Anisotropy of light propagation in human skin.

Using spatially resolved, steady state diffuse reflectometry, a directional dependence was found in the propagation of visible and near infrared light through human skin in vivo. The skin's reduced scattering coefficient mu(s)' varies by up to a factor of two between different directions of propagation at the same position. This anisotropy is believed to be caused by the preferential orientation of collagen fibres in the dermis, as described by Langer's skin tension lines. Monte Carlo simulations that examine the effect of partial collagen fibre orientation support this hypothesis. The observation has consequences for non-invasive diagnostic methods relying on skin optical properties, and it could be used non-invasively to determine the direction of lines of cleavage in order to minimize scars due to surgical incisions.

Nanoporous anti-fouling silicon membranes for biosensor applications.

The ability to create biocompatible well-controlled membranes has been an area of great interest over the last few years, particularly for biosensor applications. The present study describes the fabrication and characterization of novel nanoporous micromachined membranes that exhibit selective permeability and low biofouling. Results indicate that such membranes can be fabricated with uniform pore sizes capable of the simultaneous exclusion of albumin and diffusion of glucose. Compared to polymeric membranes of similar pore size, micromachined silicon membranes allowed more than twice the amount of glucose diffusion after 240 min and complete albumin exclusion. Moreover, membranes exhibit no morphological change or degradability in the presence of biological proteins and fluids at 37 degrees C. The results point to the potential of using such membranes for implantable biosensor applications. With monodisperse pores sizes as small as 10 nm, these membranes offer advantages in their reproducibility, stability, and ability to be integrated in silicon-based biosensing technology.

Near-infrared optical properties of ex vivo human skin and subcutaneous tissues measured using the Monte Carlo inversion technique.

The absorption and transport scattering coefficients of caucasian and negroid dermis, subdermal fat and muscle have been measured for all wavelengths between 620 and 1000 nm. Samples of tissue 2 mm thick were measured ex vivo to determine their reflectance and transmittance. A Monte Carlo model of the measurement system and light transport in tissue was then used to recover the optical coefficients. The sample reflectance and transmittance were measured using a single integrating sphere 'comparison' method. This has the advantage over conventional double-sphere techniques in that no corrections are required for sphere properties, and so measurements sufficiently accurate to recover the absorption coefficient reliably could be made. The optical properties of caucasian dermis were found to be approximately twice those of the underlying fat layer. At 633 nm, the mean optical properties over 12 samples were 0.033 mm(-1) and 0.013 mm(-1) for absorption coefficient and 2.73 mm(-1) and 1.26 mm(-1) for transport scattering coefficient for caucasian dermis and the underlying fat layer respectively. The transport scattering coefficient for all biological samples showed a monotonic decrease with increasing wavelength. The method was calibrated using solid tissue phantoms and by comparison with a temporally resolved technique.

Effect of temperature on the optical properties of ex vivo human dermis and subdermis.

The effect of temperature on the optical properties of human dermis and subdermis as a function of near-infrared wavelength has been studied between 25 degrees C and 40 degrees C. Measurements were performed ex vivo on a total of nine skin samples taken from the abdomen of three individuals. The results show a reproducible effect of temperature on the transport scattering coefficient of dermis and subdermis. The relative change of the transport scattering coefficient showed an increase for dermis ((4.7+/-0.5) x 10(-3) degrees C(-1)) and a decrease for subdermis ((-1.4+/-0.28) x 10(-3) degrees C(-1)). Note that the magnitude of the temperature coefficient of scattering was greater for dermis than subdermis. A reproducible effect of temperature on the absorption coefficient could not be found within experimental errors. System reproducibility in transport scattering coefficient with repeated removal and repositioning of the same tissue sample at the same temperature was excellent at +/-0.35% for all measurements. This reproducibility enabled such small changes in scattering coefficient to be detected.

Influence of layered tissue architecture on estimates of tissue optical properties obtained from spatially resolved diffuse reflectometry.

