WO2009077953A1 - Method for reconstructing an image of an interior of a turbid medium and device for imaging the interior of turbid media - Google Patents

Method for reconstructing an image of an interior of a turbid medium and device for imaging the interior of turbid media Download PDF

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Publication number
WO2009077953A1
WO2009077953A1 PCT/IB2008/055248 IB2008055248W WO2009077953A1 WO 2009077953 A1 WO2009077953 A1 WO 2009077953A1 IB 2008055248 W IB2008055248 W IB 2008055248W WO 2009077953 A1 WO2009077953 A1 WO 2009077953A1
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wavelength
light
measurement
turbid medium
interior
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PCT/IB2008/055248
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French (fr)
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Thomas Koehler
Tim Nielsen
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Koninklijke Philips Electronics N.V.
Philips Intellectual Property & Standards Gmbh
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Publication of WO2009077953A1 publication Critical patent/WO2009077953A1/en

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N21/4795—Scattering, i.e. diffuse reflection spatially resolved investigating of object in scattering medium
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0082—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
    • A61B5/0091—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for mammography
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/43—Detecting, measuring or recording for evaluating the reproductive systems
    • A61B5/4306—Detecting, measuring or recording for evaluating the reproductive systems for evaluating the female reproductive systems, e.g. gynaecological evaluations
    • A61B5/4312—Breast evaluation or disorder diagnosis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/39—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using tunable lasers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/314—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths
    • G01N2021/3148—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths using three or more wavelengths
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/27—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection ; circuits for computing concentration
    • G01N21/274—Calibration, base line adjustment, drift correction

Definitions

  • the present invention relates to a method for reconstructing an image of an interior of a turbid medium and to a device for imaging the interior of turbid media.
  • turbid medium is to be understood to mean a substance consisting of a material having a high light scattering coefficient, such as for example intralipid solution or biological tissue.
  • light is to be understood to mean electromagnetic radiation of a wavelength in the range from 180 nm to 1400 nm.
  • optical properties covers the reduced scattering coefficient and the absorption coefficient.
  • matching optical properties is to be understood as having a similar reduced scattering coefficient and a similar absorption coefficient.
  • “slightly differing wavelengths” is used to designate differences in wavelengths which do not exceed 30 nm.
  • breast cancer is one of the most occurring types of cancer: in 2002, for example, more that 1.1 million women were diagnosed and over 410.000 women died of breast cancer world- wide.
  • Several types of devices for imaging the interior of a turbid medium by use of light have been developed. Examples for such devices are mammography devices and devices for examining other parts of human or animal bodies.
  • a prominent example for a method for imaging the interior of a turbid medium is Diffuse Optical Tomography (DOT).
  • DOT Diffuse Optical Tomography
  • such devices are intended for the localization of inhomogeneities in in vivo breast tissue of a part of a breast of a female human body.
  • a malignant tumor is an example for such an inhomogeneity.
  • the devices are intended to detect such inhomogeneities while they are still small, so that for example carcinoma can be detected at an early stage.
  • a particular advantage of such devices is that the patient does not have to be exposed to the risks of examination by means of ionizing radiation, as e.g. X-rays.
  • US 5,907,406 discloses a device for imaging the interior of a turbid medium by using a light source to irradiate the turbid medium and photodetectors for measuring a part of the light transported through the turbid medium.
  • a control unit is provided for reconstructing an image of the interior of the turbid medium on the basis of the measured intensities.
  • the disclosed device is particularly adapted for examining female breasts.
  • the device is provided with a receptacle as a receiving volume enclosing a measuring volume and arranged to receive the turbid medium.
  • Light from the light source is coupled into the receiving volume and into the turbid medium.
  • the light is chosen such that it is capable of propagating through the turbid medium.
  • For imaging an interior of a female breast light having a wavelength within a range of 400 nm to 1400 nm is typically used.
  • Scattered light emanating from the turbid medium as a result of coupling light into the receiving volume is coupled out of the receiving volume. Light coupled out of the receiving volume is used to reconstruct an image of an interior of the turbid medium.
  • the light used for examining the turbid medium has to be transmitted from the light source to the turbid medium and from the turbid medium to the photodetectors. Due to different sizes of the turbid media to be examined, the size of the receptacle for receiving the turbid medium does not perfectly match the size of the turbid medium, i.e. a space remains between the receptacle and the turbid medium. The part of the turbid medium under investigation is surrounded by a matching medium filling the space in the receiving volume.
  • the matching medium is chosen such that the optical parameters of the matching medium, such as the absorption and scattering coefficients, are substantially identical to the corresponding optical parameters of the turbid medium.
  • optical short-circuit occurs when light is detected that has propagated along a path inside the receiving volume but outside the turbid medium and, as a consequence, has not been sufficiently scattered and attenuated. In that case the intensity of the insufficiently scattered and attenuated detected light may dwarf the intensity of detected light that has been scattered and attenuated through passage through the turbid medium.
  • the light source subsequently irradiates the turbid medium from different directions and the photodetectors measure a part of the light transmitted through the turbid medium.
  • a plurality of such measurements are performed with the light directed to the turbid medium from different directions and, based on the results of the measurements, i.e. the obtained data set, the control unit reconstructs the image of the examined turbid medium.
  • the image of the interior of the turbid medium under investigation is typically constructed by e.g. filtered backprojection or an algebraic reconstruction technique. Details on reconstruction with filtered backprojection are disclosed in “Tomographic image reconstruction from optical projections in light-diffusing media", Appl. Optics 36, 180 (1997), for example. Information on an algebraic reconstruction technique used for optical mammography is disclosed in “First results from the Philips Optical Mammoscope” in “Photon Propagation in Tissues III", Proc. SPIE Vol. 3194, 184 (1997), for example.
