Non-invasive wave intensity analysis in common carotid artery of healthy humans

This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonThe study of arterial wave propagation is essential to understand the physiopathology of the cardiovascular system, as waves carry clinically relevant information. Impedance analysis was used for such type of studies, where results were presented in the frequency domain, but it was difficult to relate specific events to time points within the cardiac cycle. Therefore, a mathematical tool called wave intensity analysis was developed, initially using measurements of pressure and velocity (PU approach). However, the need to acquire such measurements in a non-invasive, direct and simultaneous fashion led to the development of the DU approach, a type of wave intensity analysis carried out using vessel diameter and flow velocity waveforms, thus giving up the pressure measurement. It is the only available technique, at present, able to extract wave intensity information without relying on distally recorded pressure measurements and on non-simultaneous recordings. Due to its non-invasive nature for collecting the required measurements, this technique has a potential use in clinical and research settings to investigate physiological changes under rapid perturbations, such as the ones introduced by exercise. In this thesis, the DU approach is performed by only using an ultrasound device and to extract information about cardio-arterial interaction in the human common carotid artery. In the first experimental chapter of this thesis, a reproducibility study of common carotid DU-derived wave intensity parameters was conducted on a healthy young cohort, both at rest and during exercise (semi-recumbent cycling). Carotid diameter and blood flow velocity features, as well as wave intensity parameters such as forward compression, backward compression and forward expansion wave peaks and energies, were overall fairly reproducible. In particular, diameter variables exhibited higher reproducibility and lower dispersion than corresponding velocity variables, whereas wave intensity energy variables exhibited higher reproducibility and lower dispersion than corresponding peaks. Local wave speed, calculated via lnDU-loop, a technique based only on local measurements of diameter and velocity and often associated with the DU approach, was also reproducible. It is possible to conclude that the DU-derived wave intensity analysis is reliable both at rest and during exercise. In a subsequent study, DU-derived wave intensity analysis was performed on a young trained cohort to investigate the contribution of cardiac and peripheral vascular alterations to common carotid wave intensity parameters, under rapid physiological perturbations, such as semi-recumbent cycling at incremental workrates, and subsequent recovery. Judging by the increase in local wave speed, the common carotid artery stiffened substantially as workrate increased whilst peak and energy of the forward and backward compression waves also increased, due to enhanced ventricular contractility, which was associated with larger reflections from the cerebral microcirculation and other vascular beds in the head. However, the reflection indices remained unchanged during exercise, highlighting that the increased magnitude of reflections is mainly due to the enhanced contractility, rather than changes in vascular resistance, at least at the carotid artery in young healthy individuals. The forward expansion wave increased during exercise, as the left ventricle actively decelerated blood flow in late systole, potentially improving filling time during diastole. In the early recovery, the magnitude of all waves returned to baseline value. Finally, the X wave, attributed to the reflection of the backward compression wave, had a tendency to increase during exercise and to return to baseline value in early recovery. A further development of wave intensity analysis came with the reservoir-wave approach, able to separate, from the pressure and velocity waveforms, the component solely due to the reservoir volume, for the correct evaluation of backward- and forward-travelling waves. A number of issues, however, still remains, involving specifically the lack of consensus over the fitting technique and over the value of the asymptotic pressure value (P ∞),used for the determination of the reservoir waveform. Therefore, to give a contribution to the debate involving the more correct model for the pressure and velocity reservoir-wave approach, a study aimed to investigate various common carotid hemodynamic and wave intensity parameters, using different fitting techniques and values of P ∞ currently available in literature, was performed and described in the last chapter of this thesis. The study demonstrated that different fitting method and values of P ∞ could bring significant variations in values and trends of hemodynamic and wave intensity parameters. However, despite the changes in the shape of the reservoir pressure waveform, its peak and integral with respect to time tended to remain constant. This is an important feature, because both reservoir peak pressure and its integral have been used in clinical settings for the calculation of diagnostic indicators. The reservoir and excess velocity peaks, instead, changed more significantly. This outcome, together with the concomitant substantial change in excess pressure peak and integral, may greatly affect wave intensity parameters. Wave intensity parameters were, in fact, significantly more sensitive to fitting techniques and values of P ∞ than pressure parameters. Finally, the wave speed did not substantially change, leading to the conclusion that the calculation of local vessel distensibility and/or compliance, when calculated from the excess components of the waveforms, seemed insensitive to fitting techniques and values of P

