JP2018008040A - Wavefront control apparatus, wavefront control method, information acquiring apparatus, program, and storage medium - Google Patents

Abstract

An object of the present invention is to provide a wavefront control device that is advantageous in acquiring information on optical characteristics at a deep position inside a scattering medium or over a wide range. A wavefront control device includes a detection means 104 for detecting a signal generated from a medium irradiated with light, and control means 102 and 105 for controlling the wavefront of light based on the output of the detection means. The control means performs a first process of forming a first wavefront of light based on a signal generated from a first measurement position inside the medium, and a first process of forming a first wavefront of light based on a signal generated from a first measurement position inside the medium. , and a second process of forming a second wavefront of light based on a signal generated from a second measurement position different from the first measurement position. [Selection diagram] Figure 1

Description

  The present invention relates to a wavefront control device. The present invention can be applied to, for example, an apparatus for measuring or imaging optical characteristics of a scattering medium using light.

  Research for imaging non-invasively or less invasively the optical characteristics of a medium such as a living body using light from the near infrared region to the visible region is underway. In general, light propagates along an irregular locus by scattering in a scattering medium such as a living body. For this reason, in a medium in which scattering is caused multiple times, the light does not reach a deep position sufficiently, so that the imaging resolution and the imaging depth (penetration length) deteriorate. In order to image such a scattering medium with high resolution, the scattered light is removed, and only the light that becomes the signal (non-scattered light or weakly scattered light with very few scattering times) is extracted and imaging is performed. Is common. Typical examples include a confocal microscope and OCT (Optical Coherence Tomography). Such a technique is effective in a region where the depth of imaging is relatively shallow in the medium, but scattering is dominant in a deep region, and non-scattered light serving as a signal source decreases exponentially. Therefore, it becomes very difficult to perform the above-described imaging method on a deep region of the medium. The above-described imaging method is generally limited to a region having a shallow penetration depth (for example, 1 mm or less in the case of a living tissue or the like). Or, if the subject is imaged over a wide range under conditions where there are fine particles in the atmosphere called fog, smoke, or haze, or where the refractive index fluctuates spatially due to the atmosphere, light scattering may occur. Due to the influence, the captured image of the subject is distorted, making it difficult to recognize the subject.

  In recent years, a technique for efficiently sending light to a specific position inside the scattering medium by appropriately shaping the wavefront of the light incident on the medium has been proposed.

  In Non-Patent Document 1, a scattering medium is irradiated with light, fluorescence generated from a fluorescent material in the medium is monitored by a CCD, and the incident wavefront is spatially modulated (SLM: Spatial Light) so that the fluorescence signal is maximized. (Modulator). Then, it is possible to focus light on the fluorescent material efficiently by iteratively repeating the monitoring of the fluorescence signal by the CCD and the shaping of the incident wavefront by the SLM and optimizing the incident wavefront so that the fluorescence signal is maximized. Proven. Further, as disclosed in Patent Document 1, a configuration in which a photoacoustic signal is used as a wavefront optimization target instead of a fluorescent signal is also disclosed. Alternatively, as shown in Non-Patent Document 2, a configuration that targets a two-photon absorption fluorescence signal (TPF: Two-photon fluorescence) is also disclosed. In this way, various signals can be targeted for optimization, and light can be focused inside the scattering medium. At this time, a signal that can be used as an optimization target is a signal that is somehow distinguished from multiple scattered light.

  As a technique for shaping the incident wavefront, a technique using phase conjugate light has been proposed as shown in Patent Document 2, in addition to the above-described repetitive optimization processing. In Patent Document 2, an ultrasonic focusing region is generated at an arbitrary position inside a scattering medium, and light modulated in the same region (ultrasonic modulation light) is emitted to the outside of the medium. Selectively record on hologram. By generating a phase conjugate wavefront from the hologram and making it incident on the medium, the phase conjugate light propagates to the focusing region of the ultrasonic wave according to temporal reversibility. By this effect, light can be efficiently transmitted to the ultrasonic focusing region inside the medium. In addition to such ultrasonically modulated light, Non-Patent Document 3 also discloses a phase conjugate light technique using second harmonic generation (SHG) using a certain position inside the medium as a generation source. ing.

  The technique of focusing light inside the scattering medium appropriately determines the wavefront of the light irradiating the medium based on a target signal or a signal that is distinguished from the scattered light, called a guide star (repetitive optimization). Or by using a phase conjugate light technique). The signal distinguished from the scattered light is, for example, a fluorescence signal, TPF, SHG, a photoacoustic signal, an ultrasonic modulation signal, or the like. It has been proposed to use such a technique for focusing light inside a scattering medium in combination with various imaging techniques.

US Patent Application Publication No. 2012/0127557 US Patent Application Publication No. 2011/0071402

I. M.M. Vellekoop, E.C. G. Van Putten, A.M. Lagendijk and A.M. P. Mosk, “Demixing light paths insed metamaterials”, Optics Express Vol. 16, no. 1 67-80 (2008) Jianong Tang, Ronald N. Germany and Meng Cui, “Superpenetration optical microscopy by iterative multiphoton adaptive compensation techniques” (20) Xin Yang, Chia-Lung Hsieh, Ye Pu and Demetri Psaltis, “Three-dimensional scanning microscopy, thin thin turbine media,” Optics Exp. 20 No. 3 2500-2506 (2012) I. M.M. Vellekoup, A.M. P. Mosk, “Phase control algorithms for focusing light through turbid media”, Optics Communications 281 (2008) 3071-3080 Donald B.D. Conkey et al. "Genetic algorithm optimization for focusing through turbine media in noise activities", Optics Express Vol. 20, no. 5 (2012) Thomas Bifano, Yang Lu, Christopher Stockbride, Aaron Berliner, John Moore, Richard Paxman, Santosh Tripanthi and Kimani Toussaint, "MEMS spatial light modulators for controlled optical transmission through nearly opaque materials", Proc. of SPIE Vol. 8253 (2012)

  If the above-mentioned technology for focusing light to a specific position inside a scattering medium is used in combination with various measurement methods, the light is efficiently focused on the target, the signal to be measured is improved, and the optical properties of the medium are improved. It is possible to measure properties. At this time, as described above, in order to focus the light to a specific position inside the scattering medium, it is necessary to shape (optimize) the wavefront of the incident light based on the target signal generated from the same position. In other words, when the target signal cannot be measured, iterative optimization as described above and the phase conjugate light technique cannot be used. Therefore, such an optical focusing technique is effective within a range in which a target signal inside the medium can be measured from the outside of the medium. When the target is deep inside the medium, the target signal is attenuated due to the influence of multiple scattering, making it difficult to measure the signal. In such a case, the above-described iterative optimization and phase conjugation technique cannot be effectively applied. Therefore, since the light cannot be focused at a deep position inside the medium, it is impossible to measure the optical characteristics deep inside the medium. That is, the penetration length of the optical measurement cannot be improved.

  Therefore, an object of the present invention is to provide a wavefront control device, a wavefront control method, an information acquisition device, a program, and a storage medium that are advantageous for acquiring information on optical characteristics in a deep position within a scattering medium or in a wide range.

  A wavefront control device according to one aspect of the present invention includes a detection unit that detects a signal generated from a medium irradiated with light, and a control unit that controls the wavefront of the light based on an output of the detection unit. And the control means includes: a first process for forming a first wavefront of the light based on the signal generated from a first measurement position inside the medium; and the light having the first wavefront. Performing a second process of forming a second wavefront of the light based on the signal generated from a second measurement position different from the first measurement position inside the medium irradiated with It is characterized by.

  According to the present invention, it is possible to provide a wavefront control device, a wavefront control method, an information acquisition device, a program, and a storage medium that are advantageous for acquiring information on optical characteristics in a deep position within a scattering medium or in a wide range.

It is a schematic diagram which shows the structure of the measuring apparatus of Embodiment 1 of this invention. It is a figure which shows typically the whole processing flow of the measuring method of Embodiment 1 of this invention. It is a figure which shows typically the processing flow of the optimization of the incident wave front of Embodiment 1 of this invention. It is a figure showing the distribution of the depth (z) direction of the photoacoustic signal in the target area | region of Embodiment 1 of this invention. It is a schematic diagram which shows the structure of the measuring apparatus of Embodiment 2 of this invention. It is a figure showing distribution of the horizontal (xy cross section) direction of the fluorescence signal in the target area | region of Embodiment 2 of this invention. It is a schematic diagram which shows the structure of the measuring apparatus of Embodiment 3 of this invention. It is the figure which showed typically the target area | region (ultrasonic focusing area | region) which spreads in the depth direction inside the medium of Embodiment 3 of this invention. It is a schematic diagram which shows the structure of the measuring apparatus of Embodiment 4 of this invention. It is a figure which shows typically the whole processing flow of the measuring method of Embodiment 4 of this invention. It is a schematic diagram which shows the structure of the measuring apparatus of Embodiment 5 of this invention. It is a figure which shows typically the processing flow of Embodiment 5 of this invention. It is the figure which showed the effect of Embodiment 5 of this invention by simulation. In Embodiment 5 of this invention, it is the figure which showed typically the scan of the irradiation beam.

  Embodiments of the present invention will be described below with reference to the accompanying drawings. In the present invention, the wavefront control apparatus and method are an apparatus and method for controlling (adjusting) the wavefront of light applied to a medium. The wavefront control method can be realized by a program executed by a computer that constitutes control means described later. “S” in the figure represents a step. The information acquisition device is a device that acquires information on the optical characteristics inside the medium, and may include a wavefront control device. The information acquisition device includes a measuring device that measures the optical characteristics inside the medium and an imaging device that images the optical characteristics inside the medium.

