Miniature, multi-dichroic instrument for measuring the concentration of multiple fluorophores.

Identification of tumour margins during resection of the brain is critical for improving the post-operative outcomes. Due to the highly infiltrative nature of glioblastoma multiforme (GBM) and limited intraoperative visualization of the tumour margin, incomplete surgical resection has been observed to occur in up to 80 % of GBM cases, leading to nearly universal tumour recurrence and overall poor prognosis of 14.6 months median survival. This research presents a miniaturized, SiPMT-based optical system for simultaneous measurement of powerful DRS and weak auto-fluorescence for brain tumour detection. The miniaturisation of the optical elements confined the spatial separation of eight select wavelengths into footprint measuring 1.5 × 2 × 16 mm. The small footprint enables this technology to be integrated with existing surgical guidance instruments in the operating room. It's dynamic ability to subtract any background illumination and measure signal intensities across a broad range from pW to mWs make this design much more suitable for clinical environments as compared to spectrometer-based systems with limited dynamic ranges and high integration times. Measurements using optical tissue phantoms containing mixed fluorophores demonstrate correlation coefficients between the fitted response and actual concentration using PLS regression being 0.95, 0.87 and 0.97 for NADH, FAD and PpIX , respectively. These promising results indicate that our proposed miniaturized instrument could serve as an effective alternative in operating rooms, assisting surgeons in identifying brain tumours to achieving positive surgical outcomes for patients.

Laser absorption spectroscopy measurements of different pulmonary oxygen gas concentrations in transmittance and remittance geometry: phantom study.

Significance: The gas in scattering media absorption spectroscopy (GASMAS) technique has the potential for continuous, clinical monitoring of preterm infant lung function, removing the need for X-ray diagnosis and reliance on indirect and relatively slow measurement of blood oxygenation. Aim: We aim to determine the optimal source-detector configuration for reliable pathlength calculation and to estimate the oxygen gas concentration inside the lung cavities filled with humidified gas with four different oxygen gas concentrations ranging between 21% and 100%. Approach: Anthropomorphic optical phantoms of neonatal thorax with two different geometries were used to acquire GASMAS signals, for 30 source-detector configurations in transmittance and remittance geometry of phantoms in two sizes. Results: The results show that an internal light administration is more likely to provide a high GASMAS signal-to-noise ratio (SNR). In general, better SNRs were obtained with the smaller set of phantoms. The values of pathlength and O2 concentrations calculated with signals from the phantoms with optical properties at 820 nm exhibit higher variations than signals from the phantoms with optical properties at 764 nm. Conclusion: Our study shows that, by moving the source and detector over the thorax, most of the lung volumes can potentially be assessed using the GASMAS technique.

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.

Silicon Photomultiplier-A High Dynamic Range, High Sensitivity Sensor for Bio-Photonics Applications.

This work is an overview of silicon photomultipliers (SiPMs) with a view to defining their importance for bio-photonic and clinical applications. SiPMs are benchmarked against other common photodetectors, namely, PIN diodes and avalanche photodetectors (APDs) and are compared with respect to important circuit design parameters. It will be shown that careful selection of the design bias voltage, overvoltage, gain defining components and device integration to micro-optics can allow SiPM detectors to achieve considerable sensitivity for auto-fluorescence (AF) detection and a wide dynamic range at low optical powers (~1 pW to ~4 µW). The SiPM has a manageable bias voltage (~25 V to ~30 V DC) for systems integration, and with optimised sensitivity it will enhance bio-photonic research in the area of AF to detect intraoperatively, for example, brain tumour margins.

Gas in scattering media absorption spectroscopy as a potential tool in neonatal respiratory care.

Gas in scattering media absorption spectroscopy (GASMAS) is a novel optical technology employing near-infrared light. It has a potential use in the medical setting as a monitoring and diagnostic tool by detecting molecular oxygen within gas pockets and thus may be a useful adjunct in respiratory monitoring. GASMAS has potential advantages over other monitoring devices currently used in clinical practice. It is a non-invasive, continuous, non-ionising technology and provides unique information about molecular oxygen content inside the lungs. GASMAS may have a future role in optimising respiratory management of neonates in different clinical scenarios such as monitoring cardiorespiratory transition in the delivery room, assessing surfactant deficiency, and optimising endotracheal tube positioning. This article aims to summarise current evidence exploring GASMAS application in a neonate, discuss possible clinical benefits, and compare with other devices that are currently used in neonatal care. IMPACT: This article presents a novel optical technique to measure lung oxygen concentrations that may have important clinical uses. This review summarises the current literature investigating the concept of optical lung oxygen measurement. Information from this review can guide researchers in future studies.

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.

Lung tissue phantom mimicking pulmonary optical properties, relative humidity, and temperature: a tool to analyze the changes in oxygen gas absorption for different inflated volumes.

