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Department of Biomedical EngineeringThe optical imaging has a critical role in biomedical research to analyze functional and morphological variation of an organ, tissue and even a single cell of animal models. Since the optical imaging modality has features of indirect access, volumetric analysis and high resolution, it has been used for biomedical analysis. Especially, as a low coherence interferometric imaging technique, optical coherence tomography (OCT) has been applied in scientific and medical fields from few decades ago. Since OCT can provide endogenous contrast of biological tissue using the infrared light source, it has high potential to be applied in practical medical diagnosis. However, it is hard to acquire uneven or thick sample due to the limited imaging window and penetration depth. To overcome those limitations, lots of optical, mathematical and chemical solutions comes within a decade such as adaptive optics, full-range method and tissue clearing. Despite the existence of suggested solutions, practical application of OCT is limitation due to the cost of time and effort. Here, we present practical methods to enhance acquirable endogenous information of sample through versatile scanning optical coherence tomography(VS-OCT). Conventional OCT utilizes dual-axis based flat focal plane scanning method providing limited depth information of curved samples. Thus, we developed advanced OCT, called VS-OCT, which can fully optimize imaging window by changing focal plane to dual plane and cylindrical plane. The VS-OCT is demonstrated for 1) quantification of engineered skin, 2) monitoring of tadpole development, 3) screening phenotype of zebrafish and 4) quantification of spinal cord injury (SCI) of mouse.ope

Regularized Newton Methods for X-ray Phase Contrast and General Imaging Problems

Like many other advanced imaging methods, x-ray phase contrast imaging and tomography require mathematical inversion of the observed data to obtain real-space information. While an accurate forward model describing the generally nonlinear image formation from a given object to the observations is often available, explicit inversion formulas are typically not known. Moreover, the measured data might be insufficient for stable image reconstruction, in which case it has to be complemented by suitable a priori information. In this work, regularized Newton methods are presented as a general framework for the solution of such ill-posed nonlinear imaging problems. For a proof of principle, the approach is applied to x-ray phase contrast imaging in the near-field propagation regime. Simultaneous recovery of the phase- and amplitude from a single near-field diffraction pattern without homogeneity constraints is demonstrated for the first time. The presented methods further permit all-at-once phase contrast tomography, i.e. simultaneous phase retrieval and tomographic inversion. We demonstrate the potential of this approach by three-dimensional imaging of a colloidal crystal at 95 nm isotropic resolution.Comment: (C)2016 Optical Society of America. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modifications of the content of this paper are prohibite

Mathematics of biomedical imaging today—a perspective

Biomedical imaging is a fascinating, rich and dynamic research area, which has huge importance in biomedical research and clinical practice alike. The key technology behind the processing, and automated analysis and quantification of imaging data is mathematics. Starting with the optimisation of the image acquisition and the reconstruction of an image from indirect tomographic measurement data, all the way to the automated segmentation of tumours in medical images and the design of optimal treatment plans based on image biomarkers, mathematics appears in all of these in different flavours. Non-smooth optimisation in the context of sparsity-promoting image priors, partial differential equations for image registration and motion estimation, and deep neural networks for image segmentation, to name just a few. In this article, we present and review mathematical topics that arise within the whole biomedical imaging pipeline, from tomographic measurements to clinical support tools, and highlight some modern topics and open problems. The article is addressed to both biomedical researchers who want to get a taste of where mathematics arises in biomedical imaging as well as mathematicians who are interested in what mathematical challenges biomedical imaging research entails

The quantitative analysis of transonic flows by holographic interferometry

This thesis explores the feasibility of routine transonic flow analysis by holographic interferometry. Holography is potentially an important quantitative flow diagnostic, because whole-field data is acquired non-intrusively without the use of particle seeding. Holographic recording geometries are assessed and an image plane specular illumination configuration is shown to reduce speckle noise and maximise the depth-of-field of the reconstructed images. Initially, a NACA 0012 aerofoil is wind tunnel tested to investigate the analysis of two-dimensional flows. A method is developed for extracting whole-field density data from the reconstructed interferograms. Fringe analysis errors axe quantified using a combination of experimental and computer generated imagery. The results are compared quantitatively with a laminar boundary layer Navier-Stokes computational fluid dynamics (CFD) prediction. Agreement of the data is excellent, except in the separated wake where the experimental boundary layer has undergone turbulent transition. A second wind tunnel test, on a cone-cylinder model, demonstrates the feasibility of recording multi-directional interferometric projections using holographic optical elements (HOE’s). The prototype system is highly compact and combines the versatility of diffractive elements with the efficiency of refractive components. The processed interferograms are compared to an integrated Euler CFD prediction and it is shown that the experimental shock cone is elliptical due to flow confinement. Tomographic reconstruction algorithms are reviewed for analysing density projections of a three-dimensional flow. Algebraic reconstruction methods are studied in greater detail, because they produce accurate results when the data is ill-posed. The performance of these algorithms is assessed using CFD input data and it is shown that a reconstruction accuracy of approximately 1% may be obtained when sixteen projections are recorded over a viewing angle of ±58°. The effect of noise on the data is also quantified and methods are suggested for visualising and reconstructing obstructed flow regions

