Brain activity during automatic semantic priming revealed by event-related functional magnetic resonance imaging

Semantic priming occurs when a subject is faster in recognising a target word when it is preceded by a related word compared to an unrelated word. The effect is attributed to automatic or controlled processing mechanisms elicited by short or long interstimulus intervals (ISIs) between primes and targets. We employed event-related functional magnetic resonance imaging (fMRI) to investigate blood oxygen level dependent (BOLD) responses associated with automatic semantic priming using an experimental design identical to that used in standard behavioural priming tasks. Prime-target semantic strength was manipulated by using lexical ambiguity primes (e.g., bank) and target words related to dominant or subordinate meaning of the ambiguity. Subjects made speeded lexical decisions (word/nonword) on dominant related, subordinate related, and unrelated word pairs presented randomly with a short ISI. The major finding was a pattern of reduced activity in middle temporal and inferior prefrontal regions for dominant versus unrelated and subordinate versus unrelated comparisons, respectively. These findings are consistent with both a dual process model of semantic priming and recent repetition priming data that suggest that reductions in BOLD responses represent neural priming associated with automatic semantic activation and implicate the left middle temporal cortex and inferior prefrontal cortex in more automatic aspects of semantic processing.

Co-registration of magnetoencephalography with magnetic resonance imaging using bite-bar-based fiducials and surface-matching

Objective: To introduce a new technique for co-registration of Magnetoencephalography (MEG) with magnetic resonance imaging (MRI). We compare the accuracy of a new bite-bar with fixed fiducials to a previous technique whereby fiducial coils were attached proximal to landmarks on the skull. Methods: A bite-bar with fixed fiducial coils is used to determine the position of the head in the MEG co-ordinate system. Co-registration is performed by a surface-matching technique. The advantage of fixing the coils is that the co-ordinate system is not based upon arbitrary and operator dependent fiducial points that are attached to landmarks (e.g. nasion and the preauricular points), but rather on those that are permanently fixed in relation to the skull. Results: As a consequence of minimizing coil movement during digitization, errors in localization of the coils are significantly reduced, as shown by a randomization test. Displacement of the bite-bar caused by removal and repositioning between MEG recordings is minimal (∼0.5 mm), and dipole localization accuracy of a somatosensory mapping paradigm shows a repeatability of ∼5 mm. The overall accuracy of the new procedure is greatly improved compared to the previous technique. Conclusions: The test-retest reliability and accuracy of target localization with the new design is superior to techniques that incorporate anatomical-based fiducial points or coils placed on the circumference of the head. © 2003 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Attenuated total reflection-FT-IR spectroscopic imaging of protein crystallization

Protein crystallization is of strategic and commercial relevance in the post-genomic era because of its pivotal role in structural proteomics projects. Although protein structures are crucial for understanding the function of proteins and to the success of rational drug design and other biotechnology applications, obtaining high quality crystals is a major bottleneck to progress. The major means of obtaining crystals is by massive-scale screening of a target protein solution with numerous crystallizing agents. However, when crystals appear in these screens, one cannot easily know if they are crystals of protein, salt, or any other molecule that happens to be present in the trials. We present here a method based on Attenuated Total Reflection (ATR)-FT-IR imaging that reliably identifies protein crystals through a combination of chemical specificity and the visualizing capability of this approach, thus solving a major hurdle in protein crystallization. ATR-FT-IR imaging was successfully applied to study the crystallization of thaumatin and lysozyme in a high-throughput manner, simultaneously from six different solutions. This approach is fast as it studies protein crystallization in situ and provides an opportunity to examine many different samples under a range of conditions.

