# Patent

## Title
Intraoperative imaging system and apparatus

## Abstract

Systems, methods and apparatuses for an intraocular imaging system are disclosed comprising an optical coherence tomography (OCT) system. The OCT system has an imaging range that may enable substantial portions of an eye or even a whole eye to be imaged. The OCT system may be coupled to an operation microscope, such that, for example, a surgeon can visualize ocular structures like the human crystalline lens and other ocular structures such as the cornea and/or vitreous while surgical instruments are in the field of view.

## Background
RELATED APPLICATIONS
This application is a continuation of U.S. patent application Ser. No. 13/309,374, filed Dec. 1, 2011, which is a continuation-in-part of U.S. patent application Ser. No. 13/194,067, filed Jul. 29, 2011, now U.S. Pat. No. 8,425,037, and is related to and claims priority from U.S. Patent Provisional Application No. 61/369,269, filed Jul. 30, 2010. The entire content of all these applications is incorporated herein by reference.


FIELD
The present invention is directed generally to the field of methods and apparatuses for imaging internal ocular components (referred to herein as intraocular imaging methods and systems).
BACKGROUND
Typical ocular surgery, such as, for example, cataract surgery, is routinely performed without the aid of specialized imaging equipment or procedures beyond an operation microscope. However, in the case of a complex or otherwise difficult ocular surgery, including but not limited to lens refilling following capsulorhexis procedures, a surgeon would benefit greatly from the aid of a real time, cross-sectional view. For example, during cataract or other ocular surgical procedures, such a real time, cross-sectional view of the crystalline lens would greatly enhance the surgeon's ability to complete the procedure.
Optical coherence tomography (OCT) is a noninvasive imaging technique that measures backscattered light as a function of depth to provide subsurface imaging with high spatial resolution in three dimensions with no contact needed between the probe and the tissue. An OCT system uses an interferometer in which light from a broadband source is split between illuminating the sample of interest and a reference path. The interference pattern of light reflected or backscattered from the sample and light from the reference delay is used to produce an image of the sample.
Types of OCT include time domain OCT (TD-OCT) and Fourier domain OCT (FD-OCT). In TD-OCT the interference pattern is obtained by scanning the reference path delay and detecting the resulting interferogram pattern as a function of the delay. In FD-OCT, sample light is mixed with reference light at a fixed group delay as a function of optical wave number to obtain the interferogram pattern. FD-OCT has been shown to result in images with an improved signal to noise ratio (SNR). Two types of FD-OCT are typically used: spectral domain OCT (SD-OCT) and swept-source OCT (SS-OCT). SD-OCT uses a broadband light source and a dispersive spectrometer in the detector arm. SS-OCT time-encodes the wave number by rapidly tuning a narrowband source through a broad optical bandwidth.
OCT systems are described in U.S. Patent Publication Number US 2009/0257065, and U.S. Pat. Nos. 5,493,109; 6,004,314; 7,699,468, all of which are incorporated by reference herein, as if made a part of this specification.
Embodiments of an OCT system with a reference arm optical switch are described in U.S. Patent Application Publication US 2011/0102802 A1, also incorporated by reference herein, as if made a part of this specification. This patent publication describes using the switch to image two distinct structures independently.
SUMMARY
Embodiments of the present invention generally relate to ocular imaging systems for imaging over a depth range. In various embodiments, the ocular imaging system provides the imaging over the depth range by combining scans, by removing artifacts, compensating for dispersion, and positioning the depth ranges. Two of the combined scans may have overlapping image ranges.
Embodiments of the present invention also relate to an intraocular imaging method that includes receiving, with an optical coherence tomography system, image data of an ocular system at a plurality of image depth ranges, and producing a composite image. Two or more of the image depth ranges may overlap.
The scans, in combination may provide for imaging of the entire cornea and crystalline lens of an ocular system. In other embodiments, the combined scans may provide for imaging the