New Techniques in Gastrointestinal Endoscopy

As result of progress, endoscopy has became more complex, using more sophisticated devices and has claimed a special form. In this moment, the gastroenterologist performing endoscopy has to be an expert in macroscopic view of the lesions in the gut, with good skills for using standard endoscopes, with good experience in ultrasound (for performing endoscopic ultrasound), with pathology experience for confocal examination. It is compulsory to get experience and to have patience and attention for the follow-up of thousands of images transmitted during capsule endoscopy or to have knowledge in physics necessary for autofluorescence imaging endoscopy. Therefore, the idea of an endoscopist has changed. Examinations mentioned need a special formation, a superior level of instruction, accessible to those who have already gained enough experience in basic diagnostic endoscopy. This is the reason for what these new issues of endoscopy are presented in this book of New techniques in Gastrointestinal Endoscopy

Wireless capsule endoscope for targeted drug delivery

The diagnosis and treatment of pathologies of the gastrointestinal (GI) tract are performed routinely by gastroenterologists using endoscopes and colonoscopes, however the small intestinal tract is beyond the reach of these conventional systems. Attempts have been made to access the small intestines with wireless capsule endoscopes (WCE). These pill-sized cameras take pictures of the intestinal wall and then relay them back for evaluation. This practice enables the detection and diagnosis of pathologies of the GI tract such as Crohn's disease, small intestinal tumours such as lymphoma and small intestinal cancer. The problems with these systems are that they have limited diagnostic capabilities and they do not offer the ability to perform therapy to the affected areas leaving only the options of administering large quantities of drugs or surgical intervention. To address the issue of administering therapy in the small intestinal tract this thesis presents an active swallowable microrobotic platform which has novel functionality enabling the microrobot to treat pathologies through a targeted drug delivery system. This thesis first reviews the state-of-the-art in WCE through the evaluation of current and past literature. A review of current practises such as flexible sigmoidoscopy, virtual colonoscopy and wireless capsule endoscopy are presented. The following sections review the state-of-the-art in methods of resisting peristalsis, drug targeting systems and drug delivery. A review of actuators is presented, in the context of WCE, with a view to evaluate their acceptability in adding functionality to current WCEs. The thesis presents a novel biologically-inspired holding mechanism which overcomes the issue of resisting natural peristalsis in the GI tract. An analysis of the two components of peristaltic force, circumferential and longitudinal peristaltic contractions, are presented to ensure correct functionality of the holding mechanism. A detailed analysis of the motorised method employed to deploy the expanding mechanism is described and a 5:1 scale prototype is presented which characterises the gearbox and validates the holding mechanism. The functionality of WCE is further extended by the inclusion of a novel targeting mechanism capable of delivering a metered dose of medication to a target site of interest in the GI tract. A solution to the problem of positioning a needle within a 360 degree envelope, operating the needle and safely retracting the needle in the GI tract is discussed. A comprehensive analysis of the mechanism to manoeuvre the needle is presented and validation of the mechanism is demonstrated through the evaluation of scale prototypes. Finally a drug delivery system is presented which can expel a 1 ml dose of medication, stored onboard the capsule, into the subcutaneous tissue of the GI tract wall. An analysis of the force required to expel the medication in a set period of time is presented and the design and analysis of a variable pitch conical compression spring which will be used to deliver the medication is discussed. A thermo mechanical trigger mechanism is presented which will be employed to release the compressed conical spring. Experimental results using 1:1 scale prototype parts validate the performance of the mechanisms.Open Acces

Computers in Biology and Medicine / Survey on computer aided decision support for diagnosis of celiac disease

Celiac disease (CD) is a complex autoimmune disorder in genetically predisposed individuals of all age groups triggered by the ingestion of food containing gluten. A reliable diagnosis is of high interest in view of embarking on a strict gluten-free diet, which is the CD treatment modality of first choice. The gold standard for diagnosis of CD is currently based on a histological confirmation of serology, using biopsies performed during upper endoscopy. Computer aided decision support is an emerging option in medicine and endoscopy in particular. Such systems could potentially save costs and manpower while simultaneously increasing the safety of the procedure. Research focused on computer-assisted systems in the context of automated diagnosis of CD has started in 2008. Since then, over 40 publications on the topic have appeared. In this context, data from classical flexible endoscopy as well as wireless capsule endoscopy (WCE) and confocal laser endomicrosopy (CLE) has been used. In this survey paper, we try to give a comprehensive overview of the research focused on computer-assisted diagnosis of CD.FWF 24366(VLID)223161

