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

Broadband hyperspectral imaging for breast tumor detection using spectral and spatial information

Complete tumor removal during breast-conserving surgery remains challenging due to the lack of optimal intraoperative margin assessment techniques. Here, we use hyperspectral imaging for tumor detection in fresh breast tissue. We evaluated different wavelength ranges and two classification algorithms; a pixel-wise classification algorithm and a convolutional neural network that combines spectral and spatial information. The highest classification performance was obtained using the full wavelength range (450-1650nm). Adding spatial information mainly improved the differentiation of tissue classes within the malignant and healthy classes. High sensitivity and specificity were accomplished, which offers potential for hyperspectral imaging as a margin assessment technique to improve surgical outcome. (C) 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreemen

Information Extraction Techniques in Hyperspectral Imaging Biomedical Applications

Hyperspectral imaging (HSI) is a technology able to measure information about the spectral reflectance or transmission of light from the surface. The spectral data, usually within the ultraviolet and infrared regions of the electromagnetic spectrum, provide information about the interaction between light and different materials within the image. This fact enables the identification of different materials based on such spectral information. In recent years, this technology is being actively explored for clinical applications. One of the most relevant challenges in medical HSI is the information extraction, where image processing methods are used to extract useful information for disease detection and diagnosis. In this chapter, we provide an overview of the information extraction techniques for HSI. First, we introduce the background of HSI, and the main motivations of its usage for medical applications. Second, we present information extraction techniques based on both light propagation models within tissue and machine learning approaches. Then, we survey the usage of such information extraction techniques in HSI biomedical research applications. Finally, we discuss the main advantages and disadvantages of the most commonly used image processing approaches and the current challenges in HSI information extraction techniques in clinical applications

Automatic Recognition of Colon and Esophagogastric Cancer with Machine Learning and Hyperspectral Imaging

There are approximately 1.8 million diagnoses of colorectal cancer, 1 million diagnoses of stomach cancer, and 0.6 million diagnoses of esophageal cancer each year globally. An automatic computer-assisted diagnostic (CAD) tool to rapidly detect colorectal and esophagogastric cancer tissue in optical images would be hugely valuable to a surgeon during an intervention. Based on a colon dataset with 12 patients and an esophagogastric dataset of 10 patients, several state-of-the-art machine learning methods have been trained to detect cancer tissue using hyperspectral imaging (HSI), including Support Vector Machines (SVM) with radial basis function kernels, Multi-Layer Perceptrons (MLP) and 3D Convolutional Neural Networks (3DCNN). A leave-one-patient-out cross-validation (LOPOCV) with and without combining these sets was performed. The ROC-AUC score of the 3DCNN was slightly higher than the MLP and SVM with a difference of 0.04 AUC. The best performance was achieved with the 3DCNN for colon cancer and esophagogastric cancer detection with a high ROC-AUC of 0.93. The 3DCNN also achieved the best DICE scores of 0.49 and 0.41 on the colon and esophagogastric datasets, respectively. These scores were significantly improved using a patient-specific decision threshold to 0.58 and 0.51, respectively. This indicates that, in practical use, an HSI-based CAD system using an interactive decision threshold is likely to be valuable. Experiments were also performed to measure the benefits of combining the colorectal and esophagogastric datasets (22 patients), and this yielded significantly better results with the MLP and SVM models

Hyperspectral Imaging Reveals Spectral Differences and Can Distinguish Malignant Melanoma from Pigmented Basal Cell Carcinomas : A Pilot Study

Pigmented basal cell carcinomas can be difficult to distinguish from melanocytic tumours. Hyperspectral imaging is a non-invasive imaging technique that measures the reflectance spectra of skin in vivo. The aim of this prospective pilot study was to use a convolutional neural network classifier in hyperspectral images for differential diagnosis between pigmented basal cell carcinomas and melanoma. A total of 26 pigmented lesions (10 pigmented basal cell carcinomas, 12 melanomas in situ, 4 invasive melanomas) were imaged with hyperspectral imaging and excised for histopatho-logical diagnosis. For 2-class classifier (melano-cytic tumours vs pigmented basal cell carcinomas) using the majority of the pixels to predict the class of the whole lesion, the results showed a sensitivity of 100% (95% confidence interval 81-100%), specificity of 90% (95% confidence interval 60-98%) and positive predictive value of 94% (95% confidence interval 73-99%). These results indicate that a convolutional neural network classifier can differentiate melanocytic tumours from pigmented basal cell carcinomas in hyperspectral images. Further studies are warranted in order to confirm these preliminary results, using larger samples and multiple tumour types, including all types of melanocytic lesions.Peer reviewe

Comparison of preprocessing techniques to reduce nontissue-related variations in hyperspectral reflectance imaging

Significance: Hyperspectral reflectance imaging can be used in medicine to identify tissue types, such as tumor tissue. Tissue classification algorithms are developed based on, e.g., machine learning or principle component analysis. For the development of these algorithms, data are generally preprocessed to remove variability in data not related to the tissue itself since this will improve the performance of the classification algorithm. In hyperspectral imaging, the measured spectra are also influenced by reflections from the surface (glare) and height variations within and between tissue samples.Aim: To compare the ability of different preprocessing algorithms to decrease variations in spectra induced by glare and height differences while maintaining contrast based on differences in optical properties between tissue types.Approach: We compare eight preprocessing algorithms commonly used in medical hyperspectral imaging: standard normal variate, multiplicative scatter correction, min-max normalization, mean centering, area under the curve normalization, single wavelength normalization, first derivative, and second derivative. We investigate conservation of contrast stemming from differences in: blood volume fraction, presence of different absorbers, scatter amplitude, and scatter slope-while correcting for glare and height variations. We use a similarity metric, the overlap coefficient, to quantify contrast between spectra. We also investigate the algorithms for clinical datasets from the colon and breast.Conclusions: Preprocessing reduces the overlap due to glare and distance variations. In general, the algorithms standard normal variate, min-max, area under the curve, and single wavelength normalization are the most suitable to preprocess data used to develop a classification algorithm for tissue classification. The type of contrast between tissue types determines which of these four algorithms is most suitable

Surgical spectral imaging

Recent technological developments have resulted in the availability of miniaturised spectral imaging sensors capable of operating in the multi- (MSI) and hyperspectral imaging (HSI) regimes. Simultaneous advances in image-processing techniques and artificial intelligence (AI), especially in machine learning and deep learning, have made these data-rich modalities highly attractive as a means of extracting biological information non-destructively. Surgery in particular is poised to benefit from this, as spectrally-resolved tissue optical properties can offer enhanced contrast as well as diagnostic and guidance information during interventions. This is particularly relevant for procedures where inherent contrast is low under standard white light visualisation. This review summarises recent work in surgical spectral imaging (SSI) techniques, taken from Pubmed, Google Scholar and arXiv searches spanning the period 2013–2019. New hardware, optimised for use in both open and minimally-invasive surgery (MIS), is described, and recent commercial activity is summarised. Computational approaches to extract spectral information from conventional colour images are reviewed, as tip-mounted cameras become more commonplace in MIS. Model-based and machine learning methods of data analysis are discussed in addition to simulation, phantom and clinical validation experiments. A wide variety of surgical pilot studies are reported but it is apparent that further work is needed to quantify the clinical value of MSI/HSI. The current trend toward data-driven analysis emphasises the importance of widely-available, standardised spectral imaging datasets, which will aid understanding of variability across organs and patients, and drive clinical translation