Cable-driven parallel robot for transoral laser phonosurgery

Transoral laser phonosurgery (TLP) is a common surgical procedure in otolaryngology. Currently, two techniques are commonly used: free beam and fibre delivery. For free beam delivery, in combination with laser scanning techniques, accurate laser pattern scanning can be achieved. However, a line-of-sight to the target is required. A suspension laryngoscope is adopted to create a straight working channel for the scanning laser beam, which could introduce lesions to the patient, and the manipulability and ergonomics are poor. For the fibre delivery approach, a flexible fibre is used to transmit the laser beam, and the distal tip of the laser fibre can be manipulated by a flexible robotic tool. The issues related to the limitation of the line-of-sight can be avoided. However, the laser scanning function is currently lost in this approach, and the performance is inferior to that of the laser scanning technique in the free beam approach. A novel cable-driven parallel robot (CDPR), LaryngoTORS, has been developed for TLP. By using a curved laryngeal blade, a straight suspension laryngoscope will not be necessary to use, which is expected to be less traumatic to the patient. Semi-autonomous free path scanning can be executed, and high precision and high repeatability of the free path can be achieved. The performance has been verified in various bench and ex vivo tests. The technical feasibility of the LaryngoTORS robot for TLP was considered and evaluated in this thesis. The LaryngoTORS robot has demonstrated the potential to offer an acceptable and feasible solution to be used in real-world clinical applications of TLP. Furthermore, the LaryngoTORS robot can combine with fibre-based optical biopsy techniques. Experiments of probe-based confocal laser endomicroscopy (pCLE) and hyperspectral fibre-optic sensing were performed. The LaryngoTORS robot demonstrates the potential to be utilised to apply the fibre-based optical biopsy of the larynx.Open Acces

Intraoperative robotic-assisted large-area high-speed microscopic imaging and intervention

Objective: Probe-based confocal endomicroscopy is an emerging high-magnification optical imaging technique that provides in-vivo and in-situ cellular-level imaging for real-time assessment of tissue pathology. Endomicroscopy could potentially be used for intraoperative surgical guidance, but it is challenging to assess a surgical site using individual microscopic images due to the limited field-of-view and difficulties associated with manually manipulating the probe. Methods: In this paper, a novel robotic device for large-area endomicroscopy imaging is proposed, demonstrating a rapid, but highly accurate, scanning mechanism with image-based motion control which is able to generate histology-like endomicroscopy mosaics. The device also includes, for the first time in robotic-assisted endomicroscopy, the capability to ablate tissue without the need for an additional tool. Results: The device achieves pre-programmed trajectories with positioning accuracy of less than 30um, the image-based approach demonstrated that it can suppress random motion disturbances up to 1.25mm/s. Mosaics are presented from a range of ex-vivo human and animal tissues, over areas of more than 3mm², scanned in approximate 10s. Conclusion: This work demonstrates the potential of the proposed instrument to generate large-area, high-resolution microscopic images for intraoperative tissue identification and margin assessment. Significance: This approach presents an important alternative to current histology techniques, significantly reducing the tissue assessment time, while simultaneously providing the capability to mark and ablate suspicious areas intraoperatively

An Investigation of the Diagnostic Potential of Autofluorescence Lifetime Spectroscopy and Imaging for Label-Free Contrast of Disease

The work presented in this thesis aimed to study the application of fluorescence lifetime spectroscopy (FLS) and fluorescence lifetime imaging microscopy (FLIM) to investigate their potential for diagnostic contrast of diseased tissue with a particular emphasis on autofluorescence (AF) measurements of gastrointestinal (GI) disease. Initially, an ex vivo study utilising confocal FLIM was undertaken with 420 nm excitation to characterise the fluorescence lifetime (FL) images obtained from 71 GI samples from 35 patients. A significant decrease in FL was observed between normal colon and polyps (p = 0.024), and normal colon and inflammatory bowel disease (IBD) (p = 0.015). Confocal FLIM was also performed on 23 bladder samples. A longer, although not significant, FL for cancer was observed, in paired specimens (n = 5) instilled with a photosensitizer. The first in vivo study was a clinical investigation of skin cancer using a fibre-optic FL spectrofluorometer and involved the interrogation of 27 lesions from 25 patients. A significant decrease in the FL of basal cell carcinomas compared to healthy tissue was observed (p = 0.002) with 445 nm excitation. A novel clinically viable FLS fibre-optic probe was then applied ex vivo to measure 60 samples collected from 23 patients. In a paired analysis of neoplastic polyps and normal colon obtained from the same region of the colon in the same patient (n = 12), a significant decrease in FL was observed (p = 0.021) with 435 nm excitation. In contrast, with 375 nm excitation, the mean FL of IBD specimens (n = 4) was found to be longer than that of normal tissue, although not statistically significant. Finally, the FLS system was applied in vivo in 17 patients, with initial data indicating that 435 nm excitation results in AF lifetimes that are broadly consistent with ex vivo studies, although no diagnostically significant differences were observed in the signals obtained in vivo.Open Acces

