The invention of medical imaging technology revolved the process of diagnosing diseases and opened a new world for better studying inside of the human body. In order to capture images from different human organs, different devices have been developed. Gastro-Endoscopy is an example of a medical imaging device which captures images from human gastrointestinal. With the advancement of technology, the issues regarding such devices started to get rectified. For example, with the invention of swallow-able pill photographer which is called Wireless Capsule Endoscopy (WCE); pain, time, and bleeding risk for patients are radically decreased. The development of such technologies and devices has been increased and the demands for instruments providing better performance are grown along the time. In case ofWCE, the special feature requirements such as a small size (as small as an ordinary pill) and wireless transmission of the captured images dictate restrictions in power consumption and area usage. In this research, the reduction of image encoder hardware cost for endoscopic imaging application has been focused. Several encoding algorithms have been studied and the comparative results are discussed. An efficient data encoder based on Lempel-Ziv-Welch (LZW) algorithm is presented. The encoder is a library-based one where the size of library can be modified by the user, and hence, the output data rate can be controlled according to the bandwidth requirement. The simulation is carried out with several endoscopic images and the results show that a minimum compression ratio of 92.5 % can be achieved with a minimum reconstruction quality of 30 dB. The hardware architecture and implementation result in Field-Programmable Gate Array (FPGA) for the proposed window-based LZW are also presented. A new lossy LZW algorithm is proposed and implemented in FPGA which provides promising results for such an application.

The significant development in medical diagnostics and imaging has brought up a lot of new wireless capsule endoscopes coming to health care market. The capsule has been able to minimize patient discomfort and pain during digestive tract screening with less risk of infection and harmless to body organs. This kind of medical procedure is less invasive and gives a great impact compared to the traditional method. Although pill-shaped capsules have existed for over 11 years by now and are currently being used successfully in medical screening to study the GI tract, these systems are passive and are dependent to the peristaltic movement of the gastric wall to propel. The aim of this work is to provide the electronics needed to control an endoscopic capsule robot and the electronics needed to enable active locomotion and advanced vision functions (like autofocus). Enabling such functions the capsules will be able to perform screening, diagnosis and therapy. Such capsule robot has been designed in the framework of the “Versatile Endoscopic Capsule for Gastrointestinal Tumour Recognition and Therapy” (VECTOR) project. This project pursues the goal of realizing smart pill technologies and applications for gastrointestinal (GI) diagnosis and therapy. The overall medical goal of the project is to enable medical devices through advanced technology that can dramatically improve early detection and treatment of GI early cancers and cancer precursors. The main technological objective of the project is the take-up of microsystems and sub-components and their integration into robotic, mobile pill devices for useful and large impact applications in the medical field.

The main objective of this research was to develop a two-stage optical imaging platform to improve detection of cancer in Barrett’s esophagus (BE). BE caused by chronic reflux and patients with BE are at a higher risk for developing esophageal adenocarcinoma (EAC). However, neoplasia in BE is often unidentifiable under standard endoscopy, and studies have shown nearly half of early cancers can go unidentified by this method. Widefield imaging (resolves ~100 microns) allows efficient surveillance of large BE segments. Two widefield imaging techniques were identified to improve contrast between benign and abnormal lesions during an ex vivo 15 patient feasibility study. Cross-polarized imaging (CPI) reduced specular reflection and improved vascular contrast. Vital-dye fluorescence imaging (VFI) using topically-applied proflavine improved visualization of glandular pattern. Moreover, relevant pathologic features visible during VFI were seen in corresponding histology slides as well as high resolution images of the same sites. Based on these results, a cap-based Multispectral Digital Endoscope (MDE) was designed and built. The MDE can image in three different imaging modes: white light imaging, CPI, and VFI. Modifications to a Pentax EPK-i video processor and a Pentax endoscope were made to incorporate these imaging modes into one system. A 21 patient in vivo pilot study with 65 pathologically correlated sites demonstrated the feasibility of using this system in vivo; image criteria were developed to classify neoplasia with a sensitivity and specificity of 100% and 76% respectively. High resolution imaging (resolves ~2-5 micron) may verify the disease presence in suspicious areas identified using widefield techniques. 2-NBDG, a fluorescent metabolic marker, was used as to identify neoplastic biopsies. In a study with 21 patients yielding 38 pathologically correlated biopsies and 158 image sites, 2-NBDG imaging allowed classification of cancerous biopsies with a sensitivity of 96% and specificity of 90%. The unique contributions of these results is the development of a multimodal cap-based endoscopic system to identify suspicious areas in BE, and using a metabolic marker to verify the presence of disease. This application extends beyond esophageal cancer detection and may be explored for cancer detection in other organ sites characterized by columnar epithelium.