A Multi-scale Stochastic Filter Based Approach to Inverse Scattering for 3D Ultrasound Soft Tissue Characterization

The goal of this research is to achieve accurate characterization of multi-layered soft tissues in three dimensions using focused ultrasound. The characterization of the acoustic parameters of each tissue layer is formulated as recursive processes of forward- and inverse- scattering. Forward scattering deals with the modeling of focused ultrasound wave propagation in multi-layered tissues, and the computation of the focused wave amplitudes in the tissues based on the acoustic parameters of the tissue as generated by inverse scattering. The model for mapping the tissue acoustic parameters to focused waves is highly nonlinear and stochastic. In addition, solving (or inverting) the model to obtain tissue acoustic parameters is an ill-posed problem. Therefore, a nonlinear stochastic inverse scattering method is proposed such that no linearization and mathematical inversion of the model are required. Inverse scattering aims to estimate the tissue acoustic parameters based on the forward scattering model and ultrasound measurements of the tissues. A multi-scale stochastic filter (MSF) is proposed to perform inverse scattering. MSF generates a set of tissue acoustic parameters, which are then mapped into focused wave amplitudes in the multi-layered tissues by forward scattering. The tissue acoustic parameters are weighted by comparing their focused wave amplitudes to the actual ultrasound measurements. The weighted parameters are used to estimate a weighted Gaussian mixture as the posterior probability density function (PDF) of the parameters. This PDF is optimized to achieve minimum estimation error variance in the sense of the posterior Cramer-Rao bound. The optimized posterior PDF is used to produce minimum mean-square-error estimates of the tissue acoustic parameters. As a result, both the estimation error and uncertainty of the parameters are minimized. PDF optimization is formulated based on a novel multi-scale PDF analysis framework. This framework is founded based on exploiting the analogy between PDFs and analog (or digital) signals. PDFs and signals are similar in the sense that they represent characteristics of variables in their respective domains, except that there are constraints imposed on PDFs. Therefore, it is reasonable to consider a PDF as a signal that is subject to amplitude constraints, and as such apply signal processing techniques to analyze the PDF. The multi-scale PDF analysis framework is proposed to recursively decompose an arbitrary PDF from its fine to coarse scales. The recursive decompositions are designed so as to ensure that requirements such as PDF constraints, zero-phase shift and non-creation of artifacts are satisfied. The relationship between the PDFs at consecutive scales is derived in order for the PDF optimization process to recursively reconstruct the posterior PDF from its coarse to fine scales. At each scale, PDF reconstruction aims to reduce the variances of the posterior PDF Gaussian components, and as a result the confidence in the estimate is increased. The overall posterior PDF variance reduction is guided by the posterior Cramer-Rao bound. A series of experiments is conducted to investigate the performance of the proposed method on ultrasound multi-layered soft tissue characterization. Multi-layered tissue phantoms that emulate ocular components of the eye are fabricated as test subjects. Experimental results confirm that the proposed MSF inverse scattering approach is well suited for three-dimensional ultrasound tissue characterization. In addition, performance comparisons between MSF and a state-of-the-art nonlinear stochastic filter are conducted. Results show that MSF is more accurate and less computational intensive than the state-of-the-art filter

Multi-Modality Diffuse Fluorescence Imaging Applied to Preclinical Imaging in Mice

