Nienke Bosschaart

Combined Raman spectroscopy and optical coherence tomography device for tissue characterization

We report a dual-modal device capable of sequential acquisition of Raman spectroscopy (RS) and optical coherence tomography (OCT) along a common optical axis. The device enhances application of both RS and OCT by precisely guiding RS acquisition with OCT images while also compensating for the lack of molecular specificity in OCT with the biochemical specificity of RS. We characterize the system performance and demonstrate the capability to identify structurally ambiguous features within an OCT image with RS in a scattering phantom, guide acquisition of RS from a localized malignancy in ex vivo breast tissue, and perform in vivo tissue analysis of a scab.

Limitations and Opportunities of Transcutaneous Bilirubin Measurements

OBJECTIVE: Although transcutaneous bilirubinometers have existed for over 30 years, the clinical utility of the technique is limited to a screening method for hyperbilirubinemia, rather than a replacement for invasive blood sampling. In this study, we investigate the reason for this limited clinical value and address possibilities for improvement. METHODS: To obtain better insight into the physiology of bilirubin measurements, we evaluated a transcutaneous bilirubinometer that determines not only the cutaneous bilirubin concentration (TcB) but also the blood volume fraction (BVF) in the investigated skin volume. For 49 neonates (gestational age 30 ± 3.1 weeks, postnatal age 6 [4–10] days) at our NICU, we performed 124 TcB and 55 BVF measurements. RESULTS: The TcB correlated well with the total serum bilirubin concentration (TSB) (r = 0.88) with an uncertainty of 55 µmol/L. The BVF in the measured skin volume ranged between 0.1% and 0.75%. CONCLUSIONS: The performance of our bilirubinometer is comparable to existing transcutaneous devices. The limited clinical value of current bilirubinometers can be explained by the low BVF in the skin volume that is probed by these devices. Because the TcB depends for over 99% on the contribution of extravascular bilirubin, it is a physiologically different parameter from the TSB. Hence, the standard method of evaluation that compares the TcB to the TSB is insufficient to fully investigate the clinical value of transcutaneous bilirubinometers, ie, their predictive value for kernicterus. We suggest that the clinical value may be improved considerably by changing either the method of evaluation or the technological design of transcutaneous bilirubinometers.

Measurements of wavelength dependent scattering and backscattering coefficients by low-coherence spectroscopy

Quantitative measurements of scattering properties are invaluable for optical techniques in medicine. However, noninvasive, quantitative measurements of scattering properties over a large wavelength range remain challenging. We introduce low-coherence spectroscopy as a noninvasive method to locally and simultaneously measure scattering μ(s) and backscattering μ(b) coefficients from 480 to 700 nm with 8 nm spectral resolution. The method is tested on media with varying scattering properties (μ(s) = 1 to 34 mm(-1) and μ(b) = 2.10(-6) to 2.10(-3) mm(-1)), containing different sized polystyrene spheres. The results are in excellent agreement with Mie theory.

Quantitative measurements of absorption spectra in scattering media by low-coherence spectroscopy

Low-coherence spectroscopy (LCS) is a spectroscopic method that allows for quantitative and localized assessment of absorption spectra by combining reflection spectroscopy with low-coherence interferometry. We describe absorption coefficient (mu(a)) measurements by LCS in tissue simulating phantoms with varying scattering and absorbing properties. We used LCS in the 455-680 nm wavelength range with a spectral resolution of 8 nm to obtain mu(a) spectra with +/-0.5 mm(-1) accuracy. We conclude that LCS is a promising technique for the in vivo determination of tissue chromophore concentrations.

Quantitative comparison of analysis methods for spectroscopic optical coherence tomography

Spectroscopic optical coherence tomography (sOCT) enables the mapping of chromophore concentrations and image contrast enhancement in tissue. Acquisition of depth resolved spectra by sOCT requires analysis methods with optimal spectral/spatial resolution and spectral recovery. In this article, we quantitatively compare the available methods, i.e. the short time Fourier transform (STFT), wavelet transforms, the Wigner-Ville distribution and the dual window method through simulations in tissue-like media. We conclude that all methods suffer from the trade-off in spectral/spatial resolution, and that the STFT is the optimal method for the specific application of the localized quantification of hemoglobin concentration and oxygen saturation.