  • a reference measurement is performed before the actual measurement.
  • the receiving volume for receiving the turbid medium during examination having for example a cup-like shape, is completely filled with the matching medium.
  • a complete reference measurement is performed in which a set of data is generated.
  • the turbid medium to be examined for example a female human breast, is placed in the receiving volume and immersed in the matching medium.
  • the actual measurement is then performed in which a set of data corresponding to that of the reference measurement is generated.
  • the set of data generated during the reference measurement is used as a reference for the set of data generated during the actual measurement.
  • ⁇ is the measured intensity in the actual measurement
  • ⁇ o is the measured intensity in the reference measurement
  • ra is the detection position
  • r s is the source position
  • G are the respective Greens functions
  • ⁇ a denotes the difference in the absorption coefficient between the matching medium and the turbid medium under examination.
  • This object is solved by the method for reconstructing an image of an interior of a turbid medium according to claim 1.
  • the method comprises the step: performing a first measurement on a turbid medium to be examined by subsequently irradiating the turbid medium with light having a first wavelength from a plurality of different source positions and detecting light emanating from the turbid medium in a plurality of different detection positions for each source position.
  • the second wavelength differs slightly from the first wavelength and an image of the interior of the turbid medium is reconstructed using the ratio of the measurement results, wherein the first measurement is used as a reference measurement and the second measurement is used to determine deviations from the reference measurement.
  • Two measurements are performed on the turbid medium at slightly different wavelengths and one measurement is used as a reference for the other measurement. Thus, only small deviations will be present in the results from the first and second measurements. Since the deviations are small, all unknown calibration factors in the reconstruction problem can be canceled out and first order perturbation theory can be applied for reconstructing the image of the interior of the turbid medium leading to satisfactory results.
  • reconstruction can be realized using rather simple computations. Thus, reconstruction can be performed fast and efficiently.
  • the image is reconstructed by applying linear equations.
  • the computations for reconstructing the image become rather simple and thus image reconstruction can be performed efficiently.
  • the second wavelength differs from the first wavelength by less than 30 nm, preferably by less than 10 nm, the deviation in the measurement results from the first and second measurements will be particularly small such that the assumptions for first order perturbation theory are fulfilled. Further, this feature can be realized without providing an additional light source by e.g. tuning a suitable laser as a light source.
  • the light having the first wavelength and the light having the second wavelength are generated by the same light source.
  • the advantages can be realized without providing a further light source and costs can be saved.
  • a third measurement is performed similar to the first and second measurements using light having a third wavelength
  • a fourth measurement is performed similar to the first and second measurements using light having a fourth wavelength.
  • the fourth wavelength differs only slightly from the third wavelength, the third and fourth wavelengths being located in a wavelength range different from the first and second wavelengths.
  • a further image of the interior of the turbid medium is reconstructed by applying linear equations on the measurement results of the third and fourth measurements, wherein the third measurement is used as a further reference measurement and the fourth measurement is used to determine deviations from the further reference measurement.
  • the object is further solved by a device for imaging the interior of turbid media according to claim 7.
  • the device comprises: a receiving volume for receiving a turbid medium to be examined; at least one light source for irradiating an interior of the receiving volume; at least one detector for detecting light emanating from the interior of the receiving volume; and a control unit for controlling the device for imaging the interior of turbid media.
  • the device for imaging the interior of turbid media is arranged to selectively provide light having a first wavelength and light having a second wavelength which slightly differs from the first wavelength.
  • the control unit is adapted to control the device for imaging the interior of turbid media such that: a first measurement is performed in which the turbid medium is subsequently irradiated with light having the first wavelength from a plurality of different source positions and, for each source position, light emanating from the turbid medium is detected in a plurality of different detection positions by the at least one detector.
  • a second measurement is performed in which the turbid medium is subsequently irradiated with light having the second wavelength from a plurality of different source positions and, for each source position, light emanating from the turbid medium is detected in a plurality of different detection positions by the at least one detector.
  • An image of the interior of the turbid medium is reconstructed from the ratio of the measurement results, wherein the first measurement is used as a reference measurement and the second measurement is used to determine deviations from the reference measurement.
  • first order perturbation theory can be applied for reconstructing the image of the interior of the turbid medium leading to satisfactory results.
  • a wavelength control unit is provided which is capable of tuning the at least one light source to selectively emit light having the first wavelength and light having the second wavelength.
  • the image can be reliably reconstructed using linear perturbation theory without necessitating an additional light source.
  • a second light source which is capable of selectively emitting light having a third wavelength and light having a fourth wavelength slightly differing from third wavelength, the third and fourth wavelengths being in a wavelength range different from the first and second wavelengths.
  • the device can be tuned to be sensitive to specific components of the turbid medium.
  • the device is a medical image acquisition device.
  • Fig. 1 schematically shows a receptacle of a device for imaging the interior of turbid media.
  • Fig. 2 schematically shows the optical connection between the receptacle and a control unit in the device for imaging the interior of turbid media.
  • Fig. 3 schematically illustrates a particular implementation of the device.
  • the device for imaging the interior of a turbid medium is formed by a device for diffuse optical tomography (DOT), in particular by a mammography device. Since the overall construction of such a device is known to a skilled person, no detailed description of the device will be given.
  • DOT diffuse optical tomography
  • the turbid medium 1 to be examined is a female human breast.
  • the device is provided with a receptacle 2 as an example for a receiving volume enclosing a measuring volume and arranged to receive the turbid medium 1, as schematically indicated in Fig. 1.
  • the receptacle 2 has a cup-like shape with rotational symmetry with respect to a vertical axis Z and is provided with an opening 3.
