Dynamic Hyperspectral and Polarized Endoscopic Imaging

The health of rich, developed nations has seen drastic improvement in the last two centuries. For it to continue improving at a similar rate new or improved diagnostic and treatment technologies are required, especially for those diseases such as cancer which are forecast to constitute the majority of disease burden in the future. Optical techniques such as microscopy have long played their part in the diagnostic process. However there are several new biophotonic modalities that aim to exploit various interactions between light and tissue to provide enhanced diagnostic information. Many of these show promise in a laboratory setting but few have progressed to a clinical setting. We have designed and constructed a flexible, multi-modal, multi-spectral laparoscopic imaging system that could be used to demonstrate several different techniques in a clinical setting. The core of this system is a dynamic hyperspectral illumination system based around a supercontinuum laser and Digital Micromirror Device that can provide specified excitation light in the visible and near infra-red ranges. This is a powerful tool for spectroscopic techniques as it is not limited to interrogating a fixed range of wavelengths and can switch between excitation bands instantaneously. The excitation spectra can be customised to match particular fluorophores or absorption features, introducing new possibilities for spectral imaging. A standard 10 mm diameter rigid endoscope was incorporated into the system to reduce cost and demonstrate compatibility with existing equipment. The polarization properties of two commercial endoscopes were characterised and found to be unsuited to current polarization imaging techniques as birefringent materials used in their construction introduce complex, spatially dependent transformations of the polarization state. Preliminary exemplar data from phantoms and ex vivo tissue was collected and the feasibility and accuracy of different analysis techniques demonstrated including multiple class classification algorithms. Finally, a novel visualisation method was implemented in order to display the complex hyperspectral data sets in a meaningful and intuitive way to the user

Development of Fourier transform infrared spectroscopy for drug response analysis

The feasibility of FTIR-based spectroscopy as a tool to measure cellular response to therapeutics was investigated. Fourier transform mid-infrared spectroscopy has been used in conjunction with multivariate analysis (MVA) to assess the chemistry of many clinically relevant biological materials; however, the technique has not yet found its place in a clinical setting. One issue that has held the technique back is due to the spectral distortions caused by resonant Mie scattering (RMieS), which affects the ability to confidently assign molecular assignments to the spectral signals from biomaterials. In the light of recently improved understanding of RMieS, resulting in a novel correction algorithm, the analytical robustness of corrected FTIR spectra was validated against multi-discipline methods to characterise a set of renal cell lines which were selected for their difference in morphology.After validation of the FTIR methodology by discriminating different cell lines, the second stage of analyses tested the sensitivity of FTIR technique by determining if discrete chemical differences could be highlighted within a cell population of the same origin. The renal carcinoma cell line 2245R contains a sub-population to contain a sub-population of cells displaying 'stem-cell like' properties. These stem-like cells, however, are difficult to isolate and characterise by conventional '-omic' means. Finally, cellular response to chemotherapeutics was investigated using the established renal cell lines CAKI-2 and A-498. For the model, 5-fluorouracil (5FU), an established chemotherapeutic agent with known mechanisms of action was used. Novel gold-based therapeutic compounds were also assessed in parallel to determine their efficacy against renal cell carcinoma. The novel compounds displayed initial activity, as the FTIR evidence suggested compounds were able to enter the cells in the first instance, evoking a cellular response. The long-term performance, tracked with standard proliferation assays and FTIR spectroscopy in the renal cancer cell model, however, was poor. Rather than dismissing the compounds as in-active, the compounds may simply be more effective in cancer cell types of a different nature. The FTIR-based evidence provided the means to suggest such a conclusion. Overall, the initial results suggest that the combination of FTIR and MVA, in the presence of the novel RMieS-EMSC algorithm can detect differences in cellular response to chemotherapeutics. The results were also in-line with complimentary biological-based techniques, demonstrating the powerful potential of the technique as a promising drug screening tool.EThOS - Electronic Theses Online ServiceEPSRCRSCGBUnited Kingdo

Texture and Colour in Image Analysis

Research in colour and texture has experienced major changes in the last few years. This book presents some recent advances in the field, specifically in the theory and applications of colour texture analysis. This volume also features benchmarks, comparative evaluations and reviews

Fluorescence Methods for Investigation of Living Cells and Microorganisms

Fluorescence methods play a leading role in the investigation of biological objects. They are the only non-destructive methods for investigating living cells and microorganisms in vivo. Using intrinsic and artificial fluorescence methods provides deep insight into mechanisms underlying physiological and biochemical processes. This book covers a wide range of modern methods involved in experimental biology. It illustrates the use of fluorescence microscopy and spectroscopy, confocal laser scanning microscopy, flow cytometry, delayed fluorescence, pulse-amplitude-modulation fluorometry, and fluorescent dye staining protocols. This book provides an overview of practical and theoretical aspects of fluorescence methods and their successful application in the investigation of static and dynamic processes in living cells and microorganisms

