Dissertations / Theses on the topic 'Dielectric properties of biological tissues'

The present work contains two parts: nanofluids and bioheat transport, both involving multiscales and sharing some common features. The former centers on addressing the three key issues of nanofluids research: (i) what is the macroscale manifestation of microscale physics, (ii) how to optimize microscale physics for the optimal system performance, and (iii) how to effectively manipulate at microscale. The latter develops an analytical theory of bioheat transport that includes: (i) identification and contrast of the two approaches for developing macroscale bioheat models: the mixture-theory (scaling-down) and porous-media (scaling-up) approaches, (ii) rigorous development of first-principle bioheat model with the porous-media approach, (iii) solution-structure theorems of dual-phase-lagging (DPL) bioheat equations, (iv) practical case studies of bioheat transport in skin tissues and during magnetic hyperthermia, and (v) rich effects of interfacial convective heat transfer, blood velocity, blood perfusion and metabolic reaction on blood and tissue macroscale temperature fields. Nanofluids, fluid suspensions of nanostructures, find applications in various fields due to their unique thermal, electronic, magnetic, wetting and optical properties that can be obtained via engineering nanostructures. The present numerical simulation of structure-property correlation for fourteen types of two/three-dimensional nanofluids signifies the importance of nanostructure’s morphology in determining nanofluids’ thermal conductivity. The success of developing high-conductive nanofluids thus depends very much on our understanding and manipulation of the morphology. Nanofluids with conductivity of upper Hashin-Shtrikman bounds can be obtained by manipulating structures into an interconnected configuration that disperses the base fluid and thus significantly enhancing the particle-fluid interfacial energy transport. The numerical simulation also identifies the particle’s radius of gyration and non-dimensional particle-fluid interfacial area as two characteristic parameters for the effect of particles’ geometrical structures on the effective thermal conductivity. Predictive models are developed as well for the thermal conductivity of typical nanofluids. A constructal approach is developed to find the constructal microscopic physics of nanofluids for the optimal system performance. The approach is applied to design nanofluids with any branching level of tree-shaped microstructures for cooling a circular disc with uniform heat generation and central heat sink. The constructal configuration and system thermal resistance have some elegant universal features for both cases of specified aspect ratio of the periphery sectors and given the total number of slabs in the periphery sectors. The numerical simulation on the bubble formation in T-junction microchannels shows: (i) the mixing enhancement inside liquid slugs between microfluidic bubbles, (ii) the preference of T-junctions with small channel width ratio for either producing smaller microfluidic bubbles at a faster speed or enhancing mixing within the liquid phase, and (iii) the existence of a critical value of nondimensional gas pressure for bubble generation. Such a precise understanding of two-phase flow in microchannels is necessary and useful for delivering the promise of microfluidic technology in producing high-quality and microstructure-controllable nanofluids. Both blood and tissue macroscale temperatures satisfy the DPL bioheat equation with an elegant solution structure. Effectiveness and features of the developed solution structure theorems are demonstrated via examining bioheat transport in skin tissues and during magnetic hyperthermia.<br>published_or_final_version<br>Mechanical Engineering<br>Doctoral<br>Doctor of Philosophy

Knowledge of the microwave dielectric properties of human tissues is essential for the understanding and development of medical microwave techniques. In particular, microwave thermography relies on processes fundamentally determined by the high frequency electromagnetic properties of human tissues. The specific aim of this work was to provide detailed information on the dielectric properties of female human breast tissue at 3-3.5GHz, the frequency of operation of the Glasgow microwave thermography equipment. At microwave frequences the frequency variation of the dielectric properties of biological tissues is thought to be determined mainly by the dipolar relaxation of tissue water. Water exists in different states of binding within the tissue; the relaxation of each component of this water may be parameterised by the Debye or Cole-Cole equations. At a single frequency an average relaxation frequency may be calculated for a given tissue type. Mixture equations may be used to describe the dielectric properties of two-phase mixtures in terms of the dielectric properties and volume fractions of the component phases. Biological tissues are very much more complex than these two phase models. However, comparisons of the observed dielectric properties as a function of water content, with models calculated from mixture theory allow some qualitative conclusions to be drawn regarding tissue structure. Human and animal dielectric data at frequencies between 0.1 and 10GHz have been collected from the literature and are displayed in tabular form. These comprehensive tables were used to examine the widely-held assumption an animal tissue is representative of the corresponding human tissue. This assumption was concluded to be uncertain in most cases because of lack of available data, and perhaps wrong for certain tissue types. The tables were also used to compare in vivo and in vitro dielectric data. These may be expected to be different because the tissue is in a physiologically abnormal state in vitro. However at microwave frequencies in vitro data was found to be representative of the tissue in vivo provided gross deterioration of the tissue is avoided. A new resonant cavity perturbation technique was designed for dielectric measurements of small volumes of lossy materials at a fixed frequency of 3.2GHz. This technique may be used to measure materials of a wide range of permittivities and conductivities with accuracies of 3-4%. The major sources of error were found to be tissue heterogeneity and sample preparation procedures. Using this technique in vitro dielectric measurements were made on human female breast tissues. A large number of data were gathered on fat and normal breast tissues, and on benign and malignant breast tumours. Each data set was parameterised using the Debye equation. Results from this suggest that all breast tissues measured in this work contain a component of bound water. A smaller proportion of water is bound in fat than is bound in other tissues. Comparisons were made of the dielectric properties of breast tissues with values calculated from mixture theories. Permittivity data largely fall within bounds set by mixture theory: conductivity data often fall outside these limits. This may imply that physiological saline is not a good approximation to tissue waters; or it may imply that another relaxation process is occurring in addition to the dipolar relaxation of saline. Comparisons of tissue type indicate that a dielectric imaging system could be designed which would detect breast diseases, but that severe problems could arise in distinguishing disease types from dielectric imaging alone.