Developing endoscopic instrumentation and techniques for in vivo fluorescence lifetime imaging and spectroscopy

Confocal fluorescence endomicroscopes employ fibre optics along with miniaturised scanning and focussing mechanisms to allow microscopic investigation of remote tissue samples with sub-cellular resolution. For this reason they are widely used in biomedical research, both in clinical studies and in small animal imaging experiments. Fluorescence lifetime imaging microscopy (FLIM) has been shown to provide contrast between normal and unhealthy tissue in several diseases including gastro-intestinal (GI) cancer. As such, there is significant interest in developing instrumentation that will allow endoscopic confocal FLIM as this would permit the in vivo investigation of human GI tissue. This thesis describes the development and use of several instruments and techniques aimed at clinically viable in vivo fluorescence lifetime spectroscopy and confocal endomicroscopy. This research has consisted of two broad branches: the study of the fluorescence signature of healthy and diseased tissue both ex vivo and in vivo; and the development of a novel method for achieving beam scanning in confocal endomicroscopy. Firstly the tissue studies are discussed. This begins with the application of a compact steady-state diffuse reflectance/fluorescence spectrometer and a fibre-optic-coupled time-resolved spectrofluorometer to an in vivo investigation of the spectral signatures of skin cancer. This study – which involved the interrogation of 27 clinically diagnosed lesions – was carried out in collaboration with researchers at Lund University in Sweden and revealed significant differences between healthy and diseased tissue both in terms of fluorescence lifetime and steady state reflectance and fluorescence spectra. Further to this study, work is presented charting the development of a clinically viable spectrometer, which measures time-resolved fluorescence spectra with two excitation wavelengths (375 nm and 435 nm) as well as diffuse reflectance spectra. The entire system is contained within a compact trolley (120 x 70 x 55 cm) for easy transportation and safe use in a clinic. It utilises a fibre optic probe to deliver/collect light that can be inserted into the working channel of a medical endoscope meaning that the system can be used to measure diffuse reflectance and time-resolved fluorescence spectra in the GI tract in vivo. The development and testing of this system are discussed and data are presented from both ex vivo and in vivo studies of GI cancer. The second broad section of this thesis focuses more closely on confocal endomicroscopy. Firstly current methods used in this field are discussed and the sources of several drawbacks are explained. A novel approach to laser scanning endomicroscopy is then presented, which requires no moving parts and can be implemented without the need for any distal scanners or optics. This technique is similar in concept to the use of adaptive optics to focus through turbid media: it utilises a proximal spatial light modulator to correct for phase variations across a fibre imaging bundle and then to encode for arbitrary wavefronts at the distal end of that fibre bundle. Thus, it is possible to realise both focussing and beam scanning at the output of the fibre bundle with no distal components, permitting extremely compact endoscopic probes to be developed. Proof-of-principle results are presented illustrating the imaging capabilities of this novel system as well as simulations showing the achievable resolution and field of view in several feasible endoscopic configurations. Overall, this thesis contains work from two quite different projects both aimed at developing novel optical techniques for clinical diagnostic use in endoscopic procedures. The first is aimed at investigating the temporal and spectral properties of the fluorescence and reflectance signatures of cancer, while the goal of the second is to develop improved confocal endomicroscopes

