Modern optical astronomy: technology and impact of interferometry

The present `state of the art' and the path to future progress in high spatial resolution imaging interferometry is reviewed. The review begins with a treatment of the fundamentals of stellar optical interferometry, the origin, properties, optical effects of turbulence in the Earth's atmosphere, the passive methods that are applied on a single telescope to overcome atmospheric image degradation such as speckle interferometry, and various other techniques. These topics include differential speckle interferometry, speckle spectroscopy and polarimetry, phase diversity, wavefront shearing interferometry, phase-closure methods, dark speckle imaging, as well as the limitations imposed by the detectors on the performance of speckle imaging. A brief account is given of the technological innovation of adaptive-optics (AO) to compensate such atmospheric effects on the image in real time. A major advancement involves the transition from single-aperture to the dilute-aperture interferometry using multiple telescopes. Therefore, the review deals with recent developments involving ground-based, and space-based optical arrays. Emphasis is placed on the problems specific to delay-lines, beam recombination, polarization, dispersion, fringe-tracking, bootstrapping, coherencing and cophasing, and recovery of the visibility functions. The role of AO in enhancing visibilities is also discussed. The applications of interferometry, such as imaging, astrometry, and nulling are described. The mathematical intricacies of the various `post-detection' image-processing techniques are examined critically. The review concludes with a discussion of the astrophysical importance and the perspectives of interferometry.Comment: 65 pages LaTeX file including 23 figures. Reviews of Modern Physics, 2002, to appear in April issu

Improvements in the robustness and accuracy of bioluminescence tomographic reconstructions of distributed sources within small animals

High quality three-dimensional bioluminescence tomographic (BLT) images, if available, would constitute a major advance and provide much more useful information than the two-dimensional bioluminescence images that are frequently used today. To-date, high quality BLT images have not been available, largely because of the poor quality of the data being input into the reconstruction process. Many significant confounds are not routinely corrected for and the noise in this data is unnecessarily large and poorly distributed. Moreover, many of the design choices affecting image quality are not well considered, including choices regarding the number and type of filters used when making multispectral measurements and choices regarding the frequency and uniformity of the sampling of both the range and domain of the BLT inverse problem. Finally, progress in BLT image quality is difficult to gauge owing to a lack of realistic gold-standard references that engage the full complexity and uncertainty within a small animal BLT imaging experiment. Within this dissertation, I address all of these issues. I develop a Cerenkov-based gold-standard wherein a Positron Emission Tomography (PET) image can be used to gauge improvements in the accuracy of BLT reconstruction algorithms. In the process of creating this reference, I discover and describe corrections for several confounds that if left uncorrected would introduce artifacts into the BLT images. This includes corrections for the angle of the animal’s skin surface relative to the camera, for the height of each point on the skin surface relative to the focal plane, and for the variation in bioluminescence intensity as a function of luciferin concentration over time. Once applied, I go on to derive equations and algorithms that when employed are able to minimize the noise in the final images under the constraints of a multispectral BLT data acquisition. These equations and algorithms allow for an optimal choice of filters to be made and for the acquisition time to be optimally distributed among those filtered measurements. These optimizations make use of Barrett’s and Moore-Penrose pseudoinverse matrices which also come into play in a paradigm I describe that can be used to guide choices regarding sampling of the domain and range

Hyperspectral imaging of the haemodynamic and metabolic states of the exposed cortex

A hyperspectral imaging (HSI) system to measure and quantify in vivo haemodynamic and metabolic signals from the exposed cerebral cortex of small animals was designed, developed and investigated in this thesis. Imaging brain tissue at multiple narrow wavelength bands in the visible and near-infrared (NIR) range allows one not only to monitor cerebral oxygenation and haemodynamics via mapping of haemoglobin concentration changes, but also to directly target the spatial quantification of cerebral metabolic activity via measurement of the redox states of mitochondrial cytochrome-c-oxidase (CCO). Having both these sets of information in vivo at high resolution on the exposed cortex can provide impactful insight on brain physiology and can help validate corresponding data acquired non-invasively using broadband near-infrared spectroscopy (bNIRS). Several designs and HSI configurations were assessed and compared, including different customised benchtop setups. In the end, a bespoke spectral-scanning HSI system called hNIR, using a supercontinuum laser coupled with a rotating Pellin-Broca prism and a scientific complementary metal-oxide semiconductor (sCMOS) camera, was built, characterised and validated on liquid optical phantoms. In addition, an in-house Monte Carlo (MC) framework for simulating HSI of the haemodynamic and metabolic states of the exposed cortex was also developed using an open-source MC code package (Mesh-based Monte Carlo) and integrated with hNIR, for aiding image reconstruction and enhance quantification, as well as to run computational investigations on the performances of HSI for brain haemodynamic and metabolic monitoring. hNIR was finally applied in vivo on the exposed cerebral cortex of three mice during different levels of hyperoxic and hypoxic stimulation, demonstrating its capability to retrieve high resolution and accurate maps of the relative changes in the concentrations of oxyhaemoglobin (HbO₂), deoxyhaemoglobin (HHb) and the oxidative state of CCO (oxCCO)