  • the turbid medium 1 to be examined i.e. the breast
  • the turbid medium 1 to be examined i.e. the breast
  • the turbid medium 1 to be examined i.e. the breast
  • the device comprises a control unit 8 which reconstructs an image of the interior of the turbid medium 1 based on the signals from the detectors 7. For reconstruction, the signals sampled during a scan in which the light is directed to the turbid medium 1 from different directions are used. For reasons of simplicity, these elements of the device for imaging the interior of a turbid medium are only schematically indicated in Fig. 2.
  • the control unit 8 comprises the light source 6 and the plurality of detectors 7.
  • 256 different source positions are provided and 256 detector positions, i.e. respective ends of light guides are provided on the inner surface of the receptacle 2.
  • the light from the light source 6 is subsequently directed to the turbid medium 1 from the 256 source positions and for each source position, the light emanating from the turbid medium 1 is detected in the 256 detection positions.
  • the invention is not limited to these specific numbers.
  • the size of the receptacle 2 is such that a space remains between the inner surface of the receptacle 2 and the turbid medium 1.
  • this space is filled with an optically matching medium 4 which serves to provide optical coupling between the turbid medium 1 to be imaged and the inner surface of the receptacle 2.
  • the optically matching medium 4 further serves to prevent optical short-cutting between the light guides 5 coming from the light source 6 and the light guides 5 coupling to the detectors 7.
  • the optically matching medium 4 serves to counteract boundary effects in the reconstructed image which are caused by the difference in optical contrast between the interior of the turbid medium 1 and the remaining space in the receptacle 2.
  • the optically matching medium 4 is provided with optical properties which substantially match the optical properties of the turbid medium 1 to be examined.
  • a reference measurement is performed with the receptacle 2 completely filled with the optically matching medium 4 and without turbid medium 1 placed in the receptacle.
  • the turbid medium 1 to be examined is placed in the receptacle 2 and the measurement is performed. It is then assumed that the turbid medium 1 forms only small "perturbations" as compared to the reference measurement in which only the optically matching medium 4 is present in the receptacle 2, and a first order linear approximation is used for reconstructing the image of the interior of the turbid medium 1.
  • DOT diffuse optical tomography
  • the light source 6 is provided with a wavelength control unit 9 capable of tuning the light source 6 such that, in a first condition, it emits light having a first wavelength ⁇ i and, in a second condition, it emits light having a second wavelength ⁇ 2 which is slightly different from the first wavelength ⁇ i.
  • the light source 6 is formed by a laser emitting monochromatic light under pre-determined conditions.
  • the light source 6 is constructed such that, at a first operating temperature, light having the wavelength ⁇ i is emitted and, at a second operating temperature, e.g.
  • the turbid medium to be examined 1 is placed in the receptacle 2.
  • the remaining space in the receptacle 2 is filled with the optically matching medium 4.
  • a first measurement is performed in which the turbid medium 1 is subsequently irradiated with light having the first wavelength ⁇ i from the plurality of source positions and for each source position, the light emanating from the turbid medium 1 is detected in the plurality of detection positions.
  • the measured intensities ⁇ i for all pairs of source position and detection position are stored in a memory provided in the control unit 8 as a reference measurement.
  • a second measurement is performed in the same way but using light having the slightly different wavelength ⁇ 2 .
  • the measured intensities ⁇ 2 for all pairs of source positions and detection positions are stored in the memory.
  • the ratio of the measurement intensities ⁇ 2 from the second measurement and the corresponding measured intensities ⁇ i from the first measurement is computed to cancel out all unknown calibration factors present in the system such as fiber transmissions of the light guides, coupling losses between the light guides and the turbid medium, photodiode sensitivity or the like.
  • the difference in wavelengths between the first measurement and the second measurement is small.
  • first order perturbation theory for reconstructing an image of the interior of the turbid medium leads to satisfactory results.
  • an image of the interior of the turbid medium is reconstructed based on deviations between the first and second measurements at slightly different wavelengths. More particularly, the reconstruction is performed using first order perturbation theory. Further steps for reconstruction of images of the interior of turbid media using first order perturbation theory, based on the assumption that differences between a reference measurement and an actual measurement are small, are known in the art and will not be described in detail again.
  • the first measurement is performed before the second measurement and used as a reference for the second measurement, it will be evident for the skilled person that the invention is not limited thereto and the second measurement may also be performed before the first measurement.
  • a further light source 10 is provided the light emitted by which can also be used for irradiating the turbid medium 1 alternatively to the light from the first light source 6.
  • the second light source 10 can be formed by a laser emitting monochromatic light.
  • the second light source 10 is provided with a second wavelength control unit 11 capable of tuning the light source 10 such that, in a first condition, it emits light having a third wavelength ⁇ 3 and, in a second condition, it emits light having a fourth wavelength ⁇ 4 which slightly differs from the third wavelength ⁇ 3 .
  • the second light source 10 is adapted to emit light in a wavelength range which strongly differs from the first and second wavelengths ⁇ i and ⁇ 2 .
  • a strongly differing wavelength range is understood to differ by more than 30 nm from the wavelength range of the first and second wavelengths.
  • the first light source 6 is adapted to emit light in a wavelength range around 680 nm and can be controlled to emit light of at least two slightly different wavelengths ⁇ i and ⁇ 2 and the second light source 10 is adapted to emit light in a wavelength range around 830 nm.
  • first and second measurements are performed in the wavelength range of the first light source 6 and an image of the interior of the turbid medium 1 is reconstructed using first order perturbation theory, as described above.
  • third and fourth measurements are performed similar to the first and second measurements but using light from the second light source 10 for irradiating the turbid medium 1.
  • light having the third wavelength ⁇ 3 is used and, in the fourth measurement, light having the fourth wavelength ⁇ 4 which differs only slightly from the third wavelength ⁇ 3 is used.
  • a further image of the interior of the turbid medium 1 is reconstructed from the measured intensities of the third and fourth measurements using first order perturbation theory, as described above with respect to the first and second measurements.
