Two-layer reconstruction of Raman spectra in diffusive media based on an analytical model in the time domain.

We derive and validate an analytical model that describes the migration of Raman scattered photons in two-layer diffusive media, based on the diffusion equation in the time domain. The model is derived under a heuristic approximation that background optical properties are identical on the excitation and Raman emission wavelengths. Methods for the reconstruction of two-layer Raman spectra have been developed, tested in computer simulations and validated on tissue-mimicking phantom measurements data. Effects of different parameters were studied in simulations, showing that the thickness of the top layer and number of detected photon counts have the most significant impact on the reconstruction. The concept of quantitative, mathematically rigorous reconstruction using the proposed model was finally proven on experimental measurements, by successfully separating the spectra of silicone and calcium carbonate (calcite) layers, showing the potential for further development and eventual application in clinical diagnostics.

Erratum: Assessment of power spectral density of microvascular hemodynamics in skeletal muscles at very low and low-frequency via near-infrared diffuse optical spectroscopies: erratum.

[This corrects the article on p. 5994 in vol. 14, PMID: 38021143.].

Non-Invasive Monitoring of Microvascular Oxygenation and Reactive Hyperemia using Hybrid, Near-Infrared Diffuse Optical Spectroscopy for Critical Care.

The detection of levels of impairment in microvascular oxygen consumption and reactive hyperemia is vital in critical care. However, there are no practical means for a robust and quantitative evaluation. This paper describes a protocol to evaluate these impairments using a hybrid near-infrared diffuse optical device. The device contains modules for near-infrared time-resolved and diffuse correlation spectroscopies and pulse-oximetry. These modules allow the non-invasive, continuous, and real-time measurement of the absolute, microvascular blood/tissue oxygen saturation (StO2) and the blood flow index (BFI) along with the peripheral arterial oxygen saturation (SpO2). This device uses an integrated, computer-controlled tourniquet system to execute a standardized protocol with optical data acquisition from the brachioradialis muscle. The standardized vascular occlusion test (VOT) takes care of the variations in the occlusion duration and pressure reported in the literature, while the automation minimizes inter-operator differences. The protocol we describe focuses on a 3-min occlusion period but the details described in this paper can readily be adapted to other durations and cuff pressures, as well as other muscles. The inclusion of an extended baseline and post-occlusion recovery period measurement allows the quantification of the baseline values for all the parameters and the blood/tissue deoxygenation rate that corresponds to the metabolic rate of oxygen consumption. Once the cuff is released, we characterize the tissue reoxygenation rate, magnitude, and duration of the hyperemic response in BFI and StO2. These latter parameters correspond to the quantification of the reactive hyperemia, which provides information about the endothelial function. Furthermore, the above-mentioned measurements of the absolute concentration of oxygenated and deoxygenated hemoglobin, BFI, the derived metabolic rate of oxygen consumption, StO2, and SpO2 provide a yet-to-be-explored rich data set that can exhibit disease severity, personalized therapeutics, and management interventions.

Solid optical tissue phantom tools based on upconverting nanoparticles for biomedical applications.

Significance: Phantoms play a critical role in the development of biophotonics techniques. There is a lack of novel phantom tools in the emerging field of upconverting nanoparticles (UCNPs) for biophotonics application. This work provides a range of UCNP-based phantom tools and a manufacturing recipe to bridge the gap and accelerate the development of UCNP-based biophotonics applications. Aim: The study aims to provide a well-characterized UCNP-based solid phantom recipe and set of phantom tools to address a wide range of UCNP-based biophotonics applications. Approach: A solid phantom recipe based on silicone matrix was developed to manufacture UCNP-based phantoms. A lab built UCNP imaging system was used to characterize upconverted fluorescence emission of phantoms for linearity, homogeneity, and long-term stability. A photon time-of-flight spectroscopy technique was used to characterize the optical properties of the phantoms. Results: In total, 24 phantoms classified into 4 types, namely homogeneous, multilayer, inclusion, and base phantoms, were manufactured. The phantoms exhibit linear behavior over the dosage range of UCNPs. The phantoms were found to be stable over a limited observed period of 4 months with a coefficient of variation of < 4 % . The deep tissue imaging case showed that increasing the thickness of tissue reduced the UCNP emission. Conclusions: A first-of-its-kind UCNP-based solid phantom recipe was developed, and four types of UCNP phantom tools to explore biophotonics applications were presented. The UCNP phantoms exhibited a linear behavior with dosage and were stable over time. An example case showed the potential use of the phantom for deep tissue imaging applications. With recent advance in the use of UCNPs for biophotonics, we believe our recipe and tools will play a pivotal role in the growth of the UCNPs for biophotonics applications.

Microcamera Visualisation System to Overcome Specular Reflections for Tissue Imaging.

In vivo tissue imaging is an essential tool for medical diagnosis, surgical guidance, and treatment. However, specular reflections caused by glossy tissue surfaces can significantly degrade image quality and hinder the accuracy of imaging systems. In this work, we further the miniaturisation of specular reflection reduction techniques using micro cameras, which have the potential to act as intra-operative supportive tools for clinicians. In order to remove these specular reflections, two small form factor camera probes, handheld at 10 mm footprint and miniaturisable to 2.3 mm, are developed using different modalities, with line-of-sight to further miniaturisation. (1) The sample is illuminated via multi-flash technique from four different positions, causing a shift in reflections which are then filtered out in a post-processing image reconstruction step. (2) The cross-polarisation technique integrates orthogonal polarisers onto the tip of the illumination fibres and camera, respectively, to filter out the polarisation maintaining reflections. These form part of a portable imaging system that is capable of rapid image acquisition using different illumination wavelengths, and employs techniques that lend themselves well to further footprint reduction. We demonstrate the efficacy of the proposed system with validating experiments on tissue-mimicking phantoms with high surface reflection, as well as on excised human breast tissue. We show that both methods can provide clear and detailed images of tissue structures along with the effective removal of distortion or artefacts caused by specular reflections. Our results suggest that the proposed system can improve the image quality of miniature in vivo tissue imaging systems and reveal underlying feature information at depth, for both human and machine observers, leading to better diagnosis and treatment outcomes.

Label-Free Optical Spectroscopy for Early Detection of Oral Cancer.

Oral cancer is the 16th most common cancer worldwide. It commonly arises from painless white or red plaques within the oral cavity. Clinical outcome is highly related to the stage when diagnosed. However, early diagnosis is complex owing to the impracticality of biopsying every potentially premalignant intraoral lesion. Therefore, there is a need to develop a non-invasive cost-effective diagnostic technique to differentiate non-malignant and early-stage malignant lesions. Optical spectroscopy may provide an appropriate solution to facilitate early detection of these lesions. It has many advantages over traditional approaches including cost, speed, objectivity, sensitivity, painlessness, and ease-of use in clinical setting for real-time diagnosis. This review consists of a comprehensive overview of optical spectroscopy for oral cancer diagnosis, epidemiology, and recent improvements in this field for diagnostic purposes. It summarizes major developments in label-free optical spectroscopy, including Raman, fluorescence, and diffuse reflectance spectroscopy during recent years. Among the wide range of optical techniques available, we chose these three for this review because they have the ability to provide biochemical information and show great potential for real-time deep-tissue point-based in vivo analysis. This review also highlights the importance of saliva-based potential biomarkers for non-invasive early-stage diagnosis. It concludes with the discussion on the scope of development and future demands from a clinical point of view.