(Embodiment 1)
A method and apparatus for measuring the optical characteristics of the scattering medium according to the first embodiment of the present invention will be described with reference to FIGS. FIG. 1 is a schematic diagram illustrating an exemplary configuration of a measurement apparatus according to the present embodiment. The medium 107 is a test medium including a biological tissue, includes scattering particles 111, and is a scattering medium for visible to near-infrared light. Now, a case where the present invention is applied to an apparatus for imaging a medium 107 using a photoacoustic signal (Photoacoustic signal) will be described.

  The light source 100 emits pulsed light of several ns. For example, when the medium 107 is a living tissue, the light source 100 can select a plurality of wavelengths according to absorption spectra of water, fat, protein, oxyhemoglobin, deoxyhemoglobin, and the like that are constituents of the tissue. . As an example, an electromagnetic wave source that emits a wavelength in the range of visible to near infrared, such as 400 nm to 1,500 nm, is used. Similarly, when the medium 107 is a living tissue, the intensity of the emitted light is adjusted within the intensity below the safety standard that can be irradiated.

  Light emitted from the light source 100 passes through the beam splitter 101 and is irradiated onto the SLM 102. The SLM 102 can use, for example, liquid crystal on silicon (LCOS). The SLM 102 is controlled by the control device 105, and forms a wavefront (phase modulation) based on the optimization process shown in FIG. The optimization process of FIG. 3 will be described later. The SLM 102 and the control device 105 constitute control means for controlling the wavefront of light based on the output of an ultrasonic transducer described later. The wavefront shaped light 106 reflected from the SLM 102 is reflected from the beam splitter 101 and irradiated onto the medium 107 via the optical system 103.

  The light 109 incident on the scattering medium 107 propagates inside the medium 107 while being scattered, and part of the energy is absorbed by the absorber located at a specific position (region) 108, resulting in a temperature rise in the local region, and the volume. Is expanded and an acoustic wave (photoacoustic signal) 110 is generated. The ultrasonic transducer 104 functions as a detection unit (measurement unit) that detects (measures) a signal generated from a scattering medium irradiated with light, and measures the photoacoustic signal 110. At this time, the control device 105 controls the ultrasonic transducer 104 and the focus of the ultrasonic transducer is controlled so that a signal including the photoacoustic signal 110 from the local region 108 inside the scattering medium 107 is detected. Here, the ultrasonic transducer is composed of, for example, a linear array probe, and an ultrasonic focus region can be generated at an arbitrary position inside the medium 107 by electronic focusing using the array probe. As the transducer, a transducer using a piezoelectric phenomenon, a transducer using optical resonance, a transducer using capacitance change, and the like can be used. Further, the ultrasonic transducer 104 is acoustically aligned with the medium 107.

Here, the photoacoustic signal P (z) at the depth z (position z) inside the medium from the light incident position is the light intensity Φ (z) at the same position z and the absorption coefficient μ of the absorber at the same position z. _It is expressed as follows using _a (z) and a Gruneisen coefficient Γ representing the conversion efficiency from heat to acoustic waves.

As can be seen from the equation (1), if the Gruneisen coefficient Γ and the absorption coefficient μ _a (z) are constant at the position z, the photoacoustic signal changes according to the light intensity at the position z. . Therefore, if the light is efficiently focused at the position z, the signal intensity of the photoacoustic signal P (z) is improved.

  The SLM 102 is disposed on the pupil plane of the optical system 103, and each segment on the SLM (a small area whose phase can be controlled independently) independently shapes the wavefront of the incident light. Below, the measurement flow of the whole photoacoustic imaging of this embodiment including the wavefront shaping (optimization) of this incident light will be described based on the flowcharts shown in FIGS.

First, in S200, as an initial condition, a local target region 108 (target position z ₀ ) for measuring a photoacoustic signal is set. About this initial target area | region 108, the depth from the position where incident light is irradiated is arbitrarily set to the depth which can fully measure a photoacoustic signal. The measurement may be performed several times to find an appropriate depth at which the signal strength can be measured sufficiently.

Next, in S210, when the light source 100 is turned on and the ultrasonic transducer 104 starts to receive a photoacoustic signal, the process proceeds to optimization of the wavefront of incident light in the next S220. In the optimization process of S220, the wavefront of incident light is optimized so that the photoacoustic signal generated from the target region 108 set in S200 is maximized. As described above, from the equation (1), if the wavefront is shaped so that the light intensity is focused on the target region 108, the photoacoustic signal is also improved. The incident wavefront optimization process in S220 executes S220 with the incident wavefront optimized one step before the process repeated in S230 and thereafter as an initial state (see S260 described later). However, in the optimization process at the initial target position z ₀ where S230 and the subsequent steps are not yet executed, S220 may be executed using, for example, a plane wave as an initial condition for optimization.

  The optimization process in S220 will be described with reference to FIG. First, in step S221, the segment with index j is selected from the N segments divided on the SLM 102. At this time, the segment may be one pixel of the SLM 102 or may be an area composed of a plurality of pixels of the SLM 102.

When the processes from S223 to S227 are completed for all N segments in S222, the optimization process (S220) is terminated, and the process proceeds to S230 (FIG. 2). When the processing is not executed for all segments in S222, the photoacoustic signal 110 generated from the target region 108 is measured by the ultrasonic transducer 104 in S223. The measured signal value is stored in the memory of the control device 105 together with the phase value φ _j of the segment j. For example, if j = 1, the phase distribution set in S260 (wavefront optimized at the depth of z _i-1 one step before), or if the plane wave is irradiated to the medium if the position is z ₀ Of the photoacoustic signal 108 is measured.

Next, in S224 to S225, while gradually increasing the value of the phase modulation amount Δφ (incrementing according to the discretized step size), the phase modulation amount Δφ is given to the phase φ _{j of the} segment j, and Update the phase value. In S224, it is determined whether or not the phase modulation amount Δφ exceeds 2π. If not, in S225, the phase value φ _j of the segment j is changed to φ _j → φ _j + Δφ, and the phase is changed. The value of the phase φ _j is updated by adding the modulation amount Δφ. Again in step S223, the photoacoustic signal generated from the target area 108 is measured for the newly updated phase φ _j , and the data is stored in the memory of the control device 105. This is repeated until the phase modulation amount Δφ of the segment j exceeds 2π.

In S224, the phase modulation amount Δφ is finished the measurement exceeds the 2 [pi, in S226, reads out the optimum phase phi _j photoacoustic signal from the data stored in the memory is maximized, set as the phase of the segment j of SLM102 To do. In S227, the process moves to the next segment j + 1 of the SLM 102, and the above-described optimization of S222 to S227 is executed. In this way, by executing the optimization process for all the segments of the SLM 102, the incident light 106 that focuses the light on the set target area is generated.

In this embodiment, the phase φ _{j at} which the photoacoustic signal has the maximum value is read in S226, but at least 75%, preferably 85%, and more preferably 95% of the maximum value of the photoacoustic signal.

  Here, for optimization of the incident wavefront in S220, instead of the algorithm for optimizing the phase of each segment of the SLM one by one as described above, a plurality of segments disclosed in Non-Patent Document 4 are simultaneously optimized. You may use Partitioning algorithm. Alternatively, a genetic algorithm can be used as disclosed in Non-Patent Document 5. In particular, when the photoacoustic signal is weak, a partitioning algorithm that optimizes a plurality of segments simultaneously and a genetic algorithm are effective.

When the optimization process in S220 is completed, the process proceeds to S230 shown in FIG. In S230, it determines whether depth measuring the optical properties of the medium by using the photoacoustic signal (target position) to a target position z _i has reached. If not, the process proceeds to S240.

FIG. 4 shows a profile in the depth direction (z direction) of the photoacoustic signal in the target region 108 when the medium 107 is irradiated with an incident wavefront optimized at a target position at a certain depth z _i . Due to the optimization effect of S220, the intensity of the photoacoustic signal is improved as compared with normal light irradiation, the signal intensity peaks at z _i , and has a shape with a spread in the depth direction (half-value width W) ( It also spreads in the direction of the cross section perpendicular to the depth). Therefore, the profile of the photoacoustic signal shown in FIG. 4 can be measured by the ultrasonic transducer 104. In S240, the half width W of the signal distribution obtained as a result of the optimization in S220 as shown in FIG. 4 is measured.

Next, in S250, the next target position z _{i + 1} for performing wavefront optimization is determined by iterative processing. Here, the next target position z _{i + 1} is changed based on a region where the measurement signal is improved when the medium is irradiated with light having a wavefront (first wavefront) optimized at the current target position z _i . . Specifically, as shown in FIG. 4, the target position (measurement position) is changed within a range in which the value of the measurement signal that changes in accordance with the depth direction is larger than the threshold value. For example, the target position is changed within a range larger than half the maximum value of the measurement signal. In the present embodiment, as shown in FIG. 4, the next target position is set as z _{i + 1} = z _i + W / 2 based on the measured half-value width W. The target position can be changed by changing the focus position of the ultrasonic transducer 104. In S250, the target is set so that the focus of the ultrasonic transducer 104 matches the updated target position z _{i + 1} .

