Seeing blur:'Motion sharpening' without motion

It is widely supposed that things tend to look blurred when they are moving fast. Previous work has shown that this is true for sharp edges but, paradoxically, blurred edges look sharper when they are moving than when stationary. This is 'motion sharpening'. We show that blurred edges also look up to 50% sharper when they are presented briefly (8-24 ms) than at longer durations (100-500 ms) without motion. This argues strongly against high-level models of sharpening based specifically on compensation for motion blur. It also argues against a recent, low-level, linear filter model that requires motion to produce sharpening. No linear filter model can explain our finding that sharpening was similar for sinusoidal and non-sinusoidal gratings, since linear filters can never distort sine waves. We also conclude that the idea of a 'default' assumption of sharpness is not supported by experimental evidence. A possible source of sharpening is a nonlinearity in the contrast response of early visual mechanisms to fast or transient temporal changes, perhaps based on the magnocellular (M-cell) pathway. Our finding that sharpening is not diminished at low contrast sets strong constraints on the nature of the nonlinearity.

Neuronal convergence in early contrast vision: binocular summation is followed by response nonlinearity and area summation

We assessed summation of contrast across eyes and area at detection threshold ( C t). Stimuli were sine-wave gratings (2.5 c/deg) spatially modulated by cosine- and anticosine-phase raised plaids (0.5 c/deg components oriented at ±45°). When presented dichoptically the signal regions were interdigitated across eyes but produced a smooth continuous grating following their linear binocular sum. The average summation ratio ( C t1/([ C t1+2]) for this stimulus pair was 1.64 (4.3 dB). This was only slightly less than the binocular summation found for the same patch type presented to both eyes, and the area summation found for the two different patch types presented to the same eye. We considered 192 model architectures containing each of the following four elements in all possible orders: (i) linear summation or a MAX operator across eyes, (ii) linear summation or a MAX operator across area, (iii) linear or accelerating contrast transduction, and (iv) additive Gaussian, stochastic noise. Formal equivalences reduced this to 62 different models. The most successful four-element model was: linear summation across eyes followed by nonlinear contrast transduction, linear summation across area, and late noise. Model performance was enhanced when additional nonlinearities were placed before binocular summation and after area summation. The implications for models of probability summation and uncertainty are discussed.

The development and applications of the combined use of NMR and ultrasound

The objective of the research carried out in this report was to observe the first ever in-situ sonochemical reaction in the NMR Spectrometer in the megahertz region of ultrasound. Several reactions were investigated as potential systems for a sonochemical reaction followed by NMR spectroscopy. The primary problem to resolve when applying ultrasound to a chemical reaction is that of heating. Ultrasound causes the liquid to move and produces 'hot spots' resulting in an increase in sample temperature. The problem was confronted by producing a device that would counteract this effect and so remove the need to account for heating. However, the design of the device limited the length of time during which it would function. Longer reaction times were required to enable observations to be carried out in the NMR spectrometer. The fIrst and most obvious reactions attempted were those of the well-known ultrasonic dosimeter. Such a reaction would, theoretically, enable the author to simultaneously observe a reaction and determine the exact power entering the system for direct comparison of results. Unfortunately, in order to monitor the reactions in the NMR spectrometer the reactant concentrations had to be signifIcantly increased, which resulted in a notable increase in reaction time, making the experiment too lengthy to follow in the time allocated. The Diels-Alder Reaction is probably one of the most highly investigated reaction systems in the field of chemistry and it was this to which the author turned her attention. Previous authors have carried out ultrasonic investigations, with considerable success, for the reaction of anthracene with maleic anhydride. It was this reaction in particular that was next attempted. The first ever sonochemically enhanced reaction using a frequency of ultrasound in the megahertz (MHz) region was successfully carried out as bench experiments. Due to the complexity of the component reactants the product would precipitate from the solution and because the reaction could only be monitored by its formation, it was not possible to observe the reaction in the NMR spectrometer. The solvolysis of 2-chloro-2-methylpropane was examined in various solvent systems; the most suitable of which was determined to be aqueous 2-methylpropan-2-ol. The experiment was successfully enhanced by the application of ultrasound and monitored in-situ in the NMR spectrometer. The increase in product formation of an ultrasonic reaction over that of a traditional thermal reaction occurred. A range of 1.4 to 2.9 fold improvement was noted, dependent upon the reaction conditions investigated. An investigation into the effect of sonication upon a large biological molecule, in this case aqueous lysozyme, was carried out. An easily observed effect upon the sample was noted but no explanation for the observed effects could be established.