Optimization and acceptance of enteric MRI in inflammatory bowel disease

Inflammatory bowel disease is a chronic inflammatory condition of bowel. CT and barium fluoroscopy are main stay of radiological investigation but impart high radiation dose. MRI is a safe and less invasive technique to assess bowel. The thesis examines the use of magnetic resonance Imaging in enteric inflammatory bowel disease. A discussion on inflammatory bowel disease and overview of MRI techniques, diagnostic features and review of literature is described. A national survey about the uptake of MRI for the investigation of IBD showed that 38% of radiology departments offered enteric MRI and barium studies remaining the main imaging investigation performed. A proforma administered to clinicians in OPD showed significant increase in their diagnostic confidence for small bowel disease after MRE, which had positive impact on therapeutic strategy of 61% of patients. The results of a prospective studies investigating MR colonography as a biomarker of disease activity are then presented. Quantitative measurements of contrast enhancement in normal colon have shown intersegmental differences. Three proposed qualitative MRI scores of disease activity correlated with endoscopic disease activity, but correlation with histopathological scores was less apparent. The use of unprepared colonic MRI in assessment of acute colitis is then investigated. A qualitative total colonic inflammation score (TCIS) proposed and validated against clinical standards including stool frequency and CRP. It also has prognostic ability for length of hospital stay. Region of interest derived quantitative measurements from the colon wall including T2 signal and contrast enhancement are then compared to a validated clinical score of colitis activity. Quantitative markers seemed less robust then qualitative scores, although quantified contrast enhancement is correlated with disease severity. Patient experiences of MR Colonography and colonoscopy are investigated by using face-to-face qualitative interviews, together with a quantitative questionnaire. Patient preference is highly complex but patients expressed overall preference for MRC

Novel component of the fission yeast memory-based polarity landmark

Polarised cells have spatial differences in their shape, structure or function. Polarisation is essential for many cellular processes, including directional growth. This occurs at specific sites within the cell determined by polarity cues. Fission yeast are an excellent model to study how polarity cues are generated and maintained. Fission yeast are rod-shaped cells that grow exclusively from their tips, co-ordinated by two independent internal polarity cues, the Tea1-Tea4 system and the Rax1-Rax2 system. The Tea1-Tea4 polarity cue is highly dynamic and is based on the cell’s existing geometry. Tea1 and Tea4 are delivered to the cell tips on the plus ends of microtubules that run along the length of the cell. The Rax1-Rax2 system is a stable cue and is based on sites of previous growth. Rax1 and Rax2 are delivered to the cell tips through the secretory pathway during active growth. Once delivered, Rax1 and Rax2 are stably retained at the cell tips and are able to recruit growth machinery back to a previously growing cell tip in the next cell cycle. By this mechanism cell is able to ‘remember’ a site of previous cell growth and reinitiate growth from this site. In order to correctly function as a polarity landmark for growth at the cell tips, both Rax1 and Rax2 need to localise correctly. In this work I have shown that large C-terminal tags on Rax2 impair its function, despite Rax2 correctly localising to the cell tips. Additionally, I have shown that Rax1 is required for Rax2 trafficking out of the ER, and that the cytoplasmic 26 amino acids of Rax2 are also required for Rax2 trafficking. I have identified interactors of Rax2-His-Tev-Biotin using cross-linking, purification and mass spectrometry. Known polarity proteins Bgs1, Bgs3, Rga1 and Rga3 were found to interact with Rax2. Additionally, a previously uncharacterised protein, Lrx1, interacts with Rax2 and is important for the correct localisation of Rax1-Rax2 to the cell tips, and thus the correct functioning of the Rax1- Rax2 memory-based polarity cue

Small bowel motility quantitation using MRI and its relationship to gastrointestinal symptoms

