Single Fiber Reflectance Spectroscopy Research Articles

Tissue-probe contact assessment during robotic surgery using single-fiber reflectance spectroscopy

The introduction of robotic surgery has improved minimally invasive surgery, and now robotic surgery is used in several areas of surgical oncology. Several optical techniques can be used to discriminate cancer from healthy tissue based on their optical properties. These technologies can also be employed with a small fiber-optic probe during minimally invasive surgery; however, for acquiring reliable measurements, some optical techniques require the fiber-optic probe to be in direct contact with the tissue. The lack of tactile feedback in robotic surgery makes assessing tissue-probe contact suitable for optical contact measurements challenging for the surgeon. In this study, we investigated the use of single fiber reflectance (SFR) to determine tissue-probe contact adequately. A machine learning-based algorithm was developed to classify if direct tissue-probe contact was present during the measurement in an ex-vivo tissue setup. Using this classification algorithm, an average accuracy of 93.9% was achieved for assessing probe-tissue contact, suggesting that this technique can be utilized to assess tissue-probe contact in an in vivo clinical setting.

Optical fiber sensors for monitoring cement paste carbonation

The use of concrete has been widespread in our society in housing and infrastructure, despite the environmental cost associated with its production. Its decay poses a social, economic, and environmental problem. Currently, the carbonation of cement paste is monitored through the measurement of its pH, with several optical fiber sensors (OFS) have been produced for this purpose. In the current work the focus is, also, on the carbonation monitoring of cement paste through an OFS, but not through pH measurements. Single fiber reflectance spectroscopy, previously employed to measure cement paste durability, is used to monitor the discoloration of cement paste caused by carbonation. As the carbonation front reaches the fiber tip embedded in the cement paste, the signal reflected onto the fiber increases. The accelerated carbonation of two limestone cement paste samples in an atmosphere of 100% CO2 was successfully monitored. The applicability of the sensor for operational use with ambient CO2 was confirmed through the measurement of carbonation at 3% CO2. The cross interference from water ingress and egress was also evaluated, and it didn’t hinder the measurements of carbonation. Therefore, a novel OFS capable of measuring cement paste carbonation and durability, was achieved.

Opportunities and pitfalls in (sub)diffuse reflectance spectroscopy

For a long time, steady-state reflectance spectroscopy measurements have been performed so that diffusion theory could be used to extract tissue optical properties from the reflectance. The development of subdiffuse techniques, such as Single Fiber Reflectance Spectroscopy and subdiffuse SFDI, provides new opportunities for clinical applications since they have the key advantage that they are much more sensitive to the details of the tissue scattering phase function in comparison to diffuse techniques. Since the scattering phase function is related to the subcellular structure of tissue, subdiffuse measurements have the potential to provide a powerful contrast between healthy and diseased tissue. In the subdiffuse regime, the interrogated tissue volumes are much smaller than in the diffuse regime. Whether a measurement falls within the diffuse or subdiffuse regime depends on tissue optical properties and the distance between the source and detector fiber for fiber-optic techniques or the projected spatial frequency for hyperspectral imaging and SFDI. Thus, the distance between source and detector fibers or the projected spatial frequency has important implications for clinical applications of reflectance spectroscopy and should be carefully selected, since it influences which tissue optical properties the technique is sensitive to and the size of the tissue volume that is interrogated. In this paper, we will review the opportunities and pitfalls in steady-state reflectance spectroscopy in the subdiffuse and the diffuse regime. The discussed opportunities can guide the choice of either the diffuse or subdiffuse regime for a clinical application, and the discussed pitfalls can ensure these are avoided to enable the development of robust diagnostic algorithms. We will first discuss the relevant basics of light-tissue interaction. Next, we will review all the tissue scattering phase functions that have been measured and investigate which scattering phase function models are representative of tissue. Subsequently, we will discuss the sensitivity of diffuse and subdiffuse techniques to tissue optical properties and we will explore the difference in the interrogation depth probed by diffuse and subdiffuse techniques.

Monitoring of irrigated lesion formation with single fiber based multispectral system using machine learning.