The main feature of the present invention is that the target position is updated as in S250 and this is repeated. When optimization is performed so that the photoacoustic signal is maximized at the position z _i by the optimization processing in S220, a region in which the intensity of the photoacoustic signal is improved around the same position is generated. The extent of this region is the characteristics of the ultrasonic focus region set by the ultrasonic transducer 104, the correlation of the scattered wavefront when the shaped incident wavefront propagates to the target position, and the independent modes that can exist ( It is influenced by the number of optical modes. In other words, the signal intensity of the photoacoustic signal is improved with a certain spatial extent due to the influence of both the characteristics specific to the medium and the controllable characteristics such as the focus area of the ultrasonic wave. In the present invention, such an effect by the optimization process is used.

In S260, the wavefront (phase distribution) obtained by the optimization in S220 is set in the SLM 102 as it is, and the process returns to the optimization processing step in S220. In the optimization processing of S220, the wavefront optimized at the position z _i is already set in the SLM 102 as an initial condition, and optimization of the wavefront is started based on this wavefront. If the wavefront optimized at the position z _i is incident on the medium 107, a signal intensity of about half of the signal intensity obtained in the previous step is obtained at the initial condition of the optimization process at the new target position z _{i + 1} . This signal intensity is a value that greatly improves the intensity compared to the case where light is incident on the medium without wavefront shaping. Therefore, by using this signal strength as an initial condition, the optimization process of S220 can be executed efficiently. For example, the same effect is also disclosed in Non-Patent Document 6. In Non-Patent Document 6, the wavefront is shifted within a range correlated with scattering (in a range where the memory effect appears) with respect to an incident wavefront optimized so that light transmitted through the scattering medium is focused. It is disclosed that a focus spot can be efficiently generated behind the medium by optimizing the shifted wavefront as an initial value for optimization.

  In the present invention, in addition to the above-described optimization efficiency, the target signal (photoacoustic signal) at the depth of the next step is used by using the incident wavefront optimized at the depth of the previous step. Is to avoid being buried in noise. Furthermore, by performing the above iterative process, the signal is measured even from a deep position inside the medium where the signal cannot be measured by normal light irradiation, the wavefront is optimized, and the local optical characteristics are measured. It is a feature. Thus, an object of the present invention is to increase the depth (penetration length) for measuring the optical characteristics of a medium. Conventionally, even if a target is set at a deep position in a scattering medium and a signal generated from the position is measured, it is very difficult to measure the signal due to signal attenuation due to scattering and absorption. It is also difficult to optimize the incident wavefront using the signal.

  When the target position reaches the target depth for measuring the optical characteristics in S230, the process proceeds to S270. In S270, the optical characteristic based on the formula (1) is measured by irradiating the medium with the incident wavefront optimized in S220 and measuring the photoacoustic signal at the target position. When measuring the photoacoustic signal of the cross section at the same depth in S270, the above-described process optimized repeatedly in the depth direction may be executed in the horizontal direction in the cross section. For example, when moving to the process of S270 at a certain depth and measuring a photoacoustic signal, the incident wavefront optimized in S220 is set as an initial condition, and the acquisition position (target position) of the photoacoustic signal is set in the lateral direction (depth). To the cross-sectional direction). The incident wavefront is optimized again at the shifted target position, and the photoacoustic signal is measured. It is also possible to measure the photoacoustic signal in the same section while repeating this, and to image the measurement result.

  As described above, in this embodiment, first, a photoacoustic signal generated from a measurement position (first measurement position) at a relatively short distance (first distance) from the surface in the depth direction of the medium. The first wavefront is formed by performing the first optimization process so that the intensity of the first wave becomes higher. The measurement position is at a relatively long distance (second distance greater than the first distance) from the surface in the depth direction of the medium so that the distance between the measurement position and the target position is small. Change to the measurement position (second measurement position). Further, the second optimization process is performed so that the medium is irradiated with light having the first wavefront and the intensity of the photoacoustic signal generated from the changed measurement position (second measurement position) is increased. To update the first wavefront (second wavefront). The above is repeated until the second measurement position reaches the target position. That is, in the iterative process, the second measurement position is set as a new first measurement position, and the second wavefront is updated as a new first wavefront. Thus, the processing steps in the present invention include an optical focus step for shaping the wavefront to the target depth shown in S200 to S260, and a measurement step (or imaging step) for measuring optical characteristics using the optimized wavefront. ).

  In S270, the target position 108 is scanned only in the region of interest inside the medium (the region in which the photoacoustic signal is to be measured), the photoacoustic signal is measured, and the absorption coefficient distribution in the region of interest is quantitatively imaged. Also good. Furthermore, an image (absorption coefficient distribution image) generated by the imaging may be displayed on a display device 112 such as a display. Here, the control device 105 has a function as a generation unit that generates an image based on the detected photoacoustic signal, and the display device 112 has a function as a display unit that displays the generated image. When the scattering medium 107 is a living tissue and the photoacoustic imaging is for diagnostic purposes, for example, the display includes other diagnostic results and measurement data, and the absorption coefficient distribution image obtained by the present embodiment. It is also possible to superimpose and display. At this time, the region of interest for performing photoacoustic imaging can be set based on the diagnosis result. Alternatively, the ultrasonic transducer 104 may be used to transmit ultrasonic waves, and the region of interest may be set from the reflected signal (echo image).

  Furthermore, the spectral characteristics inside the medium may be measured by executing the above-described measurement and processing using a plurality of arbitrary wavelengths. Then, by using the spectral characteristics, for example, it is possible to obtain a component ratio of oxyhemoglobin, reduced hemoglobin, water, etc., and metabolic information such as oxygen saturation and image it. The distribution of metabolic information of such a medium may be obtained three-dimensionally with respect to the region of interest, and the tomographic image may be displayed on the display device.

Further, in order to reach the depth at which the photoacoustic signal is measured as fast as possible in S230, it is not always necessary to execute the process for all segments in S222 in the optimization process of S220. For example, optimization processing is executed for several segments. Thereafter, the photoacoustic signal is also at the next depth position z _{i + 1} with respect to the position z _i is sufficiently enhanced against noise, if it is measurable, optimization of S220 even if unprocessed segment The optimization process may be terminated and the next step may be performed. Alternatively, the photoacoustic signals may be monitored in parallel at both the position z _i and the position z _{i + 1} , and the SLM region may be divided into two (or two SLMs are used). At this time, on the one hand, the result of optimizing the wavefront can be monitored and optimized on the other side, and the depth of measurement can be increased sequentially in parallel.

  When sequentially optimizing in the depth direction, instead of determining the step size to the next depth based on the half width W, a certain threshold is set for the focus area, and the step size is determined based on the threshold. It is also possible to do.

(Embodiment 2)
A method and apparatus for measuring the optical characteristics of a scattering medium according to a second embodiment of the present invention will be described. FIG. 5 is a schematic diagram illustrating an exemplary configuration of the measurement apparatus according to the present embodiment. The medium 305 is a test medium including a living tissue, and is a scattering medium for visible to near-infrared light. Now, a case where the present invention is applied to an apparatus that measures and images a fluorescent signal generated from the medium 305 will be described.

  The light source 300 emits light whose wavelength, pulse width, and the like are adjusted in accordance with the characteristics of the fluorescent substance in the medium 305. Light emitted from the light source 300 passes through the beam splitter 301 and is applied to the SLM 302. The SLM 302 is controlled by the control device 308, and shapes (phase modulates) a wavefront incident on the medium 305 based on an optimization process described later. The SLM 302 and the control device 308 constitute control means for controlling the wavefront of light based on the output of the CCD described later. The wave-shaped light reflected by the SLM 302 is reflected by the beam splitter 301, reflected by the dichroic mirror 303, and irradiated onto the medium 305 via the optical system 304.

  The light incident on the scattering medium 305 propagates through the medium 305 while being scattered near the focus area set by the optical system 304. The medium 305 contains a substance that is excited by the wavelength of light emitted from the light source 300 and emits fluorescence. Now, light is intensively applied to a region focused by the optical system 304, and a fluorescent substance is excited around the region, and a fluorescent signal is generated. This fluorescence signal is collected by the optical system 304, and light having an excitation wavelength that becomes noise is removed through the dichroic mirror 303 to transmit the fluorescence signal. Further, the filtered fluorescence signal is incident on the CCD 307 by a band-pass filter 306 that selectively transmits a fluorescence wavelength signal. The CCD 307 functions as a detection unit (measurement unit) that detects (measures) a signal generated from a medium irradiated with light. Here, instead of the CCD 307, a CMOS sensor, an area sensor having an image intensifier, or an EMCCD is also applicable.

  In such a fluorescence imaging apparatus configuration, as described in the first embodiment, the incident light of the incident light is improved so that the fluorescence signal from the local position (target position) determined by the focus position of the optical system 304 is improved. Shape the wavefront. The wavefront of the light incident on the medium 305 can be optimized by controlling the SLM 302 with the control device 308 while monitoring the fluorescence signal measured by the CCD 307. Further, in the present embodiment, as in the first embodiment, the target position for measuring the fluorescence signal is gradually deepened, and the incident wavefront is sequentially optimized according to the position. By executing this processing, light is efficiently focused to a deep position in the medium, and imaging using a fluorescence signal is performed. The processing flow of this embodiment is performed in substantially the same manner as the flow of the first embodiment shown in FIGS. 2 and 3 (if the portion described as the photoacoustic signal in FIGS. 2 and 3 is replaced with a fluorescence signal). Good). Therefore, the processing flow will be described below with reference to FIGS.

