Three-dimensional Photoacoustic Tomography System Design Analysis and Optimization

Photoacoustic tomography (PAT) is an emerging imaging modality capable of mapping optical absorption in tissues. It is a hybrid technique that combines the high spatial resolution of ultrasound imaging with the high contrast of optical imaging, and has demonstrated much potential in biomedical applications. Conventional PAT systems employ raster scanning to capture a large number of projections, thus improving image reconstruction at the cost of temporal resolution. Arising from the desire for real-time 3D PA imaging, several groups have begun to design PAT systems with staring arrays, where image acquisition is only limited by the repetition rate of the laser. However, there has been little emphasis on staring array design analysis and optimization. We have developed objective figures of merit for PAT system performance and applied these metrics to improve system design. The results suggested that the developed approach could be used to objectively characterize and improve any PAT system design

Real-time Three-dimensional Photoacoustic Imaging

Photoacoustic imaging is a modality that combines the benefits of two prominent imaging techniques; the strong contrast inherent to optical imaging techniques with the enhanced penetration depth and resolution of ultrasound imaging. PA waves are generated by illuminating a light-absorbing object with a short laser pulse. The deposited energy causes a pressure change in the object and, consequently, an outwardly propagating acoustic wave. Images are produced by using characteristic optical information contained within the waves. We have developed a 3D PA imaging system by using a staring, sparse array approach to produce real-time PA images. The technique employs the use of a limited number of transducers and by solving a linear system model, 3D PA images are rendered. In this thesis, the development of an omni-directional PA source is introduced as a method to characterize the shift-variant system response. From this foundation, a technique is presented to generate an experimental estimate of the imaging operator for a PA system. This allows further characterization of the object space by two techniques; the crosstalk matrix and singular value decomposition. Finally, the results of the singular value decomposition analysis coupled with the linear system model approach to image reconstruction, 3D PA images are produced at a frame rate of 0.7 Hz. This approach to 3D PA imaging has provided the foundation for 3D PA images to be produced at frame rates limited only by the laser repetition rate, as straightforward system improvements could see the imaging process reduced to tens of milliseconds

NUTMEG:Open Source Software for M/EEG Source Reconstruction

Neurodynamic Utility Toolbox for Magnetoencephalo- and Electroencephalography (NUTMEG) is an open-source MATLAB-based toolbox for the analysis and reconstruction of magnetoencephalography/electroencephalography data in source space. NUTMEG includes a variety of options for the user in data import, preprocessing, source reconstruction, and functional connectivity. A group analysis toolbox allows the user to run a variety of inferential statistics on their data in an easy-to-use GUI-driven format. Importantly, NUTMEG features an interactive five-dimensional data visualization platform. A key feature of NUTMEG is the availability of a large menu of interference cancelation and source reconstruction algorithms. Each NUTMEG operation acts as a stand-alone MATLAB function, allowing the package to be easily adaptable and scripted for the more advanced user for interoperability with other software toolboxes. Therefore, NUTMEG enables a wide range of users access to a complete “sensor-to- source-statistics” analysis pipeline

Fourier based high-resolution near-field sound imaging

Noise pollution is a generally acknowledged problem in modern day society. The current tendencies towards lightweight and cheaper product design are primarily responsible for increasing nuisance, annoyance and environmental problems caused by acoustic noise. There are several reasons for research towards technologies that facilitate acoustic noise reduction. Nowadays, low noise design of consumer electronics, high-tech systems and automotive are restricted to increasingly stringent regulations and quality aspects. Effective countermeasures in order to reduce sound radiation are only taken when the source of sound is known. "Inverse Acoustics" is a very effective method to visualize and quantize the sound sources, which reconstructs source information based on measurements away from the source, yet in the near-field. In fact, the system is able to reconstruct the entire acoustic message that a source radiates in the direction of interest. The current methods for source reconstruction produce sound images with very little detail, they often require cumbersome numerical calculations and models, and they are often highly impractical for industrial applications. This research focuses on fast and accurate measurement and signal processing methods for inverse acoustics that are applicable in practical situations which require high resolutions under hazardous acoustic conditions. The inverse process is based upon spatial and wavenumber domain Fourier techniques, also referred to as Near-field Acoustic Holography. More in detail, spatial properties with respect to aliasing, leakage, signal-to-noise ratio and sensor set-ups are investigated and explicit methods and rules are developed to assist in proper determination of the acoustic holograms. In order to correctly transform the spatial hologram data into the wavenumber domain or k-space, a method called border-padding is developed. This method, which is an alternative to spatial windowing, is highly accurate without slowing down the processing time considerably. Another important factor is regularization, which is required since the inverse process is highly ill-posed. Without proper filtering action taken, noise blows up as the hologram-source distance or the wavenumber grows. In this research project a method is developed to automatically determine the proper filter function and filter parameters, which is a near-optimal trade-off between noise blow-up and deterioration of useful source information. These important properties are combined in a fully automated near-field sound imaging system design. At the Technical University of Eindhoven two versions of this system were developed and built; a large version that is based in the semi-anechoic room of the laboratory and a portable system that is suitable for small electronic devices and high-tech systems. A number of practical cases are used to qualitatively as well as quantitatively validate the improvements with respect to existing methods and illustrate the possibilities for industrial application

Development of three-dimensional, ex vivo optical imaging

The ability to analyse tissue in 3-D at the mesoscopic scale (resolution: 2-50 µm) has proven essential in the study of whole specimens and individual organs. Techniques such as ex vivo magnetic resonance imaging (MRI) and X-ray computed tomography (CT) have been successful in a number of applications. Although MRI has been used to image embryo development and gene expression in 3-D, its resolution is not sufficient to discriminate between the small structures in embryos and individual organs. Furthermore, since neither MRI nor X-ray CT are optical imaging techniques, none of them is able to make use of common staining techniques. 3-D images can be generated with confocal microscopy by focusing a laser beam to a point within the sample and collecting the fluorescent light coming from that specific plane, eliminating therefore out-of-focus light. However, the main drawback of this microscopy technique is the limited depth penetration of light (~1 mm). Tomographic techniques such as optical projection tomography (OPT) and light sheet fluorescence microscopy (also known as single plane illumination microscopy, SPIM) are novel methods that fulfil a requirement for imaging of specimens which are too large for confocal imaging and too small for conventional MRI. To allow sufficient depth penetration, these approaches require specimens to be rendered transparent via a process known as optical clearing, which can be achieved using a number of techniques. The aim of the work presented in this thesis was to develop methods for threedimensional, ex vivo optical imaging. This required, in first instance, sample preparation to clear (render transparent) biological tissue. In this project several optical clearing techniques have been tested in order to find the optimal method per each kind of tissue, focusing on tumour tissue. Indeed, depending on its structure and composition (e.g. amount of lipids or pigments within the tissue) every tissue clears at a different degree. Though there is currently no literature reporting quantification of the degree of optical clearing. Hence a novel, spectroscopic technique for measuring the light attenuation in optically cleared samples is described in this thesis and evaluated on mouse brain. 5 Optical clearing was applied to the study of cancer. The main cancer model investigated in this report is colorectal carcinoma. Fluorescently labelled proteins were used to analyse the vascular network of colorectal xenograft tumours and to prove the effect of vascular disrupting agents on the vascular tumour network. Furthermore, optical clearing and fluorescent compounds were used for ex vivo analysis of perfusion of a human colorectal liver metastasis model