Abstract The objectives were to study ultrasound (US), magnetic resonance imaging (MRI), single photon emission tomography (SPET) and brainstem auditory evoked potentials (BAEP) as structural and functional imaging methods for the prediction of later neuromotor outcome and to assess the reliability of auditory brainstem responses (ABR), transient evoked otoacoustic emissions (TEOAE) and free-field auditory behavioural responses (FF) for the prediction of permanent hearing loss. The series comprised 51 surviving very low birth weight preterm infants born at < 34 gestational weeks with a birth weight < 1500 grams, taking 52 full-term infants as controls with respect to hearing screening and 21 with respect to brainstem function. The imaging examinations and hearing screening were performed at term age and follow-up continued to a corrected age of 18 months for the evaluation of neurodevelopment and hearing. MRI images were analysed with regard to the degree of myelination, parenchymal lesions, ventricular-brain ratios and widths of the extracerebral spaces, and the predictive value of the findings for later neuromotor development was assessed by comparison with US. In the SPET examinations (on 34 infants) relative regional perfusion levels and hemispheric asymmetries were evaluated in slices. The predictive value of perfusion defects in SPET was similarly assessed relative to US abnormalities. Brainstem size was measured by MRI, and brainstem function evaluated by BAEP, and results being used to predict neurosensory disability. Hearing was screened by means of TEOAE, ABR and FF, and the results used to predict permanent hearing loss. Parenchymal lesions in MRI predicted cerebral palsy (CP) with a sensitivity of 82% and a specificity of 97%, the corresponding figures for US being 58% and 100%. Delayed myelination, ventricular-brain ratios and widths of the extracerebral spaces failed to predict CP. The sensitivity of perfusion defects in SPET for predicting CP was 82% and the specificity 70%, and correspondingly US attained a sensitivity of 73% and a specificity of 83%. The best brainstem dimensions for predicting neurosensory disability reached at sensitivity of 23-31% and a specificity of 97-100%. The best predictors in BAEP gave the sensitivity of 93% with a specificity of 57-59%. Bilateral failure in TEOAE predicted hearing loss with a sensitivity of 50% and with a specificity of 84%, and that in ABR with a sensitivity of 100% and a specificity of 98%. The FF examination showed a sensitivity of 50% and a specificity of 98%. In conclusion, out of the brain imaging methods used here MRI was the best for predicting abnormal neuromotor outcome. Brainstem dimensions in MRI appear to predict neurosensory disability poorly, however, whereas BAEP shows a better prediction value, but is limited by a low specificity. ABR seems to be the best hearing screening method because it includes retrocochlear involvements in preterm infants.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22149号 / 医博第4540号 / 新制||医||1039(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 川口 義弥, 教授 上本 伸二, 教授 富樫 かおり / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13397号 / 論医博第2221号 / 新制||医||1051(附属図書館) / (主査)教授 伊佐 正, 教授 中本 裕士, 教授 渡邉 大 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

In this thesis, an approach for developing single-photon sources at the 1550nm wavelength will be demonstrated, based on optical trapping of luminescent upconverting nanoparticles. A single-photon source is a source that emits a single photon at a time, and hence it is a source of quantum bits that constitutes the basic building units in quantum computers and quantum communications. The approach exploits the plasmonic properties of gold films and the waveguiding characteristics of single mode optical fibers (SMFs). We start by planar nanofabrication of subwavelength nanoapertures in a thin gold film based on finite difference time domain simulations for a peak transmission at the wavelength in question. Subsequently, using ultraviolet curable epoxy adhesion material, a nanoaperture patterned on a gold film can be transferred to an SMF tip forming a nanoantenna enhanced optical fiber tweezer (NAFT). As a final step in building the optical tweezer, a test of the capability of the integrated optical fiber tweezer to trap 20 nm, and 30nm polystyrene nanospheres, as well as luminescent upconverting nanoparticles (UCNPs), has been experimentally realized with encouraging results. In addition to the optical trapping of the luminescent nanoparticles, the nano aperture antenna can improve light coupling into the low loss optical fiber guiding channel. Also, it could have a positive influence on enhancing the photon emission rate through the Purcell effect. Furthermore, we have combined NAFT with a low insertion loss wave splitter, a wavelength-division multiplexer (WDM), to allow measuring the 1550nm photon-emission statistics on a cooled superconducting nanowire single-photon detector (SNSPD) at ~ 2.4o K. Eventually, nanoantenna enhanced optical fiber tweezers can play an essential role in optical trapping towards developing single-photon sources and the emerging technology of quantum information processing, computation, and cryptography. / Graduate