In vivo low-coherence spectroscopic measurements of local hemoglobin absorption spectra in human skin

Localized spectroscopic measurements of optical properties are invaluable for diagnostic applications that involve layered tissue structures, but conventional spectroscopic techniques lack exact control over the size and depth of the probed tissue volume. We show that low-coherence spectroscopy (LCS) overcomes these limitations by measuring local attenuation and absorption coefficient spectra in layered phantoms. In addition, we demonstrate the first in vivo LCS measurements of the human epidermis and dermis only. From the measured absorption in two distinct regions of the dermal microcirculation, we determine total hemoglobin concentration (3.0±0.5 g∕l and 7.8±1.2 g∕l) and oxygen saturation.

Validation of quantitative attenuation and backscattering coefficient measurements by optical coherence tomography in the concentration-dependent and multiple scattering regime

Abstract. Optical coherence tomography (OCT) has the potential to quantitatively measure optical properties of tissue such as the attenuation coefficient and backscattering coefficient. However, to obtain reliable values for strong scattering tissues, accurate consideration of the effects of multiple scattering and the nonlinear relation between the scattering coefficient and scatterer concentration (concentration-dependent scattering) is required. We present a comprehensive model for the OCT signal in which we quantitatively account for both effects, as well as our system parameters (confocal point spread function and sensitivity roll-off). We verify our model with experimental data from controlled phantoms of monodisperse silica beads (scattering coefficients between 1 and 30  mm−1 and scattering anisotropy between 0.4 and 0.9). The optical properties of the phantoms are calculated using Mie theory combined with the Percus–Yevick structure factor to account for concentration-dependent scattering. We demonstrate excellent agreement between the OCT attenuation and backscattering coefficient predicted by our model and experimentally derived values. We conclude that this model enables us to accurately model OCT-derived parameters (i.e., attenuation and backscattering coefficients) in the concentration-dependent and multiple scattering regime for spherical monodisperse samples.

Spectral domain detection in low-coherence spectroscopy

Low-coherence spectroscopy (LCS) offers the valuable possibility to measure quantitative and wavelength resolved optical property spectra within a tissue volume of choice that is controllable both in size and in depth. Until now, only time domain detection was investigated for LCS (tdLCS), but spectral domain detection offers a theoretical speed/sensitivity advantage over tdLCS. In this article, we introduce a method for spectral domain detection in LCS (sdLCS), with optimal sensitivity as a function of measurement depth. We validate our method computationally in a simulation and experimentally on a phantom with known optical properties. The attenuation, absorption and scattering coefficient spectra from the phantom that were measured by sdLCS agree well with the expected optical properties and the measured optical properties by tdLCS.

Imaging of venous valves with photoacoustics

We report results of a feasibility study regarding the question whether or not venous valves can be imaged using photoacoustics, and how they will appear in the images. First an in vitro study was made on tissue phantoms consisting of blood filled rubber tubes with discontinuities in the inner tube wall. We also have studied superficial veins on the ventral side of the wrist. For excitation, an Nd:YAG laser at 1064 nm was used. Detection of acoustic signals was performed with a PVdF sensor consisting of two concentric rings. Measurements were performed on valves which where first localized by palpation. The phantom studies showed that irregular structures of the tube walls could clearly be identified from the photoacoustic images. Furthermore, in a photoacoustic image of a vein at the dorsal side of the wrist, the presence of a valve could be identified from a region of increased signal intensity within the vessel lumen.

Measuring the reduced scattering coefficient and γ with SFR spectroscopy: studying the phase function dependence (Conference Presentation)

Both Optical Coherence Tomography (OCT) and Single Fiber Reflectance Spectroscopy (SFR) are used to determine various optical properties of tissue. We developed a method combining these two techniques to measure the scattering anisotropy (g1) and γ (=1-g2/1-g1), related to the 1st and 2nd order moments of the phase function. The phase function is intimately associated with the cellular organization and ultrastructure of tissue, physical parameters that may change during disease onset and progression. Quantification of these parameters may therefore allow for improved non-invasive, in vivo discrimination between healthy and diseased tissue. With SFR the reduced scattering coefficient and γ can be extracted from the reflectance spectrum (Kanick et al., Biomedical Optics Express 2(6), 2011). With OCT the scattering coefficient can be extracted from the signal as a function of depth (Faber et al., Optics Express 12(19), 2004). Consequently, by combining SFR and OCT measurements at the same wavelengths, the scattering anisotropy (g) can be resolved using µs’= µs*(1-g). We performed measurements on a suspension of silica spheres as a proof of principle. The SFR model for the reflectance as a function of the reduced scattering coefficient and γ is based on semi-empirical modelling. These models feature Monte-Carlo (MC) based model constants. The validity of these constants - and thus the accuracy of the estimated parameters - depends on the phase function employed in the MC simulations. Since the phase function is not known when measuring in tissue, we will investigate the influence of assuming an incorrect phase function on the accuracy of the derived parameters.