Teaching and learning in biophotonics: Crossing the bridge between educators and students.

As a rapidly growing field, biophotonics demonstrates an increasingly higher demand for interdisciplinary professionals and requires the implementation of a structured approach to educational and outreach activities focused on appropriate curriculum, and teaching and learning for audiences with diverse technical backgrounds and learning styles. Our study shows the main findings upon applying this approach to biophotonics workshops delivered 2 consecutive years while updating and improving learning outcomes, teaching strategies, workshop content based on student and teacher feedback. We provided resources for a variety of lecture-based, experimental, computer simulation activities. Quality of subject matter, teaching, and overall learning was rated as "Very good" or "Good" by 88%, 76%, and 82% of students in average, respectively. Application of our teaching strategies and materials during short- and long-term workshops/courses could potentially increase the interest in pursuing careers in the biophotonics field and related areas, leading to standardized approaches in designing education and outreach events across centers.

High contrast breast cancer biomarker semi-quantification and immunohistochemistry imaging using upconverting nanoparticles.

Breast cancer is the second leading cause of cancer death in women. Current clinical treatment stratification practices open up an avenue for significant improvements, potentially through advancements in immunohistochemistry (IHC) assessments of biopsies. We report a high contrast upconverting nanoparticles (UCNP) labeling to distinguish different levels of human epidermal growth factor receptor 2 (HER2) in HER2 control pellet arrays (CPAs) and HER2-positive breast cancer tissue. A simple Fourier transform algorithm trained on CPAs was sufficient to provide a semi-quantitative HER2 assessment tool for breast cancer tissues. The UCNP labeling had a signal-to-background ratio of 40 compared to the negative control.

Extended-wavelength diffuse reflectance spectroscopy dataset of animal tissues for bone-related biomedical applications.

Diffuse reflectance spectroscopy (DRS) has been extensively studied in both preclinical and clinical settings for multiple applications, notably as a minimally invasive diagnostic tool for tissue identification and disease delineation. In this study, extended-wavelength DRS (EWDRS) measurements of ex vivo tissues ranging from ultraviolet through visible to the short-wave infrared region (355-1919 nm) are presented in two datasets. The first dataset contains labelled EWDRS measurements collected from bone cement samples and ovine specimens including 10 tissue types commonly encountered in orthopedic surgeries for data curation purposes. The other dataset includes labelled EWDRS measurements of primarily bone structures at different depths during stepwise drilling into intact porcine skulls until plunging into the cranial cavity. The raw data with code for pre-processing and calibration is publicly available for reuse on figshare. The datasets can be utilized not only for exploratory purposes in machine learning model construction, but also for knowledge discovery in the orthopedic domain to identify important features for surgical guidance, extract physiological parameters and provide diagnostic insights.

Frameworks of wavelength selection in diffuse reflectance spectroscopy for tissue differentiation in orthopedic surgery.

Significance: Wavelength selection from a large diffuse reflectance spectroscopy (DRS) dataset enables removal of spectral multicollinearity and thus leads to improved understanding of the feature domain. Feature selection (FS) frameworks are essential to discover the optimal wavelengths for tissue differentiation in DRS-based measurements, which can facilitate the development of compact multispectral optical systems with suitable illumination wavelengths for clinical translation. Aim: The aim was to develop an FS methodology to determine wavelengths with optimal discriminative power for orthopedic applications, while providing the frameworks for adaptation to other clinical scenarios. Approach: An ensemble framework for FS was developed, validated, and compared with frameworks incorporating conventional algorithms, including principal component analysis (PCA), linear discriminant analysis (LDA), and backward interval partial least squares (biPLS). Results: Via the one-versus-rest binary classification approach, a feature subset of 10 wavelengths was selected from each framework yielding comparable balanced accuracy scores (PCA: 94.8±3.47%, LDA: 98.2±2.02%, biPLS: 95.8±3.04%, and ensemble: 95.8±3.16%) to those of using all features (100%) for cortical bone versus the rest class labels. One hundred percent balanced accuracy scores were generated for bone cement versus the rest. Different feature subsets achieving similar outcomes could be identified due to spectral multicollinearity. Conclusions: Wavelength selection frameworks provide a means to explore domain knowledge and discover important contributors to classification in spectroscopy. The ensemble framework generated a model with improved interpretability and preserved physical interpretation, which serves as the basis to determine illumination wavelengths in optical instrumentation design.