First, the initial target position z ₀ corresponding to S200 in FIG. 2 is set to a depth at which the fluorescence signal is sufficiently measurable without being buried in noise by appropriately adjusting the focus position of the optical system 304. When the light source 300 is turned on in S210 and measurement of the fluorescence signal is started, the process proceeds to optimization processing in S220. The optimization processing in S220 can be performed in the same manner as the processing shown in FIG. Here, instead of the optimization algorithm shown in FIG. 3, the above-mentioned Partitioning algorithm or genetic algorithm may be used. Such optimization can generate an incident wavefront that maximizes the intensity of the fluorescence signal at the target position.

Also in this embodiment, the target position z _{i + 1} in the next depth direction is determined according to the region where the fluorescence signal is improved by the optimization (S240 to S250), and the incident wavefront optimized at the position z _i is The initial conditions for optimization at the position z _{i + 1} are set (S260).

FIG. 6 is a diagram schematically showing a cross-sectional profile of the fluorescence signal measured by the CCD 307 when the optimized incident wavefront is incident on the medium 305. The horizontal axis of the plot in FIG. 6 represents the position in the horizontal direction r (xy direction) perpendicular to the depth z direction of the medium, and the vertical axis represents the intensity of the fluorescence signal to be measured. r _i is the center position in the xy cross section of the target region, and the depth is z _i . In S220, optimization is executed with the fluorescent signal generated from the same position as the target. Compared with the signal obtained by normal light irradiation, the measured fluorescence signal is greatly improved as a result of optimization. As shown in FIG. 6, the intensity of the fluorescence signal is improved with a spatial spread around the target position. Region in which the strength is improved, the focus and the spot diameter determined by the numerical aperture (NA) of the optical system 304, the incident wave front that is molded, determined by the correlation of the scattered wave front when propagated to the position r _i.

Here, in this embodiment, since the fluorescence signal of the cross section corresponding to the focus position z _i of the optical system 304 is measured by the CCD 307, the fluorescence signal in the depth direction as shown in FIG. 4 of the first embodiment. The spread of is not monitored directly. Therefore, in order to obtain a profile in the depth direction as shown in FIG. 4, the fluorescence signal may be monitored while changing the focus position z _i of the optical system 304. From the obtained profile, the half width W of the distribution shown in FIG. 4 may be directly measured (S240), and the next depth z _{i + 1} may be appropriately set (S250).

Alternatively, the next depth position z _{i + 1} may be set as follows from the profile of the fluorescent signal in the horizontal direction shown in FIG. In general, in a region (non-diffusion region) where the propagation of light within the medium is dominant in the depth z direction (forward direction), the profile of the fluorescence signal whose intensity has been improved by the optimization is the transverse direction r. The profile extends in the depth z direction. Further, in the case of a region (diffusion region) in which light propagation can be regarded as nearly isotropic as a result of multiple scattering, the profile may be regarded as broadening almost isotropically. Accordingly, in any case, if the half-value width of the fluorescence signal is W, the depth z _{i + 1} of the next target position is set to z _{i + 1} = z _i + W, or at least z _{i + 1} = z _i + W / 2. Thus, the signal strength can be improved as a result of optimization at z _{i + 1} . In this way, the next target position z _{i + 1} may be set by estimating from the intensity distribution of the signal (fluorescence signal) in a plane perpendicular to the depth direction of the medium. For the depth z _{i + 1} set in this way, the optimization is repeated again using the wavefront optimized at the depth z _i as an initial condition.

In this way, by using the incident wavefront optimized at the depth z _i of the previous step for optimization at the depth of the next step, it is possible to prevent the target fluorescence signal from being buried in noise and efficiently. The wavefront optimization can be converged to. Further, the incident wavefront is sequentially optimized according to the depth of the target, and the light is efficiently focused at a deep position (light focusing step), and the medium is imaged by the fluorescence signal. For example, when it is desired to perform fluorescence imaging at a certain target depth, S220 to S260 are repeated until the same depth. At this time, if there is no need to measure a fluorescence signal at a midway depth, it is not necessary to execute the optimization of S220 until convergence. If the signal strength is improved at the depth position of the next step and sufficient measurement is possible, the optimization may be interrupted and the wavefront formed at that time may be set as the initial condition of the next depth. As a result, the processing speed can be increased, the target depth can be reached earlier, and fluorescence imaging can be performed.

  As described above, in this embodiment, first, the fluorescence signal generated from the measurement position (first measurement position) at a relatively short distance (first distance) from the surface in the depth direction of the medium. The first wavefront is formed so as to increase the intensity. Then, the measurement position is set to a measurement position (second measurement) at a relatively long distance (second distance larger than the first distance) from the surface in the depth direction of the medium so as to approach the target position. The first wavefront is updated so that the intensity of the fluorescent signal generated from the changed measurement position (second measurement position) is increased, and the medium is irradiated with light having the first wavefront. (Second wavefront). The above is characterized by iteratively processing until the second measurement position reaches the target position.

  In addition, the repeated processing flow in the depth direction of the medium as described above may be executed in synchronization with the scanning flow for executing fluorescence imaging. For example, one-dimensional fluorescence signal profile data is obtained in the depth direction according to the processing flow shown in FIG. Next, the imaging position is shifted in the horizontal direction (for example, the stage holding the medium 305 is moved), and data in the next depth direction is similarly obtained. For example, the three-dimensional distribution of the fluorescence signal in the same region can be imaged by sequentially repeating this operation within a certain region of interest of the medium 305. In addition, using the wavefront already optimized in the vicinity region for the depth and horizontal scans as an initial condition, the optimization can be performed efficiently at the new measurement position and imaged. it can. The generated image may be displayed on a display device (not shown) such as a display.

  Here, the fluorescence signal includes a signal emitted by multiphoton excitation of a nonlinear phenomenon, such as the TPF described above. Further, the present invention is not limited to imaging using a fluorescent signal, and for example, the present invention is applied to a method of irradiating a medium with light and measuring and imaging an ultrasonically modulated optical signal as will be described in an embodiment described later. Also good. Further, the present invention may be applied to a technique for measuring and imaging the second harmonic (SHG) and the third harmonic (THG) inside the medium. Alternatively, the present invention may be applied to imaging of signals caused by Raman scattering including stimulated Raman scattering (SRS) and coherent anti-Stokes Raman scattering (CARS). Further, the present invention can also be applied to the case of measuring and imaging by identifying (sectioning) a signal generated from a specific depth inside a scattering medium, such as OCT (Optical Coherence Tomography) or a confocal microscope. . Thus, the measurement signal of the present invention can be any one of, for example, a photoacoustic signal, a fluorescence signal, an ultrasonic modulation light signal, a harmonic signal, a Raman scattering signal, an OCT signal, or a light intensity signal acquired by a confocal optical system. It may be a signal.

(Embodiment 3)
A method and apparatus for measuring the optical properties of a scattering medium according to a third embodiment of the present invention will be described. FIG. 7 is a schematic diagram illustrating an exemplary configuration of the measurement apparatus according to the present embodiment. The medium 405 is a test medium including a living tissue, and is a scattering medium for visible to near-infrared light. Now, a case where the present invention is applied to an apparatus for measuring optical characteristics by irradiating a medium 405 with ultrasonic waves and generating light modulated with ultrasonic waves (ultrasonic modulated light) will be described.

  The light source 400 outputs pulsed light having a long coherence length (for example, 1 m or more) and several tens to several hundreds of μs. As described above, the wavelength of light emitted from the light source 400 is selected from a plurality of wavelengths according to the absorption spectrum of water, fat, protein, oxyhemoglobin, deoxyhemoglobin, etc., which are elements constituting the medium 405, for example. can do.

  The pulsed light emitted from the light source 400 passes through the beam splitter 401 and is applied to the SLM 402. The SLM 402 is controlled by the control device 408, and shapes (phase modulates) a wavefront incident on the medium 405 based on an optimization process described later. The SLM 402 and the control device 408 constitute control means for controlling the wavefront of light based on the output of a detection system described later. The wave-shaped light 409 reflected from the SLM 402 is reflected from the beam splitter 401 and is incident on the medium 405 via the optical system 403.

  On the other hand, the ultrasonic transducer 404 irradiates the medium 405 with the focused ultrasonic pulse 410 and generates an ultrasonic focused region 411. At the center of the ultrasonic transducer 404, there is an opening through which the incident light 409 passes, and the medium 405 is irradiated coaxially with light and ultrasonic waves. Here, the ultrasonic wave to irradiate is in the range of 1 to several tens of MHz, for example, and the ultrasonic intensity applied by the control device 408 is appropriately adjusted. For example, when the medium 405 is a living tissue, the ultrasonic intensity is adjusted within an intensity that is less than the safety standard that can be irradiated. Further, the ultrasonic transducer 404 is acoustically aligned with the medium 405.

The light incident on the scattering medium 405 propagates inside the medium 405 while being multiple scattered, and a part of the multiple scattered light reaches the ultrasonic focusing region 411. In the ultrasonic focus region 411, the refractive index of the medium is modulated by the ultrasound, further displacement of the scatterers in the medium (scattering particles 412) is induced by the ultrasonic frequency f _a which is applied. When the light in the ultrasonic focus region 411 enters the light by the optical path length change due to scatterer displacement and the refractive index modulation described above receives the modulation effect of the phase, the frequency is shifted in accordance with the ultrasonic frequency f _a. The light whose frequency is shifted by this ultrasonic wave (ultrasonic modulated light) is emitted from the ultrasonic focusing region 411. The emitted ultrasonically modulated light propagates again while being scattered inside the medium 405 and is emitted from the medium 405.

