Browsing by Subject "Interferometry"

Alzheimer’s disease (AD) is a neurodegenerative disease currently affecting 5.8 million Americans and more than 50 million people worldwide. It is a progressive disease that destroys cognitive functions, leading to dementia. With increasing life-expectancy, important efforts have been made to clinically diagnose this age-related disease. However, definitive diagnosis of AD has been challenging, especially at an early stage, as there is a lack of quantifiable changes. Recently, many researchers have shown retinal changes as an extension of the brain pathology, leading to a window to study AD using fast and high-resolution retinal imaging tools. This dissertation will be focused on the development of low-cost imaging tools aimed to extract retinal biomarkers for AD. Specifically, the use of optical coherence tomography (OCT) and angle-resolved low-coherence interferometry (a/LCI) will be described, with steps leading to a combined optical system for retinal imaging in humans. OCT has already been established as the gold standard in ophthalmology due to its excellent axial resolution and high sensitivity. Similar to OCT, a/LCI is another interferometric technique that provides depth resolution. Previous work has supported the ability of a/LCI to retrieve depth-resolved light scattering measurements of nuclear morphology in dysplastic tissue. The use of OCT as image guidance for a/LCI can strengthen the technique, providing sample orientation as well as retinal layer segmentation to pinpoint a/LCI measurements. The dissertation starts with the development and clinical application of a low-cost OCT system. Despite the prevalence of OCT, its high-cost nature has limited its access to large eye centers and away from low-resource settings. Clinical feasibility of a complete low-cost OCT system will be evaluated, and its imaging performance compared to a commercial system. System design will be discussed, followed by a comprehensive image processing pipeline to characterize image quality for subsequent low-cost systems. The subsequent portions outline studies using a/LCI and the extraction of light scattering parameters in an AD mouse model. A benchtop co-registered system using a/LCI guided by OCT allowed measurements of depth-resolved light scattering measurements in an AD mouse retina model. Resulting parameters serve as unique quantification of AD tissue structure with potential to be translated to future human studies. A scanning mechanism for 2D a/LCI is also presented, which also allowed for the characterization of a/LCI sensitivity to anisotropic scattering that is often present in the complex retinal tissue. The last portion discusses the development of a second-generation low-cost OCT system which will be integrated in a combined imaging system for eventual AD studies in human patients. Several technical improvements are shown to facilitate clinical retinal imaging at the point-of-care. A characterization of this system in a small clinical study will illustrate the system’s capability to screen AD patients, and to serve as a morphological image guide for a clinical a/LCI system. Finally, a discussion of how the low-cost OCT system can be integrated to a multimodal imaging system for AD human retinal biomarker extraction will be provided.

Quantum communication protocols, such as quantum key distribution (QKD), are practically important in the dawning of a new quantum information age where quantum computers can perform efficient prime factorization to render public key cryptosystems obsolete. QKD is a communication scheme that utilizes the quantum state of a single photons to transmit information, such as a cryptographic key, that is robust against adversaries including those with a quantum computer. In this thesis I describe the contributions that I have made to the development of high-rate, free-space quantum communication systems.

My effort is focused on building a robust quantum receiver for a high-dimensional time-phase QKD protocol where the data is encoded and secured using a single photon's timing and phase degrees of freedom. This type of communication protocol can encode information in a high-dimensional state, allowing the transmission of $>1$ bit per photon. To realize a successful implementation of the protocol a high-performance single-photon detection system must be constructed. My contribution to the field begins with the development of low-noise, low-power cryogenic amplifiers for a detection system using superconducting nanowire single-photon detectors (SNSPDs). Detector characteristics such as maximum count rate and timing resolution are heavily influenced by the design of the read-out circuits that sense and amplify the detection signal. I demonstrate a read-out system with a maximum count rate $>20\,$million counts-per-second and timing resolution as high as $35$\,ps. These results are achieved while maintaining a low power dissipation $<3$\,mW at 4\,K operation, enabling a scalable read-out circuit strategy.