A major problem to be solved in health informatics is high quality, structured and timely data collection. Standard terminologies and uniform domain conceptual models are important steps to alleviate this problem which are also proposed to enable interoperability among systems. With the aim of contributing to the solution of this problem, this study proposes novel features for the Archetypes and multi-level modeling technique in health information and knowledge modeling. The study consists of the development of a research prototype for endoscopic data management, and based on that experience, the extension of Minimal Standard Terminology in Digestive Endoscopy (MST). A major contribution of the study consists of significant extensions to the modeling formalism. The proposed modeling approach may be used in the design and development of health information systems based on archetypes for structured data collection, validation and dynamic user interface creation. The thesis work is aimed to make considerable contribution to the emerging Electronic Health Records (EHR) standards and specifications.

We evaluate the changes in fluorescence from endogenous fluorophores such as amino acids, structural proteins and enzymatic co-factors to predict malignancy and risk of developing ovarian cancer. 249 ovarian biopsies of the surface epithelium were interrogated in vitro, over 270-550 nm excitation, and fluorescence was collected from 290-700nm. Spectroscopic data was analyzed using parallel factor analysis (PARAFAC) to determine excitation and emission spectra of the underlying fluorophores that contribute to the total detected fluorescence intensity. Using multivariate normal distribution fits and cross-validation techniques, sensitivity (SN) and specificity (SP) of 88 and 93 percent, respectively, were achieved when classifying malignant samples versus others, while 88 and 80 percent, respectively, were achieved when classifying normal post menopausal patients as being either at low- or high-risk of developing ovarian cancer based on their personal and family history of cancer. Also, the performance of classifying cancer increases when the normal group excludes benign neoplasm and endometriosis samples, while the performance of low- v. high-risk decreases when both pre- and post-menopausal samples are included. These results could potentially be useful in screening women at increased risk of developing ovarian cancer. This motivated our study to investigate similar changes in ovarian autofluorescence in vivo. 40 patients were recruited and a total of 189 samples were imaged using a fiber optic bundle and biopsied. Using PARAFAC, the factors computed from in vitro data analysis and in vitro data as a training set; pathology from each in vivo site biopsied was compared to calibrated tissue-fluorescence. It resulted in a SN and SP of 100 and 94 percent, respectively, for classifying normal versus malignant. In the case of risk assessment, cross validated in vivo data gave a SN and SP of 68 and 93%. Results obtained were consistent with those obtained in vitro, except for the presence of blood absorption peaks which affected risk assessment. Assessing endogenous fluorescence has diagnostic potential and if adapted to trans-vaginal access, would make the screening procedure less costly and less invasive, and would be most useful and economical in women at increased risk of developing ovarian cancer and might determine the ideal time to undergo an oophorectomy.

Optical coherence tomography (OCT) is a technology that enables 2D cross-sectional images of tissue microstructure. This interferometric technique provides resolutions of approximately 10-20 um with a penetration depth of 1-2 mm in highly scattering tissues. With the use of fiber optics, OCT systems have been developed for intravascular imaging with a demonstrated improvement in both resolution and dynamic range compared to commercial intravascular ultrasound systems. OCT studies of normal, atherosclerotic, and stented arteries indicate the ability of OCT to visualize arterial structures. These results suggest OCT may be a valuable tool for studying luminal structures in tissue engineered constructs.In the present study, new endoscopic OCT systems and analysis techniques were developed to visualize the growth and response of the cellular lining within a tissue engineered blood vessel mimic (BVM). The BVM consists of two primary components. A biocompatible polymeric scaffold is used to form the tubular structure. Human microvessel cells from adipose tissue are sodded on to the inner surface of the scaffold. These constructs are then developed and imaged within a sterile bioreactor.Three specific aims were defined for the present study. First, an OCT longitudinal scanning endoscope was developed. With this endoscope, a study of 16 BVMs was performed comparing images from OCT and corresponding histological sections. The study demonstrated that endoscopic imaging did not visually damage the mimic cellular lining. OCT images showed excellent correlation with corresponding histologicalsections. Second, a concentric three element endoscope was developed to provide radial cross-sections of the BVM. OCT images using this endoscope monitored lining development on three types of polymeric scaffolds. In the third specific aim, automated algorithms were developed to assess the percent cellular coverage of a stent using volumetric OCT images.The results of the present study suggest that OCT endoscopic systems may be a valuable tool for assessing and optimizing the development of tissue engineered constructs. Conversely, the BVMs modeled the arterial response to deployed stents allowing the development of automated OCT analysis software. These results suggest that blood vessel mimics may be used to advance OCT technology and techniques.