Nuclear magnetic resonance spectroscopy and ultrasound

The work described in this thesis is directed to the examination of the hypothesis that ultrasound may be used to perturb molecular motion in the liquid phase. These changes can then be detected by nuclear magnetic resonance (NMR) in spin-lattice and spin-spin relaxation times. The objective being to develop a method capable of reducing the pulsed NMR acquisition times of slowly relaxing nuclei. The thesis describes the theoretical principles underlying both NMR spectroscopy and ultrasonics with particular attention being paid to factors that impinge on testing the above hypothesis. Apparatus has been constructed to enable ultrasound at frequencies between 1 and 10 mega-hertz with a variable power up to 100W/cm-2 to be introduced in the NMR sample. A broadband high frequency generator is used to drive PZT piezo-electric transducer via various transducer to liquid coupling arrangements. A commercial instrument of 20 kilo-hertz has also been employed to test the above hypothesis and also to demonstrate the usefulness of ultrasound in sonochemistry. The latter objective being, detection of radical formation in monomer and polymer ultrasonic degradation. The principle features of the results obtained are: Ultrasonic perturbation of T1 is far smaller for pure liquids than is for mixtures. The effects appear to be greater on protons (1H) than on carbon-13 nuclei (13C) relaxation times. The observed effect of ultrasonics is not due to temperature changes in the sample. As the power applied to the transducer is progressively increased T1 decreases to a minimum and then increases. The T1's of the same nuclei in different functional groups are influenced to different extents by ultrasound. Studies of the 14N resonances from an equimolar mixture of N, N-dimethylformamide and deuterated chloroform with ultrasonic frequencies at 1.115, 6, 6.42 and 10 MHz show that as the frequency is increased the NMR signal to noise ratio decreases to zero at the Larmor frequency of 6.42 MHz and then again rises. This reveals the surprising indication that an effect corresponding to nuclear acoustic saturation in the liquid may be observable. Ultrasonic irradiation of acidified ammonium chloride solution at and around 6.42 MHz appears to cause distinctive changes in the proton-nitrogen J coupling resonance at 89.56 MHz. Ultrasonic irradiation of N, N-dimethylacetamide at 2 KHz using the lowest stable power revealed the onset of coalescence in the proton spectrum. The corresponding effect achieved by direct heating required a temperature rise of approximately 30oC. The effects of low frequency (20 KHz) on relaxation times appear to be nil. Detection of radical formation proved difficult but is still regarded as the principle route for monomer and polymer degradation. The initial hypothesis is considered proven with the results showing significant changes in the mega-hertz region and none at 20 KHz.

Local and systemic delivery of a novel group of inhibitors of transglutaminase enzyme: A potential approach for treating of catheter-related complications and liver fibrosis