Impact of soft contact lens edge design and mid-peripheral lens shape on the epithelium and its indentation with lens mobility

Purpose. To evaluate the influence of soft contact lens midperipheral shape profile and edge design on the apparent epithelial thickness and indentation of the ocular surface with lens movement. Methods. Four soft contact lens designs comprising of two different plano midperipheral shape profiles and two edge designs (chiseled and knife edge) of silicone-hydrogel material were examined in 26 subjects aged 24.7 ± 4.6 years, each worn bilaterally in randomized order. Lens movement was imaged enface on insertion, at 2 and 4 hours with a high-speed, high-resolution camera simultaneous to the cross-section of the edge of the contact lens interaction with the ocular surface captured using optical coherence tomography (OCT) nasally, temporally, and inferiorly. Optical imaging distortions were individually corrected for by imaging the apparent distortion of a glass slide surface by the removed lens. Results. Apparent epithelial thickness varied with edge position (P < 0.001). When distortion was corrected for, epithelial indentation decreased with time after insertion (P = 0.010), changed after a blink (P < 0.001), and varied with position on the lens edge (P < 0.001), with the latter being affected by midperipheral lens shape profile and edge design. Horizontal and vertical lens movement did not change with time postinsertion. Vertical motion was affected by midperipheral lens shape profile (P < 0.001) and edge design (P < 0.001). Lens movement was associated with physiologic epithelium thickness for lens midperipheral shape profile and edge designs. Conclusions. Dynamic OCT coupled with high-resolution video demonstrated that soft contact lens movement and image-corrected ocular surface indentation were influenced by both lens edge design and midperipheral lens shape profiles. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

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.

Highly efficient spectrally encoded imaging using a 45° tilted fiber grating

A novel highly efficient, fiber-compatible spectrally encoded imaging (SEI) system using a 45° tilted fiber grating (TFG) is proposed and experimentally demonstrated for the first time, to the best of our knowledge. The TFG serves as an in-fiber lateral diffraction element, eliminating the need for bulky and lossy free-space diffraction gratings in conventional SEI systems. Under proper polarization control, due to the strong tilted reflection, the 45° TFG offers a diffraction efficiency as high as 93.5%. Our new design significantly reduces the volume of the SEI system and improves energy efficiency and system stability. As a proof-ofprinciple experiment, spectrally encoded imaging of a customer-designed sample (9.6 mm x 3.0 mm) using the TFG-based system is demonstrated. The lateral resolution of the SEI system is measured to be 42 μm in our experiment.

Design and implementation of a multisite data repository for pediatric epilepsy

This dissertation established a software-hardware integrated design for a multisite data repository in pediatric epilepsy. A total of 16 institutions formed a consortium for this web-based application. This innovative fully operational web application allows users to upload and retrieve information through a unique human-computer graphical interface that is remotely accessible to all users of the consortium. A solution based on a Linux platform with My-SQL and Personal Home Page scripts (PHP) has been selected. Research was conducted to evaluate mechanisms to electronically transfer diverse datasets from different hospitals and collect the clinical data in concert with their related functional magnetic resonance imaging (fMRI). What was unique in the approach considered is that all pertinent clinical information about patients is synthesized with input from clinical experts into 4 different forms, which were: Clinical, fMRI scoring, Image information, and Neuropsychological data entry forms. A first contribution of this dissertation was in proposing an integrated processing platform that was site and scanner independent in order to uniformly process the varied fMRI datasets and to generate comparative brain activation patterns. The data collection from the consortium complied with the IRB requirements and provides all the safeguards for security and confidentiality requirements. An 1-MR1-based software library was used to perform data processing and statistical analysis to obtain the brain activation maps. Lateralization Index (LI) of healthy control (HC) subjects in contrast to localization-related epilepsy (LRE) subjects were evaluated. Over 110 activation maps were generated, and their respective LIs were computed yielding the following groups: (a) strong right lateralization: (HC=0%, LRE=18%), (b) right lateralization: (HC=2%, LRE=10%), (c) bilateral: (HC=20%, LRE=15%), (d) left lateralization: (HC=42%, LRE=26%), e) strong left lateralization: (HC=36%, LRE=31%). Moreover, nonlinear-multidimensional decision functions were used to seek an optimal separation between typical and atypical brain activations on the basis of the demographics as well as the extent and intensity of these brain activations. The intent was not to seek the highest output measures given the inherent overlap of the data, but rather to assess which of the many dimensions were critical in the overall assessment of typical and atypical language activations with the freedom to select any number of dimensions and impose any degree of complexity in the nonlinearity of the decision space.