  Here, in order to localize the ultrasonic focusing region 411, the timing of irradiation of the focused ultrasonic pulse 410 and the incident light 409 is appropriately adjusted by the control device 408, and the timing at which the focused ultrasonic pulse reaches the target position 411. Irradiated with. The pulse width of the ultrasonic wave is set according to the size of the ultrasonic focusing area 411 and the speed of the ultrasonic wave in the medium.

  The ultrasonic modulation light emitted from the medium 405 is detected by the detection system 407. The detection system 407 functions as a detection unit (measurement unit) that detects (measures) a signal generated from a medium irradiated with light. As the detection system 407, a system that monitors the light intensity of the ultrasonically modulated light that is frequency-shifted in combination with a single sensor, a lock-in amplifier, or a band-pass filter can be used. Here, a photodiode (PD), an avalanche photodiode (APD), a photomultiplier tube (PMT), or the like can be used as a single sensor. Alternatively, a CCD, CMOS, EMCCD, or a two-dimensional sensor array in which an image intensifier is combined with a CCD may be used. In addition, a system that uses a two-dimensional sensor array and measures a modulation degree signal related to the signal intensity of ultrasonically modulated light from each speckle contrast when the ultrasonic transducer 404 is on and off may be used. .

The optimization process for shaping the wavefront of the incident light 409 is basically performed in the same manner as the flow shown in FIGS. That is, based on the ultrasonic modulated optical signal measured by the detection system 407, the control device 408 controls the SLM 402 so that the signal becomes maximum, and shapes the incident wavefront in the same manner as in FIG. Since the ultrasonic modulation optical signal that is an optimization target is a signal generated from the ultrasonic focusing region 411, the incident light optimized as described above is a position where the focused ultrasonic pulse is localized (super The sound wave focusing area 411) is focused. As described in S240 to S260 of FIG. 2, the position where light is focused is set as z _i, and the next target position z _{i + 1} is set from the focus area that spreads around the position z _i, and is optimal at the updated position. To implement. At this time, the incident wavefront that has been optimized position z _i, and set as an initial condition for optimization in the next position z _{i + 1,} is repeated optimization.

At this time, the focus area of the light obtained by optimizing the incident wavefront can be controlled by parameters relating to the focus of the ultrasonic wave set by the ultrasonic transducer 404. FIG. 8 is a diagram schematically showing the localized position (target region) of the focused ultrasonic pulse inside the medium 405. Now, by appropriately adjusting the pulse width of the ultrasonic pulse, it is possible to generate an ultrasonic focusing area extending in the depth direction (z direction) as shown in FIG. If the size of the ultrasonic focusing region in the z direction is defined by the half width W of the focused ultrasonic pulse, W can be freely controlled by the pulse width of the electric signal applied to the ultrasonic transducer 404. Depth z _i is the center position of the ultrasonic pulse, and it is assumed that the light is focused on the target region 420 by the optimization process of the incident wavefront. At this time, in the present embodiment, as processing corresponding to S240 to S250 in FIG. 2, the center position z _{i + 1} of the next optimization target region 430 is set to z _{i + 1} = z based on the pulse width W set by the control device 408. Set as _i + W / 2. In this way, by irradiating the medium with ultrasonic waves, an ultrasonic focusing region in which the ultrasonic waves are focused is formed inside the medium, and the next target position z _{i + 1} is set in the depth direction of the ultrasonic focusing region. Set based on size. For the target position z _{i + 1} updated in this way, the incident wavefront optimized at the position z _i is set as an initial condition and optimized again. By repeatedly performing the above processing, the wavefront is sequentially optimized to the target depth for measuring the optical characteristics.

  The greatest feature of this embodiment is that the next step size Δz can be controlled relatively freely. If the pulse width of the ultrasonic wave is increased, Δz can be increased, and an incident wavefront that can be focused more efficiently to the target depth can be generated.

  When the target depth is reached by the above processing (Yes in S230 in FIG. 2), the optical characteristics inside the medium are measured using the ultrasonic modulation light as a measurement signal at the same depth. As described above, local optical characteristics inside the medium 405 can be imaged by measuring the ultrasonic modulation light while scanning the target region in the horizontal direction within the cross section of the same depth. At this time, the incident wavefront optimized next to one step may be set as an initial condition for optimizing the incident wavefront at the next horizontal position during the horizontal scanning. As in the depth direction, imaging can be performed while optimizing the incident wavefront sequentially in the lateral direction. Further, the ultrasonic modulation light may be measured while spatially scanning the target area inside the medium, and the imaging result may be displayed on a display device (not shown) such as a display.

  As described above, in the present embodiment, first, ultrasonic modulation generated from a measurement position (first measurement position) at a relatively short distance (first distance) from the surface in the depth direction of the medium. The first wavefront is formed so that the intensity of the optical signal is increased. Then, the measurement position is set to a measurement position (second measurement) at a relatively long distance (second distance larger than the first distance) from the surface in the depth direction of the medium so as to approach the target position. Position). In addition, the medium is irradiated with light having the first wavefront, and the first wavefront is updated so that the intensity of the ultrasonically modulated optical signal generated from the changed measurement position (second measurement position) is increased. (Second wavefront). The above is characterized by iteratively processing until the second measurement position reaches the target position.

  In S230, after reaching the target depth in the optical focus step as described above, the signal source for measuring the optical characteristics may be changed to other than the ultrasonically modulated light, and the measurement may be executed. For example, the above-described optical focusing step is executed to a certain depth using ultrasonic modulation light as an optimization target signal. Once the same depth is reached, it is also possible to measure the fluorescence signal using an optimized incident wavefront. At this time, in the optical focus step using ultrasonically modulated light, processing is performed on light having a wavelength that excites the fluorescent material. In the measurement step of S270, the light source for fluorescence imaging having the same wavelength and different output power may be switched as necessary. In this way, the signal to be measured may be switched between the optical focus step and the measurement step. In the measurement step, the ultrasonic transducer 404 is turned off. Further, in the measurement step, the intensity of incident light is changed according to the signal to be measured, or the incident light is switched to ultrashort pulse light or continuous light with constant intensity (CW light: Continuous Wave light). Also good. In addition to the fluorescence signal, various measurement methods such as SHG light and Raman scattering can be used in combination with the optical focus step as the measurement signal in the measurement step. As described above, the signal detected from the target position may be a signal different from the signal detected from the measurement position different from the target position.

(Embodiment 4)
A method and apparatus for measuring optical characteristics of a scattering medium according to a fourth embodiment of the present invention will be described. FIG. 9 is a schematic diagram illustrating an exemplary configuration of the measurement apparatus according to the present embodiment. The present embodiment relates to a measuring apparatus using ultrasonically modulated light as in the third embodiment.

  Similar to the third embodiment, the light source 500 has a relatively long coherence length, emits pulsed light of several tens to several hundreds μs, and has a wavelength of a contrast source (water, hemoglobin, etc.) to be measured inside the irradiated medium. A wavelength according to the absorption spectrum is selected. The light collimated and emitted from the light source 500 has its polarization direction controlled by the half-wave plate 501 and passes through the polarization beam splitter 502. At this time, the shutter 503 is closed and the shutter 504 is opened. The light that has passed through the shutter 504 is split into a signal light 530 and a reference light 531 through a half-wave plate 505 and a polarization beam splitter 506.

The signal light 530 is reflected by the mirror 507 and sent to acousto-optic elements (AOM) 508 and 509. The AOMs 508 and 509 are driven at individual frequencies, respectively, and the sum of the frequencies of the two AOMs is adjusted to be equal to the frequency of the ultrasonic wave applied by the ultrasonic device 550. For example, when the ultrasonic frequency f _a is 2 MHz, the frequency of the AOM 508 is set to f ₁ = −70 MHz, and the frequency f ₂ of the AOM 509 is f so that f ₁ + f ₂ = f _a (= 2 MHz). ₂ = Set to +72 MHz.

Or as another means for adjusting the frequency using AOM, to place the two AOM to respective optical paths of the signal light and the reference light, so that the frequency difference between the two AOM is equal to the ultrasonic frequency f _a You may adjust. For example, the frequency of AOM disposed in the optical path of the signal light is _f 1 (= 70MHz), and when the frequency of ultrasonic waves is _f a (= 2MHz), the frequency of which is disposed in the optical path of the reference light AOM f ₂ may be f ₁ + f _a (= 72 MHz).

  The signal light 530 whose frequency is adjusted by the AOM is irradiated to the medium 570 by the optical system 517 through the mirror 510 and the beam splitters 511 and 515. The medium 570 is a scattering medium including biological tissue.

  On the other hand, the ultrasonic device 550 includes an ultrasonic transducer, is acoustically aligned with the medium 570, and focuses and radiates ultrasonic waves to a preset region of interest inside the medium 570. The size of the ultrasonic focusing region (target) 560 to be formed is set to be the entire region of interest or a part thereof.

  Here, the region of interest inside the medium 570 refers to a region where it is desired to measure and image the distribution of optical characteristics such as absorption and scattering. For example, when the present embodiment is applied to the medical field, this attention area uses prior information provided by other modalities such as measurement results such as X-rays, MRI, and ultrasonic echo images, or some other diagnostic result. Thus, it is possible to set the attention area.

