Novel Techniques for Tissue Imaging and Characterization Using Biomedical Ultrasound

The use of ultrasound technology in the biomedical field has been widely increased in recent decades. Ultrasound modalities are considered more safe and cost effective than others that use ionizing radiation. Moreover, the use of high-frequency ultrasound provides means of high-resolution and precise tissue assessment. Consequently, ultrasound elastic waves have been widely used to develop non-invasive techniques for tissue assessment. In this work, ultrasound waves have been used to develop non-invasive techniques for tissue imaging and characterization in three different applications.;Currently, there is a lack of imaging modalities to accurately predict minute structures and defects in the jawbone. In particular, the inability of 2D radiographic images to detect bony periodontal defects resulted from infection of the periodontium. They also may carry known risks of cancer generation or may be limited in accurate diagnosis scope. Ultrasonic guided waves are sensitive to changes in microstructural properties, while high-frequency ultrasound has been used to reconstruct high-resolution images for tissue. The use of these ultrasound techniques may provide means for early diagnosis of marrow ischemic disorders via detecting focal osteoporotic marrow defect, chronic nonsuppurative osteomyelitis, and cavitations in the mandible (jawbone). The first part of this work investigates the feasibility of using guided waves and high frequency ultrasound for non-invasive human jawbone assessment. The experimental design and the signal/image processing procedures for each technique are developed, and multiple in vitro studies are carried out using dentate and non-dentate mandibles. Results from both the ultrasonic guided waves analysis and the high frequency 3D echodentographic imaging suggest that these techniques show great potential in providing non-invasive methods to characterize the jawbone and detect periodontal diseases at earlier stages.;The second part of this work describes indirect technique for characterization via reconstructing high-resolution microscopic images. The availability of well-defined genetic strains and the ability to create transgenic and knockout mice makes mouse models extremely significant tools in different kinds of research. For example, noninvasive measurement of cardiovascular function in mouse hearts has become a valuable need when studying the development or treatment of various diseases. This work describes the development and testing of a single-element ultrasound imaging system that can reconstruct high-resolution brightness mode (B-mode) images for mouse hearts and blood vessels that can be used for quantitative measurements in vitro. Signal processing algorithms are applied on the received ultrasound signals including filtering, focusing, and envelope detection prior to image reconstruction. Additionally, image enhancement techniques and speckle reduction are adopted to improve the image resolution and quality. The system performance is evaluated using both phantom and in vitro studies using isolated mouse hearts and blood vessels from APOE-KO and its wild type control. This imaging system shall provide a basis for early and accurate detection of different kinds of diseases such as atherosclerosis in mouse model.;The last part of this work is initialized by the increasing need for a non-invasive method to assess vascular wall mechanics. Endothelial dysfunction is considered a key factor in the development of atherosclerosis. Flow-mediated vasodilatation (FMD) measurement in brachial and other conduit arteries has become a common method to assess the endothelial function in vivo. In spite of the direct relationship that could be between the arterial wall multi-component strains and the FMD response, direct measurement of wall strain tensor due to FMD has not yet been reported in the literature. In this work, a noninvasive direct ultrasound-based strain tensor measuring (STM) technique is presented to assess changes in the mechanical parameters of the vascular wall during post-occlusion reactive hyperemia and/or FMD, including local velocities and displacements, diameter change, local strain tensor and strain rates. The STM technique utilizes sequences of B-mode ultrasound images as its input with no extra hardware requirement. The accuracy of the STM algorithm is assessed using phantom, and in vivo studies using human subjects during pre- and post-occlusion. Good correlations are found between the post-occlusion responses of diameter change and local wall strains. Results indicate the validity and versatility of the STM algorithm, and describe how parameters other than the diameter change are sensitive to reactive hyperemia following occlusion. This work suggests that parameters such as local strains and strain rates within the arterial wall are promising metrics for the assessment of endothelial function, which can then be used for accurate assessment of atherosclerosis

Development, Optimization and Clinical Evaluation Of Algorithms For Ultrasound Data Analysis Used In Selected Medical Applications.

The assessment of soft and hard tissues is critical when selecting appropriate protocols for restorative and regenerative therapy in the field of dental surgery. The chosen treatment methodology will have significant ramifications on healing time, success rate and overall long-time oral health. Currently used diagnostic methods are limited to visual and invasive assessments; they are often user-dependent, inaccurate and result in misinterpretation. As such, the clinical need has been identified for objective tissue characterization, and the proposed novel ultrasound-based approach was designed to address the identified need. The device prototype consists of a miniaturized probe with a specifically designed ultrasonic transducer, electronics responsible for signal generation and acquisition, as well as an optimized signal processing algorithm required for data analysis. An algorithm where signals are being processed and features extracted in real-time has been implemented and studied. An in-depth algorithm performance study has been presented on synthetic signals. Further, in-vitro laboratory experiments were performed using the developed device with the algorithm implemented in software on animal-based samples. Results validated the capabilities of the new system to reproduce gingival assessment rapidly and effectively. The developed device has met clinical usability requirements for effectiveness and performance