SIGNIFICANCE: Gas in scattering media absorption spectroscopy (GASMAS) enables noninvasive gas sensing in the body. It is developing as a tool for diagnosis and monitoring of respiratory conditions in neonates. Phantom models with relevant features to the clinical translation of GASMAS technology are necessary to understand technical challenges and potential applications of this technique. State-of-the-art phantoms designed for this purpose have focused on the optical properties and anthropomorphic geometry of the thorax, contributing to the source-detector placement, design, and optimization. Lung phantom mimicking the alveolar anatomy has not been included in the existent models due to the inherent complexity of the tissue. We present a simplified model that recreates inflated alveoli embedded in lung phantom. AIM: The goal of this study was to build a lung model with air-filled structures mimicking inflated alveoli surrounded by optical phantom with accurate optical properties (µa = 0.50 cm - 1 and µs'=5.4 cm-1) and physiological parameters [37°C and 100% relative humidity (RH)], and to control the air volume within the phantom to demonstrate the feasibility of GASMAS in sensing changes in pulmonary air volume. APPROACH: The lung model was built using a capillary structure with analogous size to alveolar units. Part of the capillaries were filled with liquid lung optical phantom to recreate scattering and absorption, whereas empty capillaries mimicked air filled alveoli. The capillary array was placed inside a custom-made chamber that maintained pulmonary temperature and RH. The geometry of the chamber permitted the placement of the laser head and detector of a GASMAS bench top system (MicroLab Dual O2 / H2O), to test the changes in volume of the lung model in transmittance geometry. RESULTS: The lung tissue model with air volume range from 6.89 × 10 - 7 m3 to 1.80 × 10 - 3 m3 was built. Two measurement sets, with 10 different capillary configurations each, were arranged to increase or decrease progressively (in steps of 3.93 × 10 - 8 m3) the air volume in the lung model. The respective GASMAS data acquisition was performed for both data sets. The maximum absorption signal was obtained for configurations with the highest number of air-filled capillaries and decreased progressively when the air spaces were replaced by capillaries filled with liquid optical phantom. Further studies are necessary to define the minimum and maximum volume of air that can be measured with GASMAS-based devices for different source-detector geometries. CONCLUSIONS: The optical properties and the structure of tissue from the respiratory zone have been modeled using a simplified capillary array immersed in a controlled environment chamber at pulmonary temperature and RH. The feasibility of measuring volume changes with GASMAS technique has been proven, stating a new possible application of GASMAS technology in respiratory treatment and diagnostics.

Combined autofluorescence and diffuse reflectance for brain tumour surgical guidance: initial ex vivo study results.

This ex vivo study was conducted to assess the potential of using a fibre optic probe system based on autofluorescence and diffuse reflectance for tissue differentiation in the brain. A total of 180 optical measurements were acquired from 28 brain specimens (five patients) with eight excitation and emission wavelengths spanning from 300 to 700 nm. Partial least square-linear discriminant analysis (PLS-LDA) was used for tissue discrimination. Leave-one-out cross validation (LOOCV) was then used to evaluate the performance of the classification model. Grey matter was differentiated from tumour tissue with sensitivity of 89.3% and specificity of 92.5%. The variable importance in projection (VIP) derived from the PLS regression was applied to wavelengths selection, and identified the biochemical sources of the detected signals. The initial results of the study were promising and point the way towards a cost-effective, miniaturized hand-held probe for real time and label-free surgical guidance.

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.

Diffuse reflectance spectroscopy-enhanced drill for bone boundary detection.

Intramedullary nailing is a routine orthopedic procedure used for treating fractures of femoral or tibial shafts. A critical part of this procedure involves the drilling of pilot holes in both ends of the bone for the placement of the screws that will secure the IM rod to sections of the fractured bone. This step introduces a risk of soft tissue damage because the drill bit, if not stopped in time, can transverse the bone-tissue boundary into the overlying muscle, causing unnecessary injury and prolonging healing time due to periosteum damage. In this respect, detecting the bone-tissue boundary before break-through can reduce the risks and complications associated with intramedullary nailing. Hence, in the present study, a two-wavelength diffuse reflectance spectroscopy technique was integrated into a surgical drill to optically detect bone-tissue boundary and automatically trigger the drill to stop. Furthermore, Monte-Carlo simulations were used to estimate the maximum distance from within the bone at which the bone-tissue boundary could be detected using DRS. The simulation results estimated that the detection distance, termed the "look-ahead-distance" was ∼1.5 mm for 1.3 mm source-detector fiber separation. Experimental measurements with 1.3 mm source-detector fiber separation showed that the look-ahead-distance was in the order of 250 µm in experiments with set drill rate and in the range of 1 mm in experiments where the holes were drilled by hand. Despite this difference, the automated DRS enhanced drill successfully detected the approaching bone tissue boundary when tested on samples of bovine femur and muscle tissue.

Finite-element modelling and preliminary validation of microneedle-based electrodes for enhanced tissue electroporation.

This paper investigates the use of microneedle-based electrodes for enhanced testis electroporation, with specific application to the production of transgenic mice. During the design phase, finite-element software has been used to construct a tissue model and to compare the relative performance of electrodes employing a) conventional flat plates, b) microneedle arrays, and c) invasive needles. Results indicate that microneedle-based electrodes can achieve internal tissue field strengths which are an order of magnitude higher than those generated using conventional flat electrodes, and which are comparable to fields produced using invasive needles. Using a double-sided etching process, conductive microneedle arrays were then fabricated and used in prototype electrodes. In a series of mouse model experiments involving injection of a DNA vector expressing Green Fluorescent Protein (GFP), the performance of flat and microneedle electrodes was compared by measuring GFP expression after electroporation. The main finding, supported by experimental and simulated data, is that use of microneedle-based electrodes significantly enhanced electroporation of testis.