  The frequency of the ultrasonic wave to be irradiated and the intensity to be irradiated are adjusted by a control device (not shown). The ultrasonic transducer included in the ultrasonic device 550 is constituted by, for example, a linear array probe, and generates an ultrasonic focusing region 560 at an arbitrary position inside the medium 570 by electronic focusing using the array probe. As the transducer, a transducer using a piezoelectric phenomenon, a transducer using optical resonance, a transducer using capacitance change, and the like can be used. In addition, as described above, pulsed ultrasonic waves are irradiated to realize a small ultrasonic focusing region 560 in the vertical direction (the ultrasonic propagation direction). The pulse width of the ultrasonic wave is set according to the size of the ultrasonic focusing region 560 and the velocity of the ultrasonic wave in the medium, and the pulsed light from the light source 500 is synchronized with the timing at which the pulse ultrasonic wave reaches the target 560. Irradiate. The light source 500 can use CW light instead of pulsed light.

The light incident on the ultrasonic focus region 560, as described above, receives the modulation effect by the ultrasound, the frequency is ± f _a shift (first order component) in accordance with the frequency of the ultrasonic wave. _Therefore, with respect to _{f 1 +} f 2 = f _a signal light 530 which frequency is incident is adjusted to be, modulated light -f _a shift has a frequency equal to the reference beam 531. Ultrasound modulated light whose frequency is shifted is emitted from the ultrasonic focusing region 560, propagates again while being scattered inside the medium 570, and is emitted out of the medium. A part 540 of this ultrasonically modulated light is emitted to the light incident side and passes through the opening of the optical system 517.

The ultrasonically modulated light 540 having _a frequency shifted by ± fa and the scattered light that has not been frequency-shifted (non-ultrasonically modulated light) that has been emitted from the medium 570 and transmitted through the optical system 517 are transmitted via the beam splitters 515 and 511. , Led to the CCD 514. The CCD 514 functions as a detection unit (measurement unit) that detects (measures) a signal generated from the medium irradiated with light. On the other hand, the reference beam 531 also enters the CCD. At this time, the optical path length of the reference light 531 may be appropriately adjusted in order to measure an interference signal described later.

A light including ultrasound modulated light (± f _a frequency shifted light) and non-ultrasound-modulated light, the reference light 531 interfere on CCD, interference fringes are formed. Of this interference fringe, which is formed by light of different frequencies (non-ultrasound-modulated light and the interference of the reference light 531, or + interference f _a of the reference beam 531 and the ultrasonic modulated light), its beat frequency ultrasonic same as waves of frequency f _a, or vibrate at higher speeds. Usually this frequency is very fast and the interference signal is not recorded by the CCD. On the other hand, an interference signal (digital hologram) between the ultrasonic modulated light 540 and the reference light 531 formed by light having the same frequency (−f _a ) is measured by the CCD 514.

  Here, the ultrasonic modulated light 540 and the reference light 531 are superimposed on a CCD (not shown) at a minute angle (for example, ˜1 degree), thereby obtaining an off-axis digital hologram. The off-axis digital hologram acquired by the CCD 514 is Fourier-transformed by a signal processing unit (not shown), and a high-pass filter is spatially executed to extract an interference term between the ultrasonic modulation light 540 and the reference light 531. The This is Fourier transformed again to calculate the amplitude and phase of the ultrasonic modulated light 540. Alternatively, the phase distribution of the ultrasonic modulated light 540 can be calculated using a phase shift method instead of using an off-axis digital hologram. When the digital hologram signal is obtained by the CCD 514, the ultrasonic irradiation of the medium 570 by the ultrasonic device 550 may be stopped.

  Here, a band-pass filter may be used in order to eliminate the non-frequency shift light and efficiently collect the frequency shift light to form a hologram. For example, a Fabry-Perot interferometer or a low-temperature cooled spectral hole burning crystal may be used.

  The phase distribution of the ultrasonic modulated light 540 obtained by the CCD 514 is digitally inverted by the signal processing unit and set in the SLM 516 in units of pixels. The SLM 516 is controlled by the control device 580 to form a wavefront of light that irradiates the medium. The SLM 516 and the control device 580 constitute control means for controlling the wavefront of light based on the output of the CCD 514. For example, when the measured phase distribution is φ (x, y) on the plane of the CCD, the inverted phase set in the SLM is −φ (x, y). At this time, the optical path lengths from the exit surface of the medium from which the ultrasonic modulated light 540 exits to the CCD 514 and similarly from the exit surface of the medium to the SLM 516 are set to be equal. In addition, the CCD 514 and the SLM 516 are adjusted or corrected so that the phase distributions match in pixel units.

  After the phase is set in the SLM 516, the shutter 504 is closed and the shutter 503 is opened. Light (reproduced light) 532 emitted from the light source 500 is reflected by the polarization beam splitter 502 and enters the SLM 516 via the mirror 512 and the beam splitter 513. Due to the phase distribution set by the SLM 516, the reproduction light 532 is wavefront shaped, converted into a phase conjugate wave of the ultrasonic modulation light 540, and irradiated onto the medium 570 as the reproduction light 541.

  The reproduction light 541 which is a phase conjugate wave follows the propagation trajectory at the time of digital hologram recording (measurement of the ultrasonic modulation light 540) in the reverse direction according to the time reversibility of the scattering, and re-propagates to the target region 560. Light irradiation using this phase conjugate light enables the energy of incident light to be sent to the target region 560 inside the medium 570 with high efficiency. Here, instead of a digital hologram, hologram recording using a holographic material such as a photorefractive crystal may be executed.

  In the optical focus inside the medium by such light irradiation, the reproduction light composed of the phase conjugate light of the ultrasonic modulated light is incident when the ultrasonic modulated light is optimized for the target in the third embodiment. It is substantially equivalent to light. Therefore, it has an effect of focusing light around the target area (ultrasonic focusing area) 560. In this embodiment, the means for shaping the wavefront is different from that in the third embodiment (the former uses iterative optimization, and the latter generates phase conjugate light from the wavefront measurement using a hologram). The signal intensity of the ultrasonic modulated light can be improved. Therefore, after irradiating the reproduction light to the medium, the depth (intrusion) at which optical measurement is performed by applying the same flow as the processing flow described in the third embodiment also in this embodiment. Can be improved.

Below, the processing flow of this embodiment is demonstrated using FIG. First, in S600, an ultrasonic focusing region 560 (target position z ₀ ) as an initial condition is set. At this time, the depth of the target position z ₀ (the depth from the medium surface when the light incident position is used as a reference) is set to a depth such that an ultrasonically modulated optical signal can be sufficiently measured. The measurement may be performed several times to find an appropriate depth at which the signal strength can be measured sufficiently.

  In step S610, the light source 500 and the ultrasonic device 550 are turned on, and wavefront measurement (hologram recording) of ultrasonically modulated light is started. In S620, as described above, the ultrasonic modulated light 540 and the reference light 531 are caused to interfere with each other, and the CCD 514 acquires a digital hologram. Subsequently, in S630, the phase distribution of the ultrasonic modulated light calculated based on the digital hologram is calculated, and the phase distribution of the phase conjugate wave is set in the SLM 516. Then, the phase conjugate light is generated as the reproduction light to be generated in the medium 570. Make it incident.

  In S640, it is determined whether the target position has reached the target depth for measuring the optical characteristics. If not, the process moves to S650.

In S650, the same processing as that described in the third embodiment is performed. That is, the depth z _{i + 1} of the next target region is set with respect to the depth z _i of the current target region, and the ultrasonic device 550 is controlled to generate an ultrasonic focusing region at the position of the depth z _{i + 1.} . At this time, as shown in FIG. 8, the pulse width of the ultrasonic wave is appropriately controlled, and the next target position z _{i + 1} can be set based on the half-value width W of the ultrasonic pulse. For the newly set target position z _{i + 1} , in S660, the phase conjugate wavefront obtained from the recording of the hologram at the position z _i is set as it is in the SLM 516, and the process returns to the wavefront measurement in S620. In S620, a hologram of ultrasonically modulated light generated from a new target position z _{i + 1} is recorded. At this time, by using the phase conjugate wavefront one step before (position z _i ) as the incident light in the wavefront measurement of the current step, the ultrasonic wave at the position z _{i + 1} compared to irradiation with normal incident light (for example, plane wave) The signal intensity of the ultrasonic modulated light generated from the focusing region 560 increases. Therefore, the hologram by the ultrasonically modulated light generated from the target position z _{i + 1} is recorded using the effect of improving the signal intensity. By repeatedly executing such processing from S620 to S660 (optical focus step), the wavefront is sequentially formed to the target depth for measurement. As described above, also in the present embodiment, by utilizing the signal improvement effect due to the spread of the ultrasonic focusing region 560 appropriately set, the incident wavefront is sequentially formed, and the light is efficiently transmitted to a deep position of the medium. Focus and measure the optical properties.

  In S640, when the optical focus step is completed and the target depth is reached (Yes in S640 in FIG. 10), the optical characteristics of the medium are measured using the ultrasonic modulation light as a measurement signal at the same depth (measurement step). As described above, by measuring the ultrasonic modulated light while scanning the ultrasonic focusing region 560 in the depth direction or in the lateral direction within the same cross section, the optical characteristics of the region can be imaged. . The result of measuring and imaging the ultrasonic modulated light while spatially scanning the ultrasonic focusing region 560 inside the medium may be displayed on a display device (not shown) such as a display.

  As described above, in this embodiment, first, the intensity of the ultrasonically modulated optical signal generated from the measurement position at a relatively short distance (first distance) from the surface in the depth direction of the medium is increased. Thus, the first wavefront is formed. Then, the measurement position is set to a measurement position (second measurement) at a relatively long distance (second distance larger than the first distance) from the surface in the depth direction of the medium so as to approach the target position. Position), the medium is irradiated with light having the first wavefront, and the intensity of the ultrasonically modulated optical signal generated from the changed measurement position (second measurement position) is increased. Update wavefront (second wavefront). The above is characterized by iteratively processing until the second measurement position reaches the target position.

