This PDF file contains the front matter associated with SPIE Proceedings Volume 12380, including the Title Page, Copyright information, Table of Contents, and Conference Committee information.

Morphine addiction causes major medical and social problems worldwide. Chronic morphine exposure results in the development of behavioral sensitization, accompanied by the disruption of brain homeostasis. As a key brain reward region, nucleus accumbens (NAc) plays a central role in brain reward mechanisms. Furthermore, neurons in NAc are impaired by chronic morphine abuse, but the contribution of morphine exposure to neurons is poorly understood. Here we indicated that morphine-induced an abnormal neuronal activation in NAc. Critically, we found a remarkable increase of mitochondrial fragmentation in neurons following burst activity. Taken together, these results define the effects of morphine on neurons in NAc, and provide a new insight for development of future morphine addiction therapeutics.

A novel biopolymer, N-dihydrogalactochitosan (GC), is developed for inducing immune responses. GC stimulates innate and adaptive antitumor and antiviral immunities. In this study, we investigated the mechanism of GC-induced immune responses through in vitro and in vivo studies. We find that GC drives type I IFN production and IFN responses in antigen presenting cells (APCs). Furthermore, GC drives alternative activation of STING leading to inflammatory cell death that enhances dendritic cell (DC) activation. In vivo, GC induced a potent response of type I IFN and upregulated genes associated with STING signaling within the tumor microenvironment (TME). Because of its potent immunological stimulation ability and its unique mechanism in inducing the immune responses, GC has been used in combination with laser photothermal (PTT) for the treatment of cancers. We find that PTT+GC induced specific modulation of immune cells, positively corresponding to long-term survival of cancer patient.

γδT cell has gained importance during tumor immunotherapy. However, the transcriptional alterations remain unknown. Here, we applied a novel localized ablative immunotherapy (LAIT) to treat tumors in MMTV-PyMT mice and used single-cell RNA-sequencing to investigate the transcriptional profiles regulated by PTT, GC and LAIT (PTT+GC) in γδT cells. Subtypes of γδT cells included activated, cytotoxic, cycling cytotoxic, interferon enriched, antigen-presenting cell (APC)-like, and IL17-expressing γδT cells. Treatments specifically induced cell proportion in Il17-γδT cells while not other subtypes. LAIT-induced Il17-γδT gene expressions were positively associated with breast cancer patients’ survival, highlighting the clinical applications of Il17-γδT for cancer therapies.

This conference presentation was prepared for SPIE BiOS, 2023.

There is solid evidence of diverse beneficial effects of the treatment with low-power near-infrared (NIR) light in the NIR I window (630-900 nm). We have demonstrated PBM with NIR-II window (1061-1301 nm) augments the immune response of the vaccine, but other beneficial effects of NIR-II laser have not been fully explored. In this study, we have shown that NIR-II laser enhances bioavailable NO in endothelial cells. Since a hallmark of endothelial dysfunction is suppressed eNOS with concomitant NO deficiency, NIR-II laser technology could be broadly used to restore endothelial NO and treat or prevent cardiovascular diseases.

Photoimmunotherapy employs antibody-photosensitizer constructs (photoimmunoconjugates) for targeted cancer ablation through the generation of reactive oxygen species. While this approach enhances cancer cell specificity, it sacrifices cellular uptake. This study addresses this limitation through two strategies with an emphasis on anti-cancer immunogenicity: 1) utilizing fluid shear stress to mediate delivery, and 2) leveraging nanoengineering approaches to maximize photoimmunoconjugate payload. Results reveal that fluid shear stress promotes photosensitizer delivery and anti-tumor immune response while modulating subcellular localization. By shedding light on improved delivery strategies and formulations, this study generates important implications for the clinical implementation of photoimmunotherapy.

A significant amount of recent studies reported use of photobiomodulation (PBM) to slow down the progression of Alzheimer’s disease. Less reports on improving the PBM therapeutic efficiency by optimizing light parameters. Our findings demonstrate that PBM effect in in vitro and in vivo AD models significantly depends on wavelength, dose and mode (continuous wave or pulsed) of irradiation. While the viability and anti-inflammatory activity of amyloid-β (Aβ) treated cultured neurons and microglia were improved after irradiation with 808 nm light, Aβ plagues accumulation and cerebral amyloid angiopathy in the AD mice brain were best attenuated after stimulation with 40 Hz pulsed 808 nm or spectrally broad visible light, which also improved spatial learning and memory abilities.Future research can involve simultaneous or sequential stimulation with visible and NIR pulsed light in optimize wavelengths, dose and frequencies to achieve efficient AD therapy.

