Patent Document

CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    The present application claims priority to U.S. Provisional Patent Application No. 61/733,969, filed on Dec. 6, 2012, entitled “Method and Apparatus for Scatterometric Measurement of Human Tissue” which is incorporated by reference in its entirety all having by same inventor. 
     
    
     BACKGROUND 
       [0002]    A scatterometer is a device that enables visualization of the angular, spectral, phase and/or polarization content of an object rather than its spatial, geometrical representation of that object (as usually done in imaging methods). In terms of Fourier optics, a scatterometer is based on data retrieval from a Fourier transform conjugate plane to the object rather than a conjugate plane to the object itself. Therefore, a scatterometer, according to its name measures scattered light from an object under test. This scattered light actually includes information not only on scattering in the conventional sense from the object, but rather also on diffraction (of different orders for example), absorption, reflection, transmission, and other optical qualities and their dependence on various radiation properties (e.g. direction (angle), wavelength, phase, polarization). 
         [0003]    Typically, the measured property in a scatterometer is intensity (as is the case when using a camera). This measured result may then be processed by various algorithms according to the scatterometer setup (e.g. the use of polarizers and wave plates to detect polarization). Additionally, different optical properties may be deduced from the measurement as well as calculating other parameters for the object under test. 
         [0004]    Most medical pathologies affect to optical properties of the affected tissue. Some of the changes manifest by increased absorption, reflection and scattering. Many changes are apparent in specific wavelengths. Current triage methods are mainly based on imaging (e.g. X-ray, OCT, tomography, microscopy etc.), namely creation of a visual representation of the affected tissue. A scatterometer measures the optical properties described above as a whole, without creating an image. Nevertheless, a scatterometer generates a distribution of the said properties that enables deduction of a myriad of parameters otherwise undetectable. Light scatter from different body parts, especially the human eye and retina can be measured by commercially available products. These use the patient subjective response to measure only the apparent stray light in the eye and is mainly only used as a cataract quantifier. 
         [0005]    What is needed is a method and apparatus that measures a “fingerprint” signature signal from the measured object (e.g. the human eye or retina) wherein the signal from every person is expected to be unique and wherein the measurement may be done from afar. 
       SUMMARY 
       [0006]    A scatterometric measurement system for measuring an object under test is disclosed. The scatterometric measurement system generates a beam of light from a light source sending the generated beam to illumination optics for transforming the beam and sending this transformed beam to a beam splitter. The beam splitter redirects the transformed beam to a first detector while deflecting the transformed light beam to the object under test which produces scattered light. Collection optics then receives this scattered light from the object under test and processes and sends the scattered light to a second detector through the beam splitter. The second detector generates a signal based on this processed scattered light and sends this result to a computation unit that calculates using the second detectors signal a desired output according to an algorithm for a given measurement for the object under test. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0007]    For a clearer understanding of the invention and to see how the same may be carried out in practice, a preferred embodiment will now be described, by way of non-limiting example only, with reference to the accompanying drawing, in which: 
           [0008]      FIG. 1  is a block-diagram of the scatterometric measurement system in accordance with the present invention; 
           [0009]      FIG. 2  is a block diagram using the scattometeric measurement system shown in  FIG. 1  for performing an eye examination; 
           [0010]      FIG. 3  is a block diagram using the scattometeric measurement system shown in  FIG. 2  for performing an eye examination incorporating a refractometer; 
           [0011]      FIG. 4  is a block diagram using the scattometeric measurement system shown in  FIG. 2  for performing an eye examination incorporating an SLO detector; and 
           [0012]      FIG. 5  is a block diagram using the scattometeric measurement system shown in  FIG. 2  for performing an eye examination incorporating a wavefront sensor and feedback system. 
       
    
    