Most instruments used to measure tissue optical properties noninvasively employ data-analysis algorithms that rely on the simplifying assumption that the tissue is semi-infinite and homogeneous. The influence of a layered tissue architecture on the determination of the scattering and absorption coefficients has been investigated in this study. Reflectance as a function of distance from a point source for a two-layered tissue architecture that simulates skin overlying fat was calculated by using a Monte Carlocode. These data were analyzed by using a diffusion theory modelfor a homogeneous semi-infinite medium to calculate the scatter and absorption coefficients. Depending on the algorithm and the radial distance, the estimated tissue optical properties were different from those of either layer, and under some circumstances, physically impossible. In addition, the sensitivity and cross talk of the estimated optical properties to changes in input optical properties were calculated for different layered geometries. For typical optical properties of skin, the sensitivity to changes in optical properties is highly dependent on the layered architecture, the measurement distance, and the fitting algorithm. Furthermore, a change in the input absorption coefficient may result in an apparent change in the measured scatter coefficient, and a change in the in put scatter coefficient may result in an apparent change in the measured absorption coefficient.

Correlation between blood glucose concentration in diabetics and noninvasively measured tissue optical scattering coefficient.

Diabetics would benefit greatly from a device capable of providing continuous noninvasive monitoring of their blood glucose levels. The optical scattering coefficient of tissue depends on the concentration of glucose in the extracellular fluid. A feasibility study was performed to evaluate the sensitivity of the tissue reduced scattering coefficient in response to step changes in the blood glucose levels of diabetic volunteers. Estimates of the scattering coefficient were based on measurements of the diffuse reflectance on the skin at distances of 1-10 mm from a point source. A correlation was observed between step changes in blood glucose concentration and tissue reduced scattering coefficient in 30 out of 41 subjects measured.

The influence of glucose concentration upon the transport of light in tissue-simulating phantoms.

The effect of glucose upon the transport of light in tissue-simulating phantoms is shown and its possible application for non-invasive glucose monitoring in diabetic patients is discussed. The aim of this paper is to investigate the physical background of this effect. The presence of glucose in an aqueous solution increases its refractive index and therefore has an influence upon the scattering properties of particles suspended in solution. Experimental data on the effect of glucose upon the scattering coefficient and the phase function of aqueous suspensions of spherical polystyrene particles are presented for near-infrared wavelengths and compared to values predicted by Mie theory. The subsequent effect upon light transport in multiple scattering, tissue-simulating phantoms is demonstrated experimentally in a slab geometry and theoretically by applying diffusion theory. It is furthermore shown that optional measurements in the frequency domain allow changes of absorption and scattering coefficient to be separately determined. The possible magnitude of this glucose effect in tissue in vivo is discussed.

Influence of glucose concentration on light scattering in tissue-simulating phantoms.

The presence of glucose dissolved in an aqueous solution increases the refractive index of the solution and therefore has an influence on the scattering properties of any particles suspended within it. We present experimental data on the effect of glucose concentration on the scattering coefficient of a suspension of spherical polystyrene particles. The experimental results are in good agreement with Mie theory. The effect of glucose on light transport in highly scattering, tissue-simulating phantoms is demonstrated both experimentally and theoretically by application of diffusion theory. The possible application of this effect for noninvasive glucose monitoring of diabetic patients is discussed.

A Monte Carlo investigation of optical pathlength in inhomogeneous tissue and its application to near-infrared spectroscopy.

