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Optical tomography is being developed as a means of detecting and specifying disease in the adult female breast. We present a series of clinical three-dimensional optical images obtained with a 32-channel time-resolved system and a liquid-coupled interface. Patients place their breasts in a hemispherical cup to which sources and detectors are coupled, and the remaining space is filled with a highly scattering fluid. A cohort of 38 patients has been scanned, with a variety of benign and malignant lesions. Images show that hypervascularization associated with tumors provides very high contrast due to increased absorption by hemoglobin. Only half of the fibroadenomas scanned could be observed, but of those that could be detected, all but one revealed an apparent increase in blood volume and a decrease in scatter and oxygen saturation.

To investigate the accuracy of measuring cerebral blood flow (CBF) using a bolus injection of Indocyanine Green (ICG) detected by near-infrared spectroscopy in adult human heads, simulations were performed using a two-layered model representing the extracerebral and intracerebral layers. Modeled optical data were converted into tissue ICG concentration using either the one-detector modified Beer-Lambert law (MBLL) method, or the two-detector partial path-length (PPL) method. The CBFs were estimated using deconvolution and blood flow index techniques. Using the MBLL method, the CBFs were significantly underestimated but the PPL method improved their accuracy and robustness, especially when used as relative measures. The dispersion of the arterial input function also affected the CBF estimates.

Most research in optical imaging incorrectly assumes that light transport in nonscattering regions in the head may be modeled by use of the diffusion approximation. The effect of this assumption is examined in a series of experiments on tissue-equivalent phantoms. Images from cylindrical and head-shaped phantoms with and without clear regions [simulating the cerebrospinal fluid (CSF) filled ventricles] and a clear layer (simulating the CSF layer surrounding the brain) are reconstructed with linear and nonlinear reconstruction techniques. The results suggest that absorbing and scattering perturbations can be identified reliably with nonlinear reconstruction methods when the clear regions are also present in the reference data but that the quality of the image degrades considerably if the reference data does not contain these features. Linear reconstruction performs similarly to nonlinear reconstruction, provided the clear regions are present in the reference data, but otherwise linear reconstruction fails. This study supports the use of linear reconstruction for dynamic imaging but suggests that, in all cases, image quality is likely to improve if the clear regions are modeled correctly.

We have begun clinical trials of optical tomography of the neonatal brain. To validate this research, we have built and imaged an anatomically realistic, tissue-equivalent neonatal head phantom that is hollow, allowing contrasting objects to be placed inside it. Images were reconstructed by use of two finite-element meshes, one generated from a computed tomography image of the phantom and the other spherical. The phantom was filled with a liquid of the same optical properties as the outer region, and two perturbations were placed inside. These were successfully imaged with good separation between the absorption and scatter coefficients. The phantom was then refilled with a liquid of increased absorption compared with the background to simulate the brain, and the absolute properties of the two regions were found. These were used as a priori information for the complete reconstruction. Both perturbations were visible, superimposed on the increased absorption of the central region. The head-shaped mesh performed slightly better than the spherical mesh, particularly when the absorption of the central region of the phantom was increased.

It is important for near-infrared spectroscopy (NIRS) and imaging to estimate the sensitivity of the detected signal to the change in hemoglobin that results from brain activation and the volume of tissue interrogated for a specific source-detector fiber spacing. In this study light propagation in adult head models is predicted by Monte Carlo simulation to investigate the effect of the superficial tissue thickness on the partial optical path length in the brain and on the spatial sensitivity profile. In the case of source-detector spacing of 30 mm, the partial optical path length depends mainly on the depth of the inner skull surface whereas the spatial sensitivity profile is significantly affected by the thickness of the cerebrospinal fluid layer. The mean optical path length that can be measured by time-resolved experiments increases when the skull thickness increases whereas the partial mean optical path length in the brain decreases when the skull thickness increases. These results indicate that it is not appropriate to use the mean optical path length as an alternative to the partial optical path length to compensate the NIRS signal for the difference in sensitivity caused by variation of the superficial tissue thickness.

