Analytical model for diffuse reflectance in single fiber reflectance spectroscopy.

Cancer progression leads to changing scattering properties of affected tissues. Single fiber reflectance (SFR) spectroscopy detects these changes at small spatial scales, making it a promising tool for early in situ detection. Despite its simplicity and versatility, SFR signal modeling is hugely complicated so that, presently, only approximate models exist. We use a classic approach from geometrical probability to derive accurate analytical expressions for diffuse reflectance in SFR that shows a strong improvement over existing models. We consider the case of limited collection efficiency and the presence of absorption. A Monte Carlo light transport study demonstrates that we adequately describe the contribution of diffuse reflectance to the SFR signal. Additional steps are required to include semi-ballistic, non-diffuse reflectance also present in the SFR measurement.

Grading upper tract urothelial carcinoma with the attenuation coefficient of in-vivo optical coherence tomography.

INTRODUCTION: With catheter based optical coherence tomography (OCT), high resolution images of the upper urinary tract can be obtained, thereby facilitating the detection of upper tract urothelial carcinomas (UTUC). We hypothesized that the attenuation coefficient of the OCT signal (µOCT ) is related to the histopathologic grade of the tumor. OBJECTIVES: In this study, we aimed to define the µOCT cut-off for discriminating high grade and low grade papillary UTUC. METHODS: For this post-hoc analysis, data from OCT imaging of papillary UTUC was obtained from patients during ureterorenoscopy. OCT images and raw data were simultaneously analyzed with in-house developed software. The µOCT determined in papillary UTUCs and corresponding histopathologic grading from either biopsies or radical resection specimens were compared. RESULTS: Thirty-five papillary UTUC from 35 patients were included. µOCT analysis was feasible in all cases. The median µOCT was 3.3 mm-1 (IQR 2.7-3.7 mm-1 ) for low-grade UTUC and 4.9 mm-1 (IQR 4.3-6.1 mm-1 ) for high-grade UTUC (P = 0.004). ROC analysis yielded a µOCT cut-off value of >4.0 mm-1 (AUC = 0.85, P < 0.001) with a sensitivity of 83% and a specificity of 94% for high-grade papillary UTUC. CONCLUSIONS: This study proposes a µOCT cut-off of 4.0 mm-1 for quantitative grading of UTUC with ureterorenoscopic OCT imaging. The promising diagnostic accuracy calculations justify further studies to validate the proposed cut-off value. Implementation of the software for the µOCT analysis in OCT systems may allow for µOCT assessment at real time during ureterorenoscopy. Lasers Surg. Med. 51:399-406, 2019. © 2019 Wiley Periodicals, Inc.

Percutaneous Needle Based Optical Coherence Tomography for the Differentiation of Renal Masses: a Pilot Cohort.

PURPOSE: We determine the ability of percutaneous needle based optical coherence tomography to differentiate renal masses by using the attenuation coefficient (µOCT, mm(-1)) as a quantitative measure. MATERIALS AND METHODS: Percutaneous needle based optical coherence tomography of the kidney was performed in patients presenting with a solid renal mass. A pathology specimen was acquired in the form of biopsies and/or a resection specimen. Optical coherence tomography results of 40 patients were correlated to pathology results of the resected specimens in order to derive µOCT values corresponding with oncocytoma and renal cell carcinoma, and with the 3 main subgroups of renal cell carcinoma. The sensitivity and specificity of optical coherence tomography in differentiating between oncocytoma and renal cell carcinoma were assessed through ROC analysis. RESULTS: The median µOCT of oncocytoma (3.38 mm(-1)) was significantly lower (p=0.043) than the median µOCT of renal cell carcinoma (4.37 mm(-1)). ROC analysis showed a µOCT cutoff value of greater than 3.8 mm(-1) to yield a sensitivity, specificity, positive predictive value and negative predictive value of 86%, 75%, 97% and 37%, respectively, to differentiate between oncocytoma and renal cell carcinoma. The area under the ROC curve was 0.81. Median µOCT was significantly lower for oncocytoma vs clear cell renal cell carcinoma (3.38 vs 4.36 mm(-1), p=0.049) and for oncocytoma vs papillary renal cell carcinoma (3.38 vs 4.79 mm(-1), p=0.027). CONCLUSIONS: We demonstrated that the µOCT is significantly higher in renal cell carcinoma vs oncocytoma, with ROC analysis showing promising results for their differentiation. This demonstrates the potential of percutaneous needle based optical coherence tomography to help in the differentiation of renal masses, thus warranting ongoing research.

