Small molecule organic dyes with absorption and emission in the near infrared region (NIR) attracted much attention for various applications such as dye sensitized solar cells, fluorescent guided surgery, stimuli responsive bioimaging and photodynamic therapy. Dyes with high absorption and emission in the NIR region are beneficial for stimuli responsive bioimaging due to the deeper penetration of NIR light, less cell damage, high resolution, and low background autofluorescence from biomolecules. Of the many small molecule dyes, xanthene-based dyes exhibit outstanding photophysical properties and good stimuli response for use in bioimaging applications. However, absorption and emission of the xanthene dyes lie in the visible region, which limit their applications in cellular imaging. Many of the NIR dyes have very poor fluorescence; consequently, an alternative approach to fluorescent imaging is photoacoustic imaging that uses sound waves to generate pictures of deep tissues. In this dissertation, we discuss the utility of xanthene based NIR dyes as photoacoustic imaging contrast agents for multiplex imaging and deep tissue nitric oxide sensing in the drug-induced liver injury. Chapter I discuss the fundamentals of fluorescence and photoacoustic imaging, background of the xanthene dyes and other fluorescent dyes, and the design strategies to develop NIR xanthene-based dyes. Chapter II is based on our approach to the design and synthesis of NIR xanthene-based dyes by C-H bond functionalization, with the first example being Rhodindolizine, which absorb and emits in NIR II or short-wave infrared (SWIR) region. In chapter III, we describe the design and synthesis of thienylpiperidine xanthene-based NIR and shortwave-infrared (SWIR) dyes for the photoacoustic imaging. One dye in particular (XanthCR-880) boasts a strong PA signal at 880 nm with good biological compatibility and photostability, yields multiplexed imaging with an aza-BODIPY reference dye, and is detected at a depth of 4 cm. In chapter IV, we report a series of SWIR dyes based on a dibenzazepine donor conjugated to thiophene (SCR-1, SCR-4), thienothiophene (SCR-2, SCR-5), and bithiophene (SCR-3, SCR-6). We leverage the fact that SCR-1 undergoes a bathochromic shift when aggregated to develop a ratiometric nanoparticle for nitric oxide (NO) (rNP-NO). rNP-NO was used to successfully perform in vivo studies to visualize pathological levels of nitric oxide in a drug-induced liver injury model via deep tissue SWIR photoacoustic (PA) imaging. Chapter V describes another series of xanthene-based dyes with a thiophene ᴫ spacer and several different donors. UV-Vis absorption studies were performed after converting the dyes to the opened form with trifluoracetic acid. These novel XanthCR-TD dyes exhibit absorption maxima in NIR I region from 700 - 900 nm.

Quantitative phase Imaging(QPI) has emerged as a valuable tool for imaging specimens with weak scattering and absorbing abilities such as cells and tissues. It is complementary to fluorescence microscopy, as such, it can be applied to unlabelled specimens without the need for fluorescent tagging. By quantitatively mapping the phase changes induced in the incident light field by the optical path length delays of the specimen, QPI provides objective measurement of the cellular dynamics and enables imaging the specimen with high contrast. Transport of Intensity Equation(TIE) is a powerful computational tool for QPI because of its experimental and computational simplicity. Using TIE, the phase can be quantitatively retrieved from defocused intensity images. However, the resolution of the phase image computed using TIE is limited by the diffraction limit of the imaging system used to capture the intensity images. In this thesis, we have developed a super resolution phase imaging technique by applying the principles of Structured Illumination Microscopy(SIM) to Transport of Intensity phase retrieval. The modulation from the illumination shifts the high frequency components of the phase object into the system pass-band. This enables phase imaging with resolutions exceeding the diffraction limit. The proposed method is experimentally validated using a custom-made upright microscope. Because of its experimental and computational simplicity, the method in this thesis should find application in biomedical laboratories where super resolution phase imaging is required / Master of Science / Transport of Intensity Equation is a quantitative phase microscopy technique that enables imaging thin transparent specimens with high phase contrast using a through focus intensity stack. It provides speckle free imaging, compatibility with bright field microscopes and valid under partial coherence. However, the Optical Transfer Function(OTF) of the imaging system or the microscope acts a low pass filter, effectively limiting the maximum spatial frequency that can pass through the system. This reduces the spatial resolution of the computed phase image to the spatial diffraction limit. There has been a continuous drive to develop Super resolution techniques that will provide sub-diffraction resolutions because it will provide better insight into the cellular structure, morphology and composition. Structured Illumination Microscopy(SIM) is one such established technique. Existing work in super resolution phase imaging using SIM is exclusively limited to holography and interferometry based techniques. However, such methods require two-beam interference, illumination sources with high coherence, high experimental stability and phase unwrapping in the postprocessing step to retrieve the true object phase. In this work, we demonstrate a single beam propagation based super resolution phase imaging technique by applying structured illumination to Transport of Intensity Equation. It is valid under partial coherence, and does not require interference, simplifying the experimental and computational requirement. We have designed an upright microscope to demonstrate high resolution phase imaging of human cheek cells.