La recherche et développement de dispositifs médicaux avec diverses applications en diagnostiques et en thérapie ont été réalisés. Actuellement, tous les systèmes micro-ondes disponibles d'hyperthermie proposent uniquement des traitements avec une puissance élevée de micro-ondes. Dans cette thèse, un nouveau système d'hyperthermie micro-ondes est étudié pour le bénéfice des fonctions de diagnostic et de thérapie. L'utilisation d'un applicateur avec un niveau très faible et inoffensif de puissance micro-ondes permet de faire le premier diagnostic. Le traitement thérapeutique thermique sera effectué en utilisant le même applicateur avec une puissance micro-ondes élevée et adaptée sur la partie pathologique. Des caractérisations micro-ondes large bande de cinq tissus biologiques différents ont été effectuées à différentes températures avec une méthode de sonde coaxiale ouverte et le modèle de ligne virtuelle. Les expérimentations ex vivo d'hyperthermie micro-ondes avec des puissances de quelques watts à 2,45GHz ont été réalisées sur ces tissus d'épaisseurs variées. L'évolution de la température des tissus a été mesurée en utilisant un capteur infrarouge. Les simulations électromagnétiques et thermiques pour les expérimentations ex vivo d'hyperthermie micro-ondes ont été effectuées en utilisant COMSOL Multiphysics avec la méthode des éléments finis et la symétrie axiale 2D en considérant les tissus variés de différentes épaisseurs et puissances micro-onde incidente. Les simulations du modèle correspondent bien aux mesures. Cette recherche illustre la possibilité d'avoir un câble coaxial souple et adapté à la fois au diagnostic et au traitement pour une thérapie mini invasive<br>Research and development of medical devices with various diagnostic and therapeutic applications have been carried out in different countries because of the great advances in electronic and electromagnetic devices during recent decades. However, at present, all of available existing microwave hyperthermia system can just offer treatment, by using high microwave power. In this thesis, a new microwave hyperemia system is researched which could have both diagnostic and therapeutic functions. One single applicator is used to measure dielectric properties of tissue with a very low harmless microwave power for diagnosis first. Then thermal therapeutic treatment will be carried out by using the same applicator with higher and adapted microwave power. Microwave broad band characterization of five different biological tissues at different temperatures with an open–ended coaxial probe method and the virtual line model has been carried out. Ex vivo microwave hyperthermia experiments using microwave power of a few Watts at 2.45GHz have been carried out on five tissues of various thicknesses. Temperature evolution of the biological tissues has been measured by using an infra-red senor. Electromagnetic and thermal simulations for ex vivo microwave hyperthermia experiment have also been achieved by using COMSOL Multiphysics software with 2D axisymmetrical finite–element method and considering different tissues of various thicknesses and incident microwave powers. Simulation results correlate well with the experimental ones. This research, illustrates the possibility to have a flexible and feasible coaxial cable for both diagnosis and treatment for a minimally invasive therapy

Rupture of abdominal aortic aneurysm (AAA) is a catastrophic event that leads to high mortality and morbidity in patients. The primary causes associated with aneurysm rupture remain poorly understood despite rigorous investigations. Reports have shown that AAA that went on to rupture or present ruptured had higher peak wall tension (stress resultant) than those that did not go on to rupture or present ruptured. Studies investigating the material strength of ruptured AAA and unruptured AAA revealed that the uniaxial failure strength in ruptured AAA is no different on average than unruptured AAA. However, it is poorly understood whether uniaxial failure properties are reliable as they are not indicative of the manner in which failure occurs in biological soft tissues. Multi-axial failure properties using a bubble inflation test (BIT) have been implemented by various groups but have not been directly compared against uniaxial failure properties. The current study seeks to develop a BIT apparatus, to compare multi-axial and uniaxial failure properties of fibrous anisotropic biological soft tissues (bovine aorta) and non-fibrous isotropic molded silicon, and to perform a survey of computational indices at the rupture sites of four ruptured AAA. Two versions of the BIT apparatus were developed: a manual that was developed allows for a large amount of failure properties to be extracted that can identify localized weaknesses. It was found that circumferentially oriented multi-axial failure was correlated with longitudinally oriented uniaxial failure properties, however, for oblique oriented multi-axial failure the correlation decreased. Utilizing the insights gained from the multi-axial experiments it was determined that the failure properties used in the computational study with the data from Raghavan et al. were appropriate for use in retrospective assessment of the rupture site in four ruptured AAA computational models. Although the study was inconclusive in finding causation, the rupture line of each aneurysm had indices ranging between the third quartile and peak values for tension to failure tension ratio, nodal displacement magnitude, strain energy per unit volume and strain energy per unit surface area. This study provides a framework for interrogating failure properties at a higher density of measurement and a heterogeneous computational model that has the potential to predict AAA rupture in the future.

Electroporation affects the dielectric properties of cells. Dielectric measurement techniques can provide a label-free and non-invasive modality to study this phenomenon. In this thesis we introduce a dielectrophoresis (DEP) based technique to study changes in the cytoplasm conductivity of single Chinese hamster ovary (CHO) cells immediately after electroporation. Using a microfluidic chip, we study changes in the DEP response of single CHO cells a few seconds after electroporation. First, in order to quantify our DEP measurement results and relate them to the cells internal conductivity, we introduce a dielectric model for CHO cells. This is achieved by measuring the DEP response of many individual cells in the β-dispersion frequency region and curve fitting to the measured data. Second, we present quantitative results for changes in the cytoplasm conductivity of single cells subjected to pulsed electric fields with various intensities. We observe that when electroporation is performed in media with lower ionic concentration than cells cytoplasm, their internal conductivity decreases after electroporation depending on the intensity of applied pulses. We also observe that with reversible electroporation there is a limit on the decrease in the cells’ internal conductivity. We hypothesize the reason is the presence of large and relatively immobile negative ions inside the cell which attract mobile positive ions (mainly sodium and potassium) to maintain cell electrical neutrality. We monitor the temporal response of cells after electroporation to measure the time constant of changes due to ion transport and observe this ranges from seconds to tens of seconds depending on the applied pulse intensity. This result can be used to infer information about the density and resealing time of very small pores (not measurable with conventional marker molecules). Lastly, we measure the electroporation of cells in media with different conductivities. Our results show that electroporation in very low conductivity media requires stronger pulses to achieve a similar poration extent as in high conductivity media. The outcome of this thesis can be used to improve our understanding of the dynamics of electroporation as well as its modelling in order to make more accurate predictions or optimize the process for specific applications.<br>February 2017

