This PDF file contains the front matter associated with SPIE Proceedings Volume 11633 including the Title Page, Copyright information, and Table of Contents.

In view of the spreading of the Covid-19 virus, Real-Time Background Oriented Schlieren (RT-BOS) and backlight scatter imaging were used to visualize the air motion and droplets during talking, coughing, sneezing, singing, playing wind instruments. The effectiveness of personal protection like face masks and shields were studied. The distance of air (aerosols) spreading depends on the diameter/shape of the opening and air volume blown out per unit of time. Remarkably, the aerosol and droplet spreading of singing is similar or less than talking and even less for wind instruments. Any mouth mask although leaking air is effective in preventing droplets to spread.

Ventilator-associated pneumonia (VAP) is pneumonia that occurs >48hrs after initiation of mechanical ventilation and is a significant cause of morbidity and mortality in patients that are hospitalized in intensive care units (ICU). The risk of developing VAP increases during use, and a diagnosis of VAP has been associated with a substantial cost. There are up to hundreds of thousands of cases in the US per year, costing the healthcare system billions annually. Patients who suffer from VAP frequently require longer ICU stays, higher exposure to antibiotics, and more hospital care at the risk of increased mortality. The SARS-CoV-2 pandemic has further increased the use of antibiotics among patients with COVID19, an indicator of increased VAP prevalence. Before 2020, strides were made to reduce the incidence of VAP through hygienic protocols known as ‘VAP bundles.’ Despite the improvements, VAP continues to be a large problem, with the inoculation of pathogens within the endotracheal tube (ETT) itself. ETTs with built-in subglottic suction devices (SSDETT) allow the removal of subglottic secretions, but this has been adopted heterogeneously. We propose novel optical device designs to be used in combination with SSD-ETTs to reduce colonization and biofilm formation on the inner lumen of ETTs and reduce the incidence of VAP and improve patient care.

Enabling technologies capable of rapid detection of severe acute respiratory syndrome coronavirus (SARS-CoV) and corona virus disease 2019 (COVID-19) and is the key for the rapid and effective control of the outbreaks. Reverse-transcription polymerase chain reaction (RT-PCR) is widely used technique for the detection of SARS-CoV-2, but it requires a time-consuming and labor-intensive platform, limiting its availability in some regions. Applications of optical detection technologies involving sensors and sensitive imaging modalities to the fast and low-cost detection of various types of viruses have been demonstrated. This paper will present a review of recent research reports involving such optical technologies for the detection of SARS-CoV-2 and COVID-19.

We developed refined methods for time-domain measurements of the optical properties of solid homogeneous turbid phantoms. Employing a reliable time-domain reference setup with a stable, narrow, and clean instrument response function and GPU-based Monte-Carlo fitting, 1% accuracy for optical properties seems realistic. An alternative space-enhanced time-domain method that combines spatially resolved amplitude with a time-domain measurement effectively reduced the crosstalk between absorption and scattering. Besides physical phantoms, we explored and characterized a digital phantom that mimics arbitrary time-of-flight distributions via time-dependent attenuation employing a spatial light modulator and a dedicated multi-fiber delay unit. We discuss potential applications in performance tests.

A standardized approach to develop a reliable, reproducible, stable phantoms was proposed. A well-established instrument validation protocol (MEDPHOT) was adopted for this purpose. This approach was tested on two phantom recipes (silicone and polyurethane) over broadband (600-1100 nm) wavelength covering a wider range of optical properties (absorption 0.1-1 cm^-1, reduced scattering 5-20 cm^-1) relevant to human tissue. As an application of the recipe, a reliable tissue-mimicking 3D anthropomorphic head phantom was presented.

Photoacoustic imaging (PAI) and photoacoustic microscopy (PAM) continue to undergo advancement, but standardized performance test methods are needed to facilitate development and translation. Most tissue-mimicking materials (TMMs) have not been adequately characterized at high acoustic frequencies relevant to PAM systems (>20 MHz). We characterized acoustic properties of various polyacrylamide TMM formulations over 10-60 MHz using a pulse-echo method, while optical properties were characterized over 400-1000 nm. We evaluated performance of a custom PAM system using phantoms containing gold nanoparticles. Polyacrylamide had highly tunable acoustic properties similar to human skin, and performance tests provided key insights into PAM system performance.