The focal plane power distribution due to a bright source is analyzed for an infrared imaging optical system. Irradiance from the bright source is spread throughout the focal plane according to the characteristics of the system. This effect is attributed to diffraction, reflection and scattering in the optical train. Expected focal plane power distributions due to diffraction and multiple reflections between dielectric surfaces are calculated and compared to measured data. The difference is attributed to scatter characteristics of the optical elements. A brief overview of the major sources of scatter lays groundwork for a further analysis of scattering characteristics in the optical system. / Master of Science

Neural Networks (NNs) (or 'deep' neural networks (DNNs)) have found great success in many applications across all fields of engineering, and in particular have found recent success in the field of Photonics. In this work we discuss the application of NNs to optical interferometry for the purpose of quantitative phase imaging (QPI). We show that NNs are capable of quantifying the optical pathlength difference in an interferogram with sensitivities that achieve the fundamental limit given by the Cramér-Rao bound (CRB). As an application, we consider a particular QPI technique known as wavelength shifting interferometry (WSI) which obtains the OPL by acquiring multiple interferograms at different, evenly spaced wavenumbers. Traditional phase demodulation algorithms for WSI fail to reach the theoretical OPL sensitivity limit set by the CRB. We have designed NNs which are capable of achieving this bound across a wide range of OPL differences. The NNs are trained on simulated data, and then applied to experimental data. In both simulation and experiment, the NNs outperform the existing analytical demodulation techniques and provide highly sensitive signal demodulation in cases where the analytical approach fails. Thus, NNs provide better performance and more flexibility in the design and use of a WSI system. We expect that the techniques developed in this work can be extended to other two-beam interference based QPI system. / M.S. / Neural Networks (NNs) (or 'deep' neural networks (DNNs)) have found great success in many applications across all fields of engineering, and in particular have found recent success in the field of Photonics. In this work we discuss the application of NNs to making so-called 'phase' images of biological cells and tissues (e.g. red blood cells, sperm cells). This is necessary for many biological samples which are transparent under traditional bright field microscopy. We show that NNs are capable of quantifying the phase of these samples to produce images with higher contrast than possible in a typical microscope image. As an example, we introduce a particular phase microscopy system and study the application of NNs to this system. We show that the NNs are capable of providing solutions for this phase in situations where existing analytical techniques fail. The NNs are also capable of making more precise calculations of the phase than the traditional algorithms in many situations where either technique could be used. Therefore, NNs can provide simultaneously higher performance and more flexibility when designing phase microscopy systems.

