Multimodal optical systems for clinical oncology

This thesis presents three multimodal optical (light-based) systems designed to improve the capabilities of existing optical modalities for cancer diagnostics and theranostics. Optical diagnostic and therapeutic modalities have seen tremendous success in improving the detection, monitoring, and treatment of cancer. For example, optical spectroscopies can accurately distinguish between healthy and diseased tissues, fluorescence imaging can light up tumours for surgical guidance, and laser systems can treat many epithelial cancers. However, despite these advances, prognoses for many cancers remain poor, positive margin rates following resection remain high, and visual inspection and palpation remain crucial for tumour detection. The synergistic combination of multiple optical modalities, as presented here, offers a promising solution. The first multimodal optical system (Chapter 3) combines Raman spectroscopic diagnostics with photodynamic therapy using a custom-built multimodal optical probe. Crucially, this system demonstrates the feasibility of nanoparticle-free theranostics, which could simplify the clinical translation of cancer theranostic systems without sacrificing diagnostic or therapeutic benefit. The second system (Chapter 4) applies computer vision to Raman spectroscopic diagnostics to achieve spatial spectroscopic diagnostics. It provides an augmented reality display of the surgical field-of-view, overlaying spatially co-registered spectroscopic diagnoses onto imaging data. This enables the translation of Raman spectroscopy from a 1D technique to a 2D diagnostic modality and overcomes the trade-off between diagnostic accuracy and field-of-view that has limited optical systems to date. The final system (Chapter 5) integrates fluorescence imaging and Raman spectroscopy for fluorescence-guided spatial spectroscopic diagnostics. This facilitates macroscopic tumour identification to guide accurate spectroscopic margin delineation, enabling the spectroscopic examination of suspicious lesions across large tissue areas. Together, these multimodal optical systems demonstrate that the integration of multiple optical modalities has potential to improve patient outcomes through enhanced tumour detection and precision-targeted therapies.Open Acces

Artificial Intelligence in Oral Health

This Special Issue is intended to lay the foundation of AI applications focusing on oral health, including general dentistry, periodontology, implantology, oral surgery, oral radiology, orthodontics, and prosthodontics, among others

Smart Sensors for Healthcare and Medical Applications

This book focuses on new sensing technologies, measurement techniques, and their applications in medicine and healthcare. Specifically, the book briefly describes the potential of smart sensors in the aforementioned applications, collecting 24 articles selected and published in the Special Issue “Smart Sensors for Healthcare and Medical Applications”. We proposed this topic, being aware of the pivotal role that smart sensors can play in the improvement of healthcare services in both acute and chronic conditions as well as in prevention for a healthy life and active aging. The articles selected in this book cover a variety of topics related to the design, validation, and application of smart sensors to healthcare

A study of Raman spectroscopy for the early detection and characterization of prostate cancer using blood plasma and prostate tissue biopsy.

