This PDF file contains the front matter associated with SPIE Proceedings Volume 12843, including the Title Page, Copyright information, Table of Contents, and Conference Committee information.

Photobiomodulation (PBM) is a type of phototherapy that uses red or near-infrared (NIR) light to stimulate healing or regeneration of tissues with injury or degradation. In recent years, PBM has been successfully used in the treatment of nervous system diseases. However, the application of optical technology in non-invasive transcranial therapy is greatly limited by the high scattering and absorbance of head tissues including scalp and skull, as well as the transcranial spread properties of light with different parameters still remain unclear. Therefore, for realization of phototherapy for brain diseases, in-depth understanding of the transcranial penetrability of light through head tissues is urgently needed. In this study, the wavelength dependence of light transmittance through scalp and skull of mice was investigated using a transcranial laser at wavelengths of 660 nm or 808 nm, which provides reference for future research and application of transcranial PBM.

Osteosarcoma (OS) is the most common primary bone tumor in dogs and humans and is considered an immunologically “cold” tumor. OS exerts devastating impacts on patients and has not seen significant improvements in survival outcomes in decades, with resistant metastatic disease remaining a main cause of death. Innovative therapies are profoundly needed to improve treatment and outcomes in OS. Canine OS shares striking similarities with human OS but occurs at a greater prevalence, allowing the dog to serve as a valuable comparative oncology research model. Histotripsy, a novel non-thermal focused ultrasound technique, has potential to ablate the primary tumor and activate an immune response to mitigate metastatic disease, thus promising to turn OS into an immunologically “hot” tumor. The objective of this study was to evaluate the immunomodulatory effects of histotripsy after in vitro and in vivo OS ablation. We utilized in vitro cell culture models for mechanistic cell death and immune response evaluation. We delivered histotripsy in vivo to canine OS patients and assessed peripheral immune cells and the tumor microenvironment. Across species, after in vitro exposure of immune cells to histotripsy-ablated OS cells, we observed cellular phenotypic changes indicative of activation and upregulation of genes associated with immune cell chemotaxis, immune and inflammatory responses such as NK cell-mediated cytotoxicity. In vivo, histotripsy ablation led to significantly greater expression of activation markers CD80 and CD62L on circulating monocytes at 1 and 5 days post histotripsy (DPH) respectively. We observed significantly higher production of TGFβ in circulating monocytes at 3 DPH compared to baseline. On an independent patient basis, we observed a greater population of infiltrating CD5⁺CD4⁺ and CD5⁺CD8⁺ T-lymphocytes within the ablated compared to unablated regions of tumor, and noted intratumoral genetic signatures that indicate immune activation at 24 hours post histotripsy. Collectively our results suggest that histotripsy ablation of OS leads to immune activation.

Vasospasm is a common complication in aneurysmal subarachnoid hemorrhage (aSAH). Currently, patients with aSAH are usually monitored at intensive care unit (ICU) for approximately 14 days for early detection and treatment of vasospasm. To facilitate the diagnosis and decision-making process, this investigation aims to combine radiomics and deep learning technologies to predict vasospasm that requires intra-arterial treatment for patients with aSAH. For this purpose, a retrospective dataset was collected, containing a total of 52 aSAH patients. Next, a total of 1032 radiomic features and 768 vision transformer (ViT) based features were computed for each case to comprehensively quantify the aSAH characteristics. Based on the initial feature pool, analysis of variance (ANOVA) F1 score was applied to select 30 best performed features as the optimal feature cluster. Finally, a support vector machine (SVM) based classifier was trained to predict the vasospasm, and the model performance was evaluated using a 4-fold cross-validation strategy. Receiver operating characteristics (ROC) curve and confusion matrix were adopted as the assessing indices. The result show that the model achieved an area under the ROC curve (AUC) of 0.86±0.03, positive predictive value of 78%, negative predictive value of 76%, and overall accuracy of 77%, respectively. This investigation initially verified the feasibility of using CT images to accurately predict cerebral vasospasm.

Red and near-infrared light therapies operate within a range of 600-1,100 nm. These wavelengths have been widely recognized with clinical versatility for stimulating, restoring, and regenerating damaged tissues. This therapy has found applications across various fields, including medicine, dentistry, dermatology, neurology, and ophthalmology. Accurately tailoring the calculation of light irradiation to specific tissue targets is fundamental for achieving optimal clinical efficacy. The precision of light delivery is often challenged by the varying optical properties of tissues, such as absorption, scattering, reflection, and refraction. To overcome this challenge, standardized treatment doses are necessary to ensure optimal light delivery and efficacy of the therapy.

The validation of the porcine model as a reliable and effective platform for in vitro and vivo dose-escalation trials is central to the success of this study. This model has been extensively studied and proven to be a valuable tool in biomedical research due to its anatomical and physiological similarities to humans. This model has the potential to refine irradiation parameters and investigate immunologic responses for consistent results. These parameters are crucial for attaining the desired therapeutic outcomes and vary depending on clinical conditions, treatment objectives, and the characteristics of the target tissue.