No description available.

Zielsetzung: In dieser Studie wurde an 15 gesunden Rindern die Methode der Thorakoskopie erprobt mit dem Ziel, eine Grundlage für den weiteren Einsatz dieses Verfahrens am bovinen Thorax zu schaffen. Im Mittelpunkt standen die Entwicklung einer geeigneten Untersuchungstechnik und die Beschreibung der endoskopisch dargestellten, im Pleuraspalt gelegenen Organe sowie möglicher pathologischer Befunde. Weiterhin galt es Komplikationen zu ermitteln und anhand der Erfahrungen aus diesem Versuch Indikationen für den Einsatz dieses minimal-invasiven Verfahrens beim Rind zu formulieren. Methodik: Alle Tiere wurden einer links- und rechtsseitigen Thorakoskopie jeweils mit und ohne intrapleurale Insufflation von Kohlenstoffdioxid über einen interkostalen Zugang unterzogen. Im Rahmen des Versuches fanden folglich vier Thorakoskopien je Rind und insgesamt 60 Thorakoskopien mit einer Wartezeit von 24 Stunden zwischen den einzelnen Untersuchungen statt. Die Untersuchungen erfolgten am im Zwangsstand fixierten, lokal anästhesierten Tier. Der endoskopische Zugang lag stets auf Höhe des Tuber coxae und variierte vom 8. bis zum 10. Interkostalraum. Nach interkostaler Schnittinzision wurde eine Zitzenkanüle bis in den Pleuraspalt vorgeschoben. Der spontane Einstrom von Raumluft in das Cavum pleurae führte zum Teilkollaps des ipsilateralen Lungenflügels. Die Kanüle wurde durch eine Trokar-Hülsen-Einheit ersetzt und die Hülse stellte nach Entfernung des Trokars den Zugang für die Optik. Je Hemithorax wurde die Untersuchungszeit auf 20 Minuten festgelegt. Sie begann im kranialen Pleuraspalt, wurde über (dorso)-kranial, (dorso)-medial, (dorso)-kaudal, ventrokaudal und ventral fortgeführt und endete mit ventrokranial ausgerichteter Optik. Ergebnisse: Die meisten im Cavum pleurae gelegenen Organe konnten ohne die Insufflation von CO2 ausreichend adspiziert werden. Während der links- und rechtsseitigen Thorakoskopien gelang die Adspektion großer Bereiche der Pleura costalis mit den Mm. intercostales interni sowie den Aa. et Vv. intercostales dorsales, Anteile der Lungenflügel und des Ligamentum pulmonale, der Aorta thoracica, des thorakalen Ösophagus, des M. longus colli, von Lymphknoten des Lc. thoracicum dorsale sowie der Lnn. mediastinales caudales, der Pars thoracica des Truncus sympathicus und des Truncus vagalis dorsalis des N. vagus. Des Weiteren konnten der M. psoas major, Anteile des Diaphragmas und der V. phrenica cranialis, der Hiatus aorticus, der Arcus lumbocostalis sowie unregelmäßig die A. et V. bronchoesophagea adspiziert werden. Die Untersuchung des rechten kranialen Pleuraspaltes war mit Einschränkungen behaftet und spiegelte sich in einer reduzierten Darstellung der sympathische Nervenfasern aus dem Ggl. cervicothoracicum, des Truncus costocervicalis dextra sowie der V. costocervicalis dextra wider. Linksseitig war die Betrachtung dieser Organe bzw. der korrespondierenden linksseitig angelegten Organe regelmäßig möglich. Weiterhin gelang während der linksseitigen Untersuchung die Adspektion des Ln. tracheobronchalis sinister, des Truncus brachiocephalicus sowie der V. azygos sinistra. Rechtsseitig konnte die V. azygos dextra stets adspiziert werden. Die Darstellung des Ductus thoracicus erfolgte nur bei einem der untersuchten Rinder infolge einer pathologischen Kompression. Während der Untersuchungen unter passivem Lungenkollaps war das Perikard nur bei einer rechtsseitigen Thorakoskopie zu sehen. Die Zweituntersuchungen des ipsilateralen Pleuraspaltes fanden während der Insufflation von CO2 bis zu einem Überdruck von 5 mm Hg statt. Dies sollte einen stärkeren Lungenkollaps bewirken und damit die Sicht auf intrapleural gelegene Organe verbessern. Während der Insufflation waren beidseits größere Anteile der Rippen und des Zwerchfells sowie das Perikard linksseitig bei drei Rindern und rechtsseitig bei einem Rind darstellbar. Postoperative Röntgenaufnahmen dienten dem Ausschluss des Vorhandenseins eines ipsi- oder kontralateralen Pneumothorax. Schlussfolgerung: Die Studie zeigt, dass Thorakoskopien an stehenden, gesunden Rindern sicher und komplikationsarm durchzuführen sind. Die beschriebene, minimal-invasive Technik stellt eine wertvolle, zusätzliche Methode zur tierschonenden Abklärung intrathorakaler Erkrankungen beim Rind dar. Der