Prostate cancer (PC) is the most common cancer in men after non-melanoma skin cancer in the United Kingdom (Cancer Research UK, 2019). Current diagnostic methods (PSA, DRE, MRI & prostate biopsy) have limitations as these are unable to distinguish between low-risk cancers that do not need active treatment from cancers which are more likely to progress. In addition, prostate biopsy is invasive with potential side effects. There is an urgent need to identify new biomarkers for early diagnosis and prognostication in PC. Raman spectroscopy (RS) is an optical technique that utilises molecular-specific, inelastic scattering of light photons to interrogate biological samples. When laser light is incident on a biological sample, the photons from the laser light can interact with the intramolecular bonds present within the sample. The Raman spectrum is a direct function of the molecular composition of the tissue, providing a molecular fingerprint of the phenotypic expression of the cells and tissues, which can give good objective information regarding the pathological state of the biological sample under interrogation. We applied a technique of drop coating deposition Raman (DCDR) spectroscopy using both blood plasma and sera to see if a more accurate prediction of the presence and progression of prostate cancer could be achieved than PSA which would allow for blood sample triage of patients into at risk groups. 100 participants were recruited for this study (100 blood plasma and 100 serum samples). Secondly, 79 prostate tissue samples (from the same cohort) were interrogated with the aid of Raman micro-spectroscopy to ascertain if Raman spectroscopy can provide molecular fingerprint that can be utilised for real time in vivo analysis. Multivariate analysis of support vector machine (SVM) learning and linear discriminant analysis (LDA) were utilised differently to test the performance accuracy of the discriminant model for distinguishing between benign and malignant mean plasma spectra. SVM gave a better performance accuracy than LDA with sensitivity and specificity of 96% and 97% respectively and an area under the curve (AUC) of 0.98 as opposed to sensitivity and specificity of 51% and 80% respectively with AUC of 0.74 using LDA. Slightly lower performance accuracy was also observed when blood serum mean spectra analysis was compared with blood plasma mean spectra analysis for both machine learning algorithms (SVM & LDA). Tissue spectral analysis on the other hand recorded an overall accuracy of 80.8% and AUC of 0.82 with the SVM algorithm compared to performance accuracy of 75% and AUC of 0.77 with LDA algorithm (better performance noted with the SVM algorithm). The small sample size of 79 prostate biopsy tissues was responsible for the low sensitivity and specificity. Therefore, the tissues were insufficient to describe all the variances in each group as well as the variability of the gold standard technique. Conclusion: Raman spectroscopy could be a potentially useful technique in the management of Prostate Cancer in areas such as tissue diagnosis, assessment of surgical margin after radical prostatectomy, detection of metastasis, Prostate Cancer screening as well as monitoring and prognosticating patients with Prostate Cancer. However, more needs to be done to validate the approaches outlined in this thesis using prospective collection of new samples to test the classification models independently with sufficient statistical power. At this stage only the fluid-based models are likely to be large enough for this validation process

Raman Spectroscopy Techniques for the Detection and Management of Breast Cancer

Breast cancer has recently become the most common cancer worldwide, and with increased incidence, there is increased pressure on health services to diagnose and treat many more patients. Mortality and survival rates for this particular disease are better than other cancer types, and part of this is due to the facilitation of early diagnosis provided by screening programmes, including the National Health Service breast screening programme in the UK. Despite the benefits of the programme, some patients undergo negative experiences in the form of false negative mammograms, overdiagnosis and subsequent overtreatment, and even a small number of cancers are induced by the use of ionising radiation. In addition to this, false positive mammograms cause a large number of unnecessary biopsies, which means significant costs, both financially and in terms of clinicians' time, and discourages patients from attending further screening. Improvement in areas of the treatment pathway is also needed. Surgery is usually the first line of treatment for early breast cancer, with breast conserving surgery being the preferred option compared to mastectomy. This type of operation achieves the same outcome as mastectomy - removal of the tumour - while allowing the patient to retain the majority of their normal breast tissue for improved aesthetic and psychological results. Yet, re-excision operations are often required when clear margins are not achieved, i.e. not all of the tumour is removed. This again has implications on cost and time, and increases the risk to the patient through additional surgery. Currently lacking in both the screening and surgical contexts is the ability to discern specific chemicals present in the breast tissue being assessed/removed. Specifically relevant to mammography is the presence of calcifications, the chemistry of which holds information indicative of pathology that cannot be accessed through x-rays. In addition, the chemical composition of breast tumour tissue has been shown to be different to normal tissue in a variety of ways, with one particular difference being a significant increase in water content. Raman spectroscopy is a rapid, non-ionising, non-destructive technique based on light scattering. It has been proven to discern between chemical types of calcification and subtleties within their spectra that indicate the malignancy status of the surrounding tissue, and differentiate between cancerous and normal breast tissue based on the relative water contents. Furthermore, this thesis presents work aimed at exploring deep Raman techniques to probe breast calcifications at depth within tissue, and using a high wavenumber Raman probe to discriminate tumour from normal tissue predominantly via changes in tissue water content. The ability of transmission Raman spectroscopy to detect different masses and distributions of calcified powder inclusions within tissue phantoms was tested, as well as elucidating a signal profile of a similar inclusion through a tissue phantom of clinically relevant thickness. The technique was then applied to the measurement of clinically active samples of bulk breast tissue from informed and consented patients to try to measure calcifications. Ex vivo specimens were also measured with a high wavenumber Raman probe, which found significant differences between tumour and normal tissue, largely due to water content, resulting in a classification model that achieved 77.1% sensitivity and 90.8% specificity. While calcifications were harder to detect in the ex vivo specimens, promising results were still achieved, potentially indicating a much more widespread influence of calcification in breast tissue, and to obtain useful signal from bulk human tissue is encouraging in itself. Consequently, this work demonstrates the potential value of both deep Raman techniques and high wavenumber Raman for future breast screening and tumour margin assessment methods