A second contribution I make to the development of detection systems utilizing SNSPDs is extending the superb performance of these detectors to include photon number resolving capabilities. I demonstrate that SNSPDs exhibit multi-photon detection up to four photons where the absorbed photo number is encoded in the rise time of the electrical waveform generated by the detector. Additionally, our experiment agrees well with the predictions of a universal model for turn-on dynamics of SNSPDs. A feature our multi-photon detection system demonstrates high resolution between $n=1$ and $n>1$ photons with a bit-error-rate (BER) of $4.2\times10^{-4}$.

Finally, I extend the utility of the time-phase QKD protocol to free-space applications. Atmospheric turbulences cause spatial mode scrambling of the optical beam during transmission. Therefore, the quantum receiver, and most importantly the time-delay interferometer needed for the measurement of a phase encoding of a single photon, must support many spatial modes. I construct and characterize an interferometer with a 5\,GHz free spectral range that has a wide field-of-view and is passively a-thermal. The results of interferometer characterization are highlighted by a $>99\,\%$ single-mode, and $>98\,\%$ multi-mode interference visibility with negligible dependence on the spatial mode structure of the input beam and modest temperature fluctuations. Additionally, the interferometer displays a small path-length shift of 130\,nm/$^{\,\circ}$C, allowing for great thermal stability with modest temperature control.

There is currently a great interest in using high-dimensional (dimension d>2) quantum states for various communication and computational tasks. High-dimensional quantum states provide an efficient and robust means of encoding information, where each photon can encode a maximum of log_2(d) bits of information. One application where this becomes a significant advantage is quantum key distribution (QKD), which is a communication technique that relies on the quantum nature of photonic states to share a classical secret key between two remote users in the presence of a powerful eavesdropper. High-dimensional QKD protocols are believed to overcome some of the practical challenges of the conventional qubit-based (d = 2) protocols, such as the long recovery time of the single-photon detectors, or the low error tolerance to quantum channel noise.

In this thesis, I demonstrate experimentally and theoretically various novel QKD protocols implemented with high-dimensional quantum photonic states, where the information is encoded using the temporal and phase degrees of freedom. One challenging aspect of high-dimensional time-phase QKD protocols is that the measurement of the phase states requires intricate experimental setups, involving time-delay interferometers, fiber Bragg gratings, or a combination of electro-optic modulators and fiber Bragg gratings, among others. Here, I explore two different measurement schemes, one involving a tree of delay line interferometers, and the other using a quantum-controlled technique, where the measurement of the phase states is performed by interfering an incoming quantum state with another locally generated quantum state. Using the interferometric method (quantum-controlled) and a d = 4 (d = 8) encoding scheme, I achieve a secret key rate of 26.2 +/- 2.8 (16.6 +/- 1.0) Mbps at a 4 (3.2) dB channel loss. Overall, the secret key rates achieved in this thesis are a few folds improvement compared to the other state-of-the-art high-rate QKD systems.

Finally, I consider the possibility of an eavesdropper attacking the high-dimensional quantum states using a universal quantum cloning machine, where she uses weak coherent states of different mean photon numbers (decoy-state technique) to estimate the single-photon fidelity. I show that an eavesdropper can estimate the unknown quantum states in the channel with a degraded but optimal cloning fidelity. Specifically, I find that the upper bound of the cloning fidelity decreases from 0.834 +/- 0.003 at d= 2 to 0.639 +/- 0.003 at d = 6, thereby providing evidence for two conclusions. First, the decoy-state technique can be used to extract single-photon contribution from intricate weak coherent states based two-photon experiments. Second, high-dimensional quantum photonic states are more robust compared to the d = 2 quantum states.

The behavior of light after interacting with a biological medium reveals a wealth of information that may be used to distinguish between normal and disease states. This may be achieved by simply imaging the morphology of tissues or individual cells, and/or by more sophisticated methods that quantify specific surrogate biomarkers of disease. To this end, the work presented in this dissertation demonstrates novel tools derived from low coherence interferometry (LCI) that quantitatively measure wavelength-dependent scattering and absorption properties of biological samples, with high spectral resolution and micrometer spatial resolution, to provide insight into disease states.

