This PDF file contains the front matter associated with SPIE Proceedings Volume 13076, including the Title Page, Copyright information, Table of Contents and Conference Committee information.

Upconverting nanoparticles (UCNPs) exhibit a unique nonlinear optical response, where the emission intensity in the UV/blue range increases non-linearly with the excitation intensity of a continuous-wave (CW) laser in the NIR range. This property can provide inherent three-dimensional (3D) capabilities for various applications. As a demonstration, we illustrate that 3D fluorescence imaging is achievable without the need for a pinhole or ultrafast pulsed lasers, allowing us to image mouse cerebrovascular networks up to the depth of around 700 μm through opaque brain tissues. Additionally, we demonstrate that co-dispersing UCNPs with photosensitizers enables depth-targeted photodynamic therapy with reduced damage to superficial cells. The nonlinear optical properties of UCNPs hold promise for providing 3D capabilities across a wide range of applications.

Nondestructive three-dimensional (3D) pathology based on high-throughput 3D microscopy holds promise as a complement to traditional hematoxylin and eosin (H&E) stained slide-based two-dimensional (2D) pathology by providing rapid 3D pathological information. However, conventional techniques provided superficial information only due to shallow imaging depth. Herein, we developed open-top two-photon light sheet microscopy (OT-TPLSM) for intraoperative 3D pathology. A two-photon excitation light sheet, generated by 1D scanning of a Bessel beam illuminated the sample and planar imaging was conducted at 400 frames/s max. An imaging depth of 60-100 μm was achieved with long excitation wavelengths, and the image throughput was up to 1 cm² per 7 min. Cells and extra-cellular matrix were visualized using extrinsic fluorescence and intrinsic second harmonic generation, respectively. OTTPLSM was tested in various human cancer specimens and cancer structures were detected via 3D visualization. OT-TPLSM may have the potential for rapid and precise 3D histopathological examination.

Micro-ischemic strokes, or microinfarcts, are small blood clots that obstruct cerebral blood flow to the brain. They are commonly observed in patients with dementia and have been linked to cognitive decline. However, the precise mechanisms underlying this association remain largely unknown. To advance our understanding of micro-strokes, it is imperative to observe real-time blood flow changes during the formation of microinfarcts. In this study, we successfully achieved in vivo real-time imaging of red blood cell (RBC) and dextran flow in a microinfarction model using a video-rate intravital confocal microscope. A cortical microinfarct was induced by photo-thrombosis in the cortex of a mouse following the intravenous injection of Rose Bengal, accompanied by a 5-second exposure to 7mW, 561nm light through a cranial window. Real-time imaging of blood flow allowed us to capture dynamic changes in RBC flow, along with changes in vessel diameter and cortical tissue volume after inducing the microinfarction. Initially, the obstruction resulted in reduced blood flow in the surrounding vessels and micro-vessels with minimal change in cortical volume. However, subsequent observations revealed an increase in cerebral volume, vessel thickness, and blood flow. These changes slightly decreased again afterward. Despite these fluctuations, no angiogenesis was observed. Further in-depth analysis of these complex microvascular changes from the acute stages of microinfarction to subsequent recovery could provide valuable insights into the pathophysiology of micro-ischemic strokes and offer clues for the development of novel therapeutic strategies.

The space-bandwidth product (SBP) is the product between the field of view (FOV) and the spatial frequency range, that is, the maximum number of resolvable point spread function (PSF) in the FOV. Establishing a high SBP system by achieving both high resolution and a wide field of view is hindered by optical diffraction, geometric aberrations, size limitations, and thermal effects, since these factors collectively limit the attainable resolution and field of view. In this study, the SBP is maximized by using the off-the-shelf high throughput lens which provides large FOV (8.1 mm) and submicron resolution (700 nm) for an effective SBP of 0.3 gigapixels. The deterioration in resolution caused by aberrations from the large aperture of the objective lens is compensated by applying adaptive optics with correcting the distorted wavefront. Galvanometer scanners transfer information to a single fixed camera to achieve a large FOV. Our method does not have any moving parts or any requirements on postprocessing enabling fast high resolution imaging across large FOVs.

