The number of skin cancer cases reported in the United States is increasing every year and nearly equals the total cancer cases detected from every other part of the body. Current detection strategies of skin cancers include a visual examination followed by a tissue biopsy. This procedure is subjective, invasive and time-consuming. Therefore, considering the number of cancer cases reported and the number biopsies performed, there is a critical need for a non-invasive diagnostic aid to help clinicians reduce the significantly large numbers of unnecessary biopsies. This dissertation presents a quantitative method based on optical spectroscopy for performing a non-invasive ‘optical biopsy’ of melanoma and non-melanoma skin cancers. We have developed the hardware, software and optical algorithms necessary to implement such a device. First, we present a novel lookup table-based model for determining the optical properties of tissue that is valid for fiber-based probe geometries with close source-detector separations and in highly absorbing tissue. These optical properties are quantitative parameters that can be correlated with the physiology of tissue. Second, we present experimental validation of the effects of microvasculature pigment packaging on diffuse reflectance spectra. We have conducted experiments using microfluidic devices over a physiologically relevant range of optical properties and blood vessel sizes. Third, we present the development of a probe-based portable and clinically compatible instrument capable of in vivo spectral measurements. The instrument combines two modalities – diffuse reflectance and intrinsic fluorescence spectroscopy – to provide complementary information regarding tissue morphology, function and biochemical composition. Finally, we present the results of a pilot clinical study using our portable instrument to determine the accuracy of spectral diagnosis of non-melanoma skin cancers. Our results show that the mean optical properties and fluorophore contributions of normal skin and non-melanoma skin cancers are significantly different from each other and can potentially be used as biomarkers for non-invasive diagnosis of skin cancer. / text

Indiana University-Purdue University Indianapolis (IUPUI) / While computed tomographic angiography (CTA) has emerged as a powerful noninvasive option that allows for direct visualization of arterial stenosis(AS), it cant assess the hemodynamic abnormality caused by an AS. Alternatively, trans-stenotic pressure gradient (TSPG) and fractional flow reserve (FFR) are well-validated hemodynamic indices to assess the ischemic severity of an AS. However, they have significant restriction in practice due to invasiveness and high cost. To fill the gap, a new computational modality, called InVascular has been developed for non-invasive quantification TSPG and/or FFR based on patient's CTA, aiming to quantify the hemodynamic abnormality of the stenosis and help to assess the therapeutic/surgical benefits of treatment for the patient. Such a new capability gives rise to a potential of computation aided diagnostics and therapeutics in a patient-specific environment for ASs, which is expected to contribute to precision planning for cardiovascular disease treatment. InVascular integrates a computational modeling of diseases arteries based on CTA and Doppler ultrasonography data, with cutting-edge Graphic Processing Unit (GPU) parallel-computing technology. Revolutionary fast computing speed enables noninvasive quantification of TSPG and/or FFR for an AS within a clinic permissible time frame. In this work, we focus on the implementation of inlet and outlet boundary condition (BC) based on physiological image date and and 3-element Windkessel model as well as lumped parameter network in volumetric lattice Boltzmann method. The application study in real human coronary and renal arterial system demonstrates the reliability of the in vivo pressure quantification through the comparisons of pressure waves between noninvasive computational and invasive measurement. In addition, parametrization of worsening renal arterial stenosis (RAS) and coronary arterial stenosis (CAS) characterized by volumetric lumen reduction (S) enables establishing the correlation between TSPG/FFR and S, from which the ischemic severity of the AS (mild, moderate, or severe) can be identified. In this study, we quantify TSPG and/or FFR for five patient cases with visualized stenosis in coronary and renal arteries and compare the non-invasive computational results with invasive measurement through catheterization. The ischemic severity of each AS is predicted. The results of this study demonstrate the reliability and clinical applicability of InVascular.

Seismocardiography (SCG) is the low frequency chest surface vibration generated by the mechanical activities of the heart. SCG has been found to have clinical utilities in diagnosis of different cardiac diseases. The first part of this study focused on the application of SCG signal in predicting hospital readmissions of the heart failure (HF) patients. Conventional machine learning and deep learning models have been developed using SCG signal acquired from the HF patients. Early HF readmissions was predicted with decent accuracies with these models. This may potentially help the clinicians to identify the patients who need special care and treatment and make timely targeted interventions. This will ensure better management of HF patients and reduce the mortality rate. One of the limitations of using SCG signal in clinical settings is its variability. To investigate SCG variability, an exercise protocol has been developed. SCG signal was acquired from the healthy subjects when they underwent the protocol. It was found that cardiopulmonary interactions may contribute to the variability in SCG signal. The study results help to better understand the source of variability which eventually may increase the clinical utility of SCG signal. Another limitation of SCG signal is that it is highly sensitive to the ambient and locomotion-induced noises. This can distort the SCG signal. Hence, removal of noises is a necessary step to use SCG in ambulatory assessment of HF patients. To encounter this problem, a healthy subject performed different maneuvers to induce few common types of noises in the SCG signal. Different signal processing techniques have been employed to remove the noises from the signal. A comparison among different techniques has been provided which may lead to developing an algorithm in the future that is capable of autodetecting noises and suppress them.