The porcine model has proven to be a highly versatile subject in a wide range of biological research fields. Its usefulness extends to studies on nerve regeneration, immunology, bone biology, and titanium osseointegration, among others. Researchers have found that the similarities between porcine and human physiology make this model an excellent tool for advancing our understanding of complex biological processes. The porcine model can facilitate various light dose escalation trial formats while enabling comprehensive assessments that integrate in vivo dosimetry. This model can also be expanded to characterize tissue optical properties, CT analysis, tissue histology, immune cell profiling, inflammatory response evaluation, histomorphometry, and biomechanical testing. This approach creates a translational framework to integrate in vivo dose-escalation trials and reinforces the importance of precision light dosimetry analysis.

Fourier ptychography microscopy (FPM) is a computational imaging technique that enables high resolution and large FOV simultaneously. For FPM, multiplexed LED illumination can significantly improve the efficiency of image data acquisition at the cost of deteriorated quality in the reconstructed images. In this study, we aim to evaluate the imaging quality of multiplexed FPM with different illumination configurations. For this purpose, a prototype FPM microscope was developed, which was equipped with a 4×/0.1 NA objective lens. This prototype was used to test 1 LED conventional, 2 LED multiplexed, and 4 LED multiplexed FPM illumination configurations on a standard USAF 1951 resolution target and a cytology sample. Modulation transfer function (MTF) curves were generated from the reconstructed images to quantitatively compare the performance of different LED combinations. The results demonstrated that the resolution target image reconstructed using 1 LED illumination raw images can resolve up to 912.3 lp/mm, but it decreased to 812.7 lp/mm and 724.1 lp/mm when 2 LED and 4 LED illumination were adopted, respectively. The corresponding MTF curves indicate decreased contrast on most spatial frequencies when comparing reconstructed results between multiplexed (2/4 LED) and conventional illumination configurations. Accordingly, the quality of reconstructed clinical cytology sample images decreases as the number of LEDs per image increases. However, all of them have satisfactory quality for most clinical applications. This preliminary study provides useful information to facilitate the development of multiplexed illumination FPM imaging systems in the future.

This study aims to investigate the effectiveness of a self-supervised deep learning based noise reduction algorithm at improving the detectability of phantom images acquired from the phase-sensitive breast tomosynthesis (PBT) system.
An ACR mammography phantom and three different Contrast Detail (CD) phantoms were used in experiments. Each phantom is 5cm in thickness and fabricated with materials simulating 50% glandular tissue and 50% adipose tissue. The phantoms were imaged by 59kV and 89kV with varying levels of external filtrations. The x-ray exposure was adjusted so that the average glandular dose was consistently to be 1.3 mGy throughout the imaging.
A noise reduction algorithm was applied to the images. The algorithm being evaluated is a state-of-the-art self-supervised single image denoising approach that can prioritize the preservation of fine-grained image structures while performing noise removal.
The contrast-to-noise (CNR) ratio was measured to conduct objective analysis. Additionally, an observer performance study was conducted in which observers were shown the images from each phantom in a randomized order before and after the denoising algorithm was applied. The observers rated the detectability of each image by identifying the minimum perceptible feature.
The results indicate some improvement from the objective studies; however, in the subjective observer studies, no improvement was observed in the detectability of the ACR images, and limited improvement was observed in the detectability of the CD phantom images.

There is a significant association between the pathogenesis of Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM), in which the blood-brain barrier (BBB), as an essential bridge connecting the periphery to the central nervous system, maybe a vital link in revealing the mechanism of the association between the two diseases. The function of the T2DM blood-brain barrier and its influence on the pathogenesis of AD remains unclear. We found reduced Glut-1 and Claudin-5 immunopositive reactive regions in the brains of spontaneous T2DM cynomolgus monkeys by multiple immunological experiments, suggesting dysfunctional transport and impaired integrity of the blood-brain barrier. Meanwhile, different degrees of AD-like pathology formation were found in the brains of spontaneous T2DM cynomolgus monkeys and were positively correlated with the degree of blood-brain barrier damage. The present study demonstrates that T2DM leads to impairmed of blood-brain barrier integrity, subsequently affecting AD pathogenesis.

Type 2 diabetes mellitus (T2DM) is associated with Alzheimer’s disease (AD). Islet amyloid polypeptide (IAPP) in pancreases and amyloid-β (Aβ) and neurogenic fibril tangles (NFT) in brains are pathologic markers of T2DM and AD, respectively. However, the relationship between the severity of T2DM pancreatic pathology and intrapancreatic AD-like pathology, including Aβ42 deposits and tau pathology, is unclear. In this study, we observed the pancreatic pathology of spontaneous T2DM cynomolgus monkeys by histological methods and immunohistochemistry. The results show that the pancreatic islet morphology was irregularly shaped, and islet cell density and IAPP-positive area were decreased in T2DM cynomolgus monkeys. Meanwhile, the severity of T2DM pancreatic pathology was evaluated based on islet β-cell volume. As a result, the decrease in β-cell volume was accompanied by increased areas of Aβ42, tau immunopositivly staining. Immunofluorescence staining of the T2DM pancreas pathology showed co-localization of IAPP with Aβ and tau, respectively. Our findings suggest that the decrease in islet β-cell volume can respond to the severity of T2DM pancreatic pathology, facilitate the formation and aggregation of Aβ42 and tau in pancreases, and play a role in AD development.