The present thesis investigates targeted (locally and systemically) delivery of a novel group of inhibitors of enzyme transglutaminases (TGs). TGs are a widely distributed group of enzymes that catalyse the formation of isopeptide bonds between the y-carboxamide group of protein-bound glutamines and the a-amino group of protein-bound lysines or polyamines. The first group of the novel inhibitors tested were the tluorescently labelled inhibitors of Factor XIIIa (FXIIIa). These small, non-toxic inhibitors have the potential to prevent stabilisation of thrombi by FXIIIa and consequently increase the natural rate of thrombolysis, in addition it reduces staphylococcal colonisation of catheters by inhibiting their FXIIIa¬mediated cross-linking to blood clot proteins on the central venous catheter (CVCs) surface. The aim of this work was to incorporate the FXIIIa inhibitor either within coating of polyurethane (PU) catheters or to integrate it into silicone catheters, so as to reduce the incidence of thrombotic occlusion and associated bacterial infection in CVCs. The initial work focused on the incorporation of FXIIIa inhibitors within polymeric coatings of PU catheters. After defining the key characteristics desired for an effective polymeric-coating, polyvinylpyrrolidone (PVP), poly(lactic-co-glycolic acid) (PLGA) or their combination were studies as polymers of choice for coating of the catheters_ The coating was conducted by dip-coating method in a polymer solution containing the inhibitor. Upon incubation of the inhibitor-and polymer-coated strips in buffer, PVP was dissolved instantly, generating fast and significant drug release, whilst PLGA did not dissolve, yielding a slow and an insufficient amount of drug release. Nevertheless, the drug release profile was enhanced upon employing a blend solution of PVP and PLGA. The second part of the study was to incorporate the FXIIIa inhibitor into a silicone elastomer; results demonstrated that FXIIIa inhibitor can be incorporated and released from silicone by using citric acid (CA) and sodium bicarbonate (SB) as additives and the drug release rate can be controlled by the amount of incorporated additives in the silicone matrix. Furthermore, it was deemed that the inhibitor was still biologically active subsequent to being released from the silicone elastomer strips. Morphological analysis confirmed the formation of channels and cracks inside the specimens upon the addition of CA and SB. Nevertheless, the tensile strength, in addition to Young's modulus of silicone elastomer strips, decreased constantly with an increasing amount of amalgamated CA/ SB in the formulations. According to our results, incorporation of FXIIIa inhibitor into catheters and other medical implant devices could offer new perspectives in preventing bio-material associated infections and thrombosis. The use of tissue transglutaminase (T02) inhibitor for treating of liver fibrosis was also investigated. Liver fibrosis is characterized by increased synthesis and decreased degradation of the extracellular matrix (ECM). Transglutaminase-mediated covalent cross-linking is involved in the stabilization of ECM in human liver fibrosis. Thus, TG2 inhibitors may be used to counteract the decreased degradation of the ECM. The potential of a liposome based drug delivery system for site specific delivery of the fluorescent TG2 inhibitor into the liver was investigated; results indicated that the TG2 inhibitor can be successfully integrated into liposomes and delivered to the liver, therefore demonstrating that liposomes can be employed for site-specific delivery of TG2 inhibitors into the liver and TG2 inhibitor incorporating liposomes could offer a new approach in treating liver fibrosis and its end stage disease cirrhosis.

Visual symptoms in Parkinson's disease

Parkinson’s disease (PD) is a common disorder of middle-aged and elderly people in which degeneration of the extrapyramidal motor system causes significant movement problems. In some patients, however, there are additional disturbances in sensory systems including loss of the sense of smell and auditory and/or visual problems. This article is a general overview of the visual problems likely to be encountered in PD. Changes in vision in PD may result from alterations in visual acuity, contrast sensitivity, colour discrimination, pupil reactivity, eye movements, motion perception, visual field sensitivity and visual processing speeds. Slower visual processing speeds can also lead to a decline in visual perception especially for rapidly changing visual stimuli. In addition, there may be disturbances of visuo-spatial orientation, facial recognition problems, and chronic visual hallucinations. Some of the treatments used in PD may also have adverse ocular reactions. The pattern electroretinogram (PERG) is useful in evaluating retinal dopamine mechanisms and in monitoring dopamine therapies in PD. If visual problems are present, they can have an important effect on the quality of life of the patient, which can be improved by accurate diagnosis and where possible, correction of such defects.

Enhanced text spacing improves reading performance in individuals with macular disease

The search by many investigators for a solution to the reading problems encountered by individuals with no central vision has been long and, to date, not very fruitful. Most textual manipulations, including font size, have led to only modest gains in reading speed. Previous work on spatial integrative properties of peripheral retina suggests that 'visual crowding' may be a major factor contributing to inefficient reading. Crowding refers to the fact that juxtaposed targets viewed eccentrically may be difficult to identify. The purpose of this study was to assess the combined effects of line spacing and word spacing on the ability of individuals with age-related macular degeneration (ARMD) to read short passages of text that were printed with either high (87.5%) or low contrast (17.5%) letters. Low contrast text was used to avoid potential ceiling effects and to mimic a possible reduction in letter contrast with light scatter from media opacities. For both low and high contrast text, the fastest reading speeds we measured were for passages of text with double line and double word spacing. In comparison with standard single spacing, double word/line spacing increased reading speed by approximately 26% with high contrast text (p < 0.001), and by 46% with low contrast text (p < 0.001). In addition, double line/word spacing more than halved the number of reading errors obtained with single spaced text. We compare our results with previous reading studies on ARMD patients, and conclude that crowding is detrimental to reading and that its effects can be reduced with enhanced text spacing. Spacing is particularly important when the contrast of the text is reduced, as may occur with intraocular light scatter or poor viewing conditions. We recommend that macular disease patients should employ double line spacing and double-character word spacing to maximize their reading efficiency. © 2013 Blackmore-Wright et al.