<p>The determination of the optical properties of biological tissue is an important issue in laser medicine. The optical properties define the tissue´s absorption and scattering behaviour, and can be expressed by quantities such as the albedo, the optical thickness and the anisotropy coefficient. During this project, a measurement system for the determination of the optical properties was built up. The system consists of a double integrating sphere set-up to perform the necessary reflection and transmission measurements, and a computer algorithm to calculate the optical properties from the measured data. This algorithm is called Inverse Adding Doubling method, and is based on a one-dimensional transport model. First measurements were conducted with the system, including measurements with phantom media (Intralipid-ink solutions) and with cartilage samples taken from the human knee joint. This work also includes an investigation about the preparation of tissue samples for optical measurements.</p>

In biomedical applications realistic phantoms are becoming more useful for validation and testing of precursor systems. These artificial phantoms require stable and flexible tissue-mimicking materials with realistic dielectric properties in order to properly model human tissues. We have fabricated a low-water-content, low cost, mechanically and electrically stable, good shelf life and multi-layered heterogeneous phantom consisting of skin, fat and muscle tissues. We have chosen semi-solid type phantom for each tissue layer. The size and thickness of the each layer is chosen based on the average thickness of human tissue. Altering the ingredient composition wisely we can alter its dielectric properties also. By reason of no osmosis occurrence, the tissues can be employed to construct heterogeneous phantoms or even anthropomorphic phantoms without causing any changes in geometry or electrical properties. The performance of the fabricated phantom is carried out using an open-ended coaxial slim probe system by Agilent Technologies. Nearly all previous studies were based on very high frequency( VHF), so we present ultra-wide band (UWB), 500MHz-20GHz multilayered phantoms. We have measured our phantom after 2 month time period and we got quite good results for the dielectric properties without having significant variations. Thus, our fabricated sets of ATE phantom have good long lasting properties with good physical and dielectric stability.

Made available in DSpace on 2014-10-09T12:50:04Z (GMT). No. of bitstreams: 0<br>Made available in DSpace on 2014-10-09T14:03:53Z (GMT). No. of bitstreams: 1 10452.pdf: 100440947 bytes, checksum: a25045222faf14cf91ac2e310d2ea37a (MD5)<br>Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)<br>Tese (Doutoramento)<br>IPEN/T<br>Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP<br>FAPESP:00/05863-7

Thesis (M.S.)--Worcester Polytechnic Institute.<br>Keywords: basis functions; perfectly matched layers; PML; neck model; parallel plate resonator; finite element; circulator; glottal waveform; multi-transmission line; dielectric properties of human tissues; radiation currents; weighted residuals; non-acoustic sensor. Includes bibliographical references (p. 104-107).

L'Elastographie par Résonance Magnétique (ERM) est une technique d'imagerie permettant de caractériser in vivo les propriétés biomécaniques des tissus de façon non invasive. Dans ce contexte, la première partie de cette thèse s'intéresse à comparer les propriétés viscoélastiques obtenues par ERM avec une technique de rhéologie haute-fréquence, pouvant atteindre des fréquences de sollicitation mécanique communes à l'ERM, contrairement à ce qui est classiquement fait dans la littérature. Pour effectuer les mesures ERM, le dispositif d'excitation mécanique et la séquence IRM ont été développés et un algorithme de reconstruction des propriétés viscoélastiques, fondé sur l'inversion de l'équation de Helmholtz, a été implémenté et évalué en simulation. La comparaison ERM/rhéologie a ensuite été effectuée, d'abord sur des fantômes de plastisol présentant différentes propriétés viscoélastiques, puis sur des échantillons de foies bovins. Dans les deux cas, les résultats ont montré un bon accord entre les valeurs obtenues en ERM et celles issues de la rhéologie. Le second volet de ces travaux s'attache à présenter une nouvelle stratégie d'acquisition en ERM. Les séquences d'ERM conventionnelle utilisent des gradients oscillants afin d'encoder la propagation de l'onde. Ces gradients peuvent cependant restreindre les applications, en raison des limitations de leur fréquence de commutation et de leur amplitude maximale. Nous proposons ici d'encoder directement la propagation de l'onde à l'aide d'impulsions RF générées par la théorie du Contrôle Optimal (CO), combinées à un gradient constant. Une première expérience simple de contrôle de la phase par impulsions RF est présentée, consistant à créer des motifs de distribution spatiale de cette phase, en l'absence de propagation d'onde. Puis, des impulsions RF adaptées à l'ERM ont été générées : les images de phase obtenues ont été comparées avec celles acquises par ERM conventionnelle. Les propriétés viscoélastiques reconstruites dans les deux cas sont similaires, validant ainsi cette nouvelle méthode d'acquisition<br>Magnetic Resonance Elastography is a non-invasive imaging method enabling in vivo characterization of viscoelastic properties of biological tissues. The first part of this thesis deals with the comparison of viscoelastic properties obtained with MRE and with a high-frequency rheometer having a large excitation frequency range. This large frequency range enables common frequency range to MRE, unlike the comparisons usually performed in the literature. To perform MRE measurements, the excitation device and the MRE sequence were developed and an algorithm reconstructing the viscoelastic properties based on an inversion of Helmholtz equation was implemented and evaluated through simulation. The comparison between MRE/rheology was then performed, first on plastisol phantoms with different viscoelastic properties, and then on bovine liver samples. In both cases, results show a very good agreement between values obtained with MRE and those coming from rheology. The second part of this work presents a new acquisition method for MRE. Conventional MRE sequences use oscillating gradients to encode the wave propagation into the phase image. However, these gradients can restrict MRE applications, as their switching frequencies as well as maximal amplitude are limited. The new acquisition strategy we propose in this thesis encodes the wave propagation directly with RF pulses generated with Optimal Control Theory (OCT), in combination with a constant gradient. An initial experiment of phase control with RF pulses is presented, consisting in creating non-trivial spatial phase patterns in MRI phase images, in the absence of wave propagation. Then, RF pulses adapted to the MRE problem are generated with OCT and phase images obtained with these pulses are compared with conventional MRE acquisitions. Viscoelastic properties reconstructed from these two techniques are similar, validating thus this new acquisition method

