Optics: measuring and testing – Of light reflection – With diffusion
Reexamination Certificate
2000-09-15
2003-04-15
Stafira, Michael P. (Department: 2877)
Optics: measuring and testing
Of light reflection
With diffusion
Reexamination Certificate
active
06549284
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to the calibration of optical techniques for imaging and spectroscopy of, e.g., biological tissue.
BACKGROUND OF THE INVENTION
Recently there has been significant interest in using optical radiation for imaging within highly scattering media, such as biological tissue. Photons travel within the highly scattering media along a distribution of paths, of which very few are straight. Thus, directing light into the highly scattering media and subsequently detecting the diffuse light emitted from the media provides information about local variations in the scattering and absorption coefficients. Such information can identify, for example, an early breast or brain tumor, a small amount of bleeding in the brain, or an early aneurysm. Furthermore, for example, multiple wavelengths can be used to spectroscopically determine local tissue concentrations of oxy-hemoglobin (HbO) and deoxy-hemoglobin (Hb) in tissue, which may be in response to some stimulus, e.g., a drug. For a general description of such applications, see, e.g., A. Yodh and B. Chance in “Spectroscopy and Imaging with Diffusing Light,”
Physics Today
, pp. 34-40 (March 1995).
If the spatially varying optical properties of the highly scattering media are known, photon propagation within the media can be calculated numerically. The numerical calculation is simplified when scattering is much larger than absorption, in which case the photon propagation can be approximated as a diffusion process. This condition is typically satisfied in biological tissue in the spectral range of about 700 nm to 900 nm. The numerical calculation gives the distribution of light inside the tissue, and is usually referred to as the “forward calculation.” For a sample being imaged, however, the “inverse calculation” needs to be solved, i.e., deducing the sample's optical properties from the diffuse light measurements. Numerical techniques for performing the inversion include singular value decomposition (SVD), simultaneous iterative reconstruction technique (SIRT), K-space diffraction tomography, and using an extended Kaman filter. For a general review of techniques for the forward and inverse calculations, see, e.g., S. R. Arridge in “Optical tomography in medical imaging,”
Inverse Problems
, 15:R41-R93 (1999).
In diffuse optical tomography (DOT), multiple sources sequentially direct light into tissue at spatially separated locations, and for each such source, multiple detectors on the tissue measure the diffuse light emitted from the sample at spatially separated locations. For every source-detector pair, one measures the local transmittance of the diffuse light, i.e., the ratio of the diffuse radiance measured by the detector and the incident radiance from the source. The measurements provide the input information for the inverse calculation. However, the measurements can include various uncertainties caused by, for example, fluctuations in the source power, variations in the detector gain, and coupling variations at the source-tissue interface as well as the tissue-detector interface.
To minimize the uncertainties, DOT systems are typically calibrated with initial measurements for a known sample, and the calibration is used to correct subsequent measurements for imaging an unknown sample. Unfortunately, coupling at the source-tissue interface and the tissue-detector interface can vary from measurement to measurement because of, for example, movement or perspiration of the patient, or movement of an optical fiber that forms part of a source or detector. Thus, the results of the inverse calculation can include systematic errors caused by measurement variations that are independent of the tissue optical properties of interest.
The systematic errors can also limit absolute spectroscopic measurements of optical properties at a particular spatial location, e.g., the absolute, rather than relative, values of absorption and scattering.
SUMMARY OF THE INVENTION
The invention features a calibration method for diffuse optical measurements that corrects transmittance measurements between a source land a detector for factors unrelated to sample properties. For imaging applications, the corrected transmittance measurements can be subject to an inverse calculation to determine spatial variations in the optical properties of the sample, i.e., to “image” the sample. For spectroscopic applications, the corrected transmittance measurements can be used to determine absolute values for the optical properties of the sample in a particular spatial region at multiple wavelengths, e.g., to determine the absolute concentrations of oxy-hemoglobin (HbO) and deoxy-hemoglobin (Hb). The calibration method is based on the same set of transmittance measurements that are subsequently corrected by the calibration and used in imaging and/or spectroscopy applications. The accuracy of the subsequent results is thus not subject to uncertainties caused by a delay between calibration and sample measurements.
The calibration method involves a forward calculation for each of multiple source-detector pairs based on an approximate model of the sample, and a minimization of an expression that depends on the forward calculations and the transmittance measurements to determine self-consistent coupling coefficients for every source-detector pair. Once the coupling coefficients have been determined, they can be used to correct the transmittance measurements. If desired, an inverse calculation can be performed on the corrected sample measurements to determine spatial variations in the optical properties of the sample. If necessary, the calibration can be repeated and iteratively improved, whereby the optical properties determined by the inverse calculation in an earlier iteration are used to improve the sample model for the forward calculation in a subsequent iteration.
In general, in one aspect, the invention features a system for making optical measurements. The system includes at least two optical sources which during operation couple optical radiation into a sample at spatially separated locations and at least two optical detectors positioned to receive optical radiation emitted from the sample at spatially separated locations in response to the optical radiation from the sources, and an analyzer.
The signal g(i,j) produced by the j
th
detector in response to the optical radiation from the i
th
source can be expressed as g(i,j)=S
i
D
j
f(i,j), where f(i,j) depends only on the properties of the sample, S
i
is a coupling coefficient for the i
th
source, and D
j
is a coupling coefficient the j
th
detector. During operation, the analyzer calculates the value of the product S
l
D
k
for at least one of the source-detector pairs based on the signals produced by the detectors and simulated values of f(i,j) corresponding to a model of the optical properties of the sample. The sources, for example, can provide continuous-wave radiation, in which case g(i,j), f(i,j), S
i
, and D
j
are all real-valued. Alternatively, the sources can provide modulated CW radiation, or short temporal pulses of optical radiation (e.g., less than about 1 to 100 ps). In these latter cases, g(i,j), f(i,j), S
i
, and D
j
can be complex, or more generally they can be vectors representing multiple values (e.g., transmittance and temporal delay).
Embodiments of the system can also include any of the following features.
The analyzer can calculate the value of the product S
i
D
j
for every source-detector pair based on the detector signals and the simulated values of f(i,j). The analyzer can further calculate experimental values of f(i,j) based on the calculated values of S
i
D
j
and the signals g(i,j) using the expression g(i,j)=S
i
D
j
f(i,j), and then perform an inverse calculation on the experimental values for f(i,j) to determine spatial variations in at least one optical property of the sample. The optical property or properties can be the absorption coefficient, the reduced scattering coefficient, or both. The analyzer can modify the model of the samp
Boas David Alan
Cheng Xuefeng
Fish & Richardson P.C.
Stafira Michael P.
The General Hospital Corporation
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