  • two images of the interior of the turbid medium 1 are obtained at different wavelength ranges and these reconstructed images can be compared.
  • the system can be tuned to be sensitive to specific tissue components.
  • the respective reconstructed images comprise particular strong tissue sensitivity.
  • the invention is not limited to the wavelength ranges described above, but other suitable wavelength ranges can be selected for the first and second measurements and the third and fourth measurements, respectively.
  • the receiving volume is enclosed by a receptacle having a cup-like shape
  • the invention is not limited to such an arrangement.
  • the receiving volume for accommodating the turbid medium during examination may also be formed by compression plates between which the turbid medium is compressed during examination.
  • no optically matching medium is required in this case and in other cases in which satisfactory results can be achieved without matching medium.
  • other suitable structures of the receiving volume are also possible.

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Abstract

A method for reconstructing an image of an interior of a turbid medium (1) is provided. The method comprises the steps: performing a first measurement on a turbid medium (1) to be examined by subsequently irradiating the turbid medium with light having a first wavelength (λi) from a plurality of different source positions and detecting light emanating from the turbid medium (1) in a plurality of different detection positions for each source position; performing a second measurement on the turbid medium (1) to be examined by subsequently irradiating the turbid medium with light having a second wavelength (λ2) from a plurality of different source positions and detecting light emanating from the turbid medium in a plurality of different detection positions for each source position. The second wavelength (λ2) differs slightly from the first wavelength (λi) and an image of the interior of the turbid medium (1) is reconstructed by using the ratio of the measurement results, wherein the first measurement is used as a reference measurement and the second measurement is used to determine deviations from the reference measurement.

Description

Method for reconstructing an image of an interior of a turbid medium and device for imaging the interior of turbid media
FIELD OF INVENTION
The present invention relates to a method for reconstructing an image of an interior of a turbid medium and to a device for imaging the interior of turbid media.
BACKGROUND OF THE INVENTION
In the context of the present application, the term turbid medium is to be understood to mean a substance consisting of a material having a high light scattering coefficient, such as for example intralipid solution or biological tissue. Further, light is to be understood to mean electromagnetic radiation of a wavelength in the range from 180 nm to 1400 nm. The term "optical properties" covers the reduced scattering coefficient and the absorption coefficient. Furthermore, "matching optical properties" is to be understood as having a similar reduced scattering coefficient and a similar absorption coefficient. Further, "slightly differing wavelengths" is used to designate differences in wavelengths which do not exceed 30 nm. In recent years, several methods and devices for examining turbid media, e.g. female breast tissue, have been developed. In particular, new devices for detection and analysis of breast cancer have been developed and existing technologies have been improved. Breast cancer is one of the most occurring types of cancer: in 2002, for example, more that 1.1 million women were diagnosed and over 410.000 women died of breast cancer world- wide. Several types of devices for imaging the interior of a turbid medium by use of light have been developed. Examples for such devices are mammography devices and devices for examining other parts of human or animal bodies. A prominent example for a method for imaging the interior of a turbid medium is Diffuse Optical Tomography (DOT). In particular, such devices are intended for the localization of inhomogeneities in in vivo breast tissue of a part of a breast of a female human body. A malignant tumor is an example for such an inhomogeneity. The devices are intended to detect such inhomogeneities while they are still small, so that for example carcinoma can be detected at an early stage. A particular advantage of such devices is that the patient does not have to be exposed to the risks of examination by means of ionizing radiation, as e.g. X-rays. US 5,907,406 discloses a device for imaging the interior of a turbid medium by using a light source to irradiate the turbid medium and photodetectors for measuring a part of the light transported through the turbid medium. A control unit is provided for reconstructing an image of the interior of the turbid medium on the basis of the measured intensities. The disclosed device is particularly adapted for examining female breasts. In order to allow the examination of the turbid medium, the device is provided with a receptacle as a receiving volume enclosing a measuring volume and arranged to receive the turbid medium. Light from the light source is coupled into the receiving volume and into the turbid medium. The light is chosen such that it is capable of propagating through the turbid medium. For imaging an interior of a female breast, light having a wavelength within a range of 400 nm to 1400 nm is typically used. Scattered light emanating from the turbid medium as a result of coupling light into the receiving volume is coupled out of the receiving volume. Light coupled out of the receiving volume is used to reconstruct an image of an interior of the turbid medium. The light used for examining the turbid medium has to be transmitted from the light source to the turbid medium and from the turbid medium to the photodetectors. Due to different sizes of the turbid media to be examined, the size of the receptacle for receiving the turbid medium does not perfectly match the size of the turbid medium, i.e. a space remains between the receptacle and the turbid medium. The part of the turbid medium under investigation is surrounded by a matching medium filling the space in the receiving volume. The matching medium is chosen such that the optical parameters of the matching medium, such as the absorption and scattering coefficients, are substantially identical to the corresponding optical parameters of the turbid medium. In this way, image artifacts resulting from optical boundary effects that occur when light is coupled into and out of the turbid medium can be reduced. Furthermore, use of the matching medium prevents the occurrence of an optical short-circuit in the receiving volume around the turbid medium. An optical short-circuit occurs when light is detected that has propagated along a path inside the receiving volume but outside the turbid medium and, as a consequence, has not been sufficiently scattered and attenuated. In that case the intensity of the insufficiently scattered and attenuated detected light may dwarf the intensity of detected light that has been scattered and attenuated through passage through the turbid medium. The light source subsequently irradiates the turbid medium from different directions and the photodetectors measure a part of the light transmitted through the turbid medium. A plurality of such measurements are performed with the light directed to the turbid medium from different directions and, based on the results of the measurements, i.e. the obtained data set, the control unit reconstructs the image of the examined turbid medium.