[ES] Conocer las propiedades electromagnéticas de los tejidos biológicos con la mayor exactitud posible tiene una gran importancia en el diseño de un elevado número de aplicaciones biomédicas. El diseño de dispositivos médicos inalámbricos, antenas superficiales e intracorporales, evaluación de tasas de absorción electromagnética, técnicas de tratamiento y detección de cáncer como la hipertermia e imágenes médicas son ejemplos de aplicaciones que requieren esta información para su desarrollo. Debido a que el cáncer provoca modificaciones estructurales en las células que a su vez generan cambios en las propiedades electromagnéticas, es posible desarrollar aplicaciones de detección de cáncer que se basen en este hecho. Un objetivo potencial es el cáncer de colon (CRC), debido a que los tejidos de colon sospechosos son accesibles de forma más o menos sencilla durante procedimientos endoscópicos. Este tipo de cáncer es uno de los más extendidos, siendo responsable de aproximadamente el 10% de casos y muertes totales. Existe un gran número de factores de riesgo que pueden explicar la aparición de la enfermedad, aunque esencialmente la probabilidad se incrementa significativamente con el aumento de la edad de la población. Los programas de cribado sobre la población son críticos: si el cáncer se detecta en etapas tempranas, la probabilidad de sobrevivir se incrementa en gran medida, y además se reducen los costes asociados. Uno de los objetivos principales de esta tesis es proponer aplicaciones que ayuden en la detección de CRC durante la colonoscopia haciendo uso de las diferencias en las propiedades electromagnéticas. Aparte de mejoras en el diagnóstico, complementar la colonoscopia puede conllevar otros beneficios colaterales como una reducción en la carga de anatomía patológica. Para demostrar la viabilidad y el potencial desarrollo futuro de estas aplicaciones, en esta tesis se miden y se trata de encontrar diferencias entre las propiedades electromagnéticas de tejidos sanos, cancerosos y patológicos de colon humano. Las medidas han sido llevadas a cabo mediante la técnica del coaxial terminado en abierto. Con el propósito de incrementar la precisión del método, se ha evaluado el principio de funcionamiento y se ha mejorado el proceso de calibración. Dos fuentes de tejido de colon han sido analizadas en esta tesis: tejidos procedentes de colonoscopias (biopsias) y tejidos obtenidos a partir de procedimientos quirúrgicos. Aparte de tejido sano, se estudian las siguientes patologías: Adenocarcinomas (CRC), adenomas sin displasia, adenomas con bajo grado de displasia, adenomas con alto grado de displasia, hiperplasias y hamartomas. Debido a la alta variabilidad entre distintos sujetos, las propiedades electromagnéticas de los tejidos sospechosos de un paciente en concreto deben ser siempre comparadas con las propiedades de sus tejidos sanos, no evaluadas de forma independiente. El segundo gran objetivo de esta tesis es el desarrollo de una nueva base de datos de las propiedades electromagnéticas de tejidos biológicos medidas in vivo. Ahora mismo, las colecciones disponibles están limitadas en número de tejidos o frecuencias caracterizadas, obligando a los investigadores a escoger bases de datos más completas pero realizadas ex vivo. No obstante, usar este tipo de colecciones tienen fuentes de incertidumbre adicionales dado que las medidas están condicionadas por la deshidratación de los tejidos y la perdida de flujo sanguíneo. El desarrollo de esta nueva base de datos puede facilitar el diseño de aplicaciones que requieran conocer las propiedades electromagnéticas con alto grado de precisión.<br>[CAT] Conéixer les propietats electromagnètiques dels teixits biològics amb la major exactitud possible té una gran importància en el disseny d'un gran nombre d'aplicacions biomèdiques. El disseny de dispositius metges sense fil, antenes superficials i intracorporales, l'avaluació de taxes d'absorció electromagnètica, tècniques de tractament i detecció de càncer com ara la hipertèrmia i imatges mediques són exemples d'aplicacions que requerixen esta informació. Com el càncer provoca modificacions estructurals en les cèl·lules que generen canvis en les propietats electromagnètiques, es possible desenrotllar aplicacions de detecció de càncer que es basen en este fet. Un objectiu potencial és el càncer de colon (CRC), pel fet que els teixits de colon sospitosos són accessibles de forma més o menys senzilla durant procediments endoscòpics. Este tipus de càncer és un dels més estesos, sent responsable d'aproximadament el 10% de casos i morts totals. N'hi ha un gran nombre de factors de risc que poden explicar l'aparició de la malaltia, encara que en resum la probabilitat s'incrementa significativament amb l'augment de l'edat de la població. Els programes de cribratge sobre la població són crítics. Si el càncer es detecta en etapes primerenques, la probabilitat de sobreviure s'incrementa en gran manera, i a més es reduïxen els costos associats. Un dels objectius principals d'esta tesi és proposar aplicacions que ajuden en la detecció de CRC durant la colonoscòpia fent ús de les diferències en les propietats electromagnètiques. A banda de millores en el diagnòstic, complementar la colonoscòpia pot comportar altres beneficis col·laterals com una reducció en la càrrega d'anatomia patològica. Per a demostrar la fiabilitat i el potencial desenrotllament d'aquestes aplicacions, en aquesta tesi es mesuren i es tracta de trobar diferències entre les propietats electromagnètiques de teixits sans, cancerosos i patològics de colon humà. Les mesures han sigut realitzades mitjançant la tècnica del coaxial acabat en obert. Amb el propòsit d'incrementar la precisió del mètode, s'ha avaluat el seu principi de funcionament i s'ha millorat el procés de calibratge. Dos fonts de teixit de colon s'han analitzat en aquesta tesi: teixits procedents de colonoscòpies (biòpsies) i teixits obtinguts a partir de procediments quirúrgics. Apart de teixit sà, s'estudien els següents teixits: Adenocarcinomes (CRC), adenomes sense displàsia, adenomes amb baix grau de displàsia, adenomes amb alt grau de displàsia, hiperplàsies y hamartomes. Degut a l'alta variabilitat entre diferents subjectes, les propietats electromagnètiques dels teixits sospitosos d'un pacient en particular han de ser comparades amb les propietats dels seus teixits sans, no avaluats independentment. El segon gran objectiu d'esta tesi és el desenrotllament d'una nova base de dades de les propietats electromagnètiques de teixits biològics mesurades in vivo. Ara mateix, les col·leccions disponibles estan limitades en nombre de teixits o freqüències caracteritzades, obligant els investigadors a triar bases de dades més completes però realitzades ex vivo. No obstant això, este tipus de col·leccions te fonts d'incertesa addicionals atés que les mesures estan condicionades per la deshidratació dels teixits i la pèrdua de flux sanguini. El desenrotllament d'esta nova base de dades pot facilitar el disseny d'aplicacions que requerisquen conéixer les propietats electromagnètiques amb alt grau de precisió.<br>[EN] Nowadays, a careful knowledge of the electromagnetic properties of biological tissues is required for developing a great number of applications. The development of wireless medical devices, the design of in-body and on-body antennas, specific absorption rate evaluations, cancer treatment techniques such as hyperthermia and detection techniques like medical imaging are some examples of applications that rely on these data. Since cancer causes modifications on the biological structure of cells that can lead in turn to changes in the electromagnetic properties of the tissues, it is possible to develop novel detection applications taking advantage of it. One potential target is colorectal cancer (CRC), as suspicious tissues can be accessed quite easily through colonoscopy procedures. This kind of cancer is one of the most spread kinds, being responsible of about 1 out of 10 new cancer cases and deaths. There are several risk factors currently related to the apprising of this cancer, although in essence the higher the age of the population, the higher the incidence of CRC. Screening programs are key for detecting and diagnosing cancer: if found at early stages, the probability of survival increases greatly, and the cost of the treatment can be reduced as well. One of the major objectives of this dissertation is proposing applications for detecting CRC that aid in the colonoscopy procedures by making use of the differences in electromagnetic properties. Aside from enhancement in the diagnosis of CRC, improving the colonoscopy procedure can lead to collateral benefits like a lowering of the burden of anatomical pathology unit. With the aim at demonstrating the feasibility and the potential future development of these applications, in the framework of this thesis the dielectric properties of healthy, cancerous and pathological human colon tissues are measured and compared in order to find electromagnetic differences. Measurements are carried out by means of an open-ended coaxial system. Its principle of operation has been revisited with the aim at maximizing the accuracy of the method, and the calibration procedure has been optimized serving the same purpose. Two main sources of colon tissue have been analyzed: samples from colonoscopy biopsies and samples from surgery resections. Besides healthy tissue, the following colon tissues have been characterized: Adenocarcinomas (CRC), adenomas without dysplasia, adenomas with low-grade dysplasia, adenomas with high-grade dysplasia, hyperplastic polyps and hamartomatous polyps. Given the variability that can appear among subjects, the electromagnetic properties of suspicious tissues from a particular patient have to be always compared with those of his healthy ones, not evaluated independently. The second major objective of this thesis involves the development of a new database of electromagnetic properties of biological tissues obtained at in vivo conditions. Nowadays, the available collections are limited either in the number of tissues or the measured frequencies, and hence researchers have to make use of more complete databases but that were performed ex vivo. The drawback of using these collections is that results can be compromised by factors such as lack of blood perfusion and tissue dehydration. Developing this new database can facilitate the design of applications that needs of a careful knowledge of these properties.<br>Fornés Leal, A. (2019). Dielectric Characterization of Biological Tissues for Medical Applications [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/132188<br>TESIS