RÉSUMÉ Cette thèse vise à explorer l'information anatomique et fonctionnelle en développant de nouveaux systèmes d'imagerie de fluorescence macroscopiques à base de multi-modalité. L‘ajout de l‘imagerie anatomique à des modalités fonctionnelles telles que la fluorescence permet une meilleure visualisation et la récupération quantitative des images de fluorescence, ce qui en retour permet d'améliorer le suivi et l'évaluation des paramètres biologiques dans les tissus. Sur la base de cette motivation, la fluorescence a été combinée avec l‘imagerie ultrasonore (US) d'abord et ensuite l'imagerie par résonance magnétique (IRM). Dans les deux cas, les performances du système ont été caractérisées et la reconstruction a été évaluée par des simulations et des expérimentations sur des fantômes. Finalement, ils ont été utilisés pour des expériences d'imagerie moléculaire in vivo dans des modèles de cancer et d‘athérosclérose chez la souris. Les résultats ont été présentés dans trois articles, qui sont inclus dans cette thèse et décrits brièvement ci-dessous. Un premier article présente un système d'imagerie bimodalité combinant fluorescence à onde continue avec l‘imagerie à trois dimensions (3D) US. A l‘aide de stages X-Y motorisés, le système d'imagerie a été en mesure de recueillir l‘émission fluorescente et les échos acoustiques délimitant la surface 3D et la position des inclusions fluorescentes dans l'échantillon. Une validation sur fantômes, a montré que l'utilisation des priors anatomiques provenant des US améliorait la qualité de la reconstruction fluorescente. En outre, un étude pilote in-vivo en utilisant une souris Apo-E a évalué la faisabilité de cette approche d'imagerie double modalité pour de futures études pré-cliniques. Dans un deuxième effort, et sur la base du premier travail, nous avons amélioré le système d'imagerie par fluorescence-US au niveau des algorithmes, de la précision----------ABSTRACT This thesis aims to explore the anatomical and functional information by developing new macroscopic multi-modality fluorescence imaging schemes. Adding anatomical imaging to functional modalities such as fluorescence enables better visualization and recovery of fluorescence images, in turn, improving the monitoring and assessment of biological parameters in tissue. Based on this motivation, fluorescence was combined with ultrasound (US) imaging first and then magnetic resonance imaging (MRI). In both cases, the systems characterization and reconstruction performance were evaluated by simulations and phantom experiments. Eventually, they were applied to in vivo molecular imaging in models of cancer and atherosclerosis in mice. Results were presented in three peer-reviewed journals, which are included in this thesis and shortly described below. A first article presented a dual-modality imaging system combining continuous-wave transmission fluorescence imaging with three dimensional (3D) US imaging. Using motorized X-Y stages, the fluorescence-US imaging system was able to collect boundary fluorescent emission, and acoustic pulse-echoes delineating the 3D surface and position of fluorescent inclusions within the sample. A validation in phantoms showed that using the US anatomical priors, the fluorescent reconstruction quality was significantly improved. Furthermore, a pilot in-vivo study using an Apo-E mouse evaluated the feasibility of this dual-modality imaging approach for future animal studies. In a second endeavor, and based on the first work, we improved the fluorescence-US imaging system in terms of sampling precision and reconstruction algorithms. Specifically, now combining US imaging and profilometry, both the fluorescent target and 3D surface of sample could be obtained in order to achieve improved fluorescence reconstruction. Furthermore,

Proceedings of the 10th International Chemical and Biological Engineering Conference - CHEMPOR 2008

This volume contains full papers presented at the 10th International Chemical and Biological Engineering Conference - CHEMPOR 2008, held in Braga, Portugal, between September 4th and 6th, 2008.FC

Graduate course catalog (Florida International University). [2016-2017]

This catalog contains a description of the various policies, graduate programs, degree requirements, and course offerings at Florida International University during the 2016-2017 academic year.https://digitalcommons.fiu.edu/catalogs/1072/thumbnail.jp

Graduate course catalog (Florida International University). [2014-2015]

This catalog contains a description of the various policies, graduate programs, degree requirements, and course offerings at Florida International University during the 2014-2015 academic year.https://digitalcommons.fiu.edu/catalogs/1065/thumbnail.jp

Graduate course catalog (Florida International University). [2015-2016]

This catalog contains a description of the various policies, graduate programs, degree requirements, and course offerings at Florida International University during the 2015-2016 academic year.https://digitalcommons.fiu.edu/catalogs/1067/thumbnail.jp