It is estimated that there are currently fifty million people living with dementia worldwide. An accurate and early diagnosis of dementia is important in order to initiate appropriate treatment programs as soon as possible. Common methods of neuropsychological assessment can be sensitive to external factors which may compromise accuracy. The aim of this thesis was to investigate techniques that have the potential for the detection of dementia that avoid some of the external influences. The thesis looked at measurements of (i) postural stability (ii) facial analysis and (iii) fully-immersive virtual reality in cognitively-healthy individuals. These techniques were chosen as postural stability and facial analysis change in dementia and whilst virtual reality has previously been used in dementia research, fully-immersive virtual reality measures have not been established. To see if the measurements were associated with cognitive function, participants completed a series of cognitive tests. Results indicate that all techniques explored shared a relationship with memory performance, with lower anteroposterior postural sway (F(1,22) = 17.76, p < 0.01), number of activities participated in that involve a posture element (F(2, 39) = 3.77, p < .05; Wilk's Λ = 0.84, partial η2 = 0.16), the greater the frequency of negative facial expressions (F(2, 18) = 4.49, p < .05; Wilk's Λ = 0.67, partial η2 = 0.33.), and low blink rate (t(11.02) = 2.62 p < .05) all showing better scores on memory tests. Moreover, better scores on the fullyimmersive virtual reality task predicted better scores on with short-term memory (F(1,22) = 20.20 p < 0.01), LTM (F(1,22) = 09.10 p < .01), associative learning (F(1,22) = 08.75 p < .01), and a dual–task test (F(1,22) = 04.64 p < .05). The novel findings that elements such as postural stability, participation in sports, facial expressions of emotion, blink rates, and spatial memory as assessed in fully-immersive virtual reality highlight that non-invasive techniques can provide measurements that correspond to cognitive ability. This may hold implications for dementia diagnoses. Future research should assess whether these relationships can also be found in an older adult population. If this relationship is found in older adults, it could justify further research into how these techniques could be applied in a clinical context.

While computed tomographic angiography (CTA) has emerged as a powerful noninvasive option that allows for direct visualization of arterial stenosis(AS), it cant assess the hemodynamic abnormality caused by an AS. Alternatively, trans-stenotic pressure gradient (TSPG) and fractional flow reserve (FFR) are well-validated hemodynamic indices to assess the ischemic severity of an AS. However, they have significant restriction in practice due to invasiveness and high cost. To fill the gap, a new computational modality, called <i>InVascular</i> has been developed for non-invasive quantification TSPG and/or FFR based on patient's CTA, aiming to quantify the hemodynamic abnormality of the stenosis and help to assess the therapeutic/surgical benefits of treatment for the patient. Such a new capability gives rise to a potential of computation aided diagnostics and therapeutics in a patient-specific environment for ASs, which is expected to contribute to precision planning for cardiovascular disease treatment. <i>InVascular</i> integrates a computational modeling of diseases arteries based on CTA and Doppler ultrasonography data, with cutting-edge Graphic Processing Unit (GPU) parallel-computing technology. Revolutionary fast computing speed enables noninvasive quantification of TSPG and/or FFR for an AS within a clinic permissible time frame. In this work, we focus on the implementation of inlet and outlet boundary condition (BC) based on physiological image date and and 3-element Windkessel model as well as lumped parameter network in volumetric lattice Boltzmann method. The application study in real human coronary and renal arterial system demonstrates the reliability of the in vivo pressure quantification through the comparisons of pressure waves between noninvasive computational and invasive measurement. In addition, parametrization of worsening renal arterial stenosis (RAS) and coronary arterial stenosis (CAS) characterized by volumetric lumen reduction (S) enables establishing the correlation between TSPG/FFR and S, from which the ischemic severity of the AS (mild, moderate, or severe) can be identified. In this study, we quantify TSPG and/or FFR for five patient cases with visualized stenosis in coronary and renal arteries and compare the non-invasive computational results with invasive measurement through catheterization. The ischemic severity of each AS is predicted. The results of this study demonstrate the reliability and clinical applicability of <i>InVascular</i>.