Adequate modeling of light propagation in a human head is important for quantitative near-infrared spectroscopy and optical imaging. The presence of a nonscattering cerebrospinal fluid (CSF) that surrounds the brain has been previously shown to have a strong effect on light propagation in the head. However, in reality, a small amount of scattering is caused by the arachnoid trabeculae in the CSF layer. In this study, light propagation in an adult head model with discrete scatterers distributed within the CSF layer has been predicted by Monte Carlo simulation to investigate the effect of the small amount of scattering caused by the arachnoid trabeculae in the CSF layer. This low scattering in the CSF layer is found to have little effect on the mean optical path length, a parameter that can be directly measured by a time-resolved experiment. However, the partial optical path length in brain tissue that relates the sensitivity of the detected signal to absorption changes in the brain is strongly affected by the presence of scattering within the CSF layer. The sensitivity of the near-infrared signal to hemoglobin changes induced by brain activation is improved by the effect of a low-scattering CSF layer.

A 32-channel time-resolved imaging device for medical optical tomography has been employed to evaluate a scheme for imaging the human female breast. The fully automated instrument and the reconstruction procedure have been tested on a conical phantom with tissue-equivalent optical properties. The imaging protocol has been designed to obviate compression of the breast and the need for coupling fluids. Images are generated from experimental data with an iterative reconstruction algorithm that employs a three-dimensional (3D) finite-element diffusion-based forward model. Embedded regions with twice the background optical properties are revealed in separate 3D absorption and scattering images of the phantom. The implications for 3D time-resolved optical tomography of the breast are discussed.

Previous modeling of near-infrared (NIR) light distribution in models of the adult head incorporating a clear nonscattering cerebrospinal fluid (CSF) layer have shown the latter to have a profound effect on the resulting photon measurement density function (PMDF). In particular, the presence of the CSF limits the PMDF largely to the outer cortical gray matter with little signal contribution from the deeper white matter. In practice, the CSF is not a simple unobstructed clear layer but contains light-scattering membranes and is crossed by various blood vessels. Using a radiosity-diffusion finite-element model, we investigated the effect on the PMDF of introducing intrusions within the clear layer. The results show that the presence of such obstructions does not significantly increase the light penetration into the brain tissue, except immediately adjacent to the obstruction and that its presence also increases the light sampling of the adjacent skull tissues, which would lead to additional contamination of the NIR spectroscopy signal by the surface tissue layers.

Following several years of development the construction of a multichannel time-resolved imaging device for medical optical tomography has been completed. Images are reconstructed from time-resolved measurements by use of a scheme that employs a finite-element diffusion-based forward model and an iterative reconstruction solver. Prior to testing on clinical subjects the fully automated instrument and the reconstruction software are evaluated with tissue-equivalent phantoms. We describe our first attempt to generate multiple-slice images of a phantom without uniform properties along the axial direction, while still using a computationally fast two-dimensional reconstruction algorithm. The image quality is improved by the employment of an approximate correction method that uses scaling factors derived from the ratios of finite-element forward simulations in two and three spatial dimensions. The 32-channel system was employed to generate maps of the internal scattering and the absorption properties at 14 different transverse planes across the phantom. The images clearly reveal the locations of small inhomogeneous regions embedded within the phantom. These results were obtained by use of purely temporal data and without resource to reference measurements.

An independent assessment is described of a dual-wavelength imaging technique, known as the temporally extrapolated absorbance method (TEAM), proposed by Yamada et al. [Opt. Eng.32, 634–641 (1993)]. The technique involves recording the temporal distribution of light transmitted across a scattering medium at two carefully chosen wavelengths at which the scattering properties of the medium are assumed to be identical. The objective is to image internal structure that absorbs more strongly at one wavelength than it does at the other. A simple theoretical treatment of TEAM is presented that employs a perturbation model of photon transport. This indicates that despite the lack of a secure theoretical basis, the technique may provide a potentially effective ad hoc method of generating images of highly scattering media. The method was also evaluated experimentally by using, for the first time to our knowledge, a single object and two wavelengths. A single-projection, two-dimensional image was obtained of a solid phantom with optical properties representative of breast tissue. The results exhibited good agreement with the theoretical model, and a small embedded feature that absorbs 3.5 times as strongly as the surrounding medium at one wavelength was revealed successfully.