Detection of buried Barrett's glands after radiofrequency ablation with volumetric laser endomicroscopy.

BACKGROUND AND AIMS: The prevalence and clinical relevance of buried Barrett's glands (BB) after radiofrequency ablation (RFA) in Barrett's esophagus (BE) are debated. Recent optical coherence tomography studies demonstrated a high prevalence of BBs. Direct histological correlation, however, has been lacking. Volumetric laser endomicroscopy (VLE) is a second-generation optical coherence tomography system capable of scanning a large surface of the esophageal wall layers with low-power microscopy resolution. The aim was to evaluate whether post-RFA subsquamous glandular structures (SGSs), detected with VLE, actually correspond to BBs by pursuing direct histological correlation with VLE images. METHODS: In vivo VLE was performed to detect SGSs in patients with endoscopic regression of BE post-RFA. A second in vivo VLE scan was performed to confirm correct delineation of the SGSs. After endoscopic resection, the specimens were imaged ex vivo with VLE. Extensive histological sectioning of SGS areas was performed, and all histology slides were evaluated by an expert BE pathologist. RESULTS: Seventeen patients underwent successful in vivo VLE (histological diagnosis before endoscopic treatment: early adenocarcinoma in 8 patients and high-grade dysplasia in 9). In 4 of 17 patients, no SGSs were identified during VLE, and a random resection was performed. In the remaining 13 patients (76%), VLE detected SGS areas, which were all confirmed on a second in vivo VLE scan and subsequently resected. Most SGSs identified by VLE corresponded to normal histological structures (eg, dilated glands and blood vessels). However, 1 area containing BBs was found on histology. No specific VLE features to distinguish between BBs and normal SGSs were identified. CONCLUSIONS: VLE is able to detect subsquamous esophageal structures. One area showed BBs beneath endoscopically normal-appearing neosquamous epithelium; however, most post-RFA SGSs identified by VLE correspond to normal histological structures. ( CLINICAL TRIAL REGISTRATION NUMBER: NTR4056.).

The value of optical coherence tomography in determining surgical margins in squamous cell carcinoma of the vulva: a single-center prospective study.

BACKGROUND: Vulvar squamous cell carcinoma (VSCC) is treated with wide local excision. The challenge is to remove as much skin as necessary to prevent recurrence, but meanwhile preserve genital skin to diminish morbidity. Optical coherence tomography (OCT) is a noninvasive imaging tool that produces cross-sectional images. Optical coherence tomography could be helpful in determining appropriate surgical margins during excision of VSCC. OBJECTIVE: This study aimed to assess the value of OCT in determining appropriate surgical margins in patients operated for VSCC. We hypothesize that benign tissue will differ qualitatively (presence of clear epidermal layers) and quantitatively (epidermal layer thickness and attenuation coefficient) from (pre)malignant tissue. MATERIALS AND METHODS: In 18 patients with a pretreatment biopsy of VSCC, before excision, areas within the center (tumor), at the margin (skin next to the center), and in normal vulvar skin outside the area of resection were imaged by OCT. Optical coherence tomography data were assessed on the presence of a clear epidermal layer, thickness of the epidermal layer, and values of µOCT. Results were grouped according to histopathological report in a benign group and a (pre)malignant group. RESULTS: A clear epidermal layer was observed in all OCT images of benign tissue and only in 6 of 23 premalignant lesions (P < 0.001). The epidermal layer thickness as well as the µOCT was significantly smaller for benign vulvar tissue than for (pre)malignant tissue (0.29 vs 1.03 mm, and 2.4 vs 4.1 mm(-1), respectively; P < 0.001). The diagnostic accuracy of OCT, as calculated by receiver operating characteristic curve analysis, showed at defined thresholds a sensitivity of 100% and specificity of 80% when considering layer thickness, and a sensitivity of 100% and specificity of 70% when considering the attenuation coefficient. CONCLUSIONS: We show that qualitative and quantitative OCT imaging can distinguish between benign and (pre)malignant vulvar tissue, enabling appropriate surgical margin detection with noninvasive in vivo OCT imaging.