Cosmic Rays: The Second Knee and Beyond

We conduct a review of experimental results on Ultra-High Energy Cosmic Rays (UHECR's) including measurements of the features of the spectrum, the composition of the primary particle flux and the search for anisotropy in event arrival direction. We find that while there is a general consensus on the features in the spectrum -- the Second Knee, the Ankle, and (to a lesser extent) the GZK Cutoff -- there is little consensus on the composition of the primaries that accompany these features. This lack of consensus on the composition makes interpretation of the agreed upon features problematic. There is also little direct evidence about potential sources of UHECRs, as early reports of arrival direction anisotropies have not been confirmed in independent measurements.Comment: 46 pages, 30 figures. Topical Review to appear in J. Physics

Phase measurement of light absorption and scatter in human tissue

Analog and digital technologies are presented for precise measurement of propagation delay of photons from source and detector placed on portions of the human body. The goal of the apparatus design is to quantify absorption (μa) and scattering (μs′) induced by biological pigments and biological structures, respectively. Body tissues are highly scattering with a mean distance between scatterers of less than a mm (at 700-850 nm). Significant absorption is mainly due to 5%-10% of the tissue volume occupied by blood. Measurement of μa and μs′ is done by both time and frequency domain equipment. This article focuses upon frequency domain equipment because of its simplicity, reduced noise bandwidth, versatility, and the strong analogy to very high frequency/ultrahigh frequency communication devices, particularly those using phase modulation. Comparisons are made of homodyne and heterodyne systems together with evaluation of single and multiple side band systems, with particular emphasis on methods for multiplexed optical and radio frequencies by frequency encoding or time-sharing technologies. The applications of these phase modulation systems to quantitative brain and muscle blood oximetry, functional activity of the forebrain, and other important problems of medical science, are presented. © 1998 American Institute of Physics

Advancing combined radiological and optical scanning for breast-conserving surgery margin guidance

Breast cancer is one of the most common types of cancer worldwide, and standard-of-care for early-stage disease typically involves a lumpectomy or breast-conserving surgery (BCS). BCS involves the local resection of cancerous tissue, while sparring as much healthy tissue as possible. State-of-the-art methods for intraoperatively evaluating BCS margins are limited. Approximately 20% of BCS cases result in a tissue resection with cancer at or near the resection surface (i.e., a positive margin). A two-fold increase in ipsilateral breast cancer recurrence is associated with the presence of one or more positive margins. Consequently, positive margins often necessitate costly re-excision procedures to achieve a curative outcome. X-ray micro-computed tomography (CT) is emerging as a powerful ex vivo specimen imaging technology, as it provides robust three-dimensional sensing of tumor morphology rapidly. However, X-ray attenuation lacks contrast between soft tissues that are important for surgical decision making during BCS. Optical structured light imaging, including spatial frequency domain imaging and active line scan imaging, can act as adjuvant tools to complement micro-CT, providing wide field-of-view, non-contact sensing of relevant breast tissue subtypes on resection margins that cannot be differentiated by micro-CT alone. This thesis is dedicated to multimodal imaging of BCS tissues to ultimately improve intraoperative BCS margin assessment, reducing the number of positive margins after initial surgeries and thereby reducing the need for costly follow-up procedures. Volumetric sensing of micro-CT is combined with surface-weighted, sub-diffuse optical reflectance derived from high spatial frequency structured light imaging. Sub-diffuse reflectance plays the key role of providing enhanced contrast to a suite of normal, abnormal benign, and malignant breast tissue subtypes. This finding is corroborated through clinical studies imaging BCS specimen slices post-operatively and is further investigated through an observational clinical trial focused on combined, intraoperative micro-CT and optical imaging of whole, freshly resected BCS tumors. The central thesis of this work is that combining volumetric X-ray imaging and sub-diffuse optical scanning provides a synergistic multimodal imaging solution to margin assessment, one that can be readily implemented or retrofitted in X-ray specimen imaging systems and that could meaningfully improve surgical guidance during initial BCS procedures

