgical guidance with optical imaging to ensure complete cancer resection in the operating room. The objective of this dissertation is to evaluate hyperspectral imaging (HSI) as a non-contact, label-free optical imaging modality to provide intraoperative diagnostic information. For comparison of different optical methods, autofluorescence, RGB composite images synthesized from HSI, and two fluorescent dyes are also acquired and investigated for head and neck cancer detection. A novel and comprehensive dataset was obtained of 585 excised tissue specimens from 204 patients undergoing routine head and neck cancer surgeries. The first aim was to use SCC tissue specimens to determine the potential of HSI for surgical guidance in the challenging task of head and neck SCC detection. It is hypothesized that HSI could reduce time and provide quantitative cancer predictions. State-of-the-art deep learning algorithms were developed for SCC detection in 102 patients and compared to other optical methods. HSI detected SCC with a median AUC score of 85%, and several anatomical locations demonstrated good SCC detection, such as the larynx, oropharynx, hypopharynx, and nasal cavity. To understand the ability of HSI for SCC detection, the most important spectral features were calculated and correlated with known cancer physiology signals, notably oxygenated and deoxygenated hemoglobin. The second aim was to evaluate HSI for tumor detection in thyroid and salivary glands, and RGB images were synthesized using the spectral response curves of the human eye for comparison. Using deep learning, HSI detected thyroid tumors with 86% average AUC score, which outperformed fluorescent dyes and autofluorescence, but HSI-synthesized RGB imagery performed with 90% AUC score. The last aim was to develop deep learning algorithms for head and neck cancer detection in hundreds of digitized histology slides. Slides containing SCC or thyroid carcinoma can be distinguished from normal slides with 94% and 99% AUC scores, respectively, and SCC and thyroid carcinoma can be localized within whole-slide images with 92% and 95% AUC scores, respectively. In conclusion, the outcomes of this thesis work demonstrate that HSI and deep learning methods could aid surgeons and pathologists in detecting head and neck cancers.Ph.D