Corneal pachymetry in normal and keratoconic eyes:Orbscan II versus ultrasound

Purpose: To compare corneal thickness measurements using Orbscan II (OII) and ultrasonic (US) pachymetry in normal and in keratoconic eyes. Setting: Eye Department, Heartlands and Solihull NHS Trust, Birmingham, United Kingdom. Methods: Central corneal thickness (CCT) was measured by means of OII and US pachymetry in 1 eye of 72 normal subjects and 36 keratoconus patients. The apical corneal thickness (ACT) in keratoconus patients was also evaluated using each method. The mean of the difference, standard deviation (SD), and 95% limits of agreement (LoA = mean ± 2 SD), with and without applying the default linear correction factor (LCF), were determined for each sample. The Student t test was used to identify significant differences between methods, and the correlation between methods was determined using the Pearson bivariate correlation. Bland-Altman analysis was performed to confirm that the results of the 2 instruments were clinically comparable. Results: In normal eyes, the mean difference (± 95% LoA) in CCT was 1.04 μm ± 68.52 (SD) (P>.05; r = 0.71) when the LCF was used and 46.73 ± 75.40 μm (P = .0001; r = 0.71) without the LCF. In keratoconus patients, the mean difference (± 95% LoA) in CCT between methods was 42.46 ± 66.56 μm (P<.0001: r = 0.85) with the LCF, and 2.51 ± 73.00 μm (P>.05: r = 0.85) without the LCF. The mean difference (± 95% LoA) in ACT for this group was 49.24 ± 60.88 μm (P<.0001: r = 0.89) with the LCF and 12.71 ± 68.14 μm (P = .0077; r = 0.89) when the LCF was not used. Conclusions: This study suggests that OII and US pachymetry provide similar readings for CCT in normal subjects when an LCF is used. In keratoconus patients, OII provides a valid clinical tool for the noninvasive assessment of CCT when the LCF is not applied. © 2004 ASCRS and ESCRS.

Higher-order aberrations in amblyopia:an analysis of pre- and post-wavefront-guided laser refractive correction

For more than a century it has been known that the eye is not a perfect optical system, but rather a system that suffers from aberrations beyond conventional prescriptive descriptions of defocus and astigmatism. Whereas traditional refraction attempts to describe the error of the eye with only two parameters, namely sphere and cylinder, measurements of wavefront aberrations depict the optical error with many more parameters. What remains questionable is the impact these additional parameters have on visual function. Some authors have argued that higher-order aberrations have a considerable effect on visual function and in certain cases this effect is significant enough to induce amblyopia. This has been referred to as ‘higher-order aberration-associated amblyopia’. In such cases, correction of higher-order aberrations would not restore visual function. Others have reported that patients with binocular asymmetric aberrations display an associated unilateral decrease in visual acuity and, if the decline in acuity results from the aberrations alone, such subjects may have been erroneously diagnosed as amblyopes. In these cases, correction of higher-order aberrations would restore visual function. This refractive entity has been termed ‘aberropia’. In order to investigate these hypotheses, the distribution of higher-order aberrations in strabismic, anisometropic and idiopathic amblyopes, and in a group of visual normals, was analysed both before and after wavefront-guided laser refractive correction. The results show: (i) there is no significant asymmetry in higher-order aberrations between amblyopic and fixing eyes prior to laser refractive treatment; (ii) the mean magnitude of higher-order aberrations is similar within the amblyopic and visually normal populations; (iii) a significant improvement in visual acuity can be realised for adult amblyopic patients utilising wavefront-guided laser refractive surgery and a modest increase in contrast sensitivity was observed for the amblyopic eye of anisometropes following treatment (iv) an overall trend towards increased higher-order aberrations following wavefront-guided laser refractive treatment was observed for both visually normal and amblyopic eyes. In conclusion, while the data do not provide any direct evidence for the concepts of either ‘aberropia’ or ‘higher-order aberration-associated amblyopia’, it is clear that gains in visual acuity and contrast sensitivity may be realised following laser refractive treatment of the amblyopic adult eye. Possible mechanisms by which these gains are realised are discussed.