In radiofrequency ablation (RFA) treatment of cardiac arrhythmias, intraprocedural assessment of treatment efficacy relies on indirect measures of adequate tissue destruction. Direct sensing of diffuse reflectance spectral changes at the ablation site using optically integrated RFA catheters has been shown to enable accurate prediction of lesion dimensions, ex vivo. Challenges of optical guidance can be due to obtaining reliable measurements under various catheter-tissue contact orientations. In this work, addressed this limitation by assessing the feasibility of monitoring lesion progression using single-fiber reflectance spectroscopy (SFRS). A total of 110 endocardial lesions of various sizes were generated in freshly excised swine right ventricular tissue using a custom-built, irrigated SFRS-RFA catheter. Models were developed for assessing catheter-tissue contact, the presence of nontransmural or transmural lesions and lesion depth percentage. These results support the use of SFRS-based catheters for irrigated lesion assessment and motivate further exploration of using multi-SFRS catheters for omnidirectionality.

Single fiber reflectance spectroscopy for pancreatic cancer detection during endoscopic ultrasound guided fine needle biopsy: a prospective cohort study.

This study aimed to determine the ability of single fiber reflectance (SFR) spectroscopy incorporated in endoscopic ultrasound fine needle biopsy (EUS-FNB) procedures in the pancreas to distinguish benign and malignant pancreatic tissue in patient with pancreatic masses suspected for malignancy.Methods: This study was designed as a prospective observational single center study and included consecutive adult patients, who were scheduled for EUS-FNB of a solid pancreatic mass suspected for pancreatic ductal adenocarcinoma (PDAC). In total, seven optical parameters, derived from the absorption acquired spectra, were analyzed: blood volume fraction (BVF), microvascular saturation, average vessel diameter, bilirubin concentration (BIL), Mie amplitude, Mie slope and Rayleigh amplitude.Results: Forty-five patients with a suspicious pancreatic lesion undergoing EUS-FNB were included, of which most of the patients (N=34) were ultimately diagnosed with PDAC. Finally, 27 out of 45 (60.0%) patients were used for the final analysis of the optical parameters. The median (IQR) BVF differed significantly in benign compared to malignant tissue (0.86 [0.30-2.03] and 4.49 [1.28-15.47]; p=0.046). Combining BVF and BIL to a new parameter (θ) improved the discrimination between PDAC and benign pancreatic tissue (p=0.026). The area under the curve of θ was 0.84, resulting in a 92.8%, 75.0%, 97.5%, 50.0% and 91.3% sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for detection of PDAC.Conclusion: Differentiation between PDAC and benign pancreatic tissue using SFR spectroscopy during EUS-FNB procedures is promising. Future work should focus on comparing the diagnostic performance combining SFR spectroscopy with EUS-FNB and EUS-FNB alone.

Detecting head and neck lymph node metastases with white light reflectance spectroscopy; a pilot study

IntroductionA challenge in the treatment of patients with head and neck cancer is the management of occult cervical lymph node (LN) metastases. Single-fiber reflectance (SFR) spectroscopy has the potential to detect physiological tissue changes that occur in a positive LN. This pilot study aimed to investigate whether SFR spectroscopy could serve as an alternative or additional technique to detect cervical lymph node metastases. Materials and MethodsWe performed intraoperative SFR spectroscopy measurements of LNs with and without malignancies. We analyzed if physiological and scattering parameters were significantly altered in positive LNs. ResultsNine patients with a total of nineteen LNs were included. Three parameters, blood volume fraction (BVF), microvascular saturation (StO2), and Rayleigh amplitude, were significantly lower in positive LNs. They were combined into one optical parameter ‘delta’, using discriminant analysis. Delta was significantly decreased in positive LNs, p = 0,0006. It had a high diagnostic accuracy where the sensitivity, specificity, PPV, and NPV were 90,0%, 88.9%, 90,0%, and 88.9%, respectively. The area under the ROC curve was 96.7% (95% confidence interval 89.7–100.0%). ConclusionThis proof of principle study is a first step in the development of an SFR spectroscopy technique to detect LN metastases in real time. A next step towards this goal is replicating these results in LNs with smaller metastases and in a larger cohort of patients. This future study will combine SFR spectroscopy with fine-needle aspiration, using the same needle, to perform preoperative in vivo measurements.