diagnostische, palliative oder therapeutische Nutzen muss in weiterführenden Untersuchungen ermittelt werden. / Objective: A study on 15 healthy cows was conducted to prove the thoracoscopic technique with the aim to establish a basis for further application of this procedure on cattle. Focus was on developing an adequate examination technique, displaying and describing of physical as well as pathological findings on intrathoracic organs examined endoscopically. Furthermore perioperative complications and indications of this minimally invasive method on cattle should be presented. Methods: The animals underwent a left and right side thoracoscopy under passive lung collapse and under insufflation of CO2. Therefore four thoracoscopies at each cow and a total of 60 thoracoscopies were performed with a waiting time of 24 hours between each examination. The cows were restrained in a stock and locally anesthetized. The endoscopic portal was lined up horizontally with the level of the ventral margin of the coxal tuber, at the point where the local anaesthetic had been injected and varied between the eighth and the tenth intercostal space. After a vertical stab incision through the skin and subcutaneous tissues a blunt stainless teat cannula was introduced into the pleural space. At this point air streamed spontaneously into the pleural space following by an ipsilateral lung collapse. The teat cannula was then removed and replaced by a sharp guarded trocar. After that the trocar was removed and the endoscope was passed through the remaining cannula. The time assessment for examination of each thorax was 20 minutes, started in the cranial pleural space, was continued in the (dorso)-cranial, (dorso)-medial, (dorso)-caudal, ventrocaudal und ventral direction and ended with ventrocranially aligned optic. Results: Most of the intrathoracic organs were seen without additional CO2 insufflation. During left and right side thoracoscopies large parts of the costal pleura, the internal intercostal muscles, the dorsal intercostal veins and arteries, parts of the lungs and the pulmonary ligament, the thoracic aorta, the thoracic part of the esophagus and the longus colli muscle, caudal mediastinal lymph nodes and lymph nodes associated with the dorsal thoracic lymph center, the thoracic part of the sympathic trunk and the dorsal vagus nerve were seen. Furthermore the psoas major muscle, parts of the diaphragm and the cranial phrenic vein, the aortic hiatus, the lumbocostal arch and intermittently the broncho-esophageal artery and vein could be identified. There were some constraints during right side thoracoscopy of the cranial pleural space which caused a limited view at the sympathic nerve fibres associated with the cervicothoracic ganglion, the right costocervical trunk and the right costocervical vein. At the left side these organs, the corresponding left side organs respectively, were constantly seen. Moreover during the exam at the left pleural space the left tracheobronchial lymph node, the brachiocephalic trunk and the left azygos could be well identified. During right side thoracoscopy the right azygos vein was always visible. In one case the presentation of the thoracic duct succeeded as a result of its pathological compression. During examination under passive lung collapse the pericard was visualized in one cow during right side thoracoscopy. The second thoracoscopies of the ipsilateral pleural space were conducted during insufflation of CO2 with a pressure of 5 mm Hg. A stronger lung collapse should result during insufflation with an enhanced view of the organs located intrapleurally. During insufflation at both sides larger parts of the ribs and diaphragm as well as the pericard on the left side at three cattle and on the right side at one cattle could be seen. Postoperative radiographies ensured the absence of an ipsi- or contralateral pneumothorax. Conclusion: This study shows that thoracoscopies on standing healthy cattle could be safely performed without major perioperative complications or side effects. The described minimally invasive procedure is a valuable, gentle and additional method to diagnose intrathoracic diseases in cattle. The use of thoracoscopy as diagnostic tool, for curative and palliative therapy should be identified in further studies.