Analysis and Optimization of Synthetic Aperture Ultrasound Imaging Using the Effective Aperture Approach

An effective aperture approach is used as a tool for analysis and parameter optimization of mostly known ultrasound imaging systems - phased array systems, compounding systems and synthetic aperture imaging systems. Both characteristics of an imaging system, the effective aperture function and the corresponding two-way radiation pattern, provide information about two of the most important parameters of images produced by an ultrasound system - lateral resolution and contrast. Therefore, in the design, optimization of the effective aperture function leads to optimal choice of such parameters of an imaging systems that influence on lateral resolution and contrast of images produced by this imaging system. It is shown that the effective aperture approach can be used for optimization of a sparse synthetic transmit aperture (STA) imaging system. A new two-stage algorithm is proposed for optimization of both the positions of the transmitted elements and the weights of the receive elements. The proposed system employs a 64-element array with only four active elements used during transmit. The numerical results show that Hamming apodization gives the best compromise between the contrast of images and the lateral resolution.

Mobile app Aston contrast sensitivity test

BACKGROUND: Contrast detection is an important aspect of the assessment of visual function; however, clinical tests evaluate limited spatial frequencies and contrasts. This study validates the accuracy and inter-test repeatability of a swept-frequency near and distance mobile app Aston contrast sensitivity test, which overcomes this limitation compared to traditional charts. METHOD: Twenty subjects wearing their full refractive correction underwent contrast sensitivity testing on the new near application (near app), distance app, CSV-1000 and Pelli-Robson charts with full correction and with vision degraded by 0.8 and 0.2 Bangerter degradation foils. In addition repeated measures using the 0.8 occluding foil were taken. RESULTS: The mobile apps (near more than distance, p = 0.005) recorded a higher contrast sensitivity than printed tests (p < 0.001); however, all charts showed a reduction in measured contrast sensitivity with degradation (p < 0.001) and a similar decrease with increasing spatial frequency (interaction > 0.05). Although the coefficient of repeatability was lowest for the Pelli-Robson charts (0.14 log units), the mobile app charts measured more spatial frequencies, took less time and were more repeatable (near: 0.26 to 0.37 log units; distance: 0.34 to 0.39 log units) than the CSV-1000 (0.30 to 0.93 log units). The duration to complete the CSV-1000 was 124 ± 37 seconds, Pelli-Robson 78 ± 27 seconds, near app 53 ± 15 seconds and distance app 107 ± 36 seconds. CONCLUSIONS: While there were differences between charts in contrast levels measured, the new Aston near and distance apps are valid, repeatable and time-efficient method of assessing contrast sensitivity at multiple spatial frequencies.

Determining which factors influence the optimum multifocal contact lens correction for presbyopia