Many biological specimens are transparent and in weak intensity contrast, making it invisible using conventional bright field microscopes. Therefore, the phase-based optical microscopy techniques play important roles in the development of the modern biomedical science. Furthermore, the ability to achieve quantitative phase measurement of the tiny structures of biomedical specimens is of great importance for many biomedical applications. Thus, quantitative phase imaging becomes an important technique to measure the phase variations due to the difference of refractive index and geometric thickness of various structures and materials within the biomedical specimens. In this thesis, a spectral modulation interferometry (SMI) is developed to achieve quantitative phase imaging. In SMI, the phase and amplitude information will simultaneously be modulated onto the interference spectrum of the broadband light. Full-field phase images can be obtained by scanning along the orthogonal direction only. SMI incorporates the advantages of low coherence from broadband light source, high sensitivity from spectral domain interferometry and the high speed from the spectral modulation technique to achieve quantitative phase measurement with free of speckle, high temporal sensitivity (~0.1nm) and fast imaging rate. The principles of SMI system and programming as well as some important image processing methods will be discussed in detail. Besides, the quantitative phase measurement of the reflective object (USAF resolution target) and the transmitted biological objects (Peranema, human cheek cells) will be shown. / Master of Science

No / The purpose of this research was to correlate in vivo spatial and spectral morphologic changes of short- to long-pulse 532 nm Nd:YAG retinal laser lesions using Fourier-domain optical coherence tomography (FD OCT), autofluorescence (AF), fluorescein angiography (FA), and multispectral imaging. Ten eyes with treatment-naive preproliferative or proliferative diabetic retinopathy were studied. A titration grid of laser burns at 20, 100, and 200 milliseconds was applied to the nasal retina and laser fluence titrated to produce four grades of laser lesion visibility: subvisible (SV), barely visible (BV, light-gray), threshold (TH, gray-white), and suprathreshold (ST, white). The AF, FA, FD-OCT, and multispectral imaging were performed 1 week before laser, and 1 hour, 4 weeks, and 3 and 6 months post-laser. Multispectral imaging measured relative tissue oxygen concentration. Laser burn visibility and lesion size increased in a linear relationship according to fixed fluence levels. At fixed pulse durations, there was a semilogarithmic increase in lesion size over 6 months. At 20 milliseconds, all grades of laser lesion were reduced significantly in size after 6 months: SV, 51%; BV, 54%; TH, 49%; and ST, 50% (P < 0.001), with retinal pigment epithelial proliferation and photoreceptor infilling. At 20 milliseconds, there was healing of photoreceptor inner segment/outer segment junction layers compared with 100- and 200-millisecond lesions. Significant increases in mean tissue oxygenation (range, four to six units) within the laser titration area and in oxygen concentration across the laser lesions (P < 0.01) were detected at 6 months. For patients undergoing therapeutic laser, there may be improved tissue oxygenation, higher predictability of burn morphology, and more spatial localization of healing responses of burns at 20 milliseconds compared with longer pulse durations over time / Optimedica Corp., the Manchester Academic Health Sciences Centre, and the NIHR Manchester Biomedical Research Centre. JD was funded by a College of Optometrists PhD Studentship, United Kingdom.

Yes / The arrival of artificially intelligent systems into the domain of medical imaging has focused attention and sparked much debate on the role and responsibilities of the radiologist. However, discussion about the impact of such technology on the radiographer role is lacking. This paper discusses the potential impact of artificial intelligence (AI) on the radiography profession by assessing current workflow and cross-mapping potential areas of AI automation such as procedure planning, image acquisition and processing. We also highlight the opportunities that AI brings including enhancing patient-facing care, increased cross-modality education and working, increased technological expertise and expansion of radiographer responsibility into AI-supported image reporting and auditing roles.

