Confocal corrected attenuation coefficient imaging in phantoms and using chromatic focal shift calibration.

Optical coherence tomography (OCT) is conventionally used for structural imaging of tissue. Calibrating the intensity values of OCT images can give information on the tissue's inherent optical properties, such as the attenuation coefficient, which can provide an additional parameter to quantify possible pathological changes. To obtain calibrated intensity values, the focus position and Rayleigh length of the incident beam need to be known.

Investigation of methods to extract confocal function parameters for the depth resolved determination of attenuation coefficients using OCT in intralipid samples, titanium oxide phantoms, and in vivo human retinas.

The attenuation coefficient provides a quantitative parameter for tissue characterization and can be calculated from optical coherence tomography (OCT) data, but accurate determination requires compensation for the confocal function. We present extensive measurement series for extraction of the focal plane and the apparent Rayleigh length from the ratios of OCT images acquired with different focus depths and compare these results with two alternative approaches. By acquiring OCT images for a range of different focus depths the optimal focus plane difference is determined for intralipid and titanium oxide (TiO) phantoms with different scatterer concentrations, which allows for calculation of the attenuation coefficient corrected for the confocal function.

Digital Resilience Biomarkers for Personalized Health Maintenance and Disease Prevention.

Health maintenance and disease prevention strategies become increasingly prioritized with increasing health and economic burden of chronic, lifestyle-related diseases. A key element in these strategies is the empowerment of individuals to control their health. Self-measurement plays an essential role in achieving such empowerment.

Early Upper Aerodigestive Tract Cancer Detection Using Electron Microscopy to Reveal Chromatin Packing Alterations in Buccal Mucosa Cells.

A profound characteristic of field cancerization is alterations in chromatin packing. This study aimed to quantify these alterations using electron microscopy image analysis of buccal mucosa cells of laryngeal, esophageal, and lung cancer patients. Analysis was done on normal-appearing mucosa, believed to be within the cancerization field, and not tumor itself.

In vivo subdiffuse scanning laser oximetry of the human retina.

Scanning laser ophthalmoscopes (SLOs) have the potential to perform high speed, high contrast, functional imaging of the human retina for diagnosis and follow-up of retinal diseases. Commercial SLOs typically use a monochromatic laser source or a superluminescent diode for imaging. Multispectral SLOs using an array of laser sources for spectral imaging have been demonstrated in research settings, with applications mainly aiming at retinal oxygenation measurements.

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.

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.

Optimal wavelengths for subdiffuse scanning laser oximetry of the human retina.

Retinal blood vessel oxygenation is considered to be an important marker for numerous eye diseases. Oxygenation is typically assessed by imaging the retinal vessels at different wavelengths using multispectral imaging techniques, where the choice of wavelengths will affect the achievable measurement accuracy. Here, we present a detailed analysis of the error propagation of measurement noise in retinal oximetry, to identify optimal wavelengths that will yield the lowest uncertainty in saturation estimation for a given measurement noise level.

Optical detection of field cancerization in the buccal mucosa of patients with esophageal cancer.

Introduction: Esophageal cancer is an increasingly common type of neoplasm with a very poor prognosis. This prognosis could improve with more early tumor detection. We have previously shown that we can use an optical spectroscopy to detect field cancerization in the buccal mucosa of patients with laryngeal cancer.

Toward optical guidance during endoscopic ultrasound-guided fine needle aspirations of pancreatic masses using single fiber reflectance spectroscopy: a feasibility study.

Endoscopic ultrasound-guided fine needle aspirations (EUS-FNA) of pancreatic masses suffer from sample errors and low-negative predictive values. Fiber-optic spectroscopy in the visible to near-infrared wavelength spectrum can noninvasively extract physiological parameters from tissue and has the potential to guide the sampling process and reduce sample errors. We assessed the feasibility of single fiber (SF) reflectance spectroscopy measurements during EUS-FNA of pancreatic masses and its ability to distinguish benign from malignant pancreatic tissue.

Sources of variability in the quantification of tissue optical properties by multidiameter single-fiber reflectance and fluorescence spectroscopy.

Recently, a multidiameter single-fiber reflectance and fluorescence spectroscopy device has been developed that enabled us to extract the autofluorescence of tissue that is corrected for the optical properties. Such a system has been incorporated in the population-based Rotterdam Study to investigate the autofluorescence of the skin. Since the device will be used by different operators over many years, it is essential that the results are comparable between users.

Correction for tissue optical properties enables quantitative skin fluorescence measurements using multi-diameter single fiber reflectance spectroscopy.

Background And Objective: Fluorescence measurements in the skin are very much affected by absorption and scattering but existing methods to correct for this are not applicable to superficial skin measurements.

Study Design/materials And Methods: The first use of multiple-diameter single fiber reflectance (MDSFR) and single fiber fluorescence (SFF) spectroscopy in human skin was investigated. MDSFR spectroscopy allows a quantification of the full optical properties in superficial skin (μa, μs' and γ), which can next be used to retrieve the corrected - intrinsic - fluorescence of a fluorophore Qμa,x(f).