Comparison of optical coherence tomography and histopathology in quantitative assessment of goat talus articular cartilage.

BACKGROUND AND PURPOSE: Optical coherence tomography (OCT) is a light-based imaging technique suitable for depiction of thin tissue layers such as articular cartilage. Quantification of results and direct comparison with a reference standard is needed to confirm the role of OCT in cartilage evaluation. MATERIALS AND METHODS: Goat talus articular cartilage repair was assessed quantitatively with OCT and compared with histopathology using semi-automated analysis software. Osteochondral defects were created centrally in goat tali with subsequent healing over 24 weeks. After sacrifice, the tali were analyzed using OCT and processed into histopathology slides. Cartilage thickness, repair tissue area, and surface roughness were measured. Also, light attenuation coefficient measurements were performed to assess differences in the properties of healthy tissue and repair tissue. RESULTS: Intra-class correlation coefficients for resemblance between the 2 techniques were 0.95 (p < 0.001) for thickness, 0.73 (p = 0.002) for repair tissue area, and 0.63 (p = 0.015) for surface roughness. Light attenuation differed significantly between healthy cartilage (8.2 (SD 3.9) mm(-1)) and repair tissue (2.8 (SD 1.5) mm(-1)) (p < 0.001). INTERPRETATION: Compared to histopathology as the standard reference method, OCT is a reproducible technique in quantitative analysis of goat talus articular cartilage, especially when assessing cartilage thickness and to a lesser extent when measuring repair tissue area and surface roughness. Moreover, differences in local light attenuation suggest measurable variation in tissue structure, enhancing the clinical applicability of quantitative measurements from cartilage OCT images.

A literature review and novel theoretical approach on the optical properties of whole blood.

Optical property measurements on blood are influenced by a large variety of factors of both physical and methodological origin. The aim of this review is to list these factors of influence and to provide the reader with optical property spectra (250­2,500 nm) for whole blood that can be used in the practice of biomedical optics (tabulated in the appendix). Hereto, we perform a critical examination and selection of the available optical property spectra of blood in literature, from which we compile average spectra for the absorption coefficient (µ(a)), scattering coefficient (µ(s)) and scattering anisotropy (g). From this, we calculate the reduced scattering coefficient (µ(s)') and the effective attenuation coefficient (µ(eff)). In the compilation of µ(a) and µ(s), we incorporate the influences of absorption flattening and dependent scattering (i.e. spatial correlations between positions of red blood cells), respectively. For the influence of dependent scattering on µ(s), we present a novel, theoretically derived formula that can be used for practical rescaling of µ(s) to other haematocrits. Since the measurement of the scattering properties of blood has been proven to be challenging, we apply an alternative, theoretical approach to calculate spectra for µ(s) and g. Hereto, we combine Kramers­Kronig analysis with analytical scattering theory, extended with Percus­Yevick structure factors that take into account the effect of dependent scattering in whole blood. We argue that our calculated spectra may provide a better estimation for µ(s) and g (and hence µ(s)' and µ(eff)) than the compiled spectra from literature for wavelengths between 300 and 600 nm.

Erratum: Model for the diffuse reflectance in spatial frequency domain imaging (Erratum).

[This corrects the article DOI: 10.1117/1.JBO.28.4.046002.].

Towards non-invasive tissue hydration measurements with optical coherence tomography.

The attenuation coefficient ( µ OCT $$ {\mu}_{\mathrm{OCT}} $$ ) measured by optical coherence tomography (OCT) has been used to determine tissue hydration. Previous dual-wavelength OCT systems could not attain the needed precision, which we attribute to the absence of wavelength-dependent scattering of tissue in the underlying model. Assuming that scattering can be described using two parameters, we propose a triple/quadrupole-OCT system to achieve clinically relevant precision in water volume fraction. In this study, we conduct a quantitative analysis to determine the necessary precision of µ OCT $$ {\mu}_{\mathrm{OCT}} $$ measurements and compare it with numerical simulation. Our findings emphasize that achieving a clinically relevant assessment of a 2% water fraction requires determining the attenuation coefficient with a remarkable precision of 0.01 m m - 1 $$ \mathrm{m}{\mathrm{m}}^{-1} $$ . This precision threshold is influenced by the chosen wavelength for attenuation measurement and can be enhanced through the inclusion of a fourth wavelength range.