     DETAILED DESCRIPTION 
       [0013]    Referring now to  FIG. 1  there is shown a block-diagram of a scatterometric measurement system  10  having a light source  12 , illumination optics  14 , beamsplitter  16 , detectors  20  and means for computation  18  for measuring an object under test or inspection  24 . The light source  12  may be a lamp, a laser, a super-continuum laser, a battery of lasers etc., wherein any of these different light sources may produce depending on the measurement test being performed delivers either a continuous or pulsed beam of light for processing through the illumination optics  14 . 
         [0014]    Referring once again to  FIG. 1 , the illumination optics  14  receives the beam of light and transforms the beam by performing optical amplitude shaping for the beam and in addition may perform polarization control, spatial control, angular control, phase control, spectral control for the same beam. It should be understood that the illumination optics  14  may be placed in a field conjugate plane (referred to as “object conjugate”), a pupil conjugate plane (which is the Fourier transform of an object plane), or anywhere in between. Therefore, any combination may be possible depending on the type of measurement being performed. 
         [0015]    By way of example and not of limitation the optical amplitude beam shaping may be performed by any known number of techniques such as utilizing apertures, apodizers, spatial light modulators or filters (e.g to control overall power—this may also be achieved by cross polarization techniques). The polarization control may also performed by any known number of techniques such as utilizing polarizers (linear, circular, elliptic, radial/tangential), waveplates, nematic liquid crystals or other any known prior art spatial polarization controllers. The angular control may be performed by magnification optical techniques using apertures, spatial light modulators or apodizers. If phase control is needed as part of the measured data required to be collected, phase modulators may be used (e.g. electrooptic, acoustoopticoptical path modifiers (e.g. glass plates of various thicknesses, wedges on a translation stage, window on a rotation stage) or spatial phase modulators (e.g. liquid crystals). Lastly, if spectral control of the beam is needed than filters or spectral shapers may be used (e.g. a combination of a grating with a spatial light modulator that enables specific on the fly (e.g. in closed loop) tailoring of the optical spectrum). Spectral control may also be performed using shutters (when a battery of lasers is used—these can control which are used at a specific measurement). 
         [0016]    Turning once again to  FIG. 1 , the beam splitter  16  receives the processed beam of light from the illumination optics  14  and directs this light to the object under inspection  24  through optional optics  23  that may include for example an objective lens (not shown). The beam splitter  16  also enables light from the illumination optics  14  to go into a first detector  20  and additionally pass through collection optics into a second detector  21 . The first and second detectors  20  and  21  respectively, may be any of the following: a power meter, energy meter (when a pulsed light is delivered), a camera, or a field detection system such as a Hartman-Shack sensor. The first detector may be used for illumination beam monitoring when a modeling algorithm is needed for producing measurement results. The first detector  20  may also be used for power monitoring for safety reasons or to enable closed loop operation with the illumination optics  14  (e.g. as in adaptive optics system) that shapes the illumination according to specified criteria. 
         [0017]    The object under inspection  24  may be any type of tissue or sample that requires testing. The collection optics  23  includes all required optics to complete a measurement test according to specific measurement metrics which may be by way of example only any of the following metrics: amplitude shaping (for example apodization of different types in either field plane (object plane) or pupil plane (Fourier transform plane)), phase control, angular control, spatial control (e.g. a collection field stop), polarization control (e.g. a polarizer for cross polarization measurement), spectral control (e.g. a grating to separate the spectrum). It should be understood that all the components that were mentioned with regards to the illumination optics  14  may also all be used here as well, along with any other known prior art components. Lastly, the second detector  21  transfers the signal received from the beam splitter  16  through the collection optics  22  into a computation unit that calculates the require output according to an algorithm for a given measurement test. 
       Eye Examination 
       [0018]    Referring now to  FIG. 2  there is shown a block diagram for the scatterometeric measurement system of  FIG. 1  used for performing an eye examination. In accordance with a preferred embodiment of the invention, a human eye is the most suitable organ for using the scattometeric measurement system of  FIG. 1 . This is due in part that an eye examination is the type of measurement test that may be non-intrusively performed using an optical system. Furthermore, it shows the most promise in a variety of test applications when it comes to this organ. Referring once again to  FIG. 2 , the following scatterometeric system  11  shows a simple measurement of the angular distribution of the scattering and reflection from the human eye  26  and especially the retina. Therefore,  FIG. 2  illustrates one example using the invention for the triage of eye disease. 
         [0019]    As shown in  FIG. 2 , the light source  12  with respect to an eye test may use any one of the following device(s): a laser, a set of lasers, a supercontinuum laser, a lamp or a lamp with different filters for transmitting a beam to the illumination optics  14 . As previously described, the illumination optics shapes the beam to be either uniformly distributed, Gaussian or other known prior art shapes of intensity and phase. The polarization state may also be controlled. The beam is made such that it covers a known portion of the eye&#39;s pupil  27 , particularly the entire pupil. The direct illumination beam goes into the first detector  20  that is used to monitor power delivered by the light source  12  (i.e. a laser) for further analysis and for safety reasons. 
         [0020]    Turning once again to  FIG. 2 , a vision camera  28  is directed at the eye  26  to measure pupil size during an eye examination test. It could be done by various means e.g. placing a ruler next to the eye or using geometrical calculations. The vision camera  28  may also be used to determine the pupil location and orientation and include a light source that does not interfere with the test itself (e.g. an infrared LED light). The deflected beam  29  from the beam splitter  16  enters the eye  26  (which optics uses as an objective for the collimated input beam) and is reflected/scattered from it. The eye  26  is held at a specific location and orientation by using for example a head and chin rest (not shown). The returned signal  25  is then brought into the collection optics  22  that consists of a focusing element such as a lens (that may by example be either achromatic, a concave mirror or a parabolic mirror). 