The presented work first describes a dual window (DW) method, which decomposes a signal sampled in a single domain (in this case the frequency domain) to a distribution that simultaneously contains information from both the original domain and the conjugate domain (here, the temporal or spatial domain). As the name suggests, the DW method utilizes two independently adjustable windows, each with different spatial and spectral properties to overcome limitations found in other processing methods that seek to obtain the same information. A theoretical treatment is provided, and the method is validated through simulations and experiments. With this tool, the spatially dependent spectral behavior of light after interacting with a biological medium may be analyzed to extract parameters of interest, such as the scattering and absorption properties.

The DW method is employed to investigate scattering properties of samples using Fourier domain LCI (fLCI). In this method, induced temporal coherence effects provide insight into structural changes in dominant scatterers, such as cell nuclei within tissue, which can reveal the early stages of cancerous development. fLCI is demonstrated in complex, three-dimensional samples using a scattering phantom and an ex-vivo animal model. The results from the latter study show that fLCI is able to detect changes in the morphology of tissues undergoing precancerous development.

The DW method is also employed to enable a novel form of optical coherence tomography (OCT), an imaging modality that uses coherence gating to obtain micrometer-scale, cross-sectional information of tissues. The novel method, named molecular imaging true color spectroscopic OCT (METRiCS OCT), analyses the depth dependent absorption of light to ascertain quantitative information of chromophore concentration, such as hemoglobin. The molecular information is also processed to yield a true color representation of the sample, a unique capability of this approach. A number of experiments, including hemoglobin absorbing phantoms and in-vivo imaging of a chick embryo model and dorsal skinfold window chamber model, demonstrate the power of the method.

The final method presented in this dissertation, consists of a spectroscopic approach that interrogates the dispersive biochemical properties of samples to independently probe the scattering and absorption coefficients. To demonstrate this method, named non-linear phase dispersion spectroscopy (NLDS), a careful analysis of LCI signals is presented. The method is verified using measurements from samples that scatter and absorb light. Lastly, NLDS is combined with phase microscopy to achieve molecular imaging with sub-micron spatial resolution. Imaging of red blood cells (RBCs) shows that the method enables highly sensitive measurements that can quantify hemoglobin content from single RBCs.

Cancer, despite its status as the second leading cause of death worldwide, is often preventable given proper surveillance and timely intervention. In the esophagus, metaplastic changes linked to reflux disease lead to alterations in cellular DNA, abnormal growth, and eventually, metastatic cancer. Fortunately, this process takes place over a period of several years, during which treatment and eradication of the precancerous lesions is possible if discovered at a sufficiently early time.

Current protocols for surveillance of the esophagus are costly and limited. As an alternative, angle-resolved low-coherence interferometry (a/LCI) is an optical technique which enables depth-resolved measurements of nuclear morphology, a biomarker of precancer. a/LCI allows for real-time identification of precancerous lesions, which may be treated using radiofrequency ablation or related techniques.

In this dissertation, several advances in a/LCI technology are presented. Measurements of the nuclear refractive index, an important parameter for a/LCI inverse light scattering analysis, are offered to settle an important debate in the literature regarding the relative density of the cell nucleus. Instrumentational advances in a/LCI are demonstrated to address the need for implementing scanning capability, which is important for screening of larger tissues such as the cervix. The properties of commercially available fiber optic imaging bundles are investigated for their capacity to support coherence-based imaging, and when these are found to be lacking, an a/LCI device based on single-mode optical fibers is designed and validated using an array of pathlength-matched individual fibers, which exhibits significant advantages over previous image bundles. Computational analysis of a previous clinical a/LCI dataset is used to provide design guidance for this methodology. Finally, this new a/LCI device is combined with a rotational endoscopic optical coherence tomography (OCT) probe to create a multimodal imaging system for comprehensive evaluation of the esophageal epithelium. The complete system includes a paddle form factor which allows it to be affixed to the exterior of a commercial endoscope for clinical compatibility, similar to related endoscopic devices. These advances demonstrate the continued applicability of a/LCI for evaluating epithelial health, and present new and attractive options for surveillance and early intervention against cancer.