[ES] La constante evolución de la tecnología y la búsqueda de nuevas aplicaciones que mejoren la vida de las personas ha llevado a la incorporación de estas tecnologías en el organismo. Las redes inalámbricas de área corporal (WBAN) son un buen ejemplo de esto, que consisten en redes de comunicaciones ubicadas en el propio cuerpo, tanto en la superficie como implantadas en su interior mediante el uso de dispositivos inalámbricos. Estas redes utilizan el cuerpo humano como medio de transmisión, por lo que debe evaluarse la influencia del mismo sobre la propagación. Además, las nuevas generaciones de comunicaciones móviles se están moviendo hacia el uso de frecuencias cada vez más altas, como las ondas milimétricas, que son más sensibles a la presencia de cualquier objeto en el entorno, incluidos los humanos. La investigación y el diseño de antenas y dispositivos que tengan en cuenta el cuerpo humano requiere pruebas en el entorno donde se supone que deben usarse. Los fantomas se convierten en una herramienta para evaluar la transmisión de señales electromagnéticas en un medio equivalente al cuerpo para evitar la experimentación en humanos o animales. Además de eso, se puede estudiar la influencia de estas ondas electromagnéticas sobre los propios tejidos en cuanto a la tasa de absorción específica (SAR).<br>[CAT] L'evolució constant de la tecnologia i la recerca de noves aplicacions que milloren la vida de les persones ha portat a la incorporació d'aquestes tecnologies en l'organisme. Les xarxes sense fils d'àrea corporal (WBAN) són un bon exemple d'açò, que consisteixen en xarxes de comunicacions ubicades al propi cos, tant en la superfície com implantades en el seu interior mitjançant l'ús de dispositius sense fils. Aquestes xarxes empren el cos humà com a medi de transmissió, per la qual cosa se n'ha d'avaluar la influència sobre la propagació. A més, les noves generacions de comunicacions mòbils s'estan movent cap a l'ús de freqüències cada vegada més altes, com les ones mil·limètriques, que són més sensibles a la presència de qualsevol objecte en l'entorn, incloent-hi els humans. La investigació i el disseny d'antenes i dispositius que tinguen en compte el cos humà requereix proves en l'entorn on se suposa que han d'usar-se. Els fantomes esdevenen una eina per a avaluar la transmissió de senyals electromagnètics en un medi equivalent al cos per tal d'evitar l'experimentació en humans o animals. A més d'això, es pot estudiar la influència d'aquestes ones electromagnètiques sobre els teixits mateixos en relació amb la taxa d'absorció específica (SAR).<br>[EN] The constant evolution of technology and the search for new applications that improve people's lives has led to the arrival of the incorporation of these technologies in the organism. Wireless body area networks (WBANs) are a good example of this, consisting of communications networks located in the body itself, both on the surface and implanted inside it through the use of wireless devices. These networks use the human body as the transmitting medium, so its influence over the propagation has to be assessed. Besides, new generations of mobile communications are moving towards the use of higher frequencies, as the millimetre waves, which are more sensitive to the presence of any object in the environment, including humans. The research and design of antennas and devices that take into account the human body requires testing in the environment where these are supposed to be used. Phantoms become a tool for evaluating the transmission of electromagnetic signals in a body-equivalent medium in order to avoid experimentation on humans or animals. In addition to that, the influence of these electromagnetic waves over the tissues themselves can be studied with regard to the specific absorption rate (SAR).<br>This thesis has been possible thanks to the funding contribution of the Universitat Polit`ecnica de Val`encia through the PAID-01-16 programme. This work was also supported by the UPV-IIS La Fe programme (STUDER, 2016 and EMOTE, 2017). The research stay was supported by the European Union’s Erasmus+ funding programme under a traineeship grant.<br>Castelló Palacios, S. (2019). Wideband Electromagnetic Body Phantoms for the Evaluation of Wireless Communications in the Microwave Spectrum [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/132182<br>TESIS