Extraction of intrinsic fluorescence from single fiber fluorescence measurements on a turbid medium: experimental validation.

The detailed mechanisms associated with the influence of scattering and absorption properties on the fluorescence intensity sampled by a single optical fiber have recently been elucidated based on Monte Carlo simulated data. Here we develop an experimental single fiber fluorescence (SFF) spectroscopy setup and validate the Monte Carlo data and semi-empirical model equation that describes the SFF signal as a function of scattering. We present a calibration procedure that corrects the SFF signal for all system-related, wavelength dependent transmission efficiencies to yield an absolute value of intrinsic fluorescence.

Differentiation between nerve and adipose tissue using wide-band (350-1,830 nm) in vivo diffuse reflectance spectroscopy.

Background: Intraoperative nerve localization is of great importance in surgery. In certain procedures, where nerves show visual resemblance to surrounding adipose tissue, this can be particularly challenging for the human eye. An example of such a delicate procedure is thyroid and parathyroid surgery, where iatrogenic injury of the recurrent laryngeal nerve can result in transient or permanent vocal problems (0.

Influence of sildenafil on blood oxygen saturation of the obstructed bladder.

Background: Blood oxygen saturation (BOS) is decreased in a low-compliant, overactive obstructed bladder. The objective of this study is to determine the effect of Sildenafil (SC) on bladder function and BOS) in an in vivo animal model of bladder outlet obstruction.

Methods: Thirty-two guinea pigs; sham operated (n = 8), sham operated + SC (n = 8), urethrally obstructed (n = 8) and urethrally obstructed + SC (n = 8) were studied during an 8 week period.

Intrinsic photosensitizer fluorescence measured using multi-diameter single-fiber spectroscopy in vivo.

Quantification of fluorescence in vivo is complicated by the influence of tissue optical properties on the collected fluorescence signal. When tissue optical properties in the measurement volume are quantified, one can obtain the intrinsic fluorescence, which equals the product of fluorophore absorption coefficient and quantum yield. We applied this method to in vivo single-fiber fluorescence spectroscopy measurements on mouse tongue, skin, liver, and oral squamous cell carcinoma, where we detected intrinsic fluorescence spectra of the photosensitizers chlorin e6 and Bremachlorin at t=[3,4.

Microscopic analysis of the localization of two chlorin-based photosensitizers in OSC19 tumors in the mouse oral cavity.

Background And Objective: The effect of photodynamic therapy (PDT) is dependent on the localization of photosensitizer in the treatment volume at the time of illumination. Investigation of photosensitizer pharmacokinetics in and around the treatment volume aids in determining the optimal drug light interval for PDT.

Materials And Methods: In this paper we have investigated the distribution of the photosensitizers chlorin e6 and Bremachlorin in the oral squamous cell carcinoma cell-line OSC19-Luc-Gfp in a tongue tumor, tumor boundary, invasive tumor boundary, and normal tongue tissue by the use of confocal microscopy of frozen sections.

Localization of liposomal mTHPC formulations within normal epithelium, dysplastic tissue, and carcinoma of oral epithelium in the 4NQO-carcinogenesis rat model.

Background And Objective: Foslip and Fospeg are liposomal formulations of the photosensitizer mTHPC (Foscan), which is used for photodynamic therapy (PDT) of malignancies. Literature suggests that liposomal mTHPC formulations have better properties and increased tumor uptake compared to Foscan. To investigate this, we used the 4NQO-induced carcinogen model to compare the localization of the different mTHPC formulations within normal, precancerous, and cancerous tissue.

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.

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.

Single fiber reflectance spectroscopy on cervical premalignancies: the potential for reduction of the number of unnecessary biopsies.

We have assessed the value of single fiber reflectance (SFR) spectroscopy in prediction of cervical squamous intraepithelial lesions (SIL). SFR was used to measure reflected light from 32 patients undergoing standard colposcopy. Seven parameters extracted from the spectra in addition to two biographic parameters were compared in biopsy-confirmed SIL versus nonSIL.

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.

In vivo quantification of photosensitizer concentration using fluorescence differential path-length spectroscopy: influence of photosensitizer formulation and tissue location.

In vivo measurement of photosensitizer concentrations may optimize clinical photodynamic therapy (PDT). Fluorescence differential path-length spectroscopy (FDPS) is a non-invasive optical technique that has been shown to accurately quantify the concentration of Foscan® in rat liver. As a next step towards clinical translation, the effect of two liposomal formulations of mTHPC, Fospeg® and Foslip®, on FDPS response was investigated.

Quantification of the reduced scattering coefficient and phase-function-dependent parameter γ of turbid media using multidiameter single fiber reflectance spectroscopy: experimental validation.

Multidiameter single fiber reflectance (MDSFR) spectroscopy is a method that allows the quantification of μs' and the phase-function-dependent parameter γ of a turbid medium by utilizing multiple fibers with different diameters. We have previously introduced the theory behind MDSFR and its limitations, and here we present an experimental validation of this method based on phantoms containing a fractal distribution of polystyrene spheres both in the absence and presence of the absorber Evans Blue.