In such devices, the image of the interior of the turbid medium under investigation is typically constructed by e.g. filtered backprojection or an algebraic reconstruction technique. Details on reconstruction with filtered backprojection are disclosed in "Tomographic image reconstruction from optical projections in light-diffusing media", Appl. Optics 36, 180 (1997), for example. Information on an algebraic reconstruction technique used for optical mammography is disclosed in "First results from the Philips Optical Mammoscope" in "Photon Propagation in Tissues III", Proc. SPIE Vol. 3194, 184 (1997), for example.
In known methods for reconstructing an image of the turbid medium under investigation, a reference measurement is performed before the actual measurement. In this reference measurement, the receiving volume for receiving the turbid medium during examination, having for example a cup-like shape, is completely filled with the matching medium. Then a complete reference measurement is performed in which a set of data is generated. Thereafter, the turbid medium to be examined, for example a female human breast, is placed in the receiving volume and immersed in the matching medium. The actual measurement is then performed in which a set of data corresponding to that of the reference measurement is generated. The set of data generated during the reference measurement is used as a reference for the set of data generated during the actual measurement. All unknown calibration factors can be canceled out according to this method by computing the ratio between the results of the actual measurement and the results of the reference measurement. In a first order approximation, the reconstruction problem based on this method can be expressed as follows for each pair of source position and detection position:
In Φ ψfoKrd .,0rs) ~ $ fdxr.A,μ. a ( rr,.,) G(rd ,r)G(r,rs) f Φh0 I(rtd ,rs \) J G(rd ,rs)
wherein Φ is the measured intensity in the actual measurement, Φo is the measured intensity in the reference measurement, ra is the detection position, rs is the source position, G are the respective Greens functions and Δμa denotes the difference in the absorption coefficient between the matching medium and the turbid medium under examination. For the purpose of the reconstruction process, it is then assumed that structures inside the examined turbid medium only constitute small deviations from the homogenous matching medium which has been used during the reference measurement, i.e. that Δμa is small. This is a condition for first order perturbation theory to be applicable. Based on this assumption, in the known methods the image of the interior of the turbid medium is then reconstructed using perturbation theory with linear approximation, since the deviations from the homogenous matching medium are treated as small perturbations to the homogenous matching medium.
However, it has been found that the linear approximation is not generally valid between first measurements with only the optically matching medium and second measurements with the turbid medium immersed in the matching medium. Optical properties of turbid media such as for example female human breasts comprise a rather large patient-to- patient variation. Large differences in the optical properties of the turbid medium and the matching medium cause artifacts in the reconstructed image. Another problem arises due to the fact that differences in the scattering, i.e. in the diffusion constant are neglected. Therefore, the reconstruction achieved using this linear approximation does not always provide satisfactory results.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a method and a device which allow reconstructing an image of the interior of a turbid medium with satisfactory accuracy using first order perturbation theory. This object is solved by the method for reconstructing an image of an interior of a turbid medium according to claim 1. The method comprises the step: performing a first measurement on a turbid medium to be examined by subsequently irradiating the turbid medium with light having a first wavelength from a plurality of different source positions and detecting light emanating from the turbid medium in a plurality of different detection positions for each source position. It further comprises the step: performing a second measurement on the turbid medium to be examined by subsequently irradiating the turbid medium with light having a second wavelength from a plurality of different source positions and detecting light emanating from the turbid medium in a plurality of different detection positions for each source position. The second wavelength differs slightly from the first wavelength and an image of the interior of the turbid medium is reconstructed using the ratio of the measurement results, wherein the first measurement is used as a reference measurement and the second measurement is used to determine deviations from the reference measurement. Two measurements are performed on the turbid medium at slightly different wavelengths and one measurement is used as a reference for the other measurement. Thus, only small deviations will be present in the results from the first and second measurements. Since the deviations are small, all unknown calibration factors in the reconstruction problem can be canceled out and first order perturbation theory can be applied for reconstructing the image of the interior of the turbid medium leading to satisfactory results.
If the image of the interior of the turbid medium is reconstructed based on deviations between the first and second measurements using first order perturbation theory, reconstruction can be realized using rather simple computations. Thus, reconstruction can be performed fast and efficiently.
Preferably, the image is reconstructed by applying linear equations. In this case, the computations for reconstructing the image become rather simple and thus image reconstruction can be performed efficiently.
If the second wavelength differs from the first wavelength by less than 30 nm, preferably by less than 10 nm, the deviation in the measurement results from the first and second measurements will be particularly small such that the assumptions for first order perturbation theory are fulfilled. Further, this feature can be realized without providing an additional light source by e.g. tuning a suitable laser as a light source.
According to an aspect, the light having the first wavelength and the light having the second wavelength are generated by the same light source. In this case, the advantages can be realized without providing a further light source and costs can be saved. Preferably, a third measurement is performed similar to the first and second measurements using light having a third wavelength, and a fourth measurement is performed similar to the first and second measurements using light having a fourth wavelength. The fourth wavelength differs only slightly from the third wavelength, the third and fourth wavelengths being located in a wavelength range different from the first and second wavelengths. A further image of the interior of the turbid medium is reconstructed by applying linear equations on the measurement results of the third and fourth measurements, wherein the third measurement is used as a further reference measurement and the fourth measurement is used to determine deviations from the further reference measurement. Thus, two distinct images can be reconstructed for different wavelength ranges and, for each image, first order perturbation theory can be applied leading to satisfactory results. As a result, the method can be tuned to be sensitive to specific components of the turbid medium under examination. The object is further solved by a device for imaging the interior of turbid media according to claim 7. The device comprises: a receiving volume for receiving a turbid medium to be examined; at least one light source for irradiating an interior of the receiving volume; at least one detector for detecting light emanating from the interior of the receiving volume; and a control unit for controlling the device for imaging the interior of turbid media. The device for imaging the interior of turbid media is arranged to selectively provide light having a first wavelength and light having a second wavelength which slightly differs from the first wavelength. The control unit is adapted to control the device for imaging the interior of turbid media such that: a first measurement is performed in which the turbid medium is subsequently irradiated with light having the first wavelength from a plurality of different source positions and, for each source position, light emanating from the turbid medium is detected in a plurality of different detection positions by the at least one detector. Further, a second measurement is performed in which the turbid medium is subsequently irradiated with light having the second wavelength from a plurality of different source positions and, for each source position, light emanating from the turbid medium is detected in a plurality of different detection positions by the at least one detector. An image of the interior of the turbid medium is reconstructed from the ratio of the measurement results, wherein the first measurement is used as a reference measurement and the second measurement is used to determine deviations from the reference measurement. As a result, first order perturbation theory can be applied for reconstructing the image of the interior of the turbid medium leading to satisfactory results.