X-ray Phase Contrast Tomography : Setup and Scintillator Development

X-ray microscopy and micro-tomography (μCT) are valuable non-destructive examination methods in many disciplines such as bio-medical research, archaeometry, material science and paleontology. Besides being implemented at synchrotrons radiation sources, laboratory setups using an X-ray tube and high-resolution scintillation detector routinely provide information on the micrometre scale. To improve the image contrast for small and low-density samples, it is possible to introduce a propagation distance between sample and detector to perform propagation-based phase contrast imaging (PB-PCI). This contrast mode relies on a sufficiently coherent illumination and is characterised by the appearance of an additional intensity modulations (‘edge enhancement fringes’) around interfaces in the image. The strength of this effect depends on hardware as well as geometry parameters. This thesis describes the development of a laboratory setup for X-ray μCT with a PB-PCI option. It contains the theoretical and technical background of the setup design as well the characterization of the achieved performance.Moreover, the optimization of the PB-PCI geometry was explored both theoretically as well as experimentally for three different setups. A simple rule for finding the optimal magnification to achieve high phase contrast for edge features was deduced. The effect of the polychromatic source spectrum und detector sensitivity was identified and included into the theoretical model.Besides application and methodological studies, the setup was used to test and characterise new X-ray scintillator materials. Recently, metal halide perovskite nanocrystals (MHP NCs) have gained attention due to their outstanding opto-electronic performance. The main challenge for their use and commercialization is their low long-term stability against humidity, temperature, and light exposure. Here, a CsPbBr3 scintillator comprised of an ordered array of nanowires (NW) in an anodized aluminium oxide (AAO) membrane is presented as a promising new scintillator for X-ray microscopy and μCT. It shows a high light yield under X-ray exposure which improves with smaller NW diameter and higher NW length. In contrast to many other MHP materials this scintillator shows good stability under continuous X-ray exposure and changing environmental conditions over extended time spans of several weeks. This makes it suitable for tomography, which is demonstrated by acquiring the first high-resolution tomogram using a MHP scintillator with the presented laboratory setup

A laboratory based edge-Illumination x-ray phase-contrast imaging setup with two-directional sensitivity

We report on a preliminary laboratory based x-ray phase-contrast imaging system capable of achieving two directional phase sensitivity thanks to the use of L-shaped apertures. We show that in addition to apparent absorption, two-directional differential phase images of an object can be quantitatively retrieved by using only three input images. We also verify that knowledge of the phase derivatives along both directions allows for straightforward phase integration with no streak artefacts, a known problem common to all differential phase techniques. In addition, an analytical method for 2-directional dark field retrieval is proposed and experimentally demonstrated

The application of low coherence interferometry to the micron scale imaging of the living human retina

Current optical and ultrasound techniques for high resolution in vivo retinal imaging cannot provide the depth accuracy required to enable sensitive ophthalmologic diagnosis to be carried out on the basis of images of retinal microstructures. The axial depth resolution of one of the recently introduced retinal imaging instruments, the scanning laser ophthalmoscope, is restricted by the combined effect of the depth of focus achievable through the eye pupil and aberrations to about 300 pm. A new imaging technique, based on low coherence interferometry, providing improved depth resolution figures of the order of a few microns, is demonstrated here. Non-invasive topographic and tomographic measurements can be performed with an instrument based on this technique. A novel path modulation procedure, the Newton rings sampling function, is presented together with experimental results obtained in its application to the imaging of various objects including human in vivo retina. The advantages and disadvantages of novel and more conventional imaging modes, their associated techniques and the overall importance and likely impact of the novel Newton rings modulation method are considered. The measurement of 3-dimensional profiles of various targets, including tomographic images of in vivo human retinas from volunteers’ eyes, is presented. The utility of OCT measurements in the high-resolution mapping of in vivo tissue and its potential usage alongside scanning laser ophthalmoscopy in identifying features in the human eye are discussed