We utilized optical coherence tomography (OCT) to monitor the longitudinal progression of the microenvironment and microvasculature of pancreatic tumors before and after the photothermal therapy-induced immunotherapy in vivo. The primary pancreatic tumors implanted on mouse legs and treated via the photothermal therapy-induced immunotherapy were observed every three days for 36 days. The intensity-based OCT structure, uniformity, texture, intrinsic optical attenuation contrast, and vascular structures were detected and analyzed. Our result demonstrated that the photothermal-induced immunotherapy could cause significant changes in the distribution of the tissue structure and vasculature within the microenvironment and microvasculature of the primary pancreatic tumors.

Common two-dimensional (2D) models are ineffective in mimicking solid tumors. Additionally, fibrotic stroma is one of the major characteristics of pancreatic tumors and it is often missing in in vitro models. Therefore, there is a need for a better in vitro model to accurately mimic the characteristics of tumor and to detect the progression of fibrosis within the tumor model. Here, we utilized polarization-sensitive optical coherence tomography (PS-OCT) to longitudinally detect the collagen progression within multicellular pancreatic tumor spheroids in vitro. Spheroids were scanned by PS-OCT every two days, and progression of fibrosis within the spheroids were detected.

Fourier Ptychography Microscopy (FPM) is considered as one emerging technology for the development of high efficiency and low-cost microscopic scanners. One of the major advantages of FPM is its large depth of field (DOF), which significantly reduces the mechanical accuracy requirement of the scanning stages. In this study, we experimentally measured the DOF for our FPM prototype under different illumination conditions. The measurements were based on the theory that the DOF is considered as the range along optical axis for which the contrast is above 80% of the maximum when adjusting the focus location. Accordingly, the contrast is estimated using the bar pattern on the standard resolution target USAF1951 where the modulation transfer function (MTF) curve value drops to 0.5. During the experiment, the FPM prototype is equipped with a 4×/0.13 NA objective lens, and the DOF measurement was conducted with conventional single LED illumination and symmetric illumination. The results demonstrate that the DOF of the single LED illumination FPM is 15.3 µm, which is close to the DOF of the objective lens (14.5 µm). The DOF increases to 22.7 µm when symmetric illumination is adopted, which agrees with the theoretical conclusion. This investigation provides meaningful information for the future optimization of the FPM-based microscopic digitizers.

Ovarian carcinoma is the most lethal malignancy in all kinds of gynecologic cancers, and radiomics based image marker is an effective tool for the early-stage prediction of the chemotherapies applied on ovarian cancer patients. This investigation aims to compare and evaluate the predicting performance of the 2D and 3D radiomics features. During the experiment, the tumors were first segmented from the CT slices, based on which a total of 1032 2D radiomics features and 1595 3D radiomics features were extracted. These features are related to tumor shape, density and texture properties. Next, a least absolute shrinkage and selection operator (LASSO) feature selection method was adopted to determine optimal features clusters for 2D and 3D feature pools respectively, which were used as the input of support vector machine (SVM) based prediction models. During the experiment, a total of 99 cases were selected from a previously established dataset at our medical center. The model performance was assessed by receiver operating characteristic (ROC) curve. The results indicated that the 2D and 3D feature based models achieved an area under the curve (AUC) of 0.85±0.03 and 0.89±0.02, while the overall accuracies were 0.76 and 0.81 respectively. These results indicate that the overall performance of the 3D feature is higher than the 2D features. But the sensitivity of the 2D model is higher at some certain specificity range. This study initially reveals the difference between the 2D and 3D features, which should be meaningful for the optimization of the radiomics based clinical decision support tools.