Presbyopia is a consequence of ageing and is therefore increasing inprevalence due to an increase in the ageing population. Of the many methods available to manage presbyopia, the use of contact lenses is indeed a tried and tested reversible option for those wishing to be spectacle free. Contact lens options to correct presbyopia include multifocal contact lenses and monovision.Several options have been available for many years with available guides to help choose multifocal contact lenses. However there is no comprehensive way to help the practitioner selecting the best option for an individual. An examination of the simplest way of predicting the most suitable multifocal lens for a patient will only enhance and add to the current evidence available. The purpose of the study was to determine the current use of presbyopic correction modalities in an optometric practice population in the UK and to evaluate and compare the optical performance of four silicone hydrogel soft multifocal contact lenses and to compare multifocal performance with contact lens monovision. The presbyopic practice cohort principal forms of refractive correction were distance spectacles (with near and intermediate vision providedby a variety of other forms of correction), varifocal spectacles and unaided distance with reading spectacles, with few patients wearing contact lenses as their primary correction modality. The results of the multifocal contact lens randomised controlled trial showed that there were only minor differences in corneal physiology between the lens options. Visual acuity differences were observed for distance targets, but only for low contrast letters and under mesopic lighting conditions. At closer distances between 20cm and 67cm, the defocus curves demonstrated that there were significant differences in acuity between lens designs (p < 0.001) and there was an interaction between the lens design and the level of defocus (p < 0.001). None of the lenses showed a clear near addition, perhaps due to their more aspheric rather than zoned design. As expected, stereoacuity was reduced with monovision compared with the multifocal contact lens designs, although there were some differences between the multifocal lens designs (p < 0.05). Reading speed did not differ between lens designs (F = 1.082, p = 0.368), whereas there was a significant difference in critical print size (F = 7.543, p < 0.001). Glare was quantified with a novel halometer and halo size was found to significantly differ between lenses(F = 4.101, p = 0.004). The rating of iPhone image clarity was significantly different between presbyopic corrections (p = 0.002) as was the Near Acuity Visual Questionnaire (NAVQ) rating of near performance (F = 3.730, p = 0.007).The pupil size did not alter with contact lens design (F = 1.614, p = 0.175), but was larger in the dominant eye (F = 5.489, p = 0.025). Pupil decentration relative to the optical axis did not alter with contact lens design (F = 0.777, p =0.542), but was also greater in the dominant eye (F = 9.917, p = 0.003). It was interesting to note that there was no difference in spherical aberrations induced between the contact lens designs (p > 0.05), with eye dominance (p > 0.05) oroptical component (ocular, corneal or internal: p > 0.05). In terms of subjective patient lens preference, 10 patients preferred monovision,12 Biofinity multifocal lens, 7 Purevision 2 for Presbyopia, 4 AirOptix multifocal and 2 Oasys multifocal contact lenses. However, there were no differences in demographic factors relating to lifestyle or personality, or physiological characteristics such as pupil size or ocular aberrations as measured at baseline,which would allow a practitioner to identify which lens modality the patient would prefer. In terms of the performance of patients with their preferred lens, it emerged that Biofinity multifocal lens preferring patients had a better high contrast acuity under photopic conditions, maintained their reading speed at smaller print sizes and subjectively rated iPhone clarity as better with this lens compared with the other lens designs trialled. Patients who preferred monovision had a lower acuity across a range of distances and a larger area of glare than those patients preferring other lens designs that was unexplained by the clinical metrics measured. However, it seemed that a complex interaction of aberrations may drive lens preference. New clinical tests or more diverse lens designs which may allow practitioners to prescribe patients the presbyopic contact lens option that will work best for them first time remains a hope for the future.

Investigating the utility of clinical assessments to predict success with presbyopic contact lens correction

PURPOSE: To determine the utility of a range of clinical and non-clinical indicators to aid the initial selection of the optimum presbyopic contact lens. In addition, to assess whether lens preference was influenced by the visual performance compared to the other designs trialled (intra-subject) or compared to participants who preferred other designs (inter-subject). METHODS: A double-masked randomised crossover trial of Air Optix Aqua multifocal, PureVision 2 for Presbyopia, Acuvue OASYS for Presbyopia, Biofinity multifocal and monovision was conducted on 35 presbyopes (54.3±6.2years). Participant lifestyle, personality, pupil characteristics and aberrometry were assessed prior to lens fitting. After 4 weeks of wear, high and low contrast visual acuity (VA) under photopic and mesopic conditions, reading speed, Near Activity Visual Questionnaire (NAVQ) rating, subjective quality-of-vision scoring, defocus curves, stereopsis, halometry, aberrometry and ocular physiology were quantified. RESULTS: After trialling all the lenses, preference was mixed (n=12 Biofinity, n=10 monovision, n=7 Purevision, n=4 Air Optix Aqua, n=2 Oasys). Lens preference was not dependent on personality (F=1.182, p=0.323) or the hours spent working at near (p=0.535) or intermediate (p=0.759) distances. No intersubject or strong intrasubject relationships emerged between lens preference and reading speed, NAVQ rating, halo size, aberrometry or ocular physiology (p>0.05). CONCLUSIONS: Participant lifestyle and personality, ocular optics, contact lens visual performance and ocular physiology provided poor indicators of the preferred lens type after 4 weeks of wear. This is confounded by the wide range of task visual demands of presbyopes and the limited optical differences between current multifocal contact lens designs.