Design of an automated book reader as an assistive technology tool for blind persons

This dissertation introduces a novel automated book reader as an assistive technology tool for persons with blindness. The literature shows extensive work in the area of optical character recognition, but the current methodologies available for the automated reading of books or bound volumes remain inadequate and are severely constrained during document scanning or image acquisition processes. The goal of the book reader design is to automate and simplify the task of reading a book while providing a user-friendly environment with a realistic but affordable system design. This design responds to the main concerns of (a) providing a method of image acquisition that maintains the integrity of the source (b) overcoming optical character recognition errors created by inherent imaging issues such as curvature effects and barrel distortion, and (c) determining a suitable method for accurate recognition of characters that yields an interface with the ability to read from any open book with a high reading accuracy nearing 98%. This research endeavor focuses in its initial aim on the development of an assistive technology tool to help persons with blindness in the reading of books and other bound volumes. But its secondary and broader aim is to also find in this design the perfect platform for the digitization process of bound documentation in line with the mission of the Open Content Alliance (OCA), a nonprofit Alliance at making reading materials available in digital form. The theoretical perspective of this research relates to the mathematical developments that are made in order to resolve both the inherent distortions due to the properties of the camera lens and the anticipated distortions of the changing page curvature as one leafs through the book. This is evidenced by the significant increase of the recognition rate of characters and a high accuracy read-out through text to speech processing. This reasonably priced interface with its high performance results and its compatibility to any computer or laptop through universal serial bus connectors extends greatly the prospects for universal accessibility to documentation.

Thermal imaging as a biometrics approach to facial signature authentication

This dissertation develops an image processing framework with unique feature extraction and similarity measurements for human face recognition in the thermal mid-wave infrared portion of the electromagnetic spectrum. The goals of this research is to design specialized algorithms that would extract facial vasculature information, create a thermal facial signature and identify the individual. The objective is to use such findings in support of a biometrics system for human identification with a high degree of accuracy and a high degree of reliability. This last assertion is due to the minimal to no risk for potential alteration of the intrinsic physiological characteristics seen through thermal infrared imaging. The proposed thermal facial signature recognition is fully integrated and consolidates the main and critical steps of feature extraction, registration, matching through similarity measures, and validation through testing our algorithm on a database, referred to as C-X1, provided by the Computer Vision Research Laboratory at the University of Notre Dame. Feature extraction was accomplished by first registering the infrared images to a reference image using the functional MRI of the Brain’s (FMRIB’s) Linear Image Registration Tool (FLIRT) modified to suit thermal infrared images. This was followed by segmentation of the facial region using an advanced localized contouring algorithm applied on anisotropically diffused thermal images. Thermal feature extraction from facial images was attained by performing morphological operations such as opening and top-hat segmentation to yield thermal signatures for each subject. Four thermal images taken over a period of six months were used to generate thermal signatures and a thermal template for each subject, the thermal template contains only the most prevalent and consistent features. Finally a similarity measure technique was used to match signatures to templates and the Principal Component Analysis (PCA) was used to validate the results of the matching process. Thirteen subjects were used for testing the developed technique on an in-house thermal imaging system. The matching using an Euclidean-based similarity measure showed 88% accuracy in the case of skeletonized signatures and templates, we obtained 90% accuracy for anisotropically diffused signatures and templates. We also employed the Manhattan-based similarity measure and obtained an accuracy of 90.39% for skeletonized and diffused templates and signatures. It was found that an average 18.9% improvement in the similarity measure was obtained when using diffused templates. The Euclidean- and Manhattan-based similarity measure was also applied to skeletonized signatures and templates of 25 subjects in the C-X1 database. The highly accurate results obtained in the matching process along with the generalized design process clearly demonstrate the ability of the thermal infrared system to be used on other thermal imaging based systems and related databases. A novel user-initialization registration of thermal facial images has been successfully implemented. Furthermore, the novel approach at developing a thermal signature template using four images taken at various times ensured that unforeseen changes in the vasculature did not affect the biometric matching process as it relied on consistent thermal features.