Ce travail a permis de développer une technique non invasive d’identification de la distribution du courant dans une pile à combustible à partir du champ magnétique externe. La mesure du champ s’effectue sur un ensemble de points de mesures choisis spécialement pour détecter les variations du champ par rapport à un fonctionnement optimal de la pile. Les deux composantes du champ magnétique sensibles aux variations sont utilisées. La mesure du champ exploitable est la différence entre un mode considéré sain et un mode quelconque de fonctionnement. Autour de ces mesures de champ magnétique, un problème inverse est modélisé en explorant plusieurs approches de paramétrisation de la distribution du courant. Le caractère mal posé du problème s’est traduit par la non-unicité de la solution et sa sensibilité au bruit. L’affranchissement de ces problèmes est atteint par la régularisation du modèle inverse. L’outil développé permis de reconstruire la distribution du courant indépendamment de la taille du défaut dans la limite de sensibilité. La validation est faite sur un simulateur électrique de pile à combustible et sur une pile de type GENEPAC dans un environnement de laboratoire. / A noninvasive technique for identifying the current distribution in a fuel cell from the external magnetic field is developed. The magnetic field measurements are carried out on a set of points chosen in order to detect only the variations of the magnetic field in a case of a faulty fuel cell. Two components of the magnetic field are used because they are sensitive to current heterogeneities. The exploitable measurement of the magnetic field is the difference between a healthy mode and a faulty mode.An ill-posed inverse problem is modeled by investigating several parametrization approaches of the current distribution. The ill-posed property of the problem conducts to a non-uniqueness of the solution and a high sensitivity to the noise. A regularization method is used in order to get a stable solution. The developed tool allows identifying the current distribution independently of the size of the fault within the sensitivity limit. A validation is done on a fuel cell simulator and on a GENEPAC fuel cell in a laboratory conditions.

No description available.