Volumetric in vivo visualization of upper urinary tract tumors using optical coherence tomography: a pilot study.

PURPOSE: Knowledge of tumor stage and grade is paramount for treatment decision making in cases of upper urinary tract urothelial carcinoma but this condition cannot be accurately assessed by current techniques. Optical coherence tomography can hypothetically provide the urologist with real-time intraoperative information on tumor grade and stage. In this pilot study we report what are to our knowledge the first results of optical coherence tomography for grading and staging upper urinary tract urothelial carcinoma. MATERIALS AND METHODS: Eight consecutive patients underwent ureterorenoscopy for suspicion or followup of upper urinary tract urothelial carcinoma. Optical coherence tomography data sets were intraoperatively obtained from the ureter and renal pelvis. All patients eventually underwent nephroureterectomy. Optical coherence tomography staging was done by visual inspection of lesions found on optical coherence tomography images. Optical coherence tomography grading was done by quantifying optical coherence tomography signal attenuation in mm(-1) on lesions and comparing results with the histopathological diagnosis. The Wilcoxon rank sum test was used for statistical analysis. RESULTS: For 7 in vivo optical coherence tomography diagnoses staging was in accordance with histology. In patient 8 tumor thickness transcended optical coherence tomography imaging depth range and, therefore, invasiveness findings were inconclusive. For grading the median attenuation coefficient for grade 2 and 3 lesions was 1.97 (IQR 1.57-2.30) and 3.53 mm(-1) (IQR 2.74-3.94), respectively (p<0.001). Healthy urothelium was too thin to reliably determine the attenuation coefficient. CONCLUSIONS: Optical coherence tomography is a promising, minimally invasive tool for real-time intraoperative optical diagnosis of tumors in the upper urinary tract. Our results warrant future research in a larger sample size to determine the accuracy of grading and staging by optical coherence tomography, and its possible implementation in the diagnostic algorithm for upper urinary tract urothelial carcinoma.

Accuracy and precision of depth-resolved estimation of attenuation coefficients in optical coherence tomography.

Significance: Parametric imaging of the attenuation coefficient µOCT using optical coherence tomography (OCT) is a promising approach for evaluating abnormalities in tissue. To date, a standardized measure of accuracy and precision of µOCT by the depth-resolved estimation (DRE) method, as an alternative to least squares fitting, is missing. Aim: We present a robust theoretical framework to determine accuracy and precision of the DRE of µOCT. Approach: We derive and validate analytical expressions for the accuracy and precision of µOCT determination by the DRE using simulated OCT signals in absence and presence of noise. We compare the theoretically achievable precisions of the DRE method and the least-squares fitting approach. Results: Our analytical expressions agree with the numerical simulations for high signal-to-noise ratios and qualitatively describe the dependence on noise otherwise. A commonly used simplification of the DRE method results in a systematic overestimation of the attenuation coefficient in the order of µOCT2×Δ, where Δ is the pixel stepsize. When µOCT·|AFR|≲1.8, µOCT is reconstructed with higher precision by the depth-resolved method compared to fitting over the length of an axial fitting range |AFR|. Conclusions: We derived and validated expressions for the accuracy and precision of DRE of µOCT. A commonly used simplification of this method is not recommended as being used for OCT-attenuation reconstruction. We give a rule of thumb providing guidance in the choice of estimation method.

Model for the diffuse reflectance in spatial frequency domain imaging.

Significance: In spatial frequency domain imaging (SDFI), tissue is illuminated with sinusoidal intensity patterns at different spatial frequencies. For low spatial frequencies, the reflectance is diffuse and a model derived by Cuccia et al. (doi 10.1117/1.3088140) is commonly used to extract optical properties. An improved model resulting in more accurate optical property extraction could lead to improved diagnostic algorithms. Aim: To develop a model that improves optical property extraction for the diffuse reflectance in SFDI compared to the model of Cuccia et al. Approach: We derive two analytical models for the diffuse reflectance, starting from the theoretical radial reflectance R ( ρ ) for a pencil-beam illumination under the partial current boundary condition (PCBC) and the extended boundary condition (EBC). We compare both models and the model of Cuccia et al. to Monte Carlo simulations. Results: The model based on the PCBC resulted in the lowest errors, improving median relative errors compared to the model of Cuccia et al. by 45% for the reflectance, 10% for the reduced scattering coefficient and 64% for the absorption coefficient. Conclusions: For the diffuse reflectance in SFDI, the model based on the PCBC provides more accurate results than the currently used model by Cuccia et al.