Silicon Carbide And Agile Optics Based Sensors For Power Plant Gas Turbines, Laser Beam Analysis And Biomedicine

Proposed are novel sensors for extreme environment power plants, laser beam analysis and biomedicine. A hybrid wireless-wired extreme environment temperature sensor using a thick single-crystal Silicon Carbide (SiC) chip embedded inside a sintered SiC probe design is investigated and experimentally demonstrated. The sensor probe employs the SiC chip as a Fabry-Perot (FP) interferometer to measure the change in refractive index and thickness of SiC with temperature. A novel temperature sensing method that combines wavelength-tuned signal processing for coarse measurements and classical FP etalon peak shift for fine measurements is proposed and demonstrated. This method gives direct unambiguous temperature measurements with a high temperature resolution over a wide temperature range. An alternative method using blackbody radiation from a SiC chip in a two-color pyrometer configuration for coarse temperature measurement and classical FP laser interferometry via the same chip for fine temperature measurement is also proposed and demonstrated. The sensor design is successfully deployed in an industrial test rig environment with gas temperatures exceeding 1200 C. This sensor is proposed as an alternate to all-electrical thermocouples that are susceptible to severe reliability and lifetime issues in such extreme environments. A few components non-contact thickness measurement system for optical quality semi-transparent samples such as Silicon (Si) and 6H SiC optical chips such as the one used in the design of this sensor is proposed and demonstrated. The proposed system is self-calibrating and ensures a true thickness measurement by taking into account material dispersion in the wavelength band of operation. For the first time, a 100% repeatable all-digital electronically-controlled pinhole laser beam profiling system using a Texas Instruments (TI) Digital Micro-mirror Device (DMD) commonly used in projectors is experimentally demonstrated using a unique liquid crystal image generation system with non-invasive qualities. Also proposed and demonstrated is the first motion-free electronically-controlled beam propagation analyzer system using a TI DMD and a variable focus liquid lens. The system can be used to find all the parameters of a laser beam including minimum waist size, minimum waist location and the beam propagation parameter M2. Given the all-digital nature of DMD-based profiling and all-analog motion-free nature of the Electronically Controlled Variable Focus Lens (ECVFL) beam focus control, the proposed analyzer versus prior-art promises better repeatability, speed and reliability. For the first time, Three Dimensional (3-D) imaging is demonstrated using an electronically controlled Liquid Crystal (LC) optical lens to accomplish a no-moving parts depth section scanning in a modified commercial 3-D confocal microscope. The proposed microscopy system within aberration limits has the potential to eliminate the sample or objective motion-caused mechanical forces that can distort the original sample structure and lead to imaging errors. A signal processing method for realizing high resolution three dimensional (3-D) optical imaging using diffraction limited low resolution optical signals is also proposed

Thérapies ultrasonores cardiaques guidées par élastographie et échographie ultrarapides

Atrial fibrillation (AF) affects 2-3% of the European and North-American population, whereas ventricular tachyarrhythmia (VT) is related to an important risk of sudden death. AF and VT originate from dysfunctional electrical activity in cardiac tissues. Minimally-invasive approaches such as Radio-Frequency Catheter Ablation (RFCA) have revolutionized the treatment of these diseases; however the success rate of RFCA is currently limited by the lack of monitoring techniques to precisely control the extent of thermally ablated tissue.The aim of this thesis is to propose novel ultrasound-based approaches for minimally invasive cardiac ablation under guidance of ultrasound imaging. For this, first, we validated the accuracy and clinical viability of Shear-Wave Elastography (SWE) as a real-time quantitative imaging modality for thermal ablation monitoring in vivo. Second we implemented SWE on an intracardiac transducer and validated the feasibility of evaluating thermal ablation in vitro and in vivo on beating hearts of a large animal model. Third, a dual-mode intracardiac transducer was developed to perform both ultrasound therapy and imaging with the same elements, on the same device. SWE-controlled High-Intensity-Focused-Ultrasound thermal lesions were successfully performed in vivo in the atria and the ventricles of a large animal model. At last, SWE was implemented on a transesophageal ultrasound imaging and therapy device and the feasibility of transesophageal approach was demonstrated in vitro and in vivo. These novel approaches may lead to new clinical devices for a safer and controlled treatment of a wide variety of cardiac arrhythmias and diseases.La fibrillation atriale affecte 2-3% des européens et nord-américains, les tachycardies ventriculaires sont liées à un risque important de mort subite. Les approches minimalement invasives comme l’Ablation par Cathéter Radiofréquence (RFCA) ont révolutionné le traitement de ces maladies, mais le taux de réussite de la RFCA est limité par le manque de techniques d’imagerie pour contrôler cette ablation thermique.Le but de cette thèse est de proposer de nouvelles approches ultrasonores pour des traitements cardiaques minimalement invasifs guidés par échographie.Pour cela nous avons d’abord validé la précision et la viabilité clinique de l’Élastographie par Ondes de Cisaillement (SWE) en tant que modalité d’imagerie quantitative et temps réel pour l’ablation thermique in vivo. Ensuite nous avons implémenté la SWE sur un transducteur intracardiaque et validé la faisabilité d’évaluer l’ablation thermique in vitro et in vivo sur cœur battant de gros animal. Puis nous avons développé un transducteur intracardiaque dual-mode pour effectuer l’ablation et l’imagerie ultrasonores avec les mêmes éléments, sur le même dispositif. Les lésions thermiques induites par Ultrasons Focalisés de Haute Intensité (HIFU) et contrôlées par la SWE ont été réalisées avec succès in vivo dans les oreillettes et les ventricules chez le gros animal. Finalement la SWE a été implémentée sur un dispositif d’imagerie et thérapie ultrasonores transœsophagien et la faisabilité de cette approche a été démontrée in vitro et in vivo. Ces approches originales pourraient conduire à de nouveaux dispositifs cliniques pour des traitements plus sûrs et contrôlés d’un large éventail d’arythmies et maladies cardiaques