         [0021]    As stated before, filters may also be included in the collection optics  22 , wherein said filters may include spectral or spatial filters, apertures or stops. For an eye examination in accordance with the invention, the second detector is a camera  24  placed at the focus plane of this element to read the signal. The camera  24  is connected to a computation unit that uses special algorithms as described before to compute the desired outcome. An example here would be a comparison to a database of known signals for different pathologies. Another example would be to use an eye model to find the main tissues that cause the signal to be as it is measured. The computation includes all data collected from the measurement including but not limited to: a signal from the vision camera  28 , a signal from the first detector  20 , an input illumination profile (not shown), a signal from the main camera  24  or knowledge and pre-measurement of the scatterometeric measurement system  11  properties, etc. 
         [0022]    In some instances it may be important to differentiate the signal from different parts of the eye, for example the reflection from the cornea. This may be done by optical means in the collection optics  22  (e.g. filters or plates), by indirect measurement and computation (for example separate measurement of the cornea and subtraction of the measurement from the given signal, or by use of different optical parameters for measurement (e.g. use of different wavelengths for reducing or eliminating corneal effects). In this case the measurement may be done for a single wavelength or for a multitude of wavelengths either sequentially or simultaneously. Further information may be derived from the spectral response of the device. Another option would be to use “white” light as the light source  12  and replace the main camera  24  with a spectrometer to determine the spectral distribution of the signal. In this case the illumination optics  14  might also include apertures and other optical devices to determine the spatial and angular content of the input signal to the eye  26  and the collection optics  22  might also include such apertures and other optics to choose from the signals the desired portions (angular or spatial) to be measured. 
         [0023]    It should be appreciated that using the scatterometeric measurement system  11  shown in  FIG. 2 , it is important to have control of several parameters wherein three of the most important are the pupil size of the eye (affected by ambient light, age, different illnesses/pathologies, treatments of different types e.g. pupil dilation drops), the angle at which the patient is looking or at which the illumination light enters the eye and the accommodation state of the human lens. The latter two may be controlled by placing accommodation targets (e.g. concentric circles, this target may also be made in a way that it glows in the dark when a dark measurements are required) at different distances and locations (lateral—these will convert into angles). 
         [0024]    Referring now to  FIG. 3  there is shown a block diagram for the scatterometeric measurement system  30  of  FIG. 2  used for performing an eye examination by incorporating a refractive power measurement system  32  (referred to as a “refractometer”) into the system  30  for the accommodation measurement. A tilting mechanism (not shown) to control the angle of incidence of the illumination light upon the pupil  27  may also be incorporated. Turning once again to  FIG. 3 , refractometer  32  is incorporated into the scatterometeric measurement system  30  as follows: A specific light source may be used or the measurement light source  12  could be used. The beam from the collection optics  22  is split to the refractometer part of the system. It passes through a refractometer lens  34  (or other collimating optics (e.g. concave mirror, parabolic mirror) and through a refractometer aperture  36 . This aperture  36  is placed in a plane conjugate to that of the eye pupil. A refractometer camera  38  then uses the distance between the two generated spots to measure the refractive power of the eye  36 . For an emmetropic eye the center of the two spots is the same as the distance between the two holes in the refractometer aperture  36  since it is expected that the beam will be parallel. For hyperopia, the distance between the spots will increase and for myopia the distance will decrease. Using ray tracing techniques and the geometry of the scatterometeric measurement system  30  enables the determination of the optical power of the eye  26 . 
         [0025]    Referring now to  FIG. 4  there is shown a block diagram of another preferred embodiment for the scatterometeric measurement system  40  of  FIG. 2  used for performing an eye examination by incorporating a scanning laser ophthalmoscope (SLO)  42  since it could benefit from the scanning capabilities of such a system (measurement of different locations of the retina). Also, the scatterometeric measurement system  11  shown in  FIG. 2  incorporates into an SLO system  40  in a relatively simple way. Here the beam scans the retina (by entering the eye at different angles) and the data received on the SLO detector  42  is used as the SLO signal. 
         [0026]    Referring now to  FIG. 5  there is shown a block diagram of yet another preferred embodiment for a scatterometeric measurement system  50  used for performing an eye examination by incorporating an adaptive optics system into the scatterometeric measurement system  11  of  FIG. 2 . The scatterometeric measurement system  50  cancels wavefront aberration that might be due to imperfections in the optics of the system or the optics of the eye. This will enable direct measurement of the retina itself without contribution from other optical elements. There is a risk though here that the correction might cause the signal to be distorted and not completely describe the actual status of the retinal tissue. Here the first detector is replaced (or in most cases it will be used in conjunction) with a wavefront sensor  52  (e.g. a Hartmann-Shack sensor) wherein the wavefront distortion is measured—this may be done by an auxiliary light source dedicated for this purpose or by the scatterometer light source. The wavefront signal is then processed by a feedback system  54  that is connected to a SLM in the illumination optics  14  (e.g. a deformable mirror or MEMs system). The feedback is processed until a defined distortion level or structure is achieved. The designed illumination is then used as the illumination for the scatterometric measurement. 
         [0027]    The measured signal may be compared to a population-wide standard for detection of different anomalies. Another option would be to compare the measured signal to a modeled signal according to some models of the tested tissue with specific qualities and quantities that will help detect abnormalities. Lastly, a third option would be to compare the tested signal to a library of signals (either measured or modeled) and find the most suitable anomaly resulting from the library comparison. In summary, use of scatterometry for triage benefits from all the properties of optical imaging such as the use of different wavelengths, different polarizations, and different phase and amplitude of the optical signal. The use of medical scatterometry may be applied to any tissue in the human body (or other) (permitting a suitable wavelength that can reach it). It should be noted that eyes and retinas are of particular suitability for the method of the present invention due to their transmission in the visible and near IR regions of the spectrum.

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