2025 / Vibrational spectroscopic imaging, leveraging the intrinsic vibrational contrast of chemical bonds, has proven to be a powerful analytical tool for characterizing biological samples. Among these, Raman scattering uniquely encodes chemical bondinformation through wavelength and molecular concentration through intensity. Stimulated Raman scattering (SRS), by amplifying spontaneous Raman processes by several orders of magnitude, enables hyperspectral visualization of subcellular features in biosamples. Despite its potential, SRS has been underutilized in complex biological systems due to two key limitations: the lack of multimodal information integration and the sensitivity constraints that limit detection to millimolar concentrations. My thesis work addresses these challenges with two major innovations. To enable multimodal understanding of complex biological systems, we developed the Stimulated Raman Scattering–Fluorescence In Situ Hybridization (SRS-FISH) platform. This technique bridges microbial identity with metabolic activityat single-cell resolution, enhancing throughput by 1-2 orders of magnitude compared to state-of-the-art approaches. The platform analyzed 30,000 cells from the human gut microbiome, combining multimodal imaging processing with statistical analysis to provide unprecedented insights into microbial dynamics in response to nutritional and pharmacological stimuli. To overcome the sensitivity limits of conventional SRS, we developed Stimulated Raman Photothermal (SRP) microscopy. This novel technique exploits photothermal effects of SRS to achieve over 500-fold improved contrast, enabling precise andquantitative metabolic imaging. We explored and optimized the influencing factors of the newly invented microscopy scheme in both hardware setup by tuning laser property and optical alignment and software part including single pulse digitization, baseline correction, and matched filtering. Additionally, the implementation of a fiber laser-based SRP system advances the translational applications of Raman microscopy, offering superior sensitivity and user-friendly design. These advancements represent a significant leap forward in the capability of stimulated Raman microscopy, establishing it as a versatile and powerful tool for investigating complex biological systems. By addressing key limitations, the innovationspresented here provide critical methodologies for exploring vibrational chemical imaging and contribute to the broader field of optical microscopy. / 2027-01-31T00:00:00Z

The objective of this research is to develop large signal modeling and optimization methods for Capacitive Micromachined Ultrasonic Transducers (CMUTs), especially when they are used in an array configuration. General modeling and optimization methods that cover a large domain of CMUT designs are crucial, as many membrane and array geometry combinations are possible using existing microfabrication technologies. Currently, large signal modeling methods for CMUTs are not well established and nonlinear imaging techniques utilizing linear piezoelectric transducers are not applicable to CMUTs because of their strong nonlinearity. In this work, the nonlinear CMUT behavior is studied, and a feedback linearization method is proposed to reduce the CMUT nonlinearity. This method is shown to improve the CMUT performance for continuous wave applications, such as high-intensity focused ultrasound or harmonic imaging, where transducer linearity is crucial. In the second part of this dissertation, a large signal model is developed that is capable of transient modeling of CMUT arrays with arbitrary electrical terminations. The developed model is suitable for iterative design optimization of CMUTs and CMUT based imaging systems with arbitrary membrane and array geometries for a variety of applications. Finally, a novel multi-pulse method for nonlinear tissue and contrast agent imaging with CMUTs is presented. It is shown that the nonlinear content can be successfully extracted from echo signals in a CMUT based imaging system using a multiple pulse scheme. The proposed method is independent of the CMUT geometry and valid for large signal operation. Experimental results verifying the developed large signal CMUT array model, proposed gap feedback and multi-pulse techniques are also presented.

ITC/USA 2009 Conference Proceedings / The Forty-Fifth Annual International Telemetering Conference and Technical Exhibition / October 26-29, 2009 / Riviera Hotel & Convention Center, Las Vegas, Nevada / The field of Terahertz (THz) radiation, electromagnetic energy, between 0.3 to 3 THz, has seen intense interest recently, because it combines some of the best properties of IR along with those of RF. For example, THz radiation can penetrate fabrics with less attenuation than IR, while its short wavelength maintains comparable imaging capabilities. We discuss major challenges in the field: designing systems and applications which fully exploit the unique properties of THz radiation. To illustrate, we present our reflective, radar-inspired THz imaging system and results, centered on biomedical burn imaging and skin hydration, and discuss challenges and ongoing research.