Preferably, a wavelength control unit is provided which is capable of tuning the at least one light source to selectively emit light having the first wavelength and light having the second wavelength. In this case, the image can be reliably reconstructed using linear perturbation theory without necessitating an additional light source.
According to an aspect, a second light source is provided which is capable of selectively emitting light having a third wavelength and light having a fourth wavelength slightly differing from third wavelength, the third and fourth wavelengths being in a wavelength range different from the first and second wavelengths. In this case, the device can be tuned to be sensitive to specific components of the turbid medium.
Preferably, the device is a medical image acquisition device.
BRIEF DESCRIPTION OF THE DRAWINGS Further features and advantages of the present invention will arise from the detailed description of embodiments with reference to the enclosed drawings.
Fig. 1 schematically shows a receptacle of a device for imaging the interior of turbid media. Fig. 2 schematically shows the optical connection between the receptacle and a control unit in the device for imaging the interior of turbid media.
Fig. 3 schematically illustrates a particular implementation of the device.
Fig. 4 illustrates the spectral dependencies of absorption for oxygenated and deoxygenated hemoglobin. Fig. 5 shows the derivatives of the spectral dependencies.
DETAILED DESCRIPTION OF AN EMBODIMENT
An embodiment of the present invention will now be described with reference to Figs. 1 and 2. In the embodiment, the device for imaging the interior of a turbid medium is formed by a device for diffuse optical tomography (DOT), in particular by a mammography device. Since the overall construction of such a device is known to a skilled person, no detailed description of the device will be given.
In the device of the embodiment, the turbid medium 1 to be examined is a female human breast. The device is provided with a receptacle 2 as an example for a receiving volume enclosing a measuring volume and arranged to receive the turbid medium 1, as schematically indicated in Fig. 1. The receptacle 2 has a cup-like shape with rotational symmetry with respect to a vertical axis Z and is provided with an opening 3. As can be seen in Fig. 1, the turbid medium 1 to be examined, i.e. the breast, is placed in the receptacle 2 such that it freely hangs in the receptacle 2 from the side of the opening 3. The inner surface of the receptacle facing the turbid medium 3 is provided with a plurality of ends of light guides 5 formed by optically guiding fibers connecting to a light source 6 and to a plurality of detectors 7. These ends of the light guides 5 are distributed on the inner surface of the receptacle 2 such that the receptacle 2 provided with the light guides 5 still comprises substantially rotational symmetry. The device is further structured such that light from the light source 6 can be directed to the turbid medium 1 from different directions and light emanating from the turbid medium 1 can be detected by a plurality of detectors 7 the corresponding light guides 5 of which are distributed on the inner surface of the receptacle 2. The device comprises a control unit 8 which reconstructs an image of the interior of the turbid medium 1 based on the signals from the detectors 7. For reconstruction, the signals sampled during a scan in which the light is directed to the turbid medium 1 from different directions are used. For reasons of simplicity, these elements of the device for imaging the interior of a turbid medium are only schematically indicated in Fig. 2. In Fig. 2, the control unit 8 comprises the light source 6 and the plurality of detectors 7. For example, in the device according to the embodiment, 256 different source positions are provided and 256 detector positions, i.e. respective ends of light guides are provided on the inner surface of the receptacle 2. The light from the light source 6 is subsequently directed to the turbid medium 1 from the 256 source positions and for each source position, the light emanating from the turbid medium 1 is detected in the 256 detection positions. However, the invention is not limited to these specific numbers.
The size of the receptacle 2 is such that a space remains between the inner surface of the receptacle 2 and the turbid medium 1. For examination, this space is filled with an optically matching medium 4 which serves to provide optical coupling between the turbid medium 1 to be imaged and the inner surface of the receptacle 2. The optically matching medium 4 further serves to prevent optical short-cutting between the light guides 5 coming from the light source 6 and the light guides 5 coupling to the detectors 7. Furthermore, the optically matching medium 4 serves to counteract boundary effects in the reconstructed image which are caused by the difference in optical contrast between the interior of the turbid medium 1 and the remaining space in the receptacle 2. For this purpose, the optically matching medium 4 is provided with optical properties which substantially match the optical properties of the turbid medium 1 to be examined.
In the conventional methods for reconstructing an image of the interior of the turbid medium, before the actual measurement is performed, a reference measurement is performed with the receptacle 2 completely filled with the optically matching medium 4 and without turbid medium 1 placed in the receptacle. In the actual measurement, the turbid medium 1 to be examined is placed in the receptacle 2 and the measurement is performed. It is then assumed that the turbid medium 1 forms only small "perturbations" as compared to the reference measurement in which only the optically matching medium 4 is present in the receptacle 2, and a first order linear approximation is used for reconstructing the image of the interior of the turbid medium 1. However, it has been found that the first order approximation does not hold in case of diffuse optical tomography (DOT) of breast tissue.