Λόγω της διαφάνειας των οφθαλμικών ιστών η σκέδαση φωτός αποτελεί ιδανικό εργαλείο για την ανίχνευση των αρχικών σταδίων ορισμένων παθολογικών τους καταστάσεων. Για παράδειγμα, η θόλωση του φακού των θηλαστικών λόγω ηλικίας ή/και άλλων εξωγενών αιτίων καλείται καταρράκτης. Ο καταρράκτης δεν μπορεί να διαγνωστεί κλινικά σε πρώιμο στάδιο με αποτέλεσμα την δημιουργία σοβαρών προβλημάτων στην όραση. Το γεγονός ότι το φως έχει την ικανότητα να ανιχνεύει τις μοριακές αλλαγές οι οποίες είναι πρόδρομα συμπτώματα του καταρράκτη αναδεικνύει την σημασία της έγκαιρης διάγνωσης στην αντιμετώπιση διάφορων οφθαλμικών παθήσεων. Ο φακός θεωρείται ως ένα πυκνό διάλυμα πρωτεϊνών (κρυσταλλίνες, ~40 % wt) σε νερό και η αδιαφάνεια η οποία αποτελεί την εκδήλωση του καταρράκτη προκαλείται ουσιαστικά από την συσσωμάτωση των πρωτεϊνών. Στόχος αυτής της διατριβής είναι η διερεύνηση των μοριακών μεταβολών οι οποίες λαμβάνουν χώρα κατά την ανάπτυξη του καταρράκτη. Ιδιαίτερη σημασία δίνεται επίσης στην ανάπτυξη μιας μη-επεμβατικής μεθοδολογίας για έγκαιρη διάγνωση οφθαλμικών παθήσεων με τη βοήθεια της δυναμικής σκέδασης φωτός. Με την βοήθεια της τεχνικής αυτής, κατάλληλα τροποποιημένης για την μελέτη οφθαλμικών ιστών, μελετήθηκαν οι δυναμικές ιδιότητες των πρωτεϊνών χοίρειων φακών (π.χ. οι συντελεστές διάχυσης, η θερμοκρασιακή τους εξάρτηση σε διάφορα μέρη του φακού, κλπ.) χρησιμοποιώντας το πειραματικό μοντέλο του “ψυχρού” καταρράκτη. Στο μοντέλο αυτό η ελεγχόμενη ψύξη φακών επιφέρει βαθμιαία καταρρακτογένεση. Ιδιαίτερη έμφαση δόθηκε σε τέσσερα κυρίως είδη περαμάτων. (α) Μελέτη της εμφάνισης του ψυχρού καταρράκτη στον πυρήνα του φακού. (β) Μελέτη της επίδρασης του μήκους κύματος της ακτινοβολίας στην εμφάνιση και στην έκταση του φαινομένου του ψυχρού καταρράκτη. (γ) Μελέτη του φαινομένου του ψυχρού καταρράκτη κατά μήκος μιας διαμέτρου του φακού, δεδομένης της βαθμίδας συγκέντρωσης των πρωτεϊνών του φακού (μεγάλη συγκέντρωση στον πυρήνα και μικρή συγκέντρωση στην περιφέρεια του φακού). (δ) Μελέτη του επίδρασης της προθέρμανσης του φακού σε θερμοκρασίες υψηλότερες της φυσιολογικής στο φαινόμενο του ψυχρού καταρράκτη. Τα βασικά συμπεράσματα της παρούσας διατριβής συνοψίζονται ως εξής. Υπάρχουν σαφείς συσχετισμοί μεταξύ των φασματικών χαρακτηριστικών (συναρτήσεις αυτοσυσχέτισης) και των ιεραρχικών σταδίων ανάπτυξης του καταρράκτη. Ποιοτικές και ποσοτικές αλλαγές στην θερμοκρασιακή εξάρτηση διαφόρων παραμέτρων, οι οποίες σχετίζονται με τις μοριακές διαμορφώσεις των αρχικών σταδίων του καταρράκτη, εμφανίζονται ήδη από τους 17 oC όπου ο πυρήνας του φακού είναι ακόμα διαυγής. Η χρήση ακτινοβολίας κοντά στο υπεριώδες μέρος τους φάσματος ενισχύει την ανάπτυξη του ψυχρού καταρράκτη στον πυρήνα του φακού. Ο ψυχρός καταρράκτης δεν αναπτύσσεται στην περιφέρεια του φακού. Η προθέρμανση του φακού σε συγκεκριμένη θερμοκρασία καθώς και ο χρόνος παραμονής σε αυτήν επηρεάζει σημαντικά την ανάπτυξη του ψυχρού καταρράκτη στον πυρήνα αλλά όχι στην περιφέρεια του φακού. Όλα τα παραπάνω δείχνουν πως η δυναμική σκέδαση φωτός μπορεί να παρέχει παραμέτρους οι οποίες μπορούν να χρησιμοποιηθούν με επιτυχία ως ευαίσθητοι και αξιόπιστοι δείκτες της έγκαιρης, μη-επεμβατικής, και in vivo διάγνωσης του καταρράκτη. / On account of the transparency of ophthalmic tissues, light scattering is an ideal tool for detecting the early stages of some of their pathological conditions. For example, the opacity of the mammalian lens due to age or other external causes is called cataract. Cataract cannot be detected clinically at early stages and as a result serious vision problems appear. The fact that, light has the ability to detect molecular changes that are related to the mechanism of cataract formation draws attention to the importance of early diagnosis in ophthalmic disorders. The lens can be considered as a dense colloidal protein dispersion (crystallins, ~ 40% wt) in water where the opacity that leads to cataract formation how its basis to the aggregation of proteins. This dissertation is aimed at studying the molecular changes that take place upon cataract development. Particular emphasis is paid to the development of a non-invasive methodology for early diagnosis of ocular diseases with the aid of dynamic light scattering. By means of this technique, suitably modified for the study of ophthalmic tissues, the dynamic properties of the proteins of porcine lenses (e.g. diffusion coefficients and their temperature dependence at various parts inside the lens, etc.) were studied by using the experimental model of ‘cold’ cataract. In cold cataract the controlled cooling of the lens at temperatures below the physiological one induces gradual cataractogenesis. In particular, we focused on four kinds of experiments. (a) Detailed study on the cold cataract onset in the lens nucleus. (b) Study on the effect of the laser light wavelength in the onset and the extent development of cold cataract. (c) Study of the cold cataract effect along an equatorial diameter of the lens, considering the gradual concentration of the lens proteins (high protein concentration in the nucleus and low concentration in the cortex). (d) Study on the effect of thermal history, i.e. by warming up the lens at temperatures higher than the physiological one on the cold cataract effect. The basic conclusions of the present dissertation are summarized as follows: There are clear correlations between the spectral characteristics (autocorrelation functions) and the hierarchical stages of the onset of cataract. Qualitative and quantitative changes in the temperature dependence of several parameters, which are related with the diffusive motions of proteins at the early stages of cataract, appear already at 17 oC while the nucleus is still clear and highly transparent. The use of laser radiation close to the ultraviolet part of the spectrum seems to enhance the formation of cold cataract in the lens nucleus. Cold cataract does not develop at the cortex of the lens, in view of the low protein concentration. The lens pre-heating at a certain temperature for various time periods affects significantly cold cataract formation in the lens nucleus but not in lens cortex. The above mentioned make clear that dynamic light scattering can indeed provide useful parameters that can be successfully used as sensitive and reliable indicators for the early, non-invasive diagnosis of cataract in mammalian lenses and in vivo.

The early non-invasive diagnosis of epithelial tissue alterations in daily clinical routine is still challenging. Since optical coherence tomography (OCT) shows the potential to differentiate between benign and malignant tissue of primal endothelium, OCT could be beneficial for the early diagnosis of malignancies in routine health checks. In this research, a new handheld endoscopic scanning unit was designed and connected to a spectral domain OCT system of our workgroup for the in vivo imaging of the human oral mucosa.