  Further, as described above, after the optical focus step is completed in S640, the imaging signal source may be changed to other than the ultrasonic modulation light, and the imaging may be executed. Or, by combining imaging using a signal source other than ultrasonically modulated light and imaging using ultrasonically modulated light, the optical characteristics inside the medium can be imaged by superimposing multiple different signal sources. Good.

  As described above, according to the present invention, the wavefront of light incident on the medium is appropriately shaped (using optimization or phase conjugate wave) and input to the medium, so that the local area (target area) inside the medium is input. Realize the focus of light. As a result of the optical focus effect, the intensity of a signal (photoacoustic signal, fluorescent signal, ultrasonic modulation signal, etc.) generated from the local region is improved. At this time, the next light focus region is set using the spread of the signal enhancement region in the depth direction at the same local position, and the incident light wavefront is sequentially shaped while repeating this repeatedly. This light focusing step is characterized by efficiently sending light to a relatively deep position in the scattering medium. This processing is the pre-stage processing, and various measurement and imaging methods are the pre-stage processing in the post-stage measurement step. Combine with. Thus, it is a feature of the present invention that the penetration length of measurement / imaging of optical characteristics inside the medium is improved.

  According to the present invention, it is possible to measure up to a relatively deep position of the scattering medium in measuring the optical characteristics inside the scattering medium.

(Embodiment 5)
A measurement apparatus according to the fifth embodiment of the present invention will be described. FIG. 11 is a diagram schematically showing the apparatus configuration of the present embodiment. A gate imaging apparatus 700 as a measurement apparatus of the present invention includes a light source unit 710, a camera unit 720, a control / processing unit 730, and a display unit 740, and can be applied to, for example, a camera that monitors a subject at a long distance. The gate imaging apparatus 700 images the subject 790 through the scatterer 780 in the atmosphere. Here, the scatterer 780 is fine particles floating in the atmosphere such as fog, haze, smoke, smog, or soil or dust having a micrometer size. Alternatively, the refractive index may be fluctuated due to snow or rain, or uneven temperature distribution in the atmosphere. Under these conditions, the gate imaging device irradiates the subject with pulsed light, and opens the camera shutter for imaging only when the pulsed light is reflected back from the subject, thus reducing the amount of scattered light. Thus, the subject can be imaged.

  The light source unit 710 mainly includes a laser light source 711 and an SLM 713. The laser light source 711 emits infrared light pulse light having a wavelength of 1.4 to 1.8 μm (short-wave infrared, SWIR: Short-wavelength infrared), generally called an eye-safe laser. To do. For example, the wavelength is 1.5 μm and the pulse width is 1 to several tens of nsec. However, depending on the imaging conditions, other wavelength bands and pulse widths may be used. In addition, as an example, the pulse repetition frequency can be arbitrarily selected in the range of several Hz to several hundred kHz, but in general, a high speed is desirable.

  A collimated pulsed light beam is emitted from the laser light source 711, reflects off the mirror 712, and enters the SLM 713. Further, the beam size of the pulsed light is set so as to be within the effective area of the SLM 713. The SLM 713 can use, for example, LCOS or Digital Mirror Device (DMD). Alternatively, a configuration using transmissive liquid crystal as the SLM 713 may be used. When the SLM 713 is a polarization-dependent device, the polarization of light incident on the SLM 713 is adjusted to coincide with the polarization direction in which phase modulation operates in the SLM 713. The light incident on the SLM 713 is phase-modulated by a process described later. The light reflected from the SLM 713 is emitted from the light source unit 710 through the optical system 714 after adjusting to a desired beam size and irradiation direction. Here, if necessary, the pulsed light beam may be scanned using a galvanometer mirror. In addition, the output intensity of the pulsed light beam 760 can be arbitrarily adjusted according to the subject (whether it is a living organism such as a person or an inanimate object) and the approximate distance to the subject. For example, the output is in the range of several tens to several hundreds mJ per pulse.

  When the pulsed light beam 760 passes through a scatterer 780 in the atmosphere, the pulsed light beam 760 is affected by scattering and propagates to the subject 790 while generating scattered light 761. Further, the light reflected by the subject 790 propagates again through the scatterer 780 and similarly propagates to the camera 720 with the scattered light 771. Here, the subject 790 is, for example, a subject existing relatively far from 100 m to several tens km. In this embodiment, the pulsed light to be irradiated is light in the infrared SWIR band, so that the scattering can be suppressed more than visible light, and when the subject 790 is a person, the output is stronger than the visible light in terms of safety standards. It is possible to illuminate the subject. The above points are advantages of using a beam in the SWIR band.

  The camera 720 includes a camera lens that sufficiently transmits light having a wavelength of 1.5 μm and an array sensor that is sensitive to the same wavelength. The focal length of the camera lens can be appropriately selected according to the distance to the subject 790. As described above, when the subject 790 is far away, for example, a telephoto lens having a focal length of 1000 mm or more is used. As the array sensor, an InGaAs sensor having sensitivity in the wavelength band can be used. The shutter time (gate time) of the camera can be selected within a range of several tens of nsec to several μsec, for example.

  Image data captured by the camera 720 is transferred to the control / processing unit 730. The control / processing unit 730 controls the light source unit 710 and the camera 720 according to a measurement flow described later. In addition, a wavefront shaping process, which will be described later, is executed, the subject 790 is irradiated with the beam 760 that has been wavefront shaped by the optimization process, and an image captured by the gate is acquired. The captured image is displayed on the display unit 740. In addition, the display unit 740 may display an image captured in the middle of the measurement flow and a progress result of the wavefront shaping process.

  FIG. 12 is an exemplary measurement flow of the gate imaging apparatus 700 in the present embodiment. First, in step S810, the pulsed light beam 760 is irradiated onto the subject 790, and a gate captured image is acquired. Now, when the delay time τ [sec] in the gate imaging is set, the light reflected from the imaging distance L = τc / 2 [m] from the imaging device 700 is imaged. Here, c is the speed of light in the atmosphere. When the subject 790 does not exist at the imaging distance L, a significant signal related to the subject 790 cannot be observed. For example, when there is no object that reflects the pulsed light beam other than the scatterer 780 in the atmosphere at the imaging distance L, nothing is reflected in the captured image except for flare due to scattering. Alternatively, when there is another reflective object other than the subject 790 to be imaged at the shooting distance L, an object other than the subject 790 is imaged. Therefore, in S810, when the imaging distance of the subject 790 to be imaged is known in advance by some other means in advance, gate imaging is executed with the delay time τ corresponding to the imaging distance L set. At this time, for the image of the subject 790 or a part of the image, the delay time at which the signal intensity is the highest or observed with high contrast may be finely adjusted before and after the delay time τ. Alternatively, when the subject 790 is not clear in advance, the gate is imaged while gradually changing the delay time τ, and when a significant signal is confirmed in the captured image, it is used as an observation signal related to the subject 790. The subsequent flow may be executed. In the present invention, first, it is necessary to acquire an observation signal (reflected light) related to the subject 790 in the gate imaging of S810. This observation signal may be a distorted image of the subject 790 due to scattering in the atmosphere or refractive index fluctuation, or may be a part of the distorted image. FIG. 13 is a diagram simulating the measurement result in the present embodiment. FIG. 13A shows an image of an ideal subject 790 having no aberration (deterioration due to scattering). FIG. 13B shows an image acquired as a result of gate imaging in S810. The image in FIG. 13A is distorted by scattering. In this way, in S810, a part of the observation signal of the subject image 790 is acquired. Here, as a condition to be set as the observation signal, the luminance value of the image may be a certain threshold value or a characteristic shape may be confirmed. A characteristic shape may be extracted by performing edge processing or filter processing on the captured image. Alternatively, it is possible to learn an image of an artificial object, a person, or the like imaged in advance under various scattering conditions and determine an observation signal with reference to the feature amount.

  Next, in S820, an optimization objective function for executing the wavefront shaping process S830 is set. In S810, since an observation signal related to the subject 790 is acquired, this is used. For example, the threshold value is set for the observation signal obtained in S810 (FIG. 13B) and binarization processing is executed, and the entire region extracted thereby is set as the target region (FIG. 13C). ). Here, the threshold value may be determined with reference to a histogram of luminance values of the captured image. Also, it is better to set the threshold value as large as possible within a range where the target area does not become extremely small. By the binarization processing, noise components such as scattered light acquired accompanying the observation signal in S810 can be removed. In the image captured by the gate, the average value or the sum of the luminance values of the pixels in the target area can be set as the objective function. Alternatively, an arbitrary partial area of one or more pixels may be set in the target area, and the sum of luminance values may be used as the objective function for the partial area as described above. The setting of the partial area may be arbitrarily set as an area of interest to the photographer. Here, even if the target area is divided into a plurality of areas in the captured image by the binarization process, the objective function may be determined as described above. Alternatively, the divided regions can be set as separate target regions, the optimization objective function can be individually set, and the wavefront shaping process of S830 can be executed independently of each other. Further, as the setting of the objective function, after setting the target area, the contrast value of the image calculated based on the luminance values of the target area in the captured image and the peripheral vicinity area may be used as the objective function. Thus, in S820, a signal (sum of luminance values or contrast value) used for the optimization objective function is set based on the observation signal derived from the subject measured in S810. As described above, when performing wavefront shaping by optimization on the gate captured image, it is necessary to clearly define the position and region of the objective function. The objective function may be set by the photographer based on the result of S810, or may be determined and executed automatically by the control / processing unit 730. If there is some prior information about the subject 790, the target area and the objective function may be set based on the information.