Single Fiber Reflectance Spectroscopy for the Monitoring of Cement Paste

Reinforced concrete structures are an essential part of our modern society, and monitoring their structural health is of paramount importance. Early detection of decay allows for the reduction of repair costs and, more importantly, the prevention of catastrophic failure. For this purpose, a single fiber reflectance spectrometer was embedded in cement paste samples for the monitoring of water at the fiber tip through its sensitivity to changes in the refractive index. It monitored the curing of samples with different water-to-cement ratios (w/c), between 0.45 and 0.60, measuring the water exhaust during the hardening of the cement paste. It also measured the capillary coefficient from cement paste samples of 0.50, 0.55 and 0.60 w/c: 0.668 ± 0.002 mm/√h, 1.771 ± 0.052 mm/√h and 6.360 ± 0.269 mm/√h, respectively. The capillary coefficient values agree with gravimetric measurements of sorptivity and are further confirmed through porosity measurements made with a scanning electron microscope. Thus, single fiber reflectance spectroscopy can be a gateway to inexpensively measure the entire life cycle of cement, from its curing until its eventual decay, assessing, in situ, its durability through the capillary coefficient.

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 , the absorption coefficient , and the phase function parameter . We validated this model with simulations.Aim: We validate our model experimentally. To prevent overfitting, we investigate the wavelength-dependence of 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% ( and at 500 nm) and eight concentrations of Evans Blue ( to at 605 nm). We parametrize as .Results: Average errors were 7% for , 11% for , and 16% with the parametrization of ; and 7%, 17%, and 16%, respectively, without. The parametrization of improved the fit speed 25 times (94 s to ). 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 parametrization prevents overfitting and speeds up the fit.

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.

The refractive index of human blood measured at the visible spectral region by single-fiber reflectance spectroscopy

The refractive index is an essential biophysical parameter used in many diagnostic and therapeutic biomedical applications. In the present study, the refractive index of control and anemic blood was measured using the total internal reflection fiber optics technique. For control, the refractive index measured by the indicated method was significantly higher than anemic blood over the wavelengths in the visible spectral region used in this study. Strong linear correlations between refractive index and hemoglobin concentration were obtained for control and anemic blood. These findings could enhance the use of the refractive index in many applications of blood analysis and hematology.

Subdiffuse scattering and absorption model for single fiber reflectance spectroscopy.

Single fiber reflectance (SFR) spectroscopy is a technique that is sensitive to small-scale changes in tissue. An additional benefit is that SFR measurements can be performed through endoscopes or biopsy needles. In SFR spectroscopy, a single fiber emits and collects light. Tissue optical properties can be extracted from SFR spectra and related to the disease state of tissue. However, the model currently used to extract optical properties was derived for tissues with modified Henyey-Greenstein phase functions only and is inadequate for other tissue phase functions. Here, we will present a model for SFR spectroscopy that provides accurate results for a large range of tissue phase functions, reduced scattering coefficients, and absorption coefficients. Our model predicts the reflectance with a median error of 5.6% compared to 19.3% for the currently used model. For two simulated tissue spectra, our model fit provides accurate results.

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.

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.

Subdiffuse scattering model for single fiber reflectance spectroscopy.

.To detect small-scale changes in tissue with optical techniques, small sampling volumes are required. Single fiber reflectance (SFR) spectroscopy has a sampling depth of a few hundred micrometers. SFR spectroscopy uses a single fiber to emit and collect light. The only available model to determine optical properties with SFR spectroscopy was derived for tissues with modified Henyey–Greenstein phase functions. Previously, we demonstrated that this model is inadequate for other tissue phase functions. We develop a model to relate SFR measurements to scattering properties for a range of phase functions, in the absence of absorption. Since the source and detector overlap, the reflectance cannot be accurately described by diffusion theory alone: SFR measurements are subdiffuse. Therefore, we describe the reflectance as a combination of a diffuse and a semiballistic component. We use the model of Farrell et al. for the diffuse component, solved for an overlapping source and detector fiber. For the semiballistic component, we derive a new parameter, , which incorporates the integrals of the phase function over 1 deg in the backward direction and 23 deg in the forward direction. Our model predicts the reflectance with a median error of 2.1%, compared to 9.0% for the currently available model.

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.

Refractive index measurement using single fiber reflectance spectroscopy.

A method using single fiber reflectance spectroscopy to measure the refractive indices of transparent and turbid media over a broad wavelength range is presented and tested. For transparent liquid samples, the accuracy is within 0.2%, and the accuracy increases with increasing wavelength. For liquid turbid media, the accuracy is within 0.3% and increases with decreasing wavelength. For solid turbid samples, such as human skin, the accuracy critically depends on the optical contact between the fiber and sample surface. It is demonstrated that this technique has the potential to measure refractive indices of biological tissue in vivo.

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.

