Multidiameter Single-fiber Reflectance Spectroscopy Research Articles

Toward improved endoscopic surveillance with multidiameter single fiber reflectance spectroscopy in patients with Barrett's esophagus.

Patients with Barrett's esophagus are at an increased risk to develop esophageal cancer and, therefore, undergo regular endoscopic surveillance. Early detection of neoplasia enables endoscopic treatment, which improves outcomes. However, early Barrett's neoplasia is easily missed during endoscopic surveillance. This study investigates multidiameter single fiber reflectance spectroscopy (MDSFR) to improve Barrett's surveillance. Based on the concept of field cancerization, it may be possible to identify the presence of a neoplastic lesion from measurements elsewhere in the esophagus or even the oral cavity. In this study, MDSFR measurements are performed on non-dysplastic Barrett's mucosa, squamous mucosa, oral mucosa, and the neoplastic lesion (if present). Based on logistic regression analysis on the scattering parameters measured by MDSFR, a classifier is developed that can predict the presence of neoplasia elsewhere in the Barrett's segment from measurements on the non-dysplastic Barrett's mucosa (sensitivity 91%, specificity 71%, AUC = 0.77). Classifiers obtained from logistic regression analysis for the squamous and oral mucosa do not result in an AUC significantly different from 0.5.

Effect of probe pressure on skin tissue optical properties measurement using multi-diameter single fiber reflectance spectroscopy

Multi-Diameter Single Fiber Reflectance spectroscopy (MDSFR) allows rapid and noninvasive extraction of tissue optical properties that requires the fiberoptic to be placed in contact with the tissue. To ensure a good optical contact, the application of probe pressure is inevitable and usually not well controlled. In this study, we investigated the effect of probe pressure by performing in vivo MDSFR measurements (400–1600 nm) on human inner forearm skin with controlled probe indentation and continuous pressure monitoring. For the probe pressures up to 28.4 s mm−2 (213 mmHg), the reduced scattering coefficient pivoted around 800 nm (increasing scattering slope) while the phase function related parameter decreased (up to 20%, depending on the wavelength). A significant decrease of hemoglobin concentration (∼81%), oxygen saturation (∼86%), apparent vessel diameter (∼100%) as well as the displacement of extracellular water (∼24%) was observed with increasing probe pressure. A correlation was observed between the changes in water volume fraction and phase function related parameter gamma . We theorize that the latter changes in phase function may be due to the induced deformation of the tissue structure and the displacement of extracellular water. The extensive analysis of the pressure induced changes in the measured MDSFR spectra and the related changes in optical properties demonstrate that the effects of probe pressure must be minimized to avoid bias in the results.

Towards the Optical Detection of Field Cancerization in the Buccal Mucosa of Patients with Lung Cancer

INTRODUCTION: An increase in detection of early-stage asymptomatic lung tumors could increase the overall survival rate of lung cancer patients. A new approach to cancer (pre-)screening focusses on detecting field cancerization instead of the tumor itself. The objective of this study was to investigate the use of optical spectroscopy to detect field cancerization in the buccal mucosa of lung cancer patients. METHODS: Optical buccal mucosa measurements were performed in lung cancer patients and controls using multidiameter single-fiber reflectance spectroscopy. We analyzed whether the measured optical parameters could distinguish lung cancer patients from controls. RESULTS: Twenty-three lung cancer patients, 24 chronic obstructive pulmonary disease (COPD) control patients, and 36 non-COPD controls were included. The majority of tumors were non-small-cell lung carcinomas (96%) and classified as stage I (48%). The tissue scattering properties μs' and γ at 800 nm and the tissue bilirubin concentration were all near-significantly different (P=.072, 0.058, and 0.060, respectively) between the lung cancer and COPD group. μs' at 800 nm had a sensitivity of 74% and a specificity of 63%. The microvascular blood oxygen saturation of the lung cancer patients was also higher than the COPD patients (78% vs. 62%, P=.002), this is probably a consequence of the systemic effect of COPD. CONCLUSIONS: We have demonstrated that μs' at 800 nm is increased in the buccal mucosa of patients with lung cancer compared to controls with COPD. This might be an indication of field cancerization in the oral cavity of patients with lung cancer.

Optical pre-screening for laryngeal cancer using reflectance spectroscopy of the buccal mucosa.

A new approach in early cancer detection focuses on detecting field cancerization (FC) instead of the tumor itself. The aim of the current study is to investigate whether reflectance spectroscopy can detect FC in the buccal mucosa of patients with laryngeal cancer. The optical properties of the buccal mucosa of patients were measured with multidiameter single-fiber reflectance spectroscopy. The blood oxygen saturation and blood volume fraction were significantly lower in the buccal mucosa of laryngeal cancer patients than in non-oncologic controls. The data of these two parameters were combined to form a single 'biomarker α', which optimally discriminates these two groups. Alpha was lower in the laryngeal cancer group (0.28) than the control group (0.30, p = 0.007). Alpha could identify oncologic patients with a sensitivity of 78% and a specificity of 74%. These results might be the first step toward optical pre-screening for laryngeal cancer.