Design rationnel de nanothermomètres programmables à base d’ADN

Développer de nouveaux nanomatériaux, interrupteurs et machines nanométriques sensibles à de petites variations de température spécifiques devrait être de grande utilité pour une multitude de domaines œuvrant dans la nanotechnologie. De plus, l’objectif est de convaincre le lecteur que les nanotechnologies à base d’ADN offrent d’énormes possibilités pour la surveillance de température en temps réel à l’échelle nanométrique. Dans la section Résultats, nous exploitons les propriétés de l’ADN pour créer des thermomètres versatiles, robustes et faciles à employer. En utilisant une série de nouvelles stratégies inspirées par la nature, nous sommes en mesure de créer des nanothermomètres d’ADN capables de mesurer des températures de 25 à 95°C avec une précision de <0.1°C. En créant de nouveaux complexes d’ADN multimériques, nous arrivons à développer des thermomètres ultrasensibles pouvant augmenter leur fluorescence 20 fois sur un intervalle de 7°C. En combinant plusieurs brins d’ADN avec des plages dynamiques différentes, nous pouvons former des thermomètres montrant une transition de phase linéaire sur 50°C. Finalement, la vitesse de réponse et la précision des thermomètres développés et leur réversibilité sont illustrées à l’aide d’une expérience de surveillance de température à l’intérieur d’un unique puits d’un appareil de qPCR. En conclusion, les applications potentielles de tels nanothermomètres en biologie synthétique, imagerie thermique cellulaire, nanomachines d’ADN et livraison contrôlée seront considérées.

Development of Swept Source Optical Coherence Tomography and Adaptive Optics Scanning Laser Ophthalmoscopy: Improved Imaging Speed and Handheld Applications

Optical coherence tomography (OCT) is a noninvasive three-dimensional interferometric imaging technique capable of achieving micrometer scale resolution. It is now a standard of care in ophthalmology, where it is used to improve the accuracy of early diagnosis, to better understand the source of pathophysiology, and to monitor disease progression and response to therapy. In particular, retinal imaging has been the most prevalent clinical application of OCT, but researchers and companies alike are developing OCT systems for cardiology, dermatology, dentistry, and many other medical and industrial applications.

Adaptive optics (AO) is a technique used to reduce monochromatic aberrations in optical instruments. It is used in astronomical telescopes, laser communications, high-power lasers, retinal imaging, optical fabrication and microscopy to improve system performance. Scanning laser ophthalmoscopy (SLO) is a noninvasive confocal imaging technique that produces high contrast two-dimensional retinal images. AO is combined with SLO (AOSLO) to compensate for the wavefront distortions caused by the optics of the eye, providing the ability to visualize the living retina with cellular resolution. AOSLO has shown great promise to advance the understanding of the etiology of retinal diseases on a cellular level.

Broadly, we endeavor to enhance the vision outcome of ophthalmic patients through improved diagnostics and personalized therapy. Toward this end, the objective of the work presented herein was the development of advanced techniques for increasing the imaging speed, reducing the form factor, and broadening the versatility of OCT and AOSLO. Despite our focus on applications in ophthalmology, the techniques developed could be applied to other medical and industrial applications. In this dissertation, a technique to quadruple the imaging speed of OCT was developed. This technique was demonstrated by imaging the retinas of healthy human subjects. A handheld, dual depth OCT system was developed. This system enabled sequential imaging of the anterior segment and retina of human eyes. Finally, handheld SLO/OCT systems were developed, culminating in the design of a handheld AOSLO system. This system has the potential to provide cellular level imaging of the human retina, resolving even the most densely packed foveal cones.