Fluorescence molecular tomography: Principles and potential for pharmaceutical research

Fluorescence microscopic imaging is widely used in biomedical research to study molecular and cellular processes in cell culture or tissue samples. This is motivated by the high inherent sensitivity of fluorescence techniques, the spatial resolution that compares favorably with cellular dimensions, the stability of the fluorescent labels used and the sophisticated labeling strategies that have been developed for selectively labeling target molecules. More recently, two and three-dimensional optical imaging methods have also been applied to monitor biological processes in intact biological organisms such as animals or even humans. These whole body optical imaging approaches have to cope with the fact that biological tissue is a highly scattering and absorbing medium. As a consequence, light propagation in tissue is well described by a diffusion approximation and accurate reconstruction of spatial information is demanding. While in vivo optical imaging is a highly sensitive method, the signal is strongly surface weighted, i.e., the signal detected from the same light source will become weaker the deeper it is embedded in tissue, and strongly depends on the optical properties of the surrounding tissue. Derivation of quantitative information, therefore, requires tomographic techniques such as fluorescence molecular tomography (FMT), which maps the three-dimensional distribution of a fluorescent probe or protein concentration. The combination of FMT with a structural imaging method such as X-ray computed tomography (CT) or Magnetic Resonance Imaging (MRI) will allow mapping molecular information on a high definition anatomical reference and enable the use of prior information on tissue’s optical properties to enhance both resolution and sensitivity. Today many of the fluorescent assays originally developed for studies in cellular systems have been successfully translated for experimental studies in animals. The opportunity of monitoring molecular processes non-invasively in the intact organism is highly attractive from a diagnostic point of view but even more so for the drug developer, who can use the techniques for proof-of-mechanism and proof-of-efficacy studies. This review shall elucidate the current status and potential of fluorescence tomography including recent advances in multimodality imaging approaches for preclinical and clinical drug development

Kinematics of Circumgalactic Gas: Feeding Galaxies and Feedback

We present observations of 50 pairs of redshift z ~ 0.2 star-forming galaxies and background quasars. These sightlines probe the circumgalactic medium (CGM) out to half the virial radius, and we describe the circumgalactic gas kinematics relative to the reference frame defined by the galactic disks. We detect halo gas in MgII absorption, measure the equivalent-width-weighted Doppler shifts relative to each galaxy, and find that the CGM has a component of angular momentum that is aligned with the galactic disk. No net counter-rotation of the CGM is detected within 45 degrees of the major axis at any impact parameter. The velocity offset of the circumgalactic gas correlates with the projected rotation speed in the disk plane out to disk radii of roughly 70 kpc. We confirm previous claims that the MgII absorption becomes stronger near the galactic minor axis and show that the equivalent width correlates with the velocity range of the absorption. We cannot directly measure the location of any absorber along the sightline, but we explore the hypothesis that individual velocity components can be associated with gas orbiting in the disk plane or flowing radially outward in a conical outflow. We conclude that centrifugal forces partially support the low-ionization gas and galactic outflows kinematically disturb the CGM producing excess absorption. Our results firmly rule out schema for the inner CGM that lack rotation and suggest that angular momentum as well as galactic winds should be included in any viable model for the low-redshift CGM.Comment: Accepted for publication in the Astrophysical Journa

Engineering aspects of photogrammetric plate measurements: Including the development of a novel interferometer

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Two different factors involved in the measurement of photogrammetric plates have been studied. A novel interferometer designed to monitor the position of a microscope stage, to be used to measure photogrammetric plates, has been built. The prototype instrument is able to give the position of the stage with a maximum error of less than 200nm. An algorithm has been developed for a motor driven x-y microscope that is able to search a photographic plate automatically for targets, and record their positions. In a trial survey this system was able to measure the positions of the targets on the plates with an uncertainty of approximately 2gm. This result is comparable with the precision that a human operator could achieve using the same equipment, but without the fatigue effect associated with visual observation. Virtually no human interaction is necessary for the system to function.This work was jointly funded by The Science and Engineering Council and The National Physical Laboratory