Three-dimensional brain fiber tracking modeling in diffusion tensor imaging

This dissertation establishes the foundation for a new 3-D visual interface integrating Magnetic Resonance Imaging (MRI) to Diffusion Tensor Imaging (DTI). The need for such an interface is critical for understanding brain dynamics, and for providing more accurate diagnosis of key brain dysfunctions in terms of neuronal connectivity. ^ This work involved two research fronts: (1) the development of new image processing and visualization techniques in order to accurately establish relational positioning of neuronal fiber tracts and key landmarks in 3-D brain atlases, and (2) the obligation to address the computational requirements such that the processing time is within the practical bounds of clinical settings. The system was evaluated using data from thirty patients and volunteers with the Brain Institute at Miami Children's Hospital. ^ Innovative visualization mechanisms allow for the first time white matter fiber tracts to be displayed alongside key anatomical structures within accurately registered 3-D semi-transparent images of the brain. ^ The segmentation algorithm is based on the calculation of mathematically-tuned thresholds and region-detection modules. The uniqueness of the algorithm is in its ability to perform fast and accurate segmentation of the ventricles. In contrast to the manual selection of the ventricles, which averaged over 12 minutes, the segmentation algorithm averaged less than 10 seconds in its execution. ^ The registration algorithm established searches and compares MR with DT images of the same subject, where derived correlation measures quantify the resulting accuracy. Overall, the images were 27% more correlated after registration, while an average of 1.5 seconds is all it took to execute the processes of registration, interpolation, and re-slicing of the images all at the same time and in all the given dimensions. ^ This interface was fully embedded into a fiber-tracking software system in order to establish an optimal research environment. This highly integrated 3-D visualization system reached a practical level that makes it ready for clinical deployment. ^

Fluorescence-enhanced optical imaging on three-dimensional phantoms using a hand-held probe based frequency-domain intensified charge coupled device (ICCD) optical imager

Fluorescence-enhanced optical imaging is an emerging non-invasive and non-ionizing modality towards breast cancer diagnosis. Various optical imaging systems are currently available, although most of them are limited by bulky instrumentation, or their inability to flexibly image different tissue volumes and shapes. Hand-held based optical imaging systems are a recent development for its improved portability, but are currently limited only to surface mapping. Herein, a novel optical imager, consisting primarily of a hand-held probe and a gain-modulated intensified charge coupled device (ICCD) detector, is developed towards both surface and tomographic breast imaging. The unique features of this hand-held probe based optical imager are its ability to; (i) image large tissue areas (5×10 sq. cm) in a single scan, (ii) reduce overall imaging time using a unique measurement geometry, and (iii) perform tomographic imaging for tumor three-dimensional (3-D) localization. Frequency-domain based experimental phantom studies have been performed on slab geometries (650 ml) under different target depths (1-2.5 cm), target volumes (0.45, 0.23 and 0.10 cc), fluorescence absorption contrast ratios (1:0, 1000:1 to 5:1), and number of targets (up to 3), using Indocyanine Green (ICG) as fluorescence contrast agents. An approximate extended Kalman filter based inverse algorithm has been adapted towards 3-D tomographic reconstructions. Single fluorescence target(s) was reconstructed when located: (i) up to 2.5 cm deep (at 1:0 contrast ratio) and 1.5 cm deep (up to 10:1 contrast ratio) for 0.45 cc-target; and (ii) 1.5 cm deep for target as small as 0.10 cc at 1:0 contrast ratio. In the case of multiple targets, two targets as close as 0.7 cm were tomographically resolved when located 1.5 cm deep. It was observed that performing multi-projection (here dual) based tomographic imaging using a priori target information from surface images, improved the target depth recovery over using single projection based imaging. From a total of 98 experimental phantom studies, the sensitivity and specificity of the imager was estimated as 81-86% and 43-50%, respectively. With 3-D tomographic imaging successfully demonstrated for the first time using a hand-held based optical imager, the clinical translation of this technology is promising upon further experimental validation from in-vitro and in-vivo studies.