Nous avons travaillé sur le développement d’un instrument de mesure de la luminescence induite par un faisceau d’ions lourds (nucléons  12) et d’énergie de l’ordre du MeV/nucléons. Basé sur une méthode de comptage de photons uniques obtenus par coïncidences, le dispositif permet d’obtenir sur 16 voies à la fois un spectre en énergie dans le domaine proche UV-visible-proche IR (185-920 nm) et la réponse temporelle sur la gamme ns-µs, avec un échantillonnage de 100 ps. Des mesures en température peuvent être réalisées depuis la température ambiante jusqu’à 30K.Ce travail met particulièrement l’accent sur les méthodes d’extraction des données : Une fois montrée la nécessité de déconvoluer les signaux, on s’intéresse dans un premier temps à évaluer différents profils instrumentaux modélisés et reconstruit à partir de mesures. A cet effet, un travail de caractérisation temporelle de chaque constituant du dispositif est mené. Puis ces profils instrumentaux sont utilisés dans deux méthodes de déconvolution par moindres carrés d’abord puis par maximum d’entropie ensuite.Deux matériaux types sont testés : Le Titanate de Strontium pour l’étude de la dynamique de l’excitation électronique, et un scintillateur plastique commercial, le BC400, pour l’étude du vieillissement et de la baisse des performances en fonction de la fluence. Dans les deux cas on a pu mettre en évidence la présence d’une composante ultra rapide de constante de temps subnanoseconde. / We developed an instrument for measuring the luminescence induced by a heavy ion beam (nucleons  12) and energy in the range of MeV / nucleon. Based on a single photon counting method obtained by coincidences, the device can provide in the same run a 16-channel energy spectrum in the UV-visible- IR region (185-920 nm) and a time-resolved response in the range of ns up to µs for each channel. Temperature measurements can be performed from room temperature down to 30K.This work places particular emphasis on data extraction methods: Once the need to deconvolve the signals demonstrated the evaluation of different instrument profiles (simulated and reconstructed from measurements) leads to a systematic temporal characterization of each component of the device. Then, these instrumental profiles are used in two deconvolution methods: least squares first followed by maximum entropy method.Two typical materials are tested: the Strontium Titanate for the study of the dynamics of the electronic excitation, and a commercial scintillator, the BC400, for the study of the aging and the decrease of performances with fluence. In both cases, we have been able to highlight the presence of an ultrafast component of subnanosecond time constant.

High resolution transient/3D imaging technology is of high interest in both scientific research and commercial application. Nowadays, all of the transient imaging methods suffer from low resolution or time consuming mechanical scanning. We proposed a new method based on TCSPC and Compressive Sensing to achieve a high resolution transient imaging with a several seconds capturing process. Picosecond laser sends a serious of equal interval pulse while synchronized SPAD camera's detecting gate window has a precise phase delay at each cycle. After capturing enough points, we are able to make up a whole signal. By inserting a DMD device into the system, we are able to modulate all the frames of data using binary random patterns to reconstruct a super resolution transient/3D image later. Because the low fill factor of SPAD sensor will make a compressive sensing scenario ill-conditioned, We designed and fabricated a diffractive microlens array. We proposed a new CS reconstruction algorithm which is able to denoise at the same time for the measurements suffering from Poisson noise. Instead of a single SPAD senor, we chose a SPAD array because it can drastically reduce the requirement for the number of measurements and its reconstruction time. Further more, it not easy to reconstruct a high resolution image with only one single sensor while for an array, it just needs to reconstruct small patches and a few measurements. In this thesis, we evaluated the reconstruction methods using both clean measurements and the version corrupted by Poisson noise. The results show how the integration over the layers influence the image quality and our algorithm works well while the measurements suffer from non-trival Poisson noise. It's a breakthrough in the areas of both transient imaging and compressive sensing.