The dendritic polymer DAB-Am16 as a novel tumoricidal compound

In the 21st century, cancer is becoming the curse of the ageing population in developed countries. No satisfactory therapies are available for many tumour types, and application of existing therapies is limited by severe side effects. Thus, there is a great need of new approaches in cancer treatment. DAB-Am16 is a dendritic polymer with a globular structure, consisting of poly(propylene imine) branches that emerge from a diaminobutane core. Its intrinsic tumoricidal activity in mouse models was published in 2005, but no information on the mechanism of action was available. This thesis presents novel findings on the pathways underlying the anti-cancer activity of this dendrimer in vitro and in vivo. Extensive chemical characterisation of DAB-Am16 confirmed its stability and purity. Severe time- and concentration-dependent cytotoxicity was observed for a panel of human tumour cell lines, while a small population of persisters was identified. Toxicity was accompanied by a delayed or abrogated cell cycle. There was an increased number of S phase cells, while the ability to synthesise DNA or to undergo mitosis was progressively lost with increasing DAB-Am16 concentration. The following cell death was found to be apoptotic and was biased in a cell cycle phase dependent manner. The order of apoptotic events upon DAB-Am16 exposure was determined. Finally, an in vivo experiment confirmed that DAB-Am16 has a pronounced effect against human pancreatic cancer xenografts in mice, while being well tolerated by the animals. Post mortem examination of tumour tissue revealed cell cycle blockage of tumour cells from DAB-Am16-treated mice. However, disposition for further proliferation was not diminished, and no significant difference in tumour vascularisation was observed

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

Intelligent Biosignal Processing in Wearable and Implantable Sensors

This reprint provides a collection of papers illustrating the state-of-the-art of smart processing of data coming from wearable, implantable or portable sensors. Each paper presents the design, databases used, methodological background, obtained results, and their interpretation for biomedical applications. Revealing examples are brain–machine interfaces for medical rehabilitation, the evaluation of sympathetic nerve activity, a novel automated diagnostic tool based on ECG data to diagnose COVID-19, machine learning-based hypertension risk assessment by means of photoplethysmography and electrocardiography signals, Parkinsonian gait assessment using machine learning tools, thorough analysis of compressive sensing of ECG signals, development of a nanotechnology application for decoding vagus-nerve activity, detection of liver dysfunction using a wearable electronic nose system, prosthetic hand control using surface electromyography, epileptic seizure detection using a CNN, and premature ventricular contraction detection using deep metric learning. Thus, this reprint presents significant clinical applications as well as valuable new research issues, providing current illustrations of this new field of research by addressing the promises, challenges, and hurdles associated with the synergy of biosignal processing and AI through 16 different pertinent studies. Covering a wide range of research and application areas, this book is an excellent resource for researchers, physicians, academics, and PhD or master students working on (bio)signal and image processing, AI, biomaterials, biomechanics, and biotechnology with applications in medicine

Non-covalent interactions in organotin(IV) derivatives of 5,7-ditertbutyl- and 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine as recognition motifs in crystalline self- assembly and their in vitro antistaphylococcal activity

Non-covalent interactions are known to play a key role in biological compounds due to their stabilization of the tertiary and quaternary structure of proteins [1]. Ligands similar to purine rings, such as triazolo pyrimidine ones, are very versatile in their interactions with metals and can act as model systems for natural bio-inorganic compounds [2]. A considerable series (twelve novel compounds are reported) of 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp) and 5,7-diphenyl- 1,2,4-triazolo[1,5-a]pyrimidine (dptp) were synthesized and investigated by FT-IR and 119Sn M\uf6ssbauer in the solid state and by 1H and 13C NMR spectroscopy, in solution [3]. The X-ray crystal and molecular structures of Et2SnCl2(dbtp)2 and Ph2SnCl2(EtOH)2(dptp)2 were described, in this latter pyrimidine molecules are not directly bound to the metal center but strictly H-bonded, through N(3), to the -OH group of the ethanol moieties. The network of hydrogen bonding and aromatic interactions involving pyrimidine and phenyl rings in both complexes drives their self-assembly. Noncovalent interactions involving aromatic rings are key processes in both chemical and biological recognition, contributing to overall complex stability and forming recognition motifs. It is noteworthy that in Ph2SnCl2(EtOH)2(dptp)2 \u3c0\u2013\u3c0 stacking interactions between pairs of antiparallel triazolopyrimidine rings mimick basepair interactions physiologically occurring in DNA (Fig.1). M\uf6ssbauer spectra suggest for Et2SnCl2(dbtp)2 a distorted octahedral structure, with C-Sn-C bond angles lower than 180\ub0. The estimated angle for Et2SnCl2(dbtp)2 is virtually identical to that determined by X-ray diffraction. Ph2SnCl2(EtOH)2(dptp)2 is characterized by an essentially linear C-Sn-C fragment according to the X-ray all-trans structure. The compounds were screened for their in vitro antibacterial activity on a group of reference staphylococcal strains susceptible or resistant to methicillin and against two reference Gramnegative pathogens [4] . We tested the biological activity of all the specimen against a group of staphylococcal reference strains (S. aureus ATCC 25923, S. aureus ATCC 29213, methicillin resistant S. aureus 43866 and S. epidermidis RP62A) along with Gram-negative pathogens (P. aeruginosa ATCC9027 and E. coli ATCC25922). Ph2SnCl2(EtOH)2(dptp)2 showed good antibacterial activity with a MIC value of 5 \u3bcg mL-1 against S. aureus ATCC29213 and also resulted active against methicillin resistant S. epidermidis RP62A