Differentiation between normal renal tissue and renal tumours using functional optical coherence tomography: a phase I in vivo human study.

OBJECTIVE: To determine the ability of optical coherence tomography (OCT) in differentiating human renal tumours in an in-vivo setting by assessing differences in attenuation coefficient (µ(OCT); mm(-1)) as a quantitative measurement. METHODS: Consecutive patients undergoing nephrectomy (partial/radical) or cryoablation for an enhancing solid renal tumour were included in our centre between October 2010 and May 2011. In vivo OCT images were obtained from renal tumour and normal parenchyma during surgery. Ex vivo OCT images of internal (subcapsular) tissue were obtained after longitudinal dissection of the extirpated specimen. Attenuation coefficients of the OCT images were determined off-line and compared between normal renal parenchyma and renal tumours (grouped per tissue type and per individual patient); and between OCT images recorded from tissue surface vs internal (subcapsular) tissue. RESULTS: In vivo OCT was performed in 16 cases (11 renal cell carcinoma, three benign tumours, one non-diagnostic biopsy and one not-accessible tumour). Median attenuation coefficient of normal renal parenchyma was 5.0 mm(-1) vs 8.2 mm(-1) for tumour tissue (P < 0.001) with normal parenchyma differing significantly from malignant tumour (9.2 mm(-1), P < 0.001) and non-significantly from benign tumour (7.0 mm(-1), P = 0.050). The attenuation coefficient of benign tumours did not differ significantly from that of malignant tumours (7.0 vs 9.2 mm(-1), P = 0.139). Using patients as their own control, attenuation coefficients of normal renal parenchyma differed significantly from malignant tumour (P < 0.001) and non-significantly from benign tumour (P = 0.109). Assessed in 10 patients, there was no significant difference between attenuation coefficients of tumour surface and internal tumour (8.5 vs 9.7 mm(-1) respectively, P = 0.260). CONCLUSIONS: In this first in vivo study on OCT for differentiation of renal tumours in humans the attenuation coefficients (as a quantitative assessment) differed significantly between normal renal parenchyma and malignant tumour. Tumour surface and internal tumour did not differ significantly, suggesting that a superficial OCT attenuation coefficient reliably assesses tissue composition inside the tumour. These results justify further research on OCT for various clinical applications in the diagnosis of renal tumours.

Precision of attenuation coefficient measurements by optical coherence tomography.

SIGNIFICANCE: Optical coherence tomography (OCT) is an interferometric imaging modality, which provides tomographic information on the microscopic scale. Furthermore, OCT signal analysis facilitates quantification of tissue optical properties (e.g., the attenuation coefficient), which provides information regarding the structure and organization of tissue. However, a rigorous and standardized measure of the precision of the OCT-derived optical properties, to date, is missing. AIM: We present a robust theoretical framework, which provides the Cramér -Rao lower bound σµOCT for the precision of OCT-derived optical attenuation coefficients. APPROACH: Using a maximum likelihood approach and Fisher information, we derive an analytical solution for σµOCT when the position and depth of focus are known. We validate this solution, using simulated OCT signals, for which attenuation coefficients are extracted using a least-squares fitting procedure. RESULTS: Our analytical solution is in perfect agreement with simulated data without shot noise. When shot noise is present, we show that the analytical solution still holds for signal-to-noise ratios (SNRs) in the fitting window being above 20 dB. For other cases (SNR<20 dB, focus position not precisely known), we show that the numerical calculation of the precision agrees with the σµOCT derived from simulated signals. CONCLUSIONS: Our analytical solution provides a fast, rigorous, and easy-to-use measure for OCT-derived attenuation coefficients for signals above 20 dB. The effect of uncertainties in the focal point position on the precision in the attenuation coefficient, the second assumption underlying our analytical solution, is also investigated by numerical calculation of the lower bounds. This method can be straightforwardly extended to uncertainty in other system parameters.

Calibration procedure for enhanced mirror artifact removal in full-range optical coherence tomography using passive quadrature demultiplexing.

