Clinical usefulness of super high-resolution liquid crystal displays using independent sub-pixel driving technology

金沢大学医薬保健研究域保健学系We have developed and reported super-high resolution liquid crystal displays (SHR-LCDs) using a new resolution enhancement technology of the independent sub-pixel driving (ISD) that utilizes three sub-pixels contained in each pixel element. This technology realizes the three-times resolution enhancement of monochrome LCDs. A 15 mega-pixel (MP) SHR-LCD out of a 5MP LCD and a 9MP SHR-LCD out of a 3MP LCD, for example, are realized by this technology, which improves the depiction ability of detailed image shapes such as micro-calcifications of a mammography. Furthermore, the ISD technology brings not only resolution enhancement but also noise reduction effect by the high-frequency data sampling in displaying the clinical images. In this study, we have investigated the clinical efficacy of the SHR-LCDs by means of phantom observation studies and blind observer comparison studies using clinical mammography images performed by radiologists. We used a conventional 5MP LCD for a comparison of a 15MP SHR-LCD and a 9MP SHR-LCD to evaluate their efficacy. From the results of the studies, it was indicated that the SHR-LCDs using the ISD technology had the excellent ability to display the high-resolution digital mammography images. © 2008 Springer-Verlag Berlin Heidelberg

Preliminary investigation of the clinical usefulness of super-high-resolution LCDs with 9 and 15 mega-sub-pixels: Observation studies with phantoms

金沢大学附属病院放射線部Our purpose in this study was to evaluate the preliminary clinical efficacy of soft-copy reading of digital mammography, for a 15-mega-sub-pixel (MsP) and a 9-MsP super-high-resolution liquid-crystal display (SHR-LCD) by use of an independent sub-pixel driving technology. We performed three kinds of phantom observation studies by six radiological technologists. Detectability of a contrast-detail phantom and simulated small objects (SSOs) resembling microcalcifications (MCLs), and shape discrimination ability of SSOs with round and square shapes, were examined and compared with a 5-MP conventional LCD (5-MP LCD). In each study, four types of display magnification ratio were used. The detectability and the shape discrimination ability of the 15-MsP SHR-LCD were highest among the three LCDs of most of the display magnification ratios. The 9-MsP SHR-LCD indicated a higher or equal performance as compared with the 5-MP LCD in the SSO detection and shape studies. The results of our study demonstrated that the SHR-LCDs had good potential to detect MCLs and to evaluate the shape in high-resolution digital mammography. © 2009 Japanese Society of Radiological Technology and Japan Society of Medical Physics

Liquid Crystal on Silicon Devices: Modeling and Advanced Spatial Light Modulation Applications

Liquid Crystal on Silicon (LCoS) has become one of the most widespread technologies for spatial light modulation in optics and photonics applications. These reflective microdisplays are composed of a high-performance silicon complementary metal oxide semiconductor (CMOS) backplane, which controls the light-modulating properties of the liquid crystal layer. State-of-the-art LCoS microdisplays may exhibit a very small pixel pitch (below 4 ?m), a very large number of pixels (resolutions larger than 4K), and high fill factors (larger than 90%). They modulate illumination sources covering the UV, visible, and far IR. LCoS are used not only as displays but also as polarization, amplitude, and phase-only spatial light modulators, where they achieve full phase modulation. Due to their excellent modulating properties and high degree of flexibility, they are found in all sorts of spatial light modulation applications, such as in LCOS-based display systems for augmented and virtual reality, true holographic displays, digital holography, diffractive optical elements, superresolution optical systems, beam-steering devices, holographic optical traps, and quantum optical computing. In order to fulfil the requirements in this extensive range of applications, specific models and characterization techniques are proposed. These devices may exhibit a number of degradation effects such as interpixel cross-talk and fringing field, and time flicker, which may also depend on the analog or digital backplane of the corresponding LCoS device. The use of appropriate characterization and compensation techniques is then necessary