Cette thèse a été consacrée à l'étude théorique et expérimentale du couplage contrôlé de la source de photon unique (SPS) aux structures photoniques multidimensionnelles, par l'utilisation de la méthode dite écriture directe par laser (DLW) par absorption ultra-faible à un photon (LOPA). La thèse est constitutée de trois parties principales suivantes:La première partie concerne le caractérisation et l'optimisation des dots quantiques (QD) colloïdaux CdSe/CdS. La dépendance de la longeur d'onde d'excitation a été étudiée. En utilisant une excitation à 532 nm, seul le core est excité et l’effet d'Auger est donc supprimé. Cette approche permet donc d'obtenir avec la suppression de la commutation intermittente et une source de photon unique très stable à température ambiante. Afin d’obtenir une meilleure performance des QDs sur une longue période, nous avons ensuite étudié l'influence du milieu dans lequel les QDs sont logés sur leurs propriétés optiques. En intégrant les QDs dans les matrices de polymère SU-8, nous avons montré que l'environnement polymérique permet non seulement de conserver de bonnes caractéristiques des QDs CdSe/CdS avec une photostabilité élevée, mais également de nous offrir une excellente accessibilité à la fabrication des structures en polymère contenant une particule unique.Dans la deuxième partie, la technique LOPA DLW est utilisée pour le couplage des QDs uniques dans diverses structures photoniques. Deux dispositifs, l’antenne du type ''pilier diélectrique'' sous-lambda et la membrane de réseau circulaire (cavité du type ''bulleye''), ont été étudiés théoriquement et expérimentalement pour améliorer l’émission du QD couplé en termes de l'émission spatiale et de l’émission radiative spontanée de l’émetteur.Dans la troisième partie, la manipulation de la SPS est démontrée en couplant le QD unique à des structures magnéto-photoniques multidimensionnelles. À l'aide d'un champ magnétique externe, le mouvement contrôlable d'un seul QD a été démontré dans un environnement fluidique. En contrôlant l'amplitude et l'orientation du champ magnétique externe, la position et l'orientation de la SPS à base d'un QD ont été manipulées à la demande. Les propriétés optiques, magnétiques et mécaniques des dispositifs magnéto-photoniques hybrides ont été étudiées pour montrer les capacités multifonctionnelles de telles structures. / The thesis has been devoted to study the controlled coupling of a colloidal quantum dot (QD) based single photon source (SPS) into multidimensional polymeric photonic structures by using low-one photon absorption (LOPA) direct laser writing (DLW) technique. The thesis consists of three main parts:The first part addresses the characteristic optimization of the CdSe/CdS based SPS. The excitation wavelength dependence of the QDs was investigated. By using 532 nm, only the core of the QD is excited with the suppression of the Auger effects. Thus, this approach allows for obtaining the suppression of fluorescence intermittency and a stable single-photon emission at ambient conditions. In order to obtain the long-term high fluorescence quality of the QDs, we then studied the influence of the local dielectric medium on the optical properties of the QDs. By incorporating the QDs into a photoresist (SU-8), we demonstrated that the polymeric environment not only enables the long-term preservation of the QD with high photostability but also provides us excellent accessibility to fabricate polymeric structures containing SPS.In the second part, the LOPA-based DLW is employed for the coupling of single QD into various photonic structures. Two devices including submicropillar dielectric antenna and 3D membrane bulleye cavity are theoretically and experimentally investigated to enhance the fluorescence emission of the single QD in terms of far-field angular radiation pattern and the spontaneous radiative emission of the emitter.In the third part, the manipulation of SPS is demonstrated by coupling the single QD into multidimensional magneto-photonic structures. With the aid of an external magnetic field, the controllable movement of the coupled QD was performed in the fluidic environment. The position and orientation of the SPS coupled in the structure were manipulated on demand. The mechanical, magnetic and optical properties of the device are investigated showing the multifunctional capabilities of magneto-photonic structures.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21671号 / 医博第4477号 / 新制||医||1035(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 髙橋 良輔, 教授 溝脇 尚志, 教授 黒田 知宏 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