Pacific Symposium on Biocomputing 2023

The Pacific Symposium on Biocomputing (PSB) 2023 is an international, multidisciplinary conference for the presentation and discussion of current research in the theory and application of computational methods in problems of biological significance. Presentations are rigorously peer reviewed and are published in an archival proceedings volume. PSB 2023 will be held on January 3-7, 2023 in Kohala Coast, Hawaii. Tutorials and workshops will be offered prior to the start of the conference.PSB 2023 will bring together top researchers from the US, the Asian Pacific nations, and around the world to exchange research results and address open issues in all aspects of computational biology. It is a forum for the presentation of work in databases, algorithms, interfaces, visualization, modeling, and other computational methods, as applied to biological problems, with emphasis on applications in data-rich areas of molecular biology.The PSB has been designed to be responsive to the need for critical mass in sub-disciplines within biocomputing. For that reason, it is the only meeting whose sessions are defined dynamically each year in response to specific proposals. PSB sessions are organized by leaders of research in biocomputing's 'hot topics.' In this way, the meeting provides an early forum for serious examination of emerging methods and approaches in this rapidly changing field

Development of an image guidance system for laparoscopic liver surgery and evaluation of optical and computer vision techniques for the assessment of liver tissue

Introduction: Liver resection is increasingly being carried out via the laparoscopic approach (keyhole surgery) because there is mounting evidence that it benefits patients by reducing pain and length of hospitalisation. There are however ongoing concerns about oncological radicality (i.e. ability to completely remove cancer) and an inability to control massive haemorrhage. These issues can partially be attributed to a loss of sensation such as depth perception, tactile feedback and a reduced field of view. Utilisation of optical imaging and computer vision may be able to compensate for some of the lost sensory input because these modalities can facilitate visualisation of liver tissue and structural anatomy. Their use in laparoscopy is attractive because it is easy to adapt or integrate with existing technology. The aim of this thesis is to explore to what extent this technology can aid in the detection of normal and abnormal liver tissue and structures. / Methods: The current state of the art for optical imaging and computer vision in laparoscopic liver surgery is assessed in a systematic review. Evaluation of confocal laser endomicroscopy is carried out on a murine and porcine model of liver disease. Multispectral near infrared imaging is evaluated on ex-vivo liver specimen. Video magnification is assessed on a mechanical flow phantom and a porcine model of liver disease. The latter model was also employed to develop a computer vision based image guidance system for laparoscopic liver surgery. This image guidance system is further evaluated in a clinical feasibility study. Where appropriate, experimental findings are substantiated with statistical analysis. / Results: Use of confocal laser endomicroscopy enabled discrimination between cancer and normal liver tissue with a sub-millimetre precision. This technology also made it possible to verify the adequacy of thermal liver ablation. Multispectral imaging, at specific wavelengths was shown to have the potential to highlight the presence of colorectal and hepatocellular cancer. An image reprocessing algorithm is proposed to simplify visual interpretation of the resulting images. It is shown that video magnification can determine the presence of pulsatile motion but that it cannot reliably determine the extent of motion. Development and performance metrics of an image guidance system for laparoscopic liver surgery are outlined. The system was found to improve intraoperative orientation more development work is however required to enable reliable prediction of oncological margins. / Discussion: The results in this thesis indicate that confocal laser endomicroscopy and image guidance systems have reached a development stage where their intraoperative use may benefit surgeons by visualising features of liver anatomy and tissue characteristics. Video magnification and multispectral imaging require more development and suggestions are made to direct this work. It is also highlighted that it is crucial to standardise assessment methods for these technologies which will allow a more direct comparison between the outcomes of different groups. Limited imaging depth is a major restriction of these technologies but this may be overcome by combining them with preoperatively obtained imaging data. Just like laparoscopy, optical imaging and computer vision use functions of light, a shared characteristic that makes their combined use complementary