Single fiber reflectance spectroscopy calibration

To accurately determine sample optical properties using single fiber reflectance spectroscopy (SFR), an absolute calibration of the reflectance is required. We investigated two SFR calibration methods, using a calibrated mirror and using the Fresnel reflection at the fiber tip as a reference. We compared these to commonly used calibration methods, using either Intralipid-20% in combination with Monte Carlo simulations or Spectralon as a reference. The Fresnel reflection method demonstrated the best reproducibility and yielded the most reliable result. We therefore recommend the Fresnel reflection method for the measured absolute reflectance calibration of SFR.

Abstract P4-01-01: Phase II in-human dose escalation study of the optical molecular imaging tracer bevacizumab-800cw for molecular fluorescence guided surgery in primary breast cancer patients

Abstract Introduction Molecular Fluorescence Guided Surgery (MFGS) might be used for intraoperative detection of positive resection margins in breast conserving surgery (BCS) for the treatment of breast cancer. Currently, the presence of tumor positive resection margins can only be assessed ex vivo by histopathological analysis of the excised tissue, which takes up to 5 working days. The current study defined the optimal dose of the near-infrared (NIR) optical imaging tracer bevacizumab-800CW to enable intraoperative detection and image-guided pathology of tumor positive resection margins in breast cancer patients. Methods Molecular Fluorescence Guided Surgery during BCS was performed in subjects treated for primary breast cancer. The NIR optical imaging tracer bevacizumab-800CW targeting vascular endothelial growth factor A was administered intravenously three days prior to surgery in four escalating dose groups (4.5mg, 10mg, 25mg and 50mg). NIR fluorescent signals were detected real-time using an intraoperative fluorescence camera system (SurgVision BV). Standardized ex vivo analyses of tumor-to-normal ratios (TNR) were performed to define the optimal tracer dose using a BlackBox imaging system (SurgVision BV) for imaging fresh bread loaf slices, a NIR fluorescence flatbed scanner (Odyssey, Li-Cor) for imaging 10µm slices of formalin-fixed paraffin-embedded (FFPE) blocks, NIR Confocal Laser Endomicroscopy (CLE, Mauna Kea Technologies) and multi-diameter single fiber reflectance and single fiber fluorescence (MDSFR/SFF) spectroscopy quantification to enable correction for the influence of tissue optical properties on fluorescence in tumor and normal breast tissue. Results Currently, 12 subjects have been included and analyzed in four dosing groups. All tumors showed specific tracer uptake at macroscopic and microscopic level during ex vivo analyses, confirmed by histopathology. Quantification of NIR fluorescent signals showed higher TNRs by increasing doses up to 25mg. No further increase in TNR was seen in the 50mg dose group. CLE showed the feasibility of visualization of the tracer accumulation in tumor tissue compared to normal tissue at a microscopic level. MDSFR/SFF spectroscopy objectively confirmed the dose dependency up to 25mg. Conclusion and future perspective Intravenous administration of bevacizumab-800CW in doses up to 50mg is safe and highly tumor specific, showing a plateau of TNR at 25mg and 50mg. Further expansion of the dosing cohorts of 10mg and 25mg with additional seven patients per group will be performed to establish the optimal dose for MFGS during BCS for an upcoming phase III multicenter randomized controlled trial. By enabling MFGS during BCS the surgical treatment of primary breast cancer patients might be optimized by a reduced need for re-excision surgery and thereby reducing the risk of co-morbidity, psychological burden, poor cosmesis and healthcare costs. Citation Format: van Dam GM, Koller M, Qiu SQ, Linssen MD, de Vries J, Jansen L, Kelder W, de Jong JS, Jorritsma-Smit A, van der Vegt B, Robinson DJ, Nagengast WB. Phase II in-human dose escalation study of the optical molecular imaging tracer bevacizumab-800cw for molecular fluorescence guided surgery in primary breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-01-01.

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. A single optical fiber was placed inside a 19-gauge biopsy needle during EUS-FNA and at least three reflectance measurements were taken prior to FNA. Spectroscopy measurements did not cause any related adverse events and prolonged procedure time with ? 5 ?? min . An accurate correlation between spectroscopy measurements and cytology could be made in nine patients (three benign and six malignant). The oxygen saturation and bilirubin concentration were significantly higher in benign tissue compared with malignant tissue (55% versus 21%, p = 0.038 ; 166 ?? ? mol / L versus 17 ?? ? mol / L , p = 0.039 , respectively). To conclude, incorporation of SF spectroscopy during EUS-FNA was feasible, safe, and relatively quick to perform. The optical properties of benign and malignant pancreatic tissue are different, implying that SF spectroscopy can potentially guide the FNA sampling.