Significance: Passive quadrature demultiplexing allows full-range optical coherence tomography (FR-OCT). However, imperfections in the wavelength- and frequency-response of the demodulation circuits can cause residual mirror artifacts, which hinder high-quality imaging on both sides of zero delay. Aim: We aim at achieving high mirror artifact extinction by calibrated postprocessing of the FR-OCT signal. Approach: We propose a mathematical framework for the origin of the residual mirror peaks as well as a protocol allowing the precise measurement and correction of the associated errors directly from mirror measurements. Results: We demonstrate high extinction of the mirror artifact over the entire imaging range, as well as an assessment of the method's robustness to time and experimental conditions. We also provide a detailed description of the practical implementation of the method to ensure optimal reproducibility. Conclusion: The proposed method is simple to implement and produces high mirror artifact extinction. This may encourage the adoption of FR-OCT in clinical and industrial systems or loosen the performance requirements on the optical demodulation circuit, as the imperfections can be handled in postprocessing.

Experimental validation of a recently developed model for single-fiber reflectance spectroscopy.

SIGNIFICANCE: We recently developed a model for the reflectance measured with (multi-diameter) single-fiber reflectance (SFR) spectroscopy as a function of the reduced scattering coefficient µs', the absorption coefficient µa, and the phase function parameter psb. We validated this model with simulations. AIM: We validate our model experimentally. To prevent overfitting, we investigate the wavelength-dependence of psb and propose a parametrization with only three parameters. We also investigate whether this parametrization enables measurements with a single fiber, as opposed to multiple fibers used in multi-diameter SFR (MDSFR). APPROACH: We validate our model on 16 phantoms with two concentrations of Intralipid-20% (µs'=13 and 21 cm - 1 at 500 nm) and eight concentrations of Evans Blue (µa = 1 to 20 cm - 1 at 605 nm). We parametrize psb as 10 - 5 · ( p1 ( λ / 650 ) + p2(λ/650)2 + p3(λ/650)3 ) . RESULTS: Average errors were 7% for µs', 11% for µa, and 16% with the parametrization of psb; and 7%, 17%, and 16%, respectively, without. The parametrization of psb improved the fit speed 25 times (94 s to <4 s). Average errors for only one fiber were 50%, 33%, and 186%, respectively. CONCLUSIONS: Our recently developed model provides accurate results for MDSFR measurements but not for a single fiber. The psb parametrization prevents overfitting and speeds up the fit.

Bayesian analysis of depth resolved OCT attenuation coefficients.

Optical coherence tomography (OCT) is an optical technique which allows for volumetric visualization of the internal structures of translucent materials. Additional information can be gained by measuring the rate of signal attenuation in depth. Techniques have been developed to estimate the rate of attenuation on a voxel by voxel basis. This depth resolved attenuation analysis gives insight into tissue structure and organization in a spatially resolved way. However, the presence of speckle in the OCT measurement causes the attenuation coefficient image to contain unrealistic fluctuations and makes the reliability of these images at the voxel level poor. While the distribution of speckle in OCT images has appeared in literature, the resulting voxelwise corruption of the attenuation analysis has not. In this work, the estimated depth resolved attenuation coefficient from OCT data with speckle is shown to be approximately exponentially distributed. After this, a prior distribution for the depth resolved attenuation coefficient is derived for a simple system using statistical mechanics. Finally, given a set of depth resolved estimates which were made from OCT data in the presence of speckle, a posterior probability distribution for the true voxelwise attenuation coefficient is derived and a Bayesian voxelwise estimator for the coefficient is given. These results are demonstrated in simulation and validated experimentally.

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.

Apoptosis- and necrosis-induced changes in light attenuation measured by optical coherence tomography.

Optical coherence tomography (OCT) was used to determine optical properties of pelleted human fibroblasts in which necrosis or apoptosis had been induced. We analysed the OCT data, including both the scattering properties of the medium and the axial point spread function of the OCT system. The optical attenuation coefficient in necrotic cells decreased from 2.2 +/- 0.3 mm(1) to 1.3 +/- 0.6 mm(-1), whereas, in the apoptotic cells, an increase to 6.4 +/- 1.7 mm(-1) was observed. The results from cultured cells, as presented in this study, indicate the ability of OCT to detect and differentiate between viable, apoptotic, and necrotic cells, based on their attenuation coefficient. This functional supplement to high-resolution OCT imaging can be of great clinical benefit, enabling on-line monitoring of tissues, e.g. for feedback in cancer treatment.