Robotic manipulators for single access surgery

This thesis explores the development of cooperative robotic manipulators for enhancing surgical precision and patient outcomes in single-access surgery and, specifically, Transanal Endoscopic Microsurgery (TEM). During these procedures, surgeons manipulate a heavy set of instruments via a mechanical clamp inserted in the patient’s body through a surgical port, resulting in imprecise movements, increased patient risks, and increased operating time. Therefore, an articulated robotic manipulator with passive joints is initially introduced, featuring built-in position and force sensors in each joint and electronic joint brakes for instant lock/release capability. The articulated manipulator concept is further improved with motorised joints, evolving into an active tool holder. The joints allow the incorporation of advanced robotic capabilities such as ultra-lightweight gravity compensation and hands-on kinematic reconfiguration, which can optimise the placement of the tool holder in the operating theatre. Due to the enhanced sensing capabilities, the application of the active robotic manipulator was further explored in conjunction with advanced image guidance approaches such as endomicroscopy. Recent advances in probe-based optical imaging such as confocal endomicroscopy is making inroads in clinical uses. However, the challenging manipulation of imaging probes hinders their practical adoption. Therefore, a combination of the fully cooperative robotic manipulator with a high-speed scanning endomicroscopy instrument is presented, simplifying the incorporation of optical biopsy techniques in routine surgical workflows. Finally, another embodiment of a cooperative robotic manipulator is presented as an input interface to control a highly-articulated robotic instrument for TEM. This master-slave interface alleviates the drawbacks of traditional master-slave devices, e.g., using clutching mechanics to compensate for the mismatch between slave and master workspaces, and the lack of intuitive manipulation feedback, e.g. joint limits, to the user. To address those drawbacks a joint-space robotic manipulator is proposed emulating the kinematic structure of the flexible robotic instrument under control.Open Acces

Fast widefield techniques for fluorescence and phase endomicroscopy

Thesis (Ph.D.)--Boston UniversityEndomicroscopy is a recent development in biomedical optics which gives researchers and physicians microscope-resolution views of intact tissue to complement macroscopic visualization during endoscopy screening. This thesis presents HiLo endomicroscopy and oblique back-illumination endomicroscopy, fast widefield imaging techniques with fluorescence and phase contrast, respectively. Fluorescence imaging in thick tissue is often hampered by strong out-of-focus background signal. Laser scanning confocal endomicroscopy has been developed for optically-sectioned imaging free from background, but reliance on mechanical scanning fundamentally limits the frame rate and represents significant complexity and expense. HiLo is a fast, simple, widefield fluorescence imaging technique which rejects out-of-focus background signal without the need for scanning. It works by acquiring two images of the sample under uniform and structured illumination and synthesizing an optically sectioned result with real-time image processing. Oblique back-illumination microscopy (OBM) is a label-free technique which allows, for the first time, phase gradient imaging of sub-surface morphology in thick scattering tissue with a reflection geometry. OBM works by back-illuminating the sample with the oblique diffuse reflectance from light delivered via off-axis optical fibers. The use of two diametrically opposed illumination fibers allows simultaneous and independent measurement of phase gradients and absorption contrast. Video-rate single-exposure operation using wavelength multiplexing is demonstrated

Progress in Probe-Based Sensing Techniques for In Vivo Diagnosis

Advancements in robotic surgery help to improve the endoluminal diagnosis and treatment with minimally invasive or non-invasive intervention in a precise and safe manner. Miniaturized probe-based sensors can be used to obtain information about endoluminal anatomy, and they can be integrated with medical robots to augment the convenience of robotic operations. The tremendous benefit of having this physiological information during the intervention has led to the development of a variety of in vivo sensing technologies over the past decades. In this paper, we review the probe-based sensing techniques for the in vivo physical and biochemical sensing in China in recent years, especially on in vivo force sensing, temperature sensing, optical coherence tomography/photoacoustic/ultrasound imaging, chemical sensing, and biomarker sensing

Flexible Robotic Scanning Device for Intraoperative Endomicroscopy in MIS

Optical biopsy methods such as probe-based confocal endomicroscopy can provide intraoperative real-time assessment of tumour margins, including during minimally invasive surgery with flexible endoscopes or robotic platforms. Mosaics can be produced by translating the probe across the target, but it remains difficult to scan over a large field-of-view with a flexible endomicroscope. In this paper, we have developed a novel flexible scanning device for intraoperative endomicroscopy in MIS. A Schott leached imaging bundle was integrated into the device and enables the approach, via a flexible path, to deep and narrow spaces in the human body that otherwise would not accessible. The proposed device uses a gear-based flexible concentric tube scanning mechanism to facilitate large field-of-view mosaicing. Experimental results show that the device is able to scan different surface trajectories (e.g. a spiral pattern over a hemi-spherical surface). Results from lens tissue paper and porcine liver tissue are demonstrated, illustrating a viable scanning approach for endomicroscopy in MIS