Cerebral saccular aneurysms represent a life-threatening condition that typically requires surgical intervention, often accomplished with a clip ligation approach across the aneurysm neck. Fluorescent angiography (FA) with indocyanine green (ICG) - a technique commonly used in neurosurgery – can be utilized to ensure that the neck of the aneurysm is fully ligated, while the adjacent vessels remain patent after clip placement. However, there is currently a lack of standardized performance test methods for surgical microscopes with FA capability. We have developed a 3D-printed, biomimetic aneurysm phantom with the potential to facilitate development and evaluation of these critical surgical instruments. Digital models of the Circle of Willis vasculature, including the multimodal imaging-based detailed anatomical (MIDA) model of the head and neck and a public domain model of a basilar tip aneurysm, were combined to generate a modular aneurysm phantom system. This system includes a basilar artery aneurysm and posterior communicator artery aneurysm phantoms. Non-fluorescent phantom components representing surrounding tissue were derived from the MIDA model. A stereolithography printer was used to create a solid vascular phantom from a custom turbid photopolymer doped with ICGsimulating dye. Feature sizes of printed components were found to be within 2.5% of digital models. Using a custom fluorescence imaging system, we were able to clearly visualize vessels and aneurysms amongst non-fluorescent background structures in the model. The methods for fabrication of a biomimetic neurovascular phantom incorporating realistic pathology have the potential to facilitate development, standardized bench testing and clinical training for intraoperative FA systems.

Fluorescence imaging for surgical guidance is a proven modality that allows for visualization of fluorescent markers in numerous biological imaging applications. As the field continues to develop there is an urgent need for fluorescence-imaging standards and targets that enable system characterization, performance monitoring, and the development of analytical algorithms. 3D-printing technology has shown promise in providing biomimicking phantoms that allow simulation of realistic clinical conditions. Here, we present a comprehensive method for 3D printing fluorescent and tissue-equivalent material using photo-curable resins. We show the ability to print Indocyanine-green (ICG) equivalent material in complex shapes that would enable the evaluation of ICG-specific clinical systems. The method presented allows tuning of both the reduced scattering and absorption coefficients at multiple wavelengths, allowing for application-specific manufacturing of 3D-printed phantoms.

The retinal imaging system, such as optical coherence tomography (OCT), OCT-angiography (OCTA) and fluorescein angiography (FA), is the important subject for ophthalmic. The use of such equipment continues to increase and retinal phantoms have also been developed to evaluate and modify its performance and image quality. In this presentation, we will show methods and results of a retinal phantom that can evaluate the optical performance of OCT, OCTA and FA. We implemented superficial vascular networks and full retinal layers which has curvature. We could obtain cross-sectional OCT images and en-face OCTA images using lab-made OCT system. In addition, FA image could also be obtained through sodium fluorescein dye injection.

Traditionally, light for phototherapy and photodynamic therapy has been administered in a clinical environment using lasers or bulky lamp systems; however light-emitting diodes (LEDs) for phototherapy and photodynamic therapy are gaining in popularity due to their high efficiencies, low-cost designs, and design versatility. In addition, LEDs can be assembled into flexible bandages to be worn on the patient’s skin to replace traditional lamp systems and increase patient comfort. However, because this brings the LEDs closer to the skin, light intensity hot spots form which is not desirable for phototherapy where uniform irradiance is required to inactivate target cells most effectively. We present an optical simulation of a blue LED array to evaluate the effects of immersion media of varying thickness on the uniformity of light distribution for near-field illumination in phototherapeutic applications. We have compared different immersion materials (air, water, and optical-grade silicone) placed in between the LED array and the skin with the goal of uniform irradiance distribution and optimized lighting efficiency. The irradiance incident on the tissue over an area of 60 cm² was simulated and compared for the three materials. Both silicone and water showed an increase in uniformity over an area of 14.4 cm² as the thickness increased without a significant decrease in irradiance at the tissue. These results show promise for future flexible photonic devices where a high degree of uniformity is required in situations where the device needs to be placed on or near the skin.

