No description available.

<p>Diffuse reflectance spectroscopy (DRS) is a simple, yet powerful technique that has the potential to offer practical, non-invasive, and cost effective information for op- tical diagnostics and therapeutics guidance. Any progress towards moving DRS systems from their current laboratory settings to clinical settings, field settings and ambitiously to home settings, is a significant contribution to society in terms of reducing ever growing healthcare expenditures of an aging society. Additionally, im- proving on the existing mathematical models used to analyze DRS signals; in terms of speed, robustness, accuracy, and capability in accounting for larger feature space dimensionality (i.e. extraction of more tissue-relevant information) is equally im- portant for real-time diagnosis in the desired settings and to enable use of DRS in as many biomedical applications (e.g. skin cancer diagnosis, diabetics care, tissue oxygenation monitoring) as possible. Improving the reflectance signal complexity and density through novel DRS instrumentation, would facilitate development of the desired models or put the existing ones built on simulations in practical use; which otherwise could not go beyond being a theoretical demonstration.</p><p>DRS studies tissue morphology and composition through quantification of one or more (ideally all of them) of the tissue- and wavelength-specific optical properties: absorption coefficient (μa), reduced scattering coefficient (μ1s), scattering anisotropy (g), tissue thickness, and scattering phase function details (e.g. higher order moments of the scattering phase function). DRS involves sampling of diffusely reflected photons which experience multiple scattering and absorption as they travel within the tissue, at the tissue surface. Spatially resolved diffuse reflectance spectroscopy (SRDRS) is a subset of general DRS technique, which involves sampling of diffuse reflectance signals at multiple distances to an illumination source. SRDRS provides additional spatial information about the photon path; yielding depth-resolved tissue information critical to layered tissue analysis and early cancer diagnostics. Exist- ing SRDRS systems use fiber optic probes, which are limited in accommodation of large number and high-density collection fibers (i.e. yielding more and dense spa- tially resolved diffuse reflectance (SRDR) measurement data) due to difficulty of fiber multiplexing. The circular shape of the fibers restricts the implementable probe ge- ometries and reduces the fill factor for a given source to detector (i.e. collection fiber) separation (SDS); resulting in reduced light collection efficiency. The finite fiber nu- merical aperture (NA) reduces the light collection efficiency well as; and prevents selective interrogation of superficial tissues where most cancers emerge. Addition- ally, SRDR systems using fiber optic probes for photon collection, require one or more photodetectors (i.e. a cooled CCD); which are often expensive components of the systems.</p><p>This thesis deals with development of an innovative silicon SRDRS probe, which partially addresses the challenge of realizing high measurement density, miniaturized, and inexpensive SRDRS systems. The probe is fabricated by conventional, flexible and inexpensive silicon fabrication technology, which demonstrates the feasibility of developing SRDRS probes in any desired geometry and complexity. Although this approach is simple and straightforward, it has been overlooked by the DRS community due to availability of the conventional fiber optic probe technology. This new probe accommodates large number and high density of detectors; and it is in the form of a concentric semi-annular photodiode (PD) array (CMPA) with a central illumination aperture. This is the first multiple source-detector spacing Si SRDRS probe reported to date, and the most densely packed SRDRS probe reported to date for all types of SRDRS systems. The closely spaced and densely packed detectors enable higher density SRDR measurements compared to fiber-based SRDR probes, and the higher PD NA compared to that of fibers results in a higher SNR increasing light collection efficiency. The higher NA of the PDs and the presence of PDs positioned at very short distances from the illumination aperture center enable superficial tissue analysis as well as depth analysis.</p> / Dissertation

<p>Breast conserving surgery (BCS) is a common treatment option for breast cancer patients. The goal of BCS is to remove the entire tumor from the breast while preserving as much normal tissue as possible for a better cosmetic outcome after surgery. Specifically, the excised specimen must have at least 2 mm of normal tissue surrounding the diseased mass. Unfortunately, a staggering 20-70% of patients undergoing BCS require repeated surgeries due to the incomplete removal of the tumor diagnosed post-operatively. Due to these high re-excision rates as well as limited post-operative histopathological sampling of the tumor specimen, there is an unmet clinical need for margin assessment. Quantitative diffuse reflectance spectral imaging has previously been explored as a promising, method for providing real-time visual maps of tissue composition to help surgeons determine breast tumor margins to ensure the complete removal of the disease during breast conserving surgery. We have leveraged the underlying sources of contrast in breast tissue, specifically total hemoglobin content, beta-carotene content, and tissue scattering, and developed various fiber optics based spectral imaging systems for this clinical application. Combined with a fast inverse Monte Carlo model of reflectance, previous studies have shown that this technology may be able to decrease re-excision rates for BCS. However, these systems, which all consist of a broadband source, fiber optics probes, an imaging spectrograph and a CCD, have severe limitations in system footprint, tumor area coverage, and speed for acquisition and analysis. The fiber based spectral imaging systems are not scalable to smaller designs that cover a large surveillance area at a very fast speed, which ultimately makes them impractical for use in the clinical environment. The objective of this dissertation was to design, develop, test, and show clinical feasibility of a novel wide field spectral imaging system that utilizes the same scientific principles of previously developed fiber optics based imaging systems, but improves upon the technical issues, such as size, complexity, and speed,to meet the demands of the intra-operative setting. </p><p>First, our simple re-design of the system completely eliminated the need for an imaging spectrograph and CCD by replacing them with an array of custom annular photodiodes. The geometry of the photodiodes were designed with the goal of minimizing optical crosstalk, maximizing SNR, and achieving the appropriate tissue sensing depth of up to 2 mm for tumor margin assessment. Without the imaging spectrograph and CCD, the system requires discrete wavelengths of light to launch into the tissue sample. A wavelength selection method that combines an inverse Monte Carlo model and a genetic algorithm was developed in order to optimize the wavelength choices specifically for the underlying breast tissue optical contrast. The final system design consisted of a broadband source with an 8-slot filter wheel containing the optimized set of wavelength choices, an optical light guide and quartz light delivery tube to send the 8 wavelengths of light in free space through the back apertures of each annular photodiode in the imaging array, an 8-channel integrating transimpedance amplifier circuit with a switch box and data acquisition card to collect the reflectance signal, and a laptop computer that controls all the components and analyzes the data.</p><p>This newly designed wide field spectral imaging system was tested in tissue-mimicking liquid phantoms and achieved comparable performance to previous clinically-validated fiber optics based systems in its ability to extract optical properties with high accuracy. The system was also tested in various biological samples, including a murine tumor model, porcine tissue, and human breast tissue, for the direct comparison with its fiber optics based counterparts. The photodiode based imaging system achieved comparable or better SNR, comparable extractions of optical properties extractions for all tissue types, and feasible improvements in speed and coverage for future iterations. We show proof of concept in performing fast, wide field spectral imaging with a simple, inexpensive design. With a reduction in size, cost, number of wavelengths used, and overall complexity, the system described by this dissertation allows for a more seamless scaling to higher pixel number and density in future iterations of the technology, which will help make this a clinically translatable tool for breast tumor margin assessment.</p> / Dissertation

No description available.

Magnetisch-induktive Techniken finden seit langer Zeit viele Anwendungsfelder in der Medizin, Sicherheitstechnik und der Industrie. Obwohl die technischen Grundlagen seit vielen Jahrzehnten bekannt sind, werden auf Basis detaillierter Analysen spezielle Lösungsansätze verfolgt, die neuartiges Anwendungspotential erschließen sollen. Dazu dienen verbesserte Werkzeuge wie Computersimulationen und analytische Berechnungen sowie neu kombinierte Methoden und Aufbauten aus Leistungselektronik und Signaldetektion. Die Vorteile magnetisch-induktiver Techniken sind dabei u.a., dass sie das Prüfobjekt nicht schädigen, berührungslos arbeiten, robust gegenüber Verschmutzungen und einfach im Aufbau sind. Ein Nachteil dieser Technik ist die unzureichende Auflösung von feinen Strukturen. In der aktuellen Forschung und Entwicklung werden unterschiedliche Spulenanordnungen zur Anwendung in industriellen und medizinischen Fragestellungen untersucht und optimiert. Thema dieser Arbeit ist es, durch Verbesserung der Spuleneigenschaften, neue Anwendungsbereiche für die zerstörungsfreie Materialprüfung zu erschließen. Es wird eine Methode vorgestellt, die Eigenschaften magnetisch-induktiver Tastspulen zu verbessern und so den Aufwand bei der Signalverarbeitung zur Rekonstruktion im Rechner zu reduzieren sowie die Auflösung zu erhöhen. Dazu werden zwei Spulenanordnungen, Transmissions - Tastspulen und Gradiometer - Tastspulen, vergleichend gegenübergestellt und ihre technischen Grenzen aufgezeigt. / Magneto-inductive techniques are found in many fields of application areas so in medicine, security technology and industry. Although the technical basis has been known for many decades, special solutions are pursued on the basis of detailed analysis that should open new application potential. These are enhanced tools such as computer simulations, analytical calculations, new combined methods and structures of power electronics and signal detection. The advantages of magneto-inductive techniques are that they do not damage the test object, are contactless, robust against dirt and simple in construction. A disadvantage of this technique is the insufficient resolution of fine structures. In current research and development different coil assemblies are investigated in industrial and medical applications. The aim of this work is to improve the coil properties by changing geometric constructions and current patterns of the coils, in order to allow a sharper localization of objects in space and to tap new application areas for non-destructive testing. A method to improve the properties of magneto-inductive coils and thus to reduce the effort in signal processing and image reconstruction as well as to increase the resolution is presented. Two different coil assemblies, gradiometer – coils and transmission – coils, are compared and their technical limits shown.

Magnetisch-induktive Techniken finden seit langer Zeit viele Anwendungsfelder in der Medizin, Sicherheitstechnik und der Industrie. Obwohl die technischen Grundlagen seit vielen Jahrzehnten bekannt sind, werden auf Basis detaillierter Analysen spezielle Lösungsansätze verfolgt, die neuartiges Anwendungspotential erschließen sollen. Dazu dienen verbesserte Werkzeuge wie Computersimulationen und analytische Berechnungen sowie neu kombinierte Methoden und Aufbauten aus Leistungselektronik und Signaldetektion. Die Vorteile magnetisch-induktiver Techniken sind dabei u.a., dass sie das Prüfobjekt nicht schädigen, berührungslos arbeiten, robust gegenüber Verschmutzungen und einfach im Aufbau sind. Ein Nachteil dieser Technik ist die unzureichende Auflösung von feinen Strukturen. In der aktuellen Forschung und Entwicklung werden unterschiedliche Spulenanordnungen zur Anwendung in industriellen und medizinischen Fragestellungen untersucht und optimiert. Thema dieser Arbeit ist es, durch Verbesserung der Spuleneigenschaften, neue Anwendungsbereiche für die zerstörungsfreie Materialprüfung zu erschließen. Es wird eine Methode vorgestellt, die Eigenschaften magnetisch-induktiver Tastspulen zu verbessern und so den Aufwand bei der Signalverarbeitung zur Rekonstruktion im Rechner zu reduzieren sowie die Auflösung zu erhöhen. Dazu werden zwei Spulenanordnungen, Transmissions - Tastspulen und Gradiometer - Tastspulen, vergleichend gegenübergestellt und ihre technischen Grenzen aufgezeigt. / Magneto-inductive techniques are found in many fields of application areas so in medicine, security technology and industry. Although the technical basis has been known for many decades, special solutions are pursued on the basis of detailed analysis that should open new application potential. These are enhanced tools such as computer simulations, analytical calculations, new combined methods and structures of power electronics and signal detection. The advantages of magneto-inductive techniques are that they do not damage the test object, are contactless, robust against dirt and simple in construction. A disadvantage of this technique is the insufficient resolution of fine structures. In current research and development different coil assemblies are investigated in industrial and medical applications. The aim of this work is to improve the coil properties by changing geometric constructions and current patterns of the coils, in order to allow a sharper localization of objects in space and to tap new application areas for non-destructive testing. A method to improve the properties of magneto-inductive coils and thus to reduce the effort in signal processing and image reconstruction as well as to increase the resolution is presented. Two different coil assemblies, gradiometer – coils and transmission – coils, are compared and their technical limits shown.

<div> Advancements in cancer treatments have increased rapidly in recent years, but cures remain elusive. Surgical tumor resection is a central treatment for many solid malignancies. Residual tumor at surgical margins leads to tumor recurrence. Novel tools for assessing residual tumor at surgical margins could improve surgical outcomes by helping to maximize the extent of resection. Ambient ionization-mass spectrometry (MS) methods generate and analyze ions from minimally prepared samples in near-real-time (e.g. seconds to minutes). These methods leverage the high sensitivity and specificity of mass spectrometry for analyzing gas phase ions and generating those ions quickly and with minimal sample preparation. Recent work has shown that differential profiles of ions, corresponding to phospholipids and small metabolites, are detected from cancerous and their respective normal tissue with ambient ionization-MS methods. When properly implemented, ambient ionization-MS could be used to assess for tumor at surgical margins and provide a molecular diagnosis during surgery. </div><div><br></div><div>The research herein reports efforts in developing rapid intraoperative ambient ionization-MS methods for the molecular assessment of cancerous tissues. Touch spray (TS) ionization and desorption electrospray ionization (DESI) were utilized to analyze kidney cancer and brain cancer.</div><div><br></div><div> As a demonstration of the applicability of TS-MS to provide diagnostic information from fresh surgical tissues, TS-MS was used to rapidly analyze renal cell carcinoma and healthy renal tissue biopsies obtained from human subjects undergoing nephrectomy surgery. Differential phospholipid profiles were identified using principal component analysis (PCA), and the significant ions were characterized using multiple stages of mass spectrometry and high resolution/exact mass MS. The same TS-MS analyzed renal tissues were subsequently analyzed with DESI-MS imaging to corroborate the TS-MS results, and the significant DESI-MS ions were also characterized with MS.</div><div><br></div><div>Significant efforts were made in developing and evaluating a standalone intraoperative DESI-MS system for analyzing brain tissue biopsies during brain tumor surgery. The intraoperative DESI-MS system consists of a linear trap quadrupole mass spectrometer placed on a custom-machined cart that contains all hardware for operating the mass spectrometer. This instrument was operated in the neurosurgical suites at Indiana University School of Medicine to rapidly analyze brain tissue biopsies obtained from glioma resection surgeries. A DESI-MS library of normal brain tissue and glioma was used to statistically classify the brain tissue biopsies collected in the operating room. Multivariate statistical methodologies were employed to predict the disease state and tumor cell percentage of the samples. A DESI-MS assay for detecting 2-hydroxyglutarate (2HG), the oncometabolic product of the isocitrate dehydrogenase (IDH) mutation (a key glioma prognostic marker), was developed and applied to determine the IDH mutation status during the surgical resection. The strengths, weaknesses, and areas of future work in this field are discussed. </div><div><br></div>