Development of a Nano-Illumination Microscope

[eng] This doctoral thesis proposes and explores a new approach to lensless microscopy, focusing on making high resolution imaging ubiquitous and low cost. A short introduction to microscopy frames the state of current techniques: Abbe’s law limits the resolving power for visible light microscopes with lenses, techniques using UV, X-rays, or electrons are incompatible with live samples and all of them, including super-resolution microscopy methods, are complex devices not suitable for being used in the field as mobile devices. Some lensless microscopy methods try to solve these issues. The microscopy method is named Nano Illumination Microscopy (NIM) because it relies on using nanometric light sources in an ordered array to illuminate a sample placed in close proximity to them, and a photodetector at the other side to measure the amount of light arriving from each LED. In a setup like this, the resolving power is provided by the nano-LEDs and their distribution instead of the sensing devices, as is the case in the other methods. Since the resolving power depends on the pitch of the LED array, this method also opens a path to obtain super-resolution images, depending only on obtaining LED arrays with pitches smaller than Abbe’s limit for the wavelength. After the introduction to microscopy setting the context of the thesis, the thesis continues explaining the main components used to build the microscope: a SPAD camera, designed within the context of this work, and the electronics to control the nano-LED array. The third chapter of this thesis provides an overview of the microscopy method and its fundaments, exploring the requirements and capabilities. Image formation is first introduced with simulations, and this information is then used to build the very first prototype, a microscope capable of forming 8x8 pixel images -since that is the form factor of the LED array used, with LEDs of 5 μm in size (and 10 μm in pitch). The first results from this technique are presented and compared with the simulations, showing the agreement between both, validating the method, and offering insight on building the next prototypes, which will use smaller LEDs in an attempt to study the technological limits. The thesis continues with the work done in search of the limits of the technique, building and testing new improved versions of the microscope and confronting the limitations which arise. Some of those came from the structure of the LED arrays themselves: while nano-LEDs well below the sizes used have been reported, those have been isolated structures or non individually addressable. Selecting exactly which LED will emit is one of the main problems to solve since with increasingly large arrays, the connections required increase exponentially until routing is impossible. The thesis also studies this problem, as the LED arrays were changed in search of the proper solution. This implied moving from a direct addressing strategy, in which each LED was selected individually, towards a matrix-addressing format, in which the LEDs are selected by polarising the appropriate row and columns. The microscopy technique is validated and the more advanced prototypes presented. Images with a maximum resolving power of 800 nm are shown, and the results discussed, since the physical limitations on fabricating the chips limit the maximum resolving power below what was theoretically expected. The thesis also offers a short overview into the future of the Nano Illumination Microscopy technique.[cat] Aquesta tesi doctoral proposa i explora una nova aproximació a la microscopia sense lents, amb la intenció de facilitar l’obtenció d’imatges d’alta resolució amb baix cost i disponible arreu. S’ha batejat aquest mètode de microscòpia com a Microscopia de Nano-Il·luminació (MNI) perquè la imatge es construeix a partir de fonts de llum de mida nanomètrica distribuïdes en una matriu que il·luminen la mostra de forma consecutiva i ordenada. Un sensor a l’altre costat recull la intensitat de llum que arriba de cada LED, creant un mapa de l’objecte observat. Aquest mètode fa que la resolució de les imatges depengui de la mida i distribució dels LEDs, en comptes de la del sensor com és el cas convencionalment, obrint la porta a noves integracions. En la tesi s’ofereix una introducció general a la microscòpia abans d’entrar a detallar els components del microscopi i com s’integren per muntar-lo. A continuació es presenta i s’estudia el funcionament del mètode, començant amb simulacions i seguint amb la construcció del primer prototip de microscopi amb el que s’obtenen les primeres imatges. La tesi procedeix a continuació a investigar els límits actuals de la tècnica de microscòpia, utilitzant noves versions de la matriu de LEDs i estratègies alternatives per intentar superar-ne les complicacions tècniques. Així, s’obtenen imatges amb una resolució de 800 nm i es discuteix la problemàtica d’implementar dispositius que s’aproximin a les expectatives teòriques per la tècnica

