Scott A. Walker

Frequency-domain multichannel optical detector for noninvasive tissue spectroscopy and oximetry

We have designed a multisource frequency-domain spectrometer for the optical study of biological tissues. Eight multiplexed, intensity-modulated LEDs are employed as the light sources. Four of them emit light at a peak wavelength of 715 nm (λ1); the other four, 850 nm (λ2). The frequency of intensity modulation is 120 MHz. This instrument measures the frequency-domain parameters phase, dc intensity, and ac amplitude at the two wavelengths λ1 and λ2 and for different distances between light source and detector. From these frequency-domain raw data, the absolute values of the absorption and reduced scattering coefficients of tissue at λ1 and λ2 are obtained. The oxy- and deoxyhemoglobin concentrations, and hence the hemoglobin saturation, are then analytically derived from the molar extinction coefficients. Acquisition times as short as hundreds of milliseconds provide real-time monitoring of the measured parameters. We performed a systematic test in vitro to quantify the precision and accuracy of the instrument reading. We also report in vivo measurements. This spectrometer can be packaged as a compact portable unit.

Assessment of the size, position, and optical properties of breast tumors in vivo by noninvasive optical methods

We present a method for the noninvasive determination of the size, position, and optical properties (absorption and reduced scattering coefficients) of tumors in the human breast. The tumor is first detected by frequency-domain optical mammography. It is then sized, located, and optically characterized by use of diffusion theory as amodel for the propagation of near-infrared light in breast tissue. Our method assumes that the tumor is a spherical inhomogeneity embedded in an otherwise homogeneous tissue. We report the results obtained on a 55-year-old patient with a papillary cancer in the right breast. We found that the tumor absorbs and scatters near-infrared light more strongly than the surrounding healthytissue. Our method has yielded a tumor diameter of 2.1 ? 0.2cm, which is comparable with the actual size of 1.6 cm, determined after surgery. From the tumor absorption coefficients at two wavelengths (690 and 825 nm), we calculated the total hemoglobin concentration (40 ? 10 muM) and saturation (71 ? 9%) of the tumor. These results can provide the clinical examiner with more detailed information about breast lesions detected by frequency-domain optical mammography, thereby enhancing its potential for specificity.

IMAGE RECONSTRUCTION BY BACKPROJECTION FROM FREQUENCY-DOMAIN OPTICAL MEASUREMENTS IN HIGHLY SCATTERING MEDIA

The reconstruction of the location and optical properties of objects in turbid media requires the solution of the inverse problem. Iterative solutions to this problem can require large amounts of computing time and may not converge to a unique solution. Instead, we propose a fast, simple method for approximately solving this problem in which calculated effective absorption and reduced scattering coefficients are backprojected to create an image of the objects. We reconstructed images of objects with centimeter dimensions embedded in a diffusive medium with optical characteristics similar to those of human tissue. Data were collected by a frequency-domain spectrometer operating at 120 MHz with a laser diode light source emitting at 793 nm. Intensity and phase of the incident photon density wave were collected from linear scans at different projection angles. Although the positions of the objects are correctly identified by the reconstructed images, the optical parameters of the objects are recovered only qualitatively.

Photon density waves scattered from cylindrical inhomogeneities: theory and experiments

We present an analytical solution for the scattering of diffuse photon density waves from an infinite circular, cylindrical inhomogeneity embedded in a homogeneous highly scattering turbid medium. The analytical solution, based on the diffusion approximation of the Boltzmann transport equation, represents the contribution of the cylindrical inhomogeneity as a series of modified Bessel functions integrated from zero to infinity and weighted by different angular dependencies. This series is truncated at the desired precision, similar to the Mie theory. We introduce new boundary conditions that account for specular reflections at the interface between the background medium and the cylindrical inhomogeneity. These new boundary conditions allow the separate recovery of the index of refraction of an object from its absorption and reduced scattering coefficients. The analytical solution is compared with data obtained experimentally to evaluate the predictive capability of the model. Optical properties of known cylindrical objects are recovered accurately. However, as the radius of the cylinder decreases, the required measurement signal-to-noise ratiorapidly increases. Because of the new boundary conditions, an upperlimit can be placed on the recovered size of cylindrical objects with radii below 0.3 cm if they have a substantially different index of refraction from that of the background medium.

Effect of index of refraction mismatch on the recovery of optical properties of cylindrical inhomogeneities in an infinite turbid medium

Optical inhomogeneities embedded in a turbid medium are characterized not only by their absorption and reduced scattering coefficients, but also by their index of refraction relative to the background medium. Although in diffusion theory it is impossible to separate the index of refraction from the absorption and reduced scattering coefficients in an infinite homogeneous medium, application of boundary conditions for an inhomogeneity adds enough information to separately determine these optical properties. A mismatched index of refraction affects diffuse photon propagation in two ways: photons travel at a different speed inside the inhomogeneity, and photons entering and leaving the inhomogeneity are influenced by Fresnel reflections at the surface of the object. We have integrated these two effects into the analytical solution to the diffusion equation for a cylinder in an infinite medium. Theoretical results are compared with experimental data, and the effect of index of refraction mismatch is evaluated for different combinations of optical properties.