  In the next S830, the wavefront of the pulsed light beam applied to the subject 790 is shaped (optimized) so that the value of the objective function set in S820 is maximized. In this optimization processing, the wavefront of the pulsed light beam 760 is shaped and irradiated on the subject 790, and gate imaging is performed to evaluate the value of the objective function. This wavefront shaping, beam irradiation, gate imaging, and objective function evaluation are repeated, and the wavefront is optimized so that the value of the objective function is improved. The iteration is executed until a preset number of iterations or a desired objective function value is reached. The wavefront shaping process in S830 is performed in the same manner as in FIG. 3 described in the first embodiment. In FIG. 3, the photoacoustic signal in the target area is monitored, and the phase at which the signal is maximized is set. On the other hand, in the present embodiment, the phase may be set so that the value of the objective function set in S820 is maximized. It is characterized in that a signal area (target area) caused by the subject 790 is identified from the gate captured image, an optimization objective function is set based on the area, and wavefront shaping is performed.

  In step S840, the subject 790 is irradiated with the pulsed light beam 760 optimized in step S830, and a captured image is acquired by performing gate imaging (FIG. 13D). By the processing of S830, the subject 790 can be more effectively irradiated, and the subject image can be captured with a higher SN by the camera 720.

  Further, as shown in FIG. 14, after execution of S840, using the wavefront 761 obtained in S830, gate imaging is performed while scanning the irradiation angle of the pulsed light beam in the horizontal direction with respect to the target region 791 in the subject 790. Run. Here, the horizontal direction means the horizontal direction (lateral direction; X) in the plane perpendicular to the depth direction (depth direction; Z) of the atmosphere (medium) including the subject as viewed from the gate imaging device 700. And Thereby, a captured image can be acquired in a wide range (wide field angle). The range (target position / range) of the area to be imaged may be determined in advance or may be determined from the captured image. For the scan amount 795, for example, the SLM 713 may be scanned by adding a linear phase shift amount corresponding to the scan amount to the phase distribution obtained in S830. Alternatively, there may be a separate scanning optical system, and scanning may be performed using that. Here, this scan is executed in a range in which the correlation of scattering is maintained. Even if the incident angle is changed, the effect of wavefront shaping by S830 is maintained in a range where there is a correlation in scattering. By utilizing this effect, it is possible to image the vicinity of the target region. The scan range may be determined by monitoring the objective function set in S820 from the result of imaging with the incident angle changed. For example, the objective function may be in a range larger than the initial value of the process in S830.

Further, when the luminance value of the image of the subject 790 in the captured image is reduced as a result of the scan as described above, the wavefront shaping process is executed again. For example, the threshold value of the objective function is determined, and the scan range is set to the maximum within a range that does not fall below the threshold value. When further scanning is performed beyond this range, the wavefront shaping process of S830 is executed again with the wavefront previously formed in S830 as the initial value. At this time, the subject 790 may be reset and the objective function may be reset (S820). In this way, the wavefront shaping process is performed again, and the gate imaging in S840 is performed. In this way, it is possible to image a wider field angle with a high SN while repeating the wavefront shaping process and the gate imaging. At this time, the wavefront shaping process is performed while utilizing the correlation of the scattering while maintaining the effect of the previous wavefront shaping process, so that the optimum incident wavefront after scanning can be obtained efficiently at high speed. The threshold value of the objective function is set to, for example, half the value obtained in S830 or 30%.
The scan may be in the vertical direction (longitudinal direction; Y) in the plane perpendicular to the depth direction (Z) with respect to the subject 790. Finally, images captured at each imaging angle of view may be connected and displayed on the display unit 140.

  As described above, in this embodiment, first, the intensity (objective function) of the luminance signal of the subject at the first measurement position at the distance to the subject (first distance) at a certain imaging angle of view is increased. The first optimization process is performed to form the first wavefront. Then, the measurement position is changed (second measurement position) by controlling the irradiation angle of the pulsed light beam so as to approach the target position (viewing angle range to be imaged), and light having the first wavefront in the medium. Irradiate and update the first wavefront by performing a second optimization process so that the intensity of the luminance signal of the subject generated from the changed measurement position (second measurement position) increases (second wavefront) Wavefront). The above is characterized by iteratively processing until the second measurement position reaches the target position.

  As mentioned above, although embodiment which concerns on this invention was described with reference to exemplary embodiment, it should be understood that this invention is not limited to the above-mentioned embodiment. The scope of the appended claims should be construed in the broadest sense to include all such variations and equivalent structures and functions.

  Also, when a software program that realizes the functions of the above-described embodiments is supplied from a recording medium directly to a system or apparatus having a computer that can execute the program using wired / wireless communication, and the program is executed Are also included in the present invention.

  Accordingly, the program code itself supplied and installed in the computer in order to implement the functional processing of the present invention by the computer also realizes the present invention. That is, the present invention includes a computer program itself in which a procedure for realizing the functional processing of the present invention is described.

  In this case, the program may be in any form as long as it has a program function, such as an object code, a program executed by an interpreter, or script data supplied to the OS. As a recording medium for supplying the program, for example, a magnetic recording medium such as a hard disk or a magnetic tape, an optical / magneto-optical storage medium, or a nonvolatile semiconductor memory may be used.

  As a program supply method, a computer program that forms the present invention is stored in a server on a computer network, and a connected client computer downloads and programs the computer program.

  The present invention can be suitably used for an apparatus that provides an image used for medical applications such as diagnosis.

102 SLM
104 Ultrasonic transducer 105 Control device

Claims (18)

Detecting means for detecting a signal generated from a medium irradiated with light;
Control means for controlling the wavefront of the light based on the output of the detection means;
Have
The control means includes
A first process for forming a first wavefront of the light based on the signal generated from a first measurement position within the medium;
A second wavefront of the light is formed based on the signal generated from a second measurement position different from the first measurement position inside the medium irradiated with the light having the first wavefront. A wavefront control device that performs the second process. In the first process, the control means forms the first wavefront so that the intensity of the signal generated from the first measurement position is higher than 75% of the maximum value,
2. The second wavefront is formed in the second process so that the intensity of the signal generated from the second measurement position is higher than 75% of the maximum value. Wavefront control device.   The control means repeats the first and second processes using the second measurement position as the first measurement position and the second wavefront as the first wavefront. The wavefront control device according to claim 1, wherein the wavefront control device is executed until the measurement position coincides with the target position.   The control means sets the second measurement position based on a region where the intensity of the signal is higher than a threshold when the medium is irradiated with light having the first wavefront. The wavefront control device according to any one of claims 1 to 3.   5. The wavefront control apparatus according to claim 4, wherein the control unit estimates the region from an intensity distribution of the signal in a plane perpendicular to the depth direction of the medium.   The control means sets the second measurement position based on the intensity of the signal that changes according to a position in a depth direction of the medium or a direction perpendicular to the depth direction. The wavefront control device according to any one of claims 1 to 5.   The said control means sets the said 2nd measurement position within the range whose intensity | strength of the said signal which changes according to the distance from the surface of the said medium is larger than a threshold value, The any one of Claim 1 thru | or 6 characterized by the above-mentioned. 2. The wavefront control device according to claim 1.   The wavefront control apparatus according to claim 7, wherein the threshold value is a half value of a maximum value of the intensity of the signal.   9. The wavefront control apparatus according to claim 1, wherein the second measurement position is a position farther from the surface of the medium than the first measurement position. 10.   The control means irradiates the medium with ultrasonic waves to form an ultrasonic focusing region in which the ultrasonic waves are focused inside the medium, and the size of the ultrasonic focusing region in the depth direction of the medium. The wavefront control device according to claim 1, wherein the second measurement position is set based on the first measurement position.   10. The wavefront control apparatus according to claim 1, wherein the control unit sets the second measurement position by controlling an irradiation angle of the light with respect to the medium. 11.   The signal is a photoacoustic signal, a fluorescence signal, an ultrasonic modulation light signal, a harmonic signal, a Raman scattering signal, an OCT signal, a light intensity signal acquired by a confocal optical system, or a luminance signal acquired by gate imaging. The wavefront control device according to claim 1, wherein the wavefront control device is any one of them.   The wavefront control device according to any one of claims 3 to 12, wherein the signal generated from the target position is a signal different from a signal generated from a measurement position other than the target position.   Detection means for detecting a signal generated from the medium irradiated with light, and control means for controlling the wavefront of the light based on the output of the detection means, wherein the control means is a first inside the medium. A first process for forming a first wavefront of the light based on the signal generated from the measurement position, and the first measurement inside the medium irradiated with the light having the first wavefront. And a second process for forming a second wavefront of the light based on the signal generated from a second measurement position different from the position, and information on optical characteristics inside the medium An information acquisition apparatus characterized by acquiring Generating means for generating an image based on the detected signal;
Display means for displaying the generated image;
The information acquisition apparatus according to claim 14, comprising: A wavefront control method for controlling a wavefront of light irradiated on a medium,
Forming a first wavefront of light irradiated on the medium based on a signal generated from a first measurement position inside the medium;
A second wavefront of the light is formed based on the signal generated from a second measurement position different from the first measurement position inside the medium irradiated with light having the first wavefront. Steps,
A measuring method characterized by comprising:   A computer-executable program in which the steps of the wavefront control method according to claim 16 are described.   A computer-readable storage medium storing a program for causing a computer to execute the steps of the wavefront control method according to claim 16.