Microscopy and Analysis

Microscopes represent tools of the utmost importance for a wide range of disciplines. Without them, it would have been impossible to stand where we stand today in terms of understanding the structure and functions of organelles and cells, tissue composition and metabolism, or the causes behind various pathologies and their progression. Our knowledge on basic and advanced materials is also intimately intertwined to the realm of microscopy, and progress in key fields of micro- and nanotechnologies critically depends on high-resolution imaging systems. This volume includes a series of chapters that address highly significant scientific subjects from diverse areas of microscopy and analysis. Authoritative voices in their fields present in this volume their work or review recent trends, concepts, and applications, in a manner that is accessible to a broad readership audience from both within and outside their specialist area

Principles of microfluidic actuation by modulation of surface stresses

Development and optimization of multifunctional devices for fluidic manipulation of films, drops, and bubbles require detailed understanding of interfacial phenomena and microhydrodynamic flows. Systems are distinguished by a large surface to volume ratio and flow at small Reynolds, capillary, and Bond numbers are strongly influenced by boundary effects and therefore amenable to control by a variety of surface treatments and surface forces. We review the principles underlying common techniques for actuation of droplets and films on homogeneous, chemically patterned, and topologically textured surfaces by modulation of normal or shear stresses

Supercontinuum in the practice of Optical Coherence Tomography with emphasis on noise effects

Optical Coherence Tomography (OCT) is an imaging modality which has proven, since the early 1990s, its incredible potential. Nowadays, numerous fields of medical investigation, such as Ophthalmology, Dermatology or Cardiovascular imaging, would not be the same without the diagnostic tools bring by OCT. This tremendous development has been supported by industry support through improvement of dedicated components such as lasers, cameras and optics. A great example of this development is the evolution of Supercontinuum (SC) sources. Due to the extremely broad spectrum cover by SC sources, their high power density and high spatial coherence, it seems obvious to use them for driving OCT systems. However, an intensity noise issue arising from the SC sources has been reported as a limitation for OCT and needs to be addressed. The aim of the work presented in this thesis is to create a link between the world of Optical Coherence Tomography and Supercontinuum physics in order to understand the origins and the impact of SC source intensity noise into the OCT systems. This work is of importance as it helps to optimize the usefulness of the current generation of SC sources. Also, this work is a part of the work necessary for developing a new generation of SC sources which completely addresses the intensity noise limitations. More precisely, a part of the work presented deals with an optimization of the association SC source and OCT. The second part of the results is an attempt for improving this association by using a new SC source design

Characterization, modeling, and simulation of multiscale directed-assembly systems

Nanoscience is a rapidly developing field at the nexus of all physical sciences which holds the potential for mankind to gain a new level of control of matter over matter and energy altogether. Directed-assembly is an emerging field within nanoscience in which non-equilibrium system dynamics are controlled to produce scalable, arbitrarily complex and interconnected multi-layered structures with custom chemical, biologically or environmentally-responsive, electronic, or optical properties. We construct mathematical models and interpret data from direct-assembly experiments via application and augmentation of classical and contemporary physics, biology, and chemistry methods. Crystal growth, protein pathway mapping, LASER tweezers optical trapping, and colloid processing are areas of directed-assembly with established experimental techniques. We apply a custom set of characterization, modeling, and simulation techniques to experiments to each of these four areas. Many of these techniques can be applied across several experimental areas within directed-assembly and to systems featuring multiscale system dynamics in general. We pay special attention to mathematical methods for bridging models of system dynamics across scale regimes, as they are particularly applicable and relevant to directed-assembly. We employ massively parallel simulations, enabled by custom software, to establish underlying system dynamics and develop new device production methods

Deformable Beamsplitters: Enhancing Perception with Wide Field of View, Varifocal Augmented Reality Displays