Fluorescence molecular imaging has been triggering interest in the scientific community for the last decade due to its great potential for improved early cancer detection and image-guided treatment. Semiconductor nanoparticles, also known as quantum dots, have been identified as potential contrast agents for molecular imaging, but there is a lack of quantitative contrast optimization studies that would enable precise and robust dosimetry calculations. These calculations are crucial to determine the feasibility, risk and cost of any contrast-enhanced clinical imaging procedure. This thesis presents a first attempt at developing a quantitative dosimetry framework for quantum dot-based contrast-enhanced fluorescence molecular imaging, by combining novel experimental methods and validated mathematical models. Three studies were completed to develop the dosimetry framework. In the first study, we design a novel homogenized optical tissue phantom approach to investigate with precision the effects of various photophysical parameters, such as the excitation and emission wavelengths, tissue absorption and scattering coefficient spectra, tissue autofluorescence spectra, target fluorescence spectra and target depth, on the detected contrast. In the second study, we use the approach to investigate the influence of tissue optical absorption and scattering on contrast behavior for various ex vivo tissue samples, and develop performance metrics to quantify the optimization results. In the third study, we perform vascular fluorescence contrast-enhanced imaging in the dorsal skinfold window chamber mouse model to investigate the effects of pharmacokinetics, blood absorption, vessel diameter and injected dose on the detected contrast. We also describe the relationship between the injected volume and vascular contrast, and transfer the performance metrics developed previously to estimate the minimum injection dose under various conditions. These studies are expected to serve as a stepping stone to further develop contrast optimization and dosimetry models for the emerging field of fluorescence molecular imaging.

Fluorescence molecular imaging has been triggering interest in the scientific community for the last decade due to its great potential for improved early cancer detection and image-guided treatment. Semiconductor nanoparticles, also known as quantum dots, have been identified as potential contrast agents for molecular imaging, but there is a lack of quantitative contrast optimization studies that would enable precise and robust dosimetry calculations. These calculations are crucial to determine the feasibility, risk and cost of any contrast-enhanced clinical imaging procedure. This thesis presents a first attempt at developing a quantitative dosimetry framework for quantum dot-based contrast-enhanced fluorescence molecular imaging, by combining novel experimental methods and validated mathematical models. Three studies were completed to develop the dosimetry framework. In the first study, we design a novel homogenized optical tissue phantom approach to investigate with precision the effects of various photophysical parameters, such as the excitation and emission wavelengths, tissue absorption and scattering coefficient spectra, tissue autofluorescence spectra, target fluorescence spectra and target depth, on the detected contrast. In the second study, we use the approach to investigate the influence of tissue optical absorption and scattering on contrast behavior for various ex vivo tissue samples, and develop performance metrics to quantify the optimization results. In the third study, we perform vascular fluorescence contrast-enhanced imaging in the dorsal skinfold window chamber mouse model to investigate the effects of pharmacokinetics, blood absorption, vessel diameter and injected dose on the detected contrast. We also describe the relationship between the injected volume and vascular contrast, and transfer the performance metrics developed previously to estimate the minimum injection dose under various conditions. These studies are expected to serve as a stepping stone to further develop contrast optimization and dosimetry models for the emerging field of fluorescence molecular imaging.