Development of Multi-modal and Super-resolved Retinal Imaging Systems

Advancements in retinal imaging technologies have drastically improved the quality of eye care in the past couple decades. Scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) are two examples of critical imaging modalities for the diagnosis of retinal pathologies. However current-generation SLO and OCT systems have limitations in diagnostic capability due to the following factors: the use of bulky tabletop systems, monochromatic imaging, and resolution degradation due to ocular aberrations and diffraction.

Bulky tabletop SLO and OCT systems are incapable of imaging patients that are supine, under anesthesia, or otherwise unable to maintain the required posture and fixation. Monochromatic SLO and OCT imaging prevents the identification of various color-specific diagnostic markers visible with color fundus photography like those of neovascular age-related macular degeneration. Resolution degradation due to ocular aberrations and diffraction has prevented the imaging of photoreceptors close to the fovea without the use of adaptive optics (AO), which require bulky and expensive components that limit the potential for widespread clinical use.

In this dissertation, techniques for extending the diagnostic capability of SLO and OCT systems are developed. These techniques include design strategies for miniaturizing and combining SLO and OCT to permit multi-modal, lightweight handheld probes to extend high quality retinal imaging to pediatric eye care. In addition, a method for extending true color retinal imaging to SLO to enable high-contrast, depth-resolved, high-fidelity color fundus imaging is demonstrated using a supercontinuum light source. Finally, the development and combination of SLO with a super-resolution confocal microscopy technique known as optical photon reassignment (OPRA) is demonstrated to enable high-resolution imaging of retinal photoreceptors without the use of adaptive optics.

Numerical Simulations for the Design of Novel Integrated Parallel Reception, Excitation, and Shimming (iPRES) Coil Arrays

Magnetic field inhomogeneity results in image artifacts including signal loss, image blurring and distortions, leading to decreased diagnostic accuracy. Conventional multi-coil (MC) shimming method employs both RF coils and shimming coils, whose mutual interference induces a tradeoff between RF signal-to-noise (SNR) ratio and shimming performance. To address this issue, RF coils were integrated with direct-current (DC) shim coils to shim field inhomogeneity while concurrently emitting and receiving RF signal without being blocked by the shim coils. The currents applied to the new coils, termed iPRES (integrated parallel reception, excitation and shimming), were optimized in the numerical simulation to improve the shimming performance. The objectives of this work is to offer a guideline for designing the optimal iPRES coil arrays to shim the abdomen.

In this thesis work, the main field () inhomogeneity was evaluated by root mean square error (RMSE). To investigate the shimming abilities of iPRES coil arrays, a set of the human abdomen MRI data was collected for the numerical simulations. Thereafter, different simplified iPRES(N) coil arrays were numerically modeled, including a 1-channel iPRES coil and 8-channel iPRES coil arrays. For 8-channel iPRES coil arrays, each RF coil was split into smaller DC loops in the x, y and z direction to provide extra shimming freedom. Additionally, the number of DC loops in a RF coil was increased from 1 to 5 to find the optimal divisions in z direction. Furthermore, switches were numerically implemented into iPRES coils to reduce the number of power supplies while still providing similar shimming performance with equivalent iPRES coil arrays.

The optimizations demonstrate that the shimming ability of an iPRES coil array increases with number of DC loops per RF coil. Furthermore, the z direction divisions tend to be more effective in reducing field inhomogeneity than the x and y divisions. Moreover, the shimming performance of an iPRES coil array gradually reach to a saturation level when the number of DC loops per RF coil is large enough. Finally, when switches were numerically implemented in the iPRES(4) coil array, the number of power supplies can be reduced from 32 to 8 while keeping the shimming performance similar to iPRES(3) and better than iPRES(1). This thesis work offers a guidance for the designs of iPRES coil arrays.