According to the American Academy of Dermatology Association, identifying the types of skin cancer depends on the origin of a cell mutation resulting in the rapid growth of these abnormal cells in the epidermis. These mutations lead the skin cells to multiply rapidly and form malignant tumors. Skin cancer is ranked as the 17th most common form of cancer worldwide according to the World Cancer Research Fund. Skin cancer treatments cost the United States more than $8 billion (about $25 per person in the US) each year, making skin cancer the fifth most costly cancer for Medicare. Furthermore, skin cancer is an under recognized problem for diverse populations, including young women and minorities. Researchers have been exploring different technologies to detect skin care at its early stage to avoid high mortality rate and expensive medical treatment.

This paper presents a novel ensembled deep learning model for the early detection of skin cancer. Our research is based on The HAM10000 dataset, a diverse collection of multi-sourced dermatoscopic images of common pigmented skin lesions which consists of 10015 dermatoscopic images. We have compared several deep learning neural network architectures and classifiers such as DNN, RNN, SVM and KNN in terms of accuracy rate and computation complexity and presented an ensembled deep learning model for early skin cancer detection. The main contribution of this paper is the productions of a comparative study of several skin cancer detection techniques using powerful computer vision techniques and deep learning models and a novel ensembled deep learning model for skin cancer detection.

This conference presentation was prepared for SPIE BiOS, 2023.

In this study, we engineered a vascularized 3D dermis by layering multiple highly aligned prevascularized sheets with human mesenchymal stem cells to mimic the capillary loops observed in native dermis tissue. Monocyte-derived macrophages were seeded onto these prevascularized constructs to mimic the innate immune-response in vitro. To evaluate macrophage responses to these scaffolds, we used multiphoton microscopy to detect the metabolic phenotypes of macrophages on engineered scaffolds over time. NADH and FAD are coenzymes that emit endogenous fluorescence and participate in various metabolic pathways, and their fluorescence lifetime is associated with different protein binding states and microenvironments. Fluorescence lifetime images of macrophages were obtained on day 3 and day 7 after seeding, and significant differences in NADH and FAD fluorescence lifetime features can be observed in macrophages on different scaffolds.

We report a single cell-based rapid natural killer (NK) cell activity measurement technique that utilizes a newly developed activation stimulator cocktail (ASC) along with the lens-free shadow imaging platform. The platform, i.e., Cellytics_NK, consists of compact and low-cost optoelectronic components such as LED and CMOS image sensor, and the shadow images of photographed NK cells in a disposable cell chip are analyzed within 30 seconds with an automated algorithm. The shadow parameters such as PPD and WSM have been employed to induce a combined shadow parameter (CSP) which precisely measures and distinguishes quiescent and activated NK cells (p < 0.0001).

This talk will present our recent results on photobiomodulation (PBM) in multiple cell types and models in vitro and in a mouse model in vivo. Different wavelengths (e.g., 650 nm, 808 nm, 1064 nm) and doses were employed and post-PBM changes in cells and animals were assessed in vitro, ex vivo and in vivo using fluorescence microscopy with fluorescent probes and label-free nonlinear optical imaging. The obtained imaging data, along with results of other assays, allowed for revealing PBM action and mechanisms. The talk will conclude with a discussion on application of red and NIR PBM to treat some diseases.

This conference presentation was prepared for the Biophotonics and Immune Responses XVIII conference at SPIE BiOS, 2023.

This study aims to investigate the impact of external filtration on image quality and exposure time of an in-line phase-contrast x-ray breast imaging prototype.
A Contrast-Detail phantom is imaged by 59 kV and 89 kV systems with a CCD camera and varying filter thicknesses, ranging from 1.0 mm to 3.3 mm of aluminum. The average glandular radiation dose is set to 1.3 mGy throughout the experiment, regardless of imaging parameters. The Contrast-Detail (CD) curves are generated from the reading results of three experienced observers. The Contrast-to-Noise-Ratio (CNR) is calculated for objective comparisons. The results show that the beam hardening with 1.3 and 2.5 mm aluminum filters in the 59 kV system provides the most desirable CNRs and CD curves, whereas a 3.3 mm aluminum might be a preferable external filtration in the 89 kV system. It can be concluded that the 59 KV beam, filtered by a 1.3 mm aluminum, is a better choice, as it results in comparable image quality and a 35% shorter exposure time. On the other hand, the 89 KV beam filtered by 3.3 mm aluminum results in higher image quality at the expense of slightly increased acquisition time. The prolonged acquisition effect on the image blurring should be evaluated in patient studies where the object is not immobile like imaging phantoms.