In the following it will be described how this problem is solved according to the embodiment. In the device for imaging the interior of turbid media according to the embodiment, the light source 6 is provided with a wavelength control unit 9 capable of tuning the light source 6 such that, in a first condition, it emits light having a first wavelength λi and, in a second condition, it emits light having a second wavelength λ2 which is slightly different from the first wavelength λi. In the embodiment, the light source 6 is formed by a laser emitting monochromatic light under pre-determined conditions. However, the light source 6 is constructed such that, at a first operating temperature, light having the wavelength λi is emitted and, at a second operating temperature, e.g. several degrees higher or lower, light having a slightly different wavelength λ2 is emitted. The first wavelength λi differs from the second wavelength λ2 by a wavelength difference Δλ which is small, e.g. Δλ = λi - λ2 = ± 10 nm. Typical slight differences in wavelengths which are small and relevant for the present invention are ± 30 nm or smaller. Thus, the temperature dependence of the light source 6 is used to provide light having two slightly different wavelengths.
As an alternative, not only the temperature difference can be used to tune the light source 6 to emit light of two slightly differing wavelengths, but also other parameters known in the art for tuning the wavelength of e.g. lasers can be used to provide the first wavelength λi and the slightly different second wavelength λ2. The wavelength control unit 9 controls the light source 6 such that it emits either light having the first wavelength λi or light having the second wavelength λ2. The desired wavelength can be selected by the control unit 8. It should be noted that the tuning is not limited to two distinct wavelengths but may also extend to further wavelengths in a small range around the first wavelength λi. For example, in the embodiment the light source 6 is capable of alternatively emitting light having a first wavelength λi of 680 nm and light having a second wavelength λ2 = λi + Δλ = 690 nm.
In operation, the turbid medium to be examined 1 is placed in the receptacle 2. The remaining space in the receptacle 2 is filled with the optically matching medium 4. Then, a first measurement is performed in which the turbid medium 1 is subsequently irradiated with light having the first wavelength λi from the plurality of source positions and for each source position, the light emanating from the turbid medium 1 is detected in the plurality of detection positions. The measured intensities Φλi for all pairs of source position and detection position are stored in a memory provided in the control unit 8 as a reference measurement. Then, a second measurement is performed in the same way but using light having the slightly different wavelength λ2. The measured intensities Φχ2 for all pairs of source positions and detection positions are stored in the memory.
Then, for reconstructing an image of the interior of the turbid medium 1, the ratio of the measurement intensities Φχ2 from the second measurement and the corresponding measured intensities Φλi from the first measurement is computed to cancel out all unknown calibration factors present in the system such as fiber transmissions of the light guides, coupling losses between the light guides and the turbid medium, photodiode sensitivity or the like. The difference in wavelengths between the first measurement and the second measurement is small. Thus, reconstruction of an image of the interior of the turbid medium 1 can be based on the first order reconstruction problem:
Figure imgf000012_0001
since the differences in absorption Δμa between the first and second measurements, i.e. the differences in absorption at the slightly different wavelengths λi and λ2 will be small. In the above formula, ra and rs designate the respective detection and source positions, and G designates the Greens functions of the problem. Since the differences between the first and second measurements are small, application of first order perturbation theory for reconstructing an image of the interior of the turbid medium leads to satisfactory results. Thus, according to the embodiment, an image of the interior of the turbid medium is reconstructed based on deviations between the first and second measurements at slightly different wavelengths. More particularly, the reconstruction is performed using first order perturbation theory. Further steps for reconstruction of images of the interior of turbid media using first order perturbation theory, based on the assumption that differences between a reference measurement and an actual measurement are small, are known in the art and will not be described in detail again.
Although it has been described that the first measurement is performed before the second measurement and used as a reference for the second measurement, it will be evident for the skilled person that the invention is not limited thereto and the second measurement may also be performed before the first measurement.
A particular implementation will now be described with respect to Figs. 3 to 5. In this particular implementation, a further light source 10 is provided the light emitted by which can also be used for irradiating the turbid medium 1 alternatively to the light from the first light source 6. Similar to the light source 6, the second light source 10 can be formed by a laser emitting monochromatic light. Further, the second light source 10 is provided with a second wavelength control unit 11 capable of tuning the light source 10 such that, in a first condition, it emits light having a third wavelength λ3 and, in a second condition, it emits light having a fourth wavelength λ4 which slightly differs from the third wavelength λ3. However, the second light source 10 is adapted to emit light in a wavelength range which strongly differs from the first and second wavelengths λi and λ2. A strongly differing wavelength range is understood to differ by more than 30 nm from the wavelength range of the first and second wavelengths. For example, the first light source 6 is adapted to emit light in a wavelength range around 680 nm and can be controlled to emit light of at least two slightly different wavelengths λi and λ2 and the second light source 10 is adapted to emit light in a wavelength range around 830 nm.
According to the modification, first and second measurements are performed in the wavelength range of the first light source 6 and an image of the interior of the turbid medium 1 is reconstructed using first order perturbation theory, as described above. Additionally, third and fourth measurements are performed similar to the first and second measurements but using light from the second light source 10 for irradiating the turbid medium 1. In the third measurement, light having the third wavelength λ3 is used and, in the fourth measurement, light having the fourth wavelength λ4 which differs only slightly from the third wavelength λ3 is used. Then, a further image of the interior of the turbid medium 1 is reconstructed from the measured intensities of the third and fourth measurements using first order perturbation theory, as described above with respect to the first and second measurements. As a result, two images of the interior of the turbid medium 1 are obtained at different wavelength ranges and these reconstructed images can be compared.