Proceedings of the International Workshop on Medical Ultrasound Tomography: 1.- 3. Nov. 2017, Speyer, Germany

Ultrasound Tomography is an emerging technology for medical imaging that is quickly approaching its clinical utility. Research groups around the globe are engaged in research spanning from theory to practical applications. The International Workshop on Medical Ultrasound Tomography (1.-3. November 2017, Speyer, Germany) brought together scientists to exchange their knowledge and discuss new ideas and results in order to boost the research in Ultrasound Tomography

Progress Report No. 13

Progress report of the Biomedical Computer Laboratory, covering period 1 July 1976 to 30 June 1977

HIGH-SPEED ENDOSCOPIC OPTICAL COHERENCE TOMOGRAPHY AND ITS APPLICATIONS

Optical coherence tomography (OCT) is a real-time high-resolution imaging technology providing cross-sectional images of biological structures at a resolution of <1 to 20 µm and a penetration depth of 1 to 3 mm in most highly scattering tissues. OCT is in general non-invasive and can perform real-time ‘optical biopsy’ with a resolution approaching standard low magnification histopathology but without tissue removal. Conventional OCT requires a bulky imaging probe, which limits most of the in vivo applications to ophthalmology and dermatology. The development of miniature OCT imaging probe has greatly expanded the scope of the applications (e.g., cardiology, gastroenterology, etc.). Recent technical advances in OCT has extended the imaging speed from a few kHz to a few hundreds kHz, enabling in vivo three-dimensional (3D) imaging. This dissertation describes the development of a high-speed endoscopic OCT imaging system. The system employs the Fourier domain mode locking laser technology at a wavelength range of 1300 nm to reach an axial resolution of 9.7 µm and an A-scan rate of 220 kHz. A Mach-Zehnder interferometer setup is used to achieve shot-noise limited detection. A generic OCT software platform is developed for data acquisition, processing, display, storage, and 3D visualization. Miniature OCT imaging probes are designed and fabricated for in vivo 3D OCT imaging. The utility of the high-speed endoscopic OCT system is demonstrated for clinical and basic researches in pulmonology and gastroenterology. In addition, an ultrahigh-resolution endoscopic OCT system is developed at a wavelength range of 800 nm to reach an axial resolution of 3.0 µm and an A-scan rate of up to 20 kHz. Furthermore, a novel type of OCT contrast agents, scattering dominant gold nanocages, is developed with the aid of a cross-reference OCT imaging method. Finally, a multimodal endoscopic imaging system combines 1300 nm en face OCT and 1550 nm two photon fluorescence is developed. Compared with most of other imaging modalities, high-speed endoscopic OCT has unmatched advantages including high spatial resolution, imaging speed, and non-invasiveness / minimal invasiveness. The results in this dissertation suggest that high-speed endoscopic OCT may has a great impact on healthcare as well as basic research

HIGH INTENSITY FOCUSED ULTRASOUND AND OXYGEN LOAD NANOBUBBLES: TWO DIFFERENT APPROCHES FOR CANCER TREATMENT

The study of applications based on the use of ultrasound in medicine and biology for therapeutic purposes is under strong development at international level and joins the notoriously well-established and widespread use of diagnostic applications [1]. In the past few years, High Intensity Focused Ultrasound (HIFU) has developed from a scientific curiosity to an accepted therapeutic modality. HIFU is a non invasive technique for the treatment of various types of cancer, as well as non-malignant pathologies, by inducing localized hyperthermia that causes necrosis of the tissue. Beside HIFU technology, other innovative therapeutic modalities to treat cancer are emerging. Among them, an extremely innovative technique is represented by oxygen loaded nanobubbles (OLNs): gas cavities confined by an appropriately functionalized coating. This is an oxygenating drugs aimed at re-oxygenation of cancerous tissue. Oxygen deficiency, in fact, is the main hallmark of cancerous solid tumors and a major factor limiting the effectiveness of radiotherapy. In this work, these two approaches to treat tumours are under study from a metrological point of view. In particular, a complete characterization of an HIFU fields regarding power, pressure and temperature is provided while oxygen load nanobubbles are synthesized, characterized and applied in in vitro and in vivo experiments