In order to quantify near-infrared spectroscopic (NIRS) data on an inhomogeneous medium, knowledge of the contribution of the various parts of the medium to the total NIRS signal is required. This is particularly true in the monitoring of cerebral oxygenation by NIRS, where the contribution of the overlying tissues must be known. The concept of the time point spread function (TPSF), which is used extensively in NIRS to determine the effective optical pathlength, is expanded to the more general inhomogeneous case. This is achieved through the introduction of the partial differential pathlength, which is the effective optical pathlength in the inhomogeneous medium, and an analytical proof of the applicability of the modified Beer-Lambert law in an inhomogeneous medium is shown. To demonstrate the use of partial differential pathlength, a Monte Carlo simulation of a two-concentric-sphere medium representing a simplified structure of the head is presented, and the possible contribution of the overlying medium to the total NIRS signal is discussed.

Measurement of the optical properties of the skull in the wavelength range 650-950 nm.

The optical properties of samples of bone from pig skull have been measured over the wavelength range 650-950 nm. The scattering phase function was measured on thin samples of the bone using a goniometer, and a value for the mean cosine g, of the scattering angle, was calculated. The scattering and absorption coefficients, mu s and mu a were then determined from measurements of diffuse reflectance and transmittance made with a pair of integrating spheres, by a step-wise search through a table of diffuse reflectance and transmittance versus mu a and mu s generated by a Monte Carlo model incorporating the measured scattering phase function. Values for g measured on six samples varied from 0.925 +/- 0.014 at 650 nm to 0.945 +/- 0.013 at 950 nm. Corresponding values for mu a and mu s measured on 18 samples were mu a = 0.04 +/- 0.002 mm-1, mu s = 35 +/- 0.7 mm-1 at 650 nm to mu a = 0.05 +/- 0.002 mm-1, mu s = 24 +/- 0.6 mm-1 at 950 nm.

Spectral dependence of temporal point spread functions in human tissues.

We have determined the spectral dependence of the temporal point spread functions of human tissues experimentally between 740 and 840 nm in transmittance measurements on the adult head, forearm, and calf (in vivo) and the infant head (post mortem) by using picosecond laser pulses and a streak camera detector. Two parameters are extracted from the temporal point spread function; the differential path-length factor (DPF), calculated from the mean time, and the slope of the logarithmic intensity decay. In all tissues the DPF and the logarithmic slope show a reciprocal relationship and exhibit characteristics of the absorption spectra of hemoglobin. The DPF falls with increasing wavelength, the variation being typically 12%, while the logarithmic slope increases with wavelength. A quantitative analysis of the logarithmic slope spectrum significantly underestimated expected tissue chromophore concentrations. The absolute magnitudes of the DPF showed considerable intersubject variation, but the variation with wavelength was consistent and thus may be used in the correction of tissue attenuation spectra.

Experimentally measured optical pathlengths for the adult head, calf and forearm and the head of the newborn infant as a function of inter optode spacing.

The Differential Pathlength Factor (DPF) has been measured for several different tissues. The results showed that the DPF varied with the type of tissue studied, and in the case of the adult calf with sex. However, the DPF for all tissues studied was constant once the inter optode spacing exceeded 2.5 cm. Thus, measurements can be made by NIR spectroscopy at a range of inter optode spacings, and a single DPF used in the calculation of chromophore concentration. The results also showed that the major source of error in the DPF lay in the measurement of the inter optode spacing. To improve accuracy, two options are possible. Firstly, some means of continuous measurement of inter optode spacing could be incorporated in the NIR instrumentation. The better alternative would be an instrument incorporating a method of directly measuring the optical pathlength at each wavelength. This could be done either by time of flight measurement, or if it can be validated, by phase shift measurement.

Krypton filled flashlamp: a possible new light source for near infrared spectroscopy in vivo.

We have designed a reliable and flexible low cost instrument for NIR spectroscopy. A krypton filled flashlamp was used as inexpensive light source. Providing a number of suitable emission peaks in the NIR, this flashlamp is ideal for NIR spectroscopy. Application to other NIR spectroscopy systems, e.g. to CCD (Charge Coupled Device) spectrophotometers, should be possible. The introduced system was tested on human arm tissue during arterial occlusion. Results equivalent to those described by other authors could be obtained by this new technical approach.