Fig. 4 shows the spectral dependence of absorption for oxygenated hemoglobin (μa(HbO)) and deoxygenated hemoglobin (μa(HbR)), respectively. Fig. 5 shows the respective derivatives with respect to the wavelength (dμa(Hb0)/dλ and dμa(HbR)/dλ). As can be seen from Figs. 4 and 5, by using for example two wavelengths in a range around 680 nm for the first and second measurements, there will be almost no signal from oxygenated hemoglobin but a significant signal from deoxygenated hemoglobin. This is due to the fact that the absorption of deoxygenated hemoglobin strongly varies in dependence of the wavelength in this range, as can be seen in Fig. 5. In contrast, by using two wavelengths e.g. in a range around 830 nm for the third and fourth measurements, there will be almost no signal from deoxygenated hemoglobin as compared to the signal from oxygenated hemoglobin. The presence of deoxygenated and oxygenated hemoglobin in turbid media varies between different tissue components, e.g. if the turbid medium 1 is a female human breast. In particular, there are strong variations between cancerous tissue and healthy tissue. Therefore, by proper selection of the wavelength ranges for the reconstruction of the first and second images, i.e. for the first and second measurements and for the third and fourth measurements, the system can be tuned to be sensitive to specific tissue components. Since two wavelengths (λi and λ2) which differ only slightly are used for the first and second measurements in the first wavelength range and two wavelengths (λ3 and λ4) which differ only slightly are used for the third and fourth measurements in the second wavelength range, the respective reconstructed images comprise particular strong tissue sensitivity.
It should be noted that the invention is not limited to the wavelength ranges described above, but other suitable wavelength ranges can be selected for the first and second measurements and the third and fourth measurements, respectively.
Although it has been described throughout the specification that the receiving volume is enclosed by a receptacle having a cup-like shape, the invention is not limited to such an arrangement. For example, the receiving volume for accommodating the turbid medium during examination may also be formed by compression plates between which the turbid medium is compressed during examination. Further, no optically matching medium is required in this case and in other cases in which satisfactory results can be achieved without matching medium. Further, other suitable structures of the receiving volume are also possible.

Claims

CLAIMS:
1. Method for reconstructing an image of an interior of a turbid medium (1); the method comprising the steps: performing a first measurement on a turbid medium (1) to be examined by subsequently irradiating the turbid medium with light having a first wavelength (λi) from a plurality of different source positions and detecting light emanating from the turbid medium (1) in a plurality of different detection positions for each source position; performing a second measurement on the turbid medium (1) to be examined by subsequently irradiating the turbid medium with light having a second wavelength (λ2) from a plurality of different source positions and detecting light emanating from the turbid medium in a plurality of different detection positions for each source position; wherein the second wavelength (λ2) differs slightly from the first wavelength (λi) and an image of the interior of the turbid medium (1) is reconstructed by using the ratio of the measurement results, wherein the first measurement is used as a reference measurement and the second measurement is used to determine deviations from the reference measurement.
2. The method according to claim 1, wherein the image of the interior of the turbid medium (1) is reconstructed based on deviations between the first and second measurements using first order perturbation theory.
3. The method according to any one of claims 1 or 2, wherein the image is reconstructed by applying linear equations on the measurement results.
4. The method according to any one of claims 1 to 3, wherein the second wavelength (λ2) differs from the first wavelength (λi) by less than 30 nm, preferably by less than 10 nm.
5. The method according to any one of claims 1 to 4, wherein the light having the first wavelength (λi) and the light having the second wavelength (λ2) are generated by the same light source (6).
6. The method according to any one of claims 1 to 5, wherein a third measurement is performed similar to the first and second measurements using light having a third wavelength (λ^), and a fourth measurement is performed similar to the first and second measurements using light having a fourth wavelength (λ4), the fourth wavelength (λ4) differing only slightly from the third wavelength (λs), the third and fourth wavelengths being located in a wavelength range different from the first and second wavelengths (λi, λ2), and a further image of the interior of the turbid medium (1) is reconstructed by applying linear equations on the measurement results of the third and fourth measurements, wherein the third measurement is used as a further reference measurement and the fourth measurement is used to determine deviations from the further reference measurement.
7. A device for imaging the interior of turbid media, the device comprising: a receiving volume (2) for receiving a turbid medium (1) to be examined; at least one light source (6) for irradiating an interior of the receiving volume (2); at least one detector (7) for detecting light emanating from the interior of the receiving volume (2); and a control unit (8) for controlling the device for imaging the interior of turbid media; the device for imaging the interior of turbid media being arranged to selectively provide light having a first wavelength (λi) and light having a second wavelength (λ2) which slightly differs from the first wavelength (λi), wherein the control unit (8) is adapted to control the device for imaging the interior of turbid media such that: a first measurement is performed in which the turbid medium (1) is subsequently irradiated with light having the first wavelength (λi) from a plurality of different source positions and, for each source position, light emanating from the turbid medium is detected in a plurality of different detection positions by the at least one detector
(V); a second measurement is performed in which the turbid medium (1) is subsequently irradiated with light having the second wavelength (λ2) from a plurality of different source positions and, for each source position, light emanating from the turbid medium is detected in a plurality of different detection positions by the at least one detector (7); and an image of the interior of the turbid medium (1) is reconstructed from the ratio of the measurement results, wherein the first measurement is used as a reference measurement and the second measurement is used to determine deviations from the reference measurement.
8. The device according to claim 7, wherein a wavelength control unit (9) is provided which is capable of tuning the at least one light source (6) to selectively emit light having the first wavelength (λi) and light having the second wavelength (λ2).
9. The device according to any one of claims 7 or 8, wherein a second light source (10) is provided which is capable of selectively emitting light having a third wavelength (λ3) and light having a fourth wavelength (λ4) slightly differing from third wavelength (λ3), the third and fourth wavelengths being in a wavelength range different from the first and second wavelengths (λi, λ2).
10. The device according to any one of claims 7 to 9, wherein the device is a medical image acquisition device.
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