The small bowel is difficult to analyse due to its deep anatomical location and the large variation seen in individuals, in regard to both anatomy and function including motility. Dynamic MRI allows small bowel motility to be captured and visually assessed by radiologists, but there is often large inter-observer variation and a lack of complicated motility patterns being investigated. This thesis aims to explore the link between abnormal motility and gastrointestinal (GI) symptoms in Crohn’s disease (CD) and irritable bowel syndrome (IBS) using MRI. Firstly, a scan duration of 15 seconds and a temporal resolution of 1 image per second were shown to be sufficient for robust small bowel MRI motility measurements. Next, a validation study confirmed an association between aberrant motility and CD patient symptoms, particularly diarrhoeal stools (rho = -0.29). The strongest association was in patients with higher symptom severity (rho = -0.633). Building on this work, more complex motility metrics were developed and compared to subjective radiological scoring. Spatial and temporal variation were found to be associated with CD patient symptoms and were also particularly difficult to visually assess. The motility metrics were applied in clinical IBS data to explore differences in IBS subgroups. Significantly reduced temporal variation of motility (P < 0.001) and area of motile bowel (P < 0.001) was found in IBS-C (constipation-predominant) compared to IBS-M (mixed constipation and diarrhoea). Finally, texture analysis (TA) terminal ileum (TI) to colon ratios were found to be higher for TA contrast (P = 0.005) and lower for TA energy (P = 0.03) in IBS-C compared to healthy controls (HCs). Ascending colon diameter was shown to be significantly larger in IBS-C than HCs (P = 0.005)

Shape Memory Alloy Actuators and Sensors for Applications in Minimally Invasive Interventions

Reduced access size in minimally invasive surgery and therapy (MIST) poses several restriction on the design of the dexterous robotic instruments. The instruments should be developed that are slender enough to pass through the small sized incisions and able to effectively operate in a compact workspace. Most existing robotic instruments are operated by big actuators, located outside the patient’s body, that transfer forces to the end effector via cables or magnetically controlled actuation mechanism. These instruments are certainly far from optimal in terms of their cost and the space they require in operating room. The lack of adequate sensing technologies make it very challenging to measure bending of the flexible instruments, and to measure tool-tissue contact forces of the both flexible and rigid instruments during MIST. Therefore, it requires the development of the cost effective miniature actuators and strain/force sensors. Having several unique features such as bio-compatibility, low cost, light weight, large actuation forces and electrical resistivity variations, the shape memory alloys (SMAs) show promising applications both as the actuators and strain sensors in MIST. However, highly nonlinear hysteretic behavior of the SMAs hinders their use as actuators. To overcome this problem, an adaptive artificial neural network (ANN) based Preisach model and a model predictive controller have been developed in this thesis to precisely control the output of the SMA actuators. A novel ultra thin strain sensor is also designed using a superelastic SMA wire, which can be used to measure strain and forces for many surgical and intervention instruments. A da Vinci surgical instrument is sensorized with these sensors in order to validate their force sensing capability

Evaluation of intestinal motility with Magnetic Resonance Enterography and computer post-processing

Small bowel motility is an essential, physiological process central to the processing of ingested food. The small bowel is however anatomically and functionally complex, varying greatly between individuals and located deep within the abdomen making it extremely difficult to access with instrumentation. As a consequence, and in spite of its known or suspected role in a range of diseases, there remain little in the way of objective tests to evaluate or even observe this process in vivo. This thesis details the validation and application of a novel computer post-processing technique that allows the quantification of Magnetic Resonance Enterography derived time-series image data. A background to small bowel physiology and existing techniques is first provided along with an introduction to the registration algorithm used throughout this thesis to quantify small bowel motility. The technique is then applied retrospectively to two Crohn’s disease patient cohorts to explore how this inflammatory bowel disease influences contractility. A prospective evaluation of segmental motility analysis is then presented drawing attention to large within subject variation, in a cohort of healthy volunteers, as a limitation for this technique. As an alternative, a global motility analysis approach is described and validated. Although global measures of motility appeared robust, factors influencing clinical application are further addressed by expanding the technique to allow motility analysis in free-breathing data. In the final piece of research presented, the application of the global technique to a cohort of Chronic Intestinal Pseudo-Obstruction patients is detailed. The thesis is concluded with a reflection of the results and a chapter dedicated to the commercial exploitation of the research to address the ongoing need for a robust test to quantise intestinal motility