We present in vivo values for the optical transport coefficients (μ_a, μ_s′) of the adult human forearm, calf, and head from 760 to 900 nm measured with time-resolved spectroscopy. The accuracy of the method is tested with tissue-simulating phantoms. We obtain μ_s′(λ) ≈ 1.1 - (5.1 × 10^-4 λ) mm^-1 (forearm), 1.6 - (8.9 × 10^-4 λ) mm^-1 (calf), and 1.45 - (6.5 × 10^-4 λ) mm^-1 (head), where λ is measured in nanometers. At 800 nm we obtain μ_a = 0.023 ± 0.004 mm^-1 (forearm), 0.017 ± 0.005 mm^-1 (calf), and 0.016 ± 0.001 mm^-1 (head). Our values differ substantially from published in vitro data. In particular, our transport coefficients for the adult head are substantially lower than previously reported values for adult human cerebral matter and pig skull cortical bone measured in vitro.

To validate models of light propagation in biological tissue, experiments to measure the mean time of flight have been carried out on several solid cylindrical layered phantoms. The optical properties of the inner cylinders of the phantoms were close to those of adult brain white matter, whereas a range of scattering or absorption coefficients was chosen for the outer layer. Experimental results for the mean optical path length have been compared with the predictions of both an exact Monte Carlo (MC) model and a diffusion equation, with two differing boundary conditions implemented in a finite-element method (FEM). The MC and experimental results are in good agreement despite poor statistics for large fiber spacings, whereas good agreement with the FEM prediction requires a careful choice of proper boundary conditions.

A Monte Carlo model of light backscattered from turbid media has been used to simulate the effects of weak localization in biological tissues. A validation technique is used that implies that for the scattering and absorption coefficients and for refractive index mismatches found in tissues, the Monte Carlo method is likely to provide more accurate results than the methods previously used. The model also has the ability to simulate the effects of various illumination profiles and other laboratory-imposed conditions. A curve-fitting routine has been developed that might be used to extract the optical coefficients from the angular intensity profiles seen in experiments on turbid biological tissues, data that could be obtained in vivo.

An investigation was performed of the effectiveness of a time-resolved method for imaging very-low-contrast features embedded in highly scattering media. Experiments employed slabs of breastlike material into which were inserted small cylindrical objects having either a scattering or an absorption coefficient of 4, 2, 1.5, and 1.1 times greater than the surrounding medium. An attempt was made to quantify the degree of contrast produced by each object. The results indicate that time-gating is far more effective at enhancing the contrast of the scattering inhomogeneities than of the absorbing inhomogeneities. This observation is shown to agree with a diffusion-based model, which also predicts that time-gating can decrease the contrast of absorbing inhomogeneities unless very short time-gates can be employed.

Near-infrared light propagation in various models of the adult head is analyzed by both time-of-flight measurements and mathematical prediction. The models consist of three- or four-layered slabs, the latter incorporating a clear cerebrospinal fluid (CSF) layer. The most sophisticated model also incorporates slots that imitate sulci on the brain surface. For each model, the experimentally measured mean optical path length as a function of source–detector spacing agrees well with predictions from either a Monte Carlo model or a finite-element method based on diffusion theory or a hybrid radiosity–diffusion theory. Light propagation in the adult head is shown to be highly affected by the presence of the clear CSF layer, and both the optical path length and the spatial sensitivity profile of the models with a CSF layer are quite different from those without the CSF layer. However, the geometry of the sulci and the boundary between the gray and the white matter have little effect on the detected light distribution.

A solid plastic phantom has been developed with optical properties that closely match those of human breast tissue at near-IR wavelengths. The phantom is a 54-mm-thick slab containing four small cylinders of contrasting scatter and absorption. A detailed description of the phantom is followed by an account of an attempt to image the phantom by a time-resolved imaging technique. Images generated with transmitted light with the shortest flight times revealed the embedded cylinders with greater visibility than images obtained with continuous light transillumination. However, images corresponding to flight times of less than ~700 ps were severely degraded from a lack of detected photons. An attempt was made to overcome this degradation by extrapolating the measured temporal distributions with an analytic model of photon transport. Results suggest that subcentimeter resolution imaging of low-contrast tumors in the breast is scientifically possible. Our phantom is available to any other research groups wishing to evaluate their systems.

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 (inυivo) 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.