Method for rapid multidiameter single-fiber reflectance and fluorescence spectroscopy through a fiber bundle

We have recently demonstrated a means for quantifying the absorption and scattering properties of biological tissue through multidiameter single-fiber reflectance (MDSFR) spectroscopy. These measurements can be used to correct single-fiber fluorescence (SFF) spectra for the influence of optical properties, enabling quantification of intrinsic fluorescence. In our previous work, we have used a series of pinholes to show that selective illumination and light collection using a coherent fiber bundle can simulate a single solid-core optical fiber with variable diameter for the purposes of MDSFR spectroscopy. Here, we describe the construction and validation of a clinical MDSFR/SFF spectroscopy system that avoids the limitations encountered with pinholes and free-space optics. During one measurement, the new system acquires reflectance spectra at the effective diameters of 200, 600, and 1000 μm, and a fluorescence spectrum at an effective diameter of 1000 μm. From these spectra, we measure the absolute absorption coefficient, μ(a), reduced scattering coefficient, μ'(s'), phase function parameter, γ, and intrinsic fluorescence, Qμ(a,x)(f), across the measured spectrum. We validate the system using Intralipid- and polystyrene sphere-based scattering phantoms, with and without the addition of the absorber Evans Blue. Finally, we demonstrate the combined MDSFR/SFF of phantoms with varying concentrations of Intralipid and fluorescein, wherein the scattering properties are measured by MDSFR and used to correct the SFF spectrum for accurate quantification of Qμ(a,x)(f).

In vivo quantification of the scattering properties of tissue using multi-diameter single fiber reflectance spectroscopy

Multi diameter single fiber reflectance (MDSFR) spectroscopy is a non-invasive optical technique based on using multiple fibers of different diameters to determine both the reduced scattering coefficient (μs′) and a parameter γ that is related to the angular distribution of scattering, where γ = (1-g2)/(1-g1) and g1 and g2 the first and second moment of the phase function, respectively. Here we present the first in vivo MDSFR measurements of μs′(λ) and γ(λ) and their wavelength dependence. MDSFR is performed on nineteen mice in four tissue types including skin, liver, normal tongue and in an orthotopic oral squamous cell carcinoma. The wavelength-dependent slope of μs′(λ) (scattering power) is significantly higher for tongue and skin than for oral cancer and liver. The reduced scattering coefficient at 800 nm of oral cancer is significantly higher than of normal tongue and liver. Gamma generally increases with increasing wavelength; for tumor it increases monotonically with wavelength, while for skin, liver and tongue γ(λ) reaches a plateau or even decreases for longer wavelengths. The mean γ(λ) in the wavelength range 400-850 nm is highest for liver (1.87 ± 0.07) and lowest for skin (1.37 ± 0.14). Gamma of tumor and normal tongue falls in between these values where tumor exhibits a higher average γ(λ) (1.72 ± 0.09) than normal tongue (1.58 ± 0.07). This study shows the potential of using light scattering spectroscopy to optically characterize tissue in vivo.

Use of a coherent fiber bundle for multi-diameter single fiber reflectance spectroscopy

Multi-diameter single fiber reflectance (MDSFR) spectroscopy enables quantitative measurement of tissue optical properties, including the reduced scattering coefficient and the phase function parameter γ. However, the accuracy and speed of the procedure are currently limited by the need for co-localized measurements using multiple fiber optic probes with different fiber diameters. This study demonstrates the use of a coherent fiber bundle acting as a single fiber with a variable diameter for the purposes of MDSFR spectroscopy. Using Intralipid optical phantoms with reduced scattering coefficients between 0.24 and 3 mm−1, we find that the spectral reflectance and effective path lengths measured by the fiber bundle (NA = 0.40) are equivalent to those measured by single solid-core fibers (NA = 0.22) for fiber diameters between 0.4 and 1.0 mm (r ≥ 0.997). This one-to-one correlation may hold for a 0.2 mm fiber diameter as well (r = 0.816); however, the experimental system used in this study suffers from a low signal-to-noise for small dimensionless reduced scattering coefficients due to spurious back reflections within the experimental system. Based on these results, the coherent fiber bundle is suitable for use as a variable-diameter fiber in clinical MDSFR quantification of tissue optical properties.

Measurement of tissue scattering properties using multi-diameter single fiber reflectance spectroscopy: in silico sensitivity analysis

Multiple diameter single fiber reflectance (MDSFR) measurements of turbid media can be used to determine the reduced scattering coefficient (μ′s) and a parameter that characterizes the phase function (γ). The MDSFR method utilizes a semi-empirical model that expresses the collected single fiber reflectance intensity as a function of fiber diameter (dfiber), μ′s, and γ. This study investigated the sensitivity of the MDSFR estimates of μ′s and γ to the choice of fiber diameters and spectral information incorporated into the fitting procedure. The fit algorithm was tested using Monte Carlo simulations of single fiber reflectance intensities that investigated biologically relevant ranges of scattering properties (μ′s ∈ [0.4 – 4]mm−1) and phase functions (γ ∈ [1.4 – 1.9]) and for multiple fiber diameters (dfiber ∈ [0.2 – 1.5] mm). MDSFR analysis yielded accurate estimates of μ′s and γ over the wide range of scattering combinations; parameter accuracy was shown to be sensitive to the range of fiber diameters included in the analysis, but not to the number of intermediate fibers. Moreover, accurate parameter estimates were obtained without a priori knowledge about the spectral shape of γ. Observations were used to develop heuristic guidelines for the design of clinically applicable MDSFR probes.