Rapid and accurate disease diagnosis is important to determine appropriate treatment methods in clinics. Optical properties of tissue, such as absorption and scattering coefficients, could be a useful marker as disease progression occurs structural and biochemical alterations of biological tissue, resulting in chances of its optical properties. In addition, optical imaging methods are usually cost-effective and safe compared to other medical imaging techniques; thus, optical imaging could be used as a versatile tool for disease diagnosis. In this study, we have developed a multimodal imaging system that combines hyperspectral imaging and spatial-frequency domain imaging techniques. The proposed optical system enables quantitative measurement of scattering and absorption coefficients in biological tissue. We demonstrated the capability of the proposed optical system in measuring optical properties by exploiting a tissue-mimicking phantom and color chart, indicating that it has potential as a useful tool for characterizing the optical properties of tissue.

Multiphoton microscopy, especially two-photon microscopy has become a gold-standard technique for in vivo biological tissue imaging, specifically for neural activity recording. However, due to the heterogeneity of the biological tissue, the excitation beam will undergo wavefront distortion and temporal broadening while passing through the scattering layer such as the skull and cortex. To overcome this challenge, wavefront shaping has been explored. Iterative modulation of the wavefront modulator using indirect wavefront measurement or transmission matrix approaches in a close-looped feedback system is widely used to compensate the effect of scattering for the ultrashort pulse laser source. However, these techniques, entailing multiple manipulations and calibrations for optimization, are time-intensive and restrictive in achieving high temporal resolution for simultaneous neural recording. In this research, by applying a ‘time-gating’ technique to digital optical phase conjugation (DOPC), or time-reversal, we can make an optimal wavefront to make a focus, both spatially and temporally. Consequently, it proposes the potential of this approach for non-invasive deep tissue neural recording in vivo. Since this process is open-looped system, this method is much faster than conventional feedback-based optimization and suitable for application in simultaneous neural recording.

Non-Line of Sight (NLoS) imaging represents a crucial technology with significant potential across numerous applications including autonomous vehicles, robotics, biomedicine, and state-of-the-art weaponry. NLoS technology primarily aims to rapidly and accurately reconstruct hidden objects following light perception. Existing methodologies predominantly employ active laser illumination. However, there is a burgeoning necessity for comprehensive research within passive NLoS systems, where objects self-emit light. In our study, we introduce a novel technique using a straightforward imaging setup composed of a standard digital camera and an occluder. By leveraging the power of deep learning, we demonstrate the capability to reconstruct hidden objects swiftly, significantly surpassing the time efficiency of existing techniques. Moreover, our method exhibits a high degree of reliability. Our research opens the door to further investigations into a universal and highly reliable passive NLoS reconstruction algorithm. This algorithm's defining feature is its resilience to changes in both the occluder and object positions within the imaging setup. Such imaging techniques, which eliminate the requirement for an auxiliary light source, offer promising prospects for the proactive detection of concealed adversaries or objects, thereby providing a valuable tool across various domains.

We report on the design and construction of a goggle-type eye tracker using a low-cost and high-speed lensless camera for monitoring eye movements in neurodegenerative diseases. A Rolling Shutter image sensor combined with lensless computational imaging allows for the reconstruction of a time sequence of images from a single snapshot, effectively improving the framerate of the camera. We constructed and demonstrated the prototype device using a commercial-grade CMOS image sensor and achieved the improvement of framerate from 15 to 480Hz, with the tracking results for 28 clinical measured data. Our device can potentially measure microsaccadic eye movements in a wearable camera format, allowing routine monitoring of abnormal eye movements for the early diagnosis and tracking of Alzheimer’s and Parkinson’s disease.

Integrated optical biosensors are capable of combining properties of miniaturization, stability and high sensitivity. In this paper a novel integrated optic biosensor for the measurement of glucose concentration in the blood design is proposed and analysed mathematically. The configuration is based on silicon on insulator technology and consists of four layers, the oxide substrate layer, thin silicon nitride layer to enhance the sensitivity, the silicon ridge waveguide optical guiding layer, and the cover layer consisting of bio-analyte to be measured. The main idea in this configuration is the introduction of thin nitride layer in between silicon and silicon dioxide. Then it was observed that in the case of three layer waveguide the mode penetration into the cladding influences the sensitivity. Introduction of silicon nitride layer between the oxide and guiding layer reduces the refractive index contrast between the substrate and the guiding layer resulting in increased penetration depth. We obtain a sensitivity of 1%, in terms of effective refractive index change.