Single-photon avalanche diodes’ (SPADs) capabilities of detecting even a single photon with excellent timing resolution and compatibility with strong magnetic fields make them the most promising sensor for positron emission tomography imaging systems. With the advancements of silicon fabrication techniques, SPADs designed in standard planar complementary metal-oxide-semiconductor (CMOS) processes show competitive performance and a lower manufacturing cost. Additionally, CMOS SPADs have the potential for monolithic integration with other CMOS signal conditioning and processing circuits to achieve simple, low-cost, and high-performance imaging solutions. This work targets the design and optimization of SPAD sensors to improve their performance using low-cost standard CMOS technologies. Firstly, a detailed review on the SPADs in recent literature is presented. Then, the random telegraph signal (RTS) noise is investigated based on n+/p-well SPADs fabricated in a standard 130 nm CMOS process. Through the measurements and analysis, the RTS noise of a SPAD is found to correlate with its dark count rate and afterpulsing. Next, we design n+/p-well SPADs with field poly gates to improve the noise performance. Furthermore, a SPAD pixel, consisting of a p+/n-well SPAD and a compact and high-speed active quench and reset circuit is designed and fabricated in a standard TSMC 65 nm CMOS process. The post-layout simulations show that this pixel achieves a short 0.1 ns quenching time and a 3.35 ns minimum dead time. The measurement results show that the SPAD pixel has a dark count rate of 21 kHz, a peak photon detection probability of 23.8% at a 420 nm wavelength and a timing jitter of 139 ps using a 405 nm pulsed laser when the excess voltage is set to 0.5 V. Due to the short quenching time, almost no afterpulsing is observed even at a low operating temperature of -35 °C. Finally, a new differential quench and reset (QR) circuit consisting of two QR circuits on both the cathode and anode to quench and reset the SPAD through both terminals is proposed to reduce the reset time, to increase the count rate, to reduce the afterpulsing and to reject the common-mode noise. / Thesis / Doctor of Philosophy (PhD) / Positron emission tomography (PET) imaging is a powerful tool for diagnosis and assessment of cancers and tumors in the clinical field. Due to their capabilities of detecting even a single photon, excellent timing resolution, and their compatibility with magnetic fields to build PET/MRI (magnetic resonance imaging) multimodal imaging systems; single-photon avalanche diodes (SPADs) become the most promising sensor technology for PET imaging applications. SPADs fabricated in standard complementary metal-oxide-semiconductor (CMOS) technologies allow for a lower manufacturing cost and present the potential to integrate with other CMOS circuits to form a complete imaging system. In this thesis, random telegraph signal noise in SPADs is investigated first. Then, the poly gate is used in the design of an n+/p-well SPAD to improve the noise performance. In addition, a compact and high-speed SPAD pixel is designed and fabricated using an advanced standard CMOS process. Thanks to the fast quench and reset circuit, the SPAD pixel achieves a very short quenching time and a high-count rate. Finally, a differential quench and reset (QR) circuit consisting of two QR circuits on both the cathode and anode to quench and reset the SPAD through both terminals is proposed and studied.