Design rationnel de nanothermomètres programmables à base d’ADN

Développer de nouveaux nanomatériaux, interrupteurs et machines nanométriques sensibles à de petites variations de température spécifiques devrait être de grande utilité pour une multitude de domaines œuvrant dans la nanotechnologie. De plus, l’objectif est de convaincre le lecteur que les nanotechnologies à base d’ADN offrent d’énormes possibilités pour la surveillance de température en temps réel à l’échelle nanométrique. Dans la section Résultats, nous exploitons les propriétés de l’ADN pour créer des thermomètres versatiles, robustes et faciles à employer. En utilisant une série de nouvelles stratégies inspirées par la nature, nous sommes en mesure de créer des nanothermomètres d’ADN capables de mesurer des températures de 25 à 95°C avec une précision de <0.1°C. En créant de nouveaux complexes d’ADN multimériques, nous arrivons à développer des thermomètres ultrasensibles pouvant augmenter leur fluorescence 20 fois sur un intervalle de 7°C. En combinant plusieurs brins d’ADN avec des plages dynamiques différentes, nous pouvons former des thermomètres montrant une transition de phase linéaire sur 50°C. Finalement, la vitesse de réponse et la précision des thermomètres développés et leur réversibilité sont illustrées à l’aide d’une expérience de surveillance de température à l’intérieur d’un unique puits d’un appareil de qPCR. En conclusion, les applications potentielles de tels nanothermomètres en biologie synthétique, imagerie thermique cellulaire, nanomachines d’ADN et livraison contrôlée seront considérées.

Design and Synthesis of 4-N-Alkanoyl and 4-N-Alkyl Gemcitabine Analogues Suitable for Positron Emission Tomography

Gemcitabine is a highly potent chemotherapeutic nucleoside agent used in the treatment of several cancers and solid tumors. However, it is therapeutically limitated because of toxicity to normal cells and its rapid intracellular deamination by cytidine deaminase into the inactive uracil derivative. Modification at the 4-(N) position of gemcitabine's exocyclic amine to an -amide functionality is a well reported prodrug strategy which has been that confers a resistance to intracellular deamination while also altering pharmacokinetics of the parent drug. Coupling of gemcitabine to carboxylic acids with varying terminal moieties afforded the 4-N-alkanoylgemcitabines whereas reaction of 4-N-tosylgemcitabine with the corresponding alkyl amines gave the 4-N-alkylgemcitabines. The 4-N-alkanoyl and 4-N-alkyl gemcitabine analogues with a terminal hydroxyl group on the 4-N-alkanoyl or 4-N-alkyl chain were efficiently fluorinated either with diethylaminosulfur trifluoride or under conditions that are compatible with the synthetic protocols for 18F labeling, such as displacement of the corresponding mesylate with KF/Kryptofix 2.2.2. The 4-N-alkanoylgemcitabine analogues displayed potent cytostatic activities against murine and human tumor cell lines with 50% inhibitory concentration (IC50) values in the range of low nM, whereas cytotoxicity of the 4-N-alkylgemcitabine derivatives were in the low to modest µM range. The cytostatic activity of the 4-N-alkanoylgemcitabines was reduced by several orders of magnitude in the 2'-deoxycytidine kinase (dCK)-deficient CEM/dCK- cell line while the 4-N-alkylgemcitabines were only lowered by 2-5 times. None of the 4-N-modified gemcitabines were found to be substrates for cytosolic dCK, however all were found to inhibit DNA synthesis. As such, the 4-N-alkanoyl gemcitabine derivatives likely need to be converted to gemcitabine prior to achieving their significant cytostatic potential, whereas the 4-N-alkylgemcitabines reach their modest activity without "measurable" conversion to gemcitabine. Thus, the 4-N-alkylgemcitabines provide valuable insight on the metabolism of 4-N-modified gemcitabine prodrugs.