Multi-variable compensated quantum yield measurements of upconverting nanoparticles with high dynamic range: a systematic approach.

Non-linear materials such as upconverting nanoparticles (UCNPs) are emerging technology with fast-growing applications in various fields. The power density dependence of the emission quantum yield (QY) of these non-linear materials makes them challenging to characterize using currently available commercial QY systems. We propose a multimodal system to measure QY over a wide dynamic range (1:104), which takes into account and compensates for various distorting parameters (scattering, beam profile, inner filter effect and bandwidth of emission lines). For this, a beam shaping approach enabling speckle free beam profiles of two different sizes (530 µm or 106 µm) was employed. This provides low noise high-resolution QY curves. In particular, at low power densities, a signal-to-noise ratio of >50 was found. A Tm-based core-shell UCNP with excitation at 976 nm and emission at 804 nm was investigated with the system.

Perspective on the integration of optical sensing into orthopedic surgical devices.

SIGNIFICANCE: Orthopedic surgery currently comprises over 1.5 million cases annually in the United States alone and is growing rapidly with aging populations. Emerging optical sensing techniques promise fewer side effects with new, more effective approaches aimed at improving patient outcomes following orthopedic surgery. AIM: The aim of this perspective paper is to outline potential applications where fiberoptic-based approaches can complement ongoing development of minimally invasive surgical procedures for use in orthopedic applications. APPROACH: Several procedures involving orthopedic and spinal surgery, along with the clinical challenge associated with each, are considered. The current and potential applications of optical sensing within these procedures are discussed and future opportunities, challenges, and competing technologies are presented for each surgical application. RESULTS: Strong research efforts involving sensor miniaturization and integration of optics into existing surgical devices, including K-wires and cranial perforators, provided the impetus for this perspective analysis. These advances have made it possible to envision a next-generation set of devices that can be rigorously evaluated in controlled clinical trials to become routine tools for orthopedic surgery. CONCLUSIONS: Integration of optical devices into surgical drills and burrs to discern bone/tissue interfaces could be used to reduce complication rates across a spectrum of orthopedic surgery procedures or to aid less-experienced surgeons in complex techniques, such as laminoplasty or osteotomy. These developments present both opportunities and challenges for the biomedical optics community.

Perspectives on interstitial photodynamic therapy for malignant tumors.

SIGNIFICANCE: Despite remarkable advances in the core modalities used in combating cancer, malignant diseases remain the second largest cause of death globally. Interstitial photodynamic therapy (IPDT) has emerged as an alternative approach for the treatment of solid tumors. AIM: The aim of our study is to outline the advancements in IPDT in recent years and provide our vision for the inclusion of IPDT in standard-of-care (SoC) treatment guidelines of specific malignant diseases. APPROACH: First, the SoC treatment for solid tumors is described, and the attractive properties of IPDT are presented. Second, the application of IPDT for selected types of tumors is discussed. Finally, future opportunities are considered. RESULTS: Strong research efforts in academic, clinical, and industrial settings have led to significant improvements in the current implementation of IPDT, and these studies have demonstrated the unique advantages of this modality for the treatment of solid tumors. It is envisioned that further randomized prospective clinical trials and treatment optimization will enable a wide acceptance of IPDT in the clinical community and inclusion in SoC guidelines for well-defined clinical indications. CONCLUSIONS: The minimally invasive nature of this treatment modality combined with the relatively mild side effects makes IPDT a compelling alternative option for treatment in a number of clinical applications. The adaptability of this technique provides many opportunities to both optimize and personalize the treatment.

Cranial Perforation Using an Optically-Enhanced Surgical Drill.

The design of mechanically clutched cranial perforators, used in craniotomy procedures, limits their performance under certain clinical conditions and can, in some cases, impose the risk of severe brain injury on patients undergoing the procedure. An additional safety mechanism could help in mitigating these risks. In this work, we examine the use of diffuse reflectance spectroscopy as a potential fallback mechanism for near real-time detection of the bone-brain boundary. Monte Carlo simulation of a two layer model with optical properties of bone and brain at 530 and 850 nm resulted in a detectable change in diffuse reflectance signal when approaching the boundary. The simulated results were used to guide the development of an experimental drill control system, which was tested on 10 sheep craniums and yielded 88.1 % success rate in the detection of the approaching bone-brain boundary.