An augmented reality head-mounted display with full environmental awareness could present data in new ways and provide a new type of experience, allowing seamless transitions between real life and virtual content. However, creating a light-weight, optical see-through display providing both focus support and wide field of view remains a challenge. This dissertation describes a new dynamic optical element, the deformable beamsplitter, and its applications for wide field of view, varifocal, augmented reality displays. Deformable beamsplitters combine a traditional deformable membrane mirror and a beamsplitter into a single element, allowing reflected light to be manipulated by the deforming membrane mirror, while transmitted light remains unchanged. This research enables both single element optical design and correct focus while maintaining a wide field of view, as demonstrated by the description and analysis of two prototype hardware display systems which incorporate deformable beamsplitters. As a user changes the depth of their gaze when looking through these displays, the focus of virtual content can quickly be altered to match the real world by simply modulating air pressure in a chamber behind the deformable beamsplitter; thus ameliorating vergence–accommodation conflict. Two user studies verify the display prototypes’ capabilities and show the potential of the display in enhancing human performance at quickly perceiving visual stimuli. This work shows that near-eye displays built with deformable beamsplitters allow for simple optical designs that enable wide field of view and comfortable viewing experiences with the potential to enhance user perception.Doctor of Philosoph

MSI-based mapping strategies in tumour-heterogeneity

Since the early 2000s, considerable innovations in MS technology and associated gene sequencing systems have enabled the "-omics" revolution. The data collected from multiple omics research can be combined to gain a better understanding of cancer's biological activity. Breast and ovarian cancer are among the most common cancers worldwide in women. Despite significant advances in diagnosis, treatment, and subtype identification, breast cancer remains the world's second leading cause of cancer-related deaths in women, with ovarian cancer ranking fifth. Tumour heterogeneity is a significant hurdle in cancer patient prognosis, response to therapy, and metastasis. As such, heterogeneity is one of the most significant and clinically relevant areas of cancer research nowadays. Metabolic reprogramming is a hallmark of malignancy that has been widely acknowledged in recent literature. Metabolic heterogeneity in tumours poses a challenge in developing therapies that exploit metabolic vulnerabilities. Consequently, it is crucial to approach tumour heterogeneity with an unlabeled yet spatially specific read-out of metabolic and genetic information. The advantage of DESI-MSI technology originates from its untargeted nature, which allows for the investigation of thousands of component distributions, at a micrometre scale, in a single experiment. Most notably, using a DESI-MSI clustering approach could potentially offer novel insights into metabolism, providing a method to characterise metabolically distinct sub-regions and subsequently delineate the underlying genetic drivers through genomic analyses. Hence, in this study, we aim to map the inter-and intra-tumour metabolic heterogeneity in breast and ovarian cancer by integrating multimodal MSI-based mapping strategies, comprising DESI and MALDI, with IMC (Imaging Mass Cytometry) analysis of the tumour section, using CyTOF, and high- throughput genetic characterisation of metabolically-distinct regions by transcriptomics. The multimodal analysis workflow was initially performed using sequential breast cancer Patient-Derived Xenografts (PDX) models and was expanded on primary tumour sections. Moreover, a newly developed DESI-MSI friendly, hydroxypropyl-methylcellulose and polyvinylpyrrolidone (HPMC/PVP) hydrogel-based embedding was successfully established to allow simultaneous preparation and analysis of numerous fresh frozen core-size biopsies in the same Tissue Microarray (TMA) block for the investigation of tumour heterogeneity. Additionally, a single section strategy was combined with DESI-MSI coupled to Laser Capture Microdissection (LCM) application to integrate gene expression analysis and Liquid Chromatography-Mass Spectrometry (LC-MS) on the same tissue segment. The developed single section methodology was then tested with multi-region collected ovarian tumours. DESI-MSI-guided spatial transcriptomics was performed for co-registration of different omics datasets on the same regions of interest (ROIs). This co-registration of various omics could unravel possible interactions between distinct metabolic profiles and specific genetic drivers that can lead to intra-tumour heterogeneity. Linking all these findings from MSI-based or guided various strategies allows for a transition from a qualitative approach to a conceptual understanding of the architecture of multiple molecular networks responsible for cellular metabolism in tumour heterogeneity.Open Acces