碩士<br>國立成功大學<br>生物醫學工程學系<br>100<br>In clinics, the manual palpation is used to diagnose the pathological and stiffness changes. But palpation highly depends on the judgment of the physician to perform the diagnosis. The techniques of ultrasonic elastography have been used to characterize the palpation. It provides the objective and alternative information for clinical diagnosis. The study aims to implement an ultrasound elasticity image system for evaluating the biological tissue elasticity. The pressure sensor and 5MHz ultrasound pulser are combined with the two single axis (X axis, Z axis) step motors to scan and compress the objects. The cross-correlation technique is used to process the pre- and post-compression of radio frequency (RF) signals. From the measured data we can calculate the elasticity modulus and strain distribution of the objects. The custom-made gelatin and pork tissue was used as phantoms for system validation. Our results show that system can effectively differentiate the objects within the elasticity difference. Our approach can provide the elasticity information and increase the discernment which cannot obtain from tradition B-mode images. The signal-to-noise ratio of strain was increased by increasing the compression depth. The traditional cross-correlation method has decorrelation when the deformation of objects causes the waveform changes. Our method relies on the significant interface echo signal can reduce the correlation noise interference. If we cannot observe the boundary in B-mode, we cannot estimate the elastic correctly. If the interference can be removed we can use the correlation technique to measure the elasticity accurately.

Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Engenharia Clínica e Instrumentação Médica), Universidade de Lisboa, Faculdade de Ciências, 2019<br>A translação de equipamentos médicos surge como complemente ao nível científico e de desenvolvimento dos mesmos. Ao nível do seu desenvolvimento surge a investigação e, consequentemente, a otimização de novos produtos para mercado médico. Esta dissertação de mestrado aborda a otimização de equipamentos já no mercado, os quais necessitam de maior desenvolvimento, de modo a colmatar falhas inerentes. Adicionalmente, a dissertação aborda o desenvolvimento de um novo dispositivo médico, nomeadamente na validação do conceito para a sua conceção. Aplicações hipertérmicas são procedimentos que utilizam energia eletromagnética de modo a induzir um aumento de temperatura para modificar ou destruir tecidos alvo, como tumores. A interação do campo eletromagnético com o tecido biológico e determinada pelas propriedades dielétricas e térmicas do tecido. Enquanto que as propriedades térmicas determinam a distribuição do calor e o aumento da temperatura nos tecidos biológicos. A caraterização das propriedades dielétricas e térmicas e importante no desenvolvimento de planos de tratamento aquando da utilização de aplicações hipertérmicas. Diversos estudos tem sido desenvolvidos de modo a caracterizar as propriedades dielétricas do tecido. Contudo, muito poucos estudos foram realizados de modo a determinar as propriedades térmicas dos tecidos (condutividade térmica, capacidade volumétrica calorifica especifica e difusidade térmica), nomeadamente a sua dependência com a temperatura e composição de água. Os estudos realizados modelam as propriedades térmicas dependentes da temperatura baseando-se em equações lineares. Adicionalmente, a determinação das propriedades térmicas esta limitada a estudos a temperatura ambiente ou corporal, sem ter em conta as suas alterações com o aumento de temperatura, perfusão sanguínea ou da composição de agua no tecido. A caraterização das propriedades térmicas de diversos tecidos biológicos foi realizada neste estudo. Foi utilizado fígado de ovino ex vivo, de modo a estudar a alteração das propriedades térmicas dependendo da sua temperatura, desde a temperatura ambiente ate 95º C. Os resultados mostram que não se verificam alterações nas propriedades térmicas ate aproximadamente 90º C, observando-se significativamente o seu aumento depois da referida temperatura. Adicionalmente, foi realizado um estudo para determinar o comportamento das propriedades térmicas num período de arrefecimento. Deste modo, o tecido foi aquecido até uma temperatura entre 90º C e 95º C, e depois as propriedades térmicas foram medidas ao longo de um arrefecimento controlado. Os resultados mostram que as propriedades térmicas seguem o mesmo comportamento do que havia sido observado durante o seu aquecimento. Ao longo do estudo, a densidade e água perdida devido ao aquecimento do tecido foi avaliada. Os resultados mostram que a densidade do tecido permanece aproximadamente igual ao longo do seu aquecimento. Esta igualdade com a temperatura surge devido a mecanismos de compensação que inter-relacionam a perda de água devido a sua vaporização e o encolhimento do tecido devido a essa perda, resultando numa diminuição do volume relativamente proporcional a percentagem de água perdida. A maior percentagem de perda de água foi observada para temperaturas superiores a 80º C, coincidente com as alterações observadas para as propriedades térmicas do tecido. Um estudo adicional foi conduzido em diferentes tipos de tecidos biológicos, nomeadamente: pulmão, fígado, músculo e rim de ovino ex vivo e em medula óssea de bovino ex vivo. O estudo determinou as propriedades térmicas dos tecidos a temperatura ambiente e corporal. Resultados semelhantes foram obtidos para as propriedades térmicas do fígado, rim e músculo. Estes três tecidos apresentam caraterísticas semelhantes ao nível de densidade e composição de água. Contudo tal semelhança não se verificou para a medula óssea (que apresenta baixa composição de agua) e para o pulmão (que apresenta baixa densidade). Esta caraterização implica que em aplicações ao nível de hipertermia diferenças na condução de calor permanecem iguais independentemente da temperatura. Um método de deteção de uma sonda nasogástrica foi desenvolvido durante esta dissertação de modo a facilitar a sua deteção no interior do organismo. Sondas nasogástrica são utilizadas por pacientes que tem dificuldade de deglutição ou que estão a ser ventilados por mecanismos externos. Estas sondas, tem como principal função alimentar e fornecer medicação via oral aos pacientes que estão internados. As sondas são introduzidas via cavidade nasal ate ao estomago, sendo a sua colocação complexa, visto que na laringofaringe a sonda pode ser introduzida erroneamente, entrando assim nas vias respiratórias. Estatisticamente, cerca de 3-4 % das sondas nasogástrica são introduzidas incorretamente em pacientes. Neste momento, apenas dois métodos de deteção são recomendados: um teste pH feito ao fluido aspirado pela sonda, ao qual se verifica a sua acidez comprovando que se encontra no estomago; o estomago apresenta um pH muito mais acido que os pulmões. Outro teste recomendado e a radiografia ao tórax, no qual se observa o trajeto do tubo ao longo do organismo, e se verifica onde se encontra a sua ponta. Ambos os testes apresentam grande ocorrência de falso positivos, e adicionalmente, impõem ao paciente grandes tempos de espera, sem este ser alimentado ou medicado, de modo a confirmação da correta posição da sonda nasogástrica. O método de deteção foi primordialmente desenvolvido de modo a validar o conceito de deteção. Foi utilizado como deteção um mecanismo de indução eletromagnética entre dois indutores que estão dimensionados para oscilarem a mesma frequência de ressonância. Deste modo, um simples circuito LC – circuito recetor – foi criado para ser colocado no interior da ponta da sonda nasogástrica, enquanto um outro circuito de maiores dimensões – circuito transmissor – foi desenvolvido para se acoplar ao circuito recetor. Ao circuito transmissor e aplicada uma corrente alternada com frequência igual a frequência de ressonância. Quando existe transferência de energia entre os dois circuitos, significa que ambos os circuitos estão acoplados, evidenciando onde se encontra anatomicamente o circuito recetor, ou seja, onde se encontra a ponta da sonda nasogástrica. Devido às diferenças anatómicas de localização dos órgãos em causa é possível identificar externamente ao organismo, se a ponta da sonda se encontra no estomago ou nos pulmões. Este método de deteção facilita a confirmação da posição da sonda nasogástrica num período de tempo bastante curto, e possibilita a sua reconfirmação ao longo do tempo. Apresenta ainda como vantagens a diminuição da radiação a que os pacientes são expostos, não sendo necessário radiografias para confirmar a posição da sonda. Adicionalmente, apresenta vantagens ao nível de custos e recursos ao nível do sistema de saúde. Tanto a caraterização das propriedades térmicas ao nível dos tecidos biológicos, nomeadamente a sua dependência com a temperatura como composição de água, assim como, o conceito de prova demonstrados, permitirão avanços tecnológicos ao nível do desenvolvimento e otimização de equipamentos médicos, obviamente especializados a cada uma das áreas.<br>The translation of medical devices requires the coupling of science and technology in order to develop better equipment in the treatment and diagnosis of diseases or even to be use in the comfort of the patients. In this Masters’ dissertation a study of the characterisation of the thermal properties of biological tissues was developed, considering its temperature and water content dependency. This study aims to optimise treatment plans for patients that will be treated using hyperthermic applications. No literature information sufficiently reports the thermal properties (thermal conductivity, specific heat capacity and thermal diffusivity) of biological tissues considering their dependency in temperature and water content. The knowledge of thermal properties plays an important role in the development of hyperthermic applications. It was found that above 90o C the thermal properties of ex vivo ovine tissue increase significantly. Such observation is due to the water vaporisation process that occurs at temperatures close to 100o C. Additional measurements were performed in ex vivo ovine kidney, lung and muscle and in ex vivo bovine bone marrow. The results showed that differences in water content and density of the tissues are related to the differences observed in thermal properties at room and body temperatures. Additionally, the proof of concept for a new medical device was developed. This medical device aims to detect the placement of a nasogastric tube. Studies reveal that 3-4% of the tubes are placed incorrectly in the patient’s body, which may result in severe injuries. The proof of concept design of the medical device uses magnetic inductive coupling to detect the right position of the nasogastric tube tip.