Back-projection image reconstruction using photon density waves in tissues

The reconstruction of scattering and absorption inhomogeneities in tissues generally involves the solution of the inverse scattering problem. This is a computationally intesive task that cannot be easily performed during image acquisition. Instead, we obtain approximate spatial maps of absorption and scattering coefficients using a back-projection algorithm, similar in principle to that used in computerized tomography. Given the nonlinear nature of light propagation in tissue, we expect that this approach can only give a first approximation solution of the reconstruction problem. Our preliminary results indicate that relatively accurate maps are rapidly obtained. We have reconstructed, to a first approximation, the optical parameters and positions of scattering and partially absorbing objects. Our back-projection approach employs frequency-domain methods using a light emitting diode as the light source (100 MHz modulation frequency, peak wavelength 715 nm). Data is collected from multiple linear scans of the investigated area at different projection angles, as in computerized tomography.

In vivo study of human tissues with a portable near-infrared tissue spectrometer

In this paper, we present a series of measurements made with a portable frequency-domain near-infrared tissue spectrometer (OMNIA). This is the first application of the OMNIA in a clinical setting. All of the measurements presented here were taken in vivo, most were on human subjects. We report the results of three experiments: (1) A simple ischemia/plethysmography experiment, which indicates ability of the instrument to noninvasively, continuously monitor the hemoglobin saturation of a limb. (2) A survey of hemoglobin saturation in patients with peripheral vascular disease. (3) An animal experiment to demonstrate the correlation of our instrument readings with results from established techniques for measuring hemoglobin saturation. We measured the absorption and reduced scattering coefficients of the tissue at two wavelengths (715 nm and 850 nm). From the absorption coefficients, we calculated the concentrations of oxygenated and deoxygenated hemoglobin ([HbO2] and [Hb]), which immediately yield the hemoglobin saturation (Y) and the total blood volume (T) in the tissue. Our preliminary results indicate some of the potential of the instrument and the areas for future improvement of it.

Tissue optical parameter map generated with frequency-domain spectroscopy

Near infrared optical imaging is emerging as a potentially important imaging modality, because it offers real time data access, portability, cost-effectiveness, and the relatively safe use of non-ionizing radiation. Reconstruction of images by optical tomography is complicated by the diffusive character of light propagation in optically heterogeneous tissue. The spatial volume element probed by the light path between the light source and optical detector is rather wide and depends on a variety of experimental and instrumental factors. We have published an optical image of the hand in air based on photon density wave distribution characteristics, using both steady-state (intensity) and frequency-domain (phase and modulation) experimental conditions. Since then, we have developed new instrumentation, better measurement protocols, some reconstruction algorithms and a more complete theoretical understanding of photon diffusion in both homogeneous and heterogeneous media. We have now performed frequency-domain measurements (at a modulation frequency of 160 MHz with 760 nm near infrared light) with the hand immersed in a scattering fluid (the infinite geometry arrangement). The advantages of our current approach include the spectroscopic resolution of physiologically interesting tissue regions, greater spatial resolution, the generation of absorption and reduced scattering coefficient maps of the image, rapid data acquisition, real time simultaneous display of the experimental parameters and calculated optical parameters and the possibility of obtaining some tomographic reconstruction.

Study of the FMRI blood oxygen level dependent effect by near-infrared spectroscopy

In order to study the behavior of cerebral physiological parameters and to further the understanding of the fMRI blood-oxygen-level-dependent (BOLD) effect, we have recorded simultaneously multi-source frequency-domain near-infrared and BOLD fMRI signals during motor functional activation in humans. From the near-infrared data we obtained information on the changes in cerebral blood volume and oxygenation. In order to relate our observations to changes in cerebral blood flow we employed the “balloon” model of cerebral perfusion. Our data showed that the deoxyhemoglobin concentration is the major factor determining the time course of the BOLD signal.

Spectroscopy and Tomography of Tissues in the Frequency-Domain

Substantial progress in the field of light spectroscopy and imaging of tissues was achieved when the group of Chance, Patterson and Wilson showed that the optical parameters of a turbid medium can be obtained from time resolved measurements of short light pulses propagating in the medium (Patterson et al, 1991a). Essentially, a fit of the intensity as a function of time, measured at some distance from the source, can provide separately the values of the absorption and of the reduced scattering coefficients. This demonstration was important because the focus was shifted from attempts to separate the scattering from absorption, using empirical corrections to the Beer-Lambert law, to a rigorous application of a physical model. During the same period, our lab proposed employing the Fourier transform equivalent concept using an intensity modulated light source (Gratton et al, 1990). Since frequency domain methods have better resolution and sensitivity and are much faster than the time domain methods, our proposal was followed by many others including Chance, Patterson and Wilson (Boas et al, 1993, 1994; Cui and Ostrander, 1993; Duncan et al, 1993; Kaltenbach and Kaschke, 1993; O’Leary et al, 1992; Patterson et al, 1991b; Tromberg et al, 1993). It is well known that time domain and frequency domain measurements are mathematically equivalent, when the frequency domain measurement is carried out using a wide range of modulation frequencies (Gratton et al, 1983; Alcala et al, 1984). However, frequency domain measurements can be made at a single modulation frequency, thereby sacrificing some of the information. The advantage of measurements at a single frequency is that they can be very fast, accurate and have an excellent signal-to-noise ratio.