When monitoring patients with a skin contact sensor it is important to ensure that this is properly attached to the skin. This is important both for patient safety and data quality. We have developed a skin-contact sensitive technology that exploits the capacitive coupling of the sensor to detect the quality of the attachment to the subject’s skin and ensure galvanic isolation between patient and sensor. The developed technology can be easily embedded in any optical probe design without adding weight of bulkiness to the probe and provides the capability to detect optical probe displacements and alert user/operators/ hospital staff.

In this work, the investigation of thrombin concentration using microresonator functionalized with thiol-modified thrombin-binding aptamer (TBA) is reported. Resonator is a ball shaped structure on a tip of an optical fiber. Thrombin is a serine protease that plays an important role during blood coagulation; therefore, it is substantial to detect its levels in blood of the patient. The structure has been manufactured using standard single-mode fibers on CO₂ laser splicing system. Further, the resonator of diameter 518 µm has been calibrated with sucrose for refractive index changes with optical backscatter reflectometer. Changes in sensitivity and reflectivity in wavelength shift and amplitude fluctuation were measured. This was followed by coating the resonator with gold and functionalizing surface with TBA. Following aptamer immobilization, the performance of 518 µm resonator was examined in different concentrations of thrombin protein from 4.01 nM to 66.84 nM. We report here a sample presenting a sensitivity of (122.65 nm/RIU, RIU = refractive index units), which allows thrombin detection with an average wavelength shift of 1.034 nm.

Detection of scattering and absorption properties in both visible and near-infrared regions are crucial to quantify multiple functional responses in tissue. We developed a compact, clinical spatial frequency domain imaging (SFDI) system around a custom, nine wavelength, compound-eye camera, spanning ~450-1000nm. In addition to the characterization and validation of this device, we performed a preliminary in-vivo investigation to evaluate the imager’s ability to characterize dermal response under a noxious heating protocol. Increases in hemoglobin and water concentration are detected as well as slight alterations in the reduced scattering spectrum that maybe correlated with cellular and extra-cellular reactivity.

Clinical detection of premalignant lesions often requires labeling with molecular probes. In the gastrointestinal tract, most cancers originate in epithelial layers which are interrogated using topically-applied probes with conjugated fluorescence dyes. As part of clinical trials using fluorescence peptide probes, we have developed two different instruments that rapidly image the biopsy at the bedside before fixation. These multimodal images (visible light reflectance and near infrared fluorescence) provide verification that the targeted lesion was sampled, and provide feedback to the clinician at the bedside for any follow-up procedure. Performance of these two prototypes are compared for fluorescence sensitivity and multimodal image quality.

A study evaluating the use of multimodal widefield fluorescence imaging with nonlinear optical microscopy for detection of oral neoplasia was carried out using human clinical samples alongside a preclinical model with the goal of optimizing the most relevant endpoint measures to facilitate development and translation. Samples (in vivo buccal mucosa and surgical samples of oral cancer) were imaged by WF imaging using filter selection of red and green spectral windows, multispectral WF imaging to obtain WF spectral characteristics, and multiphoton autofluorescence microscopy. Features between preclinical and human samples were compared. Similarities and relevant endpoints for pursuing further development of a multimodal workflow will be discussed.

Fluorescence optical projection tomography with angular restriction is a promising technique for mesoscopic imaging of low scattering biological samples. As such, an angular domain system is being developed to address the problem of undetected micrometastases in lymph node biopsy tissues. Previous studies demonstrated its utility for lymph node applications and rigorously characterized imaging performance of the system. Through this evaluation, image artifacts were revealed in the reconstructions that limit achievable contrast and resolution. The objective of this work was to investigate the cause of those artifacts and potential remedies. Results demonstrated that an incorrect axis of rotation and detector response were the significant contributors of image artifacts, but post-acquisition calibration could account for the errors.

The visualization of the whole eye fundus with enough resolution to discriminate single photoreceptors would be of an enormous interest for understanding retinal diseases and distrophies. In this work, we present a versatile and flexible SLO device that is able to provide high quality images in real time either in large field of view (40ºx30º) or small field of view but with high-resolution (4ºx3º). The combination of an efficient electronics design and the optical system with adaptive optics provides a large set of customization parameters.