The research results contained in this dissertation relate to the novel field of engineered tissue optics. Biological tissue such as skin is highly opaque due to multiple light scattering. However, it has been shown that certain hyper-osmotic chemicals can temporarily render turbid tissues such as skin optically transparent by reducing light scattering. The mechanisms involved in this process are believed to be a combination of dehydration and index matching. In order to capitalize on the non-invasive nature of light-tissue interactions for diagnostic and therapeutic purposes, hyper-osmotic optical clearing agents need to be delivered transepidermally. The first part of this dissertation is devoted to investigation of different methods to temporarily reduce the natural skin barrier posed by the stratum corneum in order to allow topically applied optical clearing agents to diffuse into epidermis and dermis. Methods such as needle-free injection gun, micro-needles, Er:YAG surface ablation, use of a 980 nm diode laser and mild surface abrasion using sandpaper were investigated. The second part of this dissertation investigated the effects of optical tissue clearing on tissue structure and influence on blood flow. Various imaging modalities such as optical coherence tomography (OCT), microscopy, confocal microscopy as well as transmission electron microscopy were employed to deduce how tissue structural changes can explain the temporary reduction of light scattering.<br>text

Indiana University-Purdue University Indianapolis (IUPUI)<br>Photoacoustic Imaging is a non-invasive optical imaging modality used to image biological tissues. In this method, a pulsating laser illuminates a region of tissues to be imaged, which then generates an acoustic wave due to thermal volume expansion. This wave is then sensed using an acoustic sensor such as a piezoelectric transducer and the resultant signal is converted into an imaging using the back projection algorithm. Since different types of tissues have different photo-acoustic properties, this imaging modality can be used for imaging different types of tissues and bodily organ systems. This study aims at quantifying the process of light conversion into the acoustic signal. Light travels through tissues and gets attenuated (scattered or absorbed) or reflected depending on the optical properties of the tissues. The process of light propagation through tissues is studied using Monte Carlo simulation software which predicts the propagation of light through tissues of various shapes and with different optical properties. This simulation gives the resultant energy distribution due to light absorption and scattering on a voxel by voxel basis. The Monte Carlo code alone is not sufficient to validate the photon propagation. The success of the Monte Carlo code depends on accurate prediction of the optical properties of the tissues. It also depends on accurately depicting tissue boundaries and thus the resolution of the imaging space. Hence, a validation algorithm has been designed so as to recover the optical properties of the tissues which are imaged and to successfully validate the simulation results. The accuracy of the validation code is studied for various optical properties and boundary conditions. The results are then compared and validated with real time images obtained from the photoacoustic scanner. The various parameters for the successful validation of Monte Carlo method are studied and presented. This study is then validated using the algorithm to study the conversion of light to sound. Thus it is a significant step in the quantification of the photoacoustic effect so as to accurately predict tissue properties.

碩士<br>國立成功大學<br>光電科學與工程學系<br>102<br>Typical diffuse reflectance systems can work with photon diffusion models to accurately determine the absorption coefficient (μ_a) and reduced scattering coefficient (μ_s') of tissues in the wavelength range from 650 to 1000 nm, where tissues have high-albedo so that the diffusion approximation is satisfied. In this thesis, we used a steady state diffuse reflectance system and a novel algorithm to determine the physiological parameters of superficial biological tissues at wavelengths ranging from 500 to 1350 nm. We combined the Monte Carlo method (which is accepted as the gold standard approach for photon migration modeling) with Compute Unified Device Architecture, in which a parallel computing platform and programming model were implemented by the graphics processing units to establish the reflectance database with high speed. We further utilize the database to establish a connection between the optical properties and diffuse reflectance spectra with Artificial Neural Network. With this novel model, we can accurately and immediately simulate every conditions of photon migrating in the tissue without any limitation. In this study, we employ this new algorithm to reveal the optical properties of different liquid phantoms and the performance of this model will be surveyed. We also measured different positions of human skin and recovered the absorption and reduces scattering spectra. The derived absorption spectra can be fit linearly with the known chromophore absorption spectra to obtain the concentration of chromophores including oxygenated hemoglobin, deoxygenated hemoglobin, water, melanin, and collagen. We found that the chromophore fitting performance by taking longer wavelength (1000 to 1350 nm) into account is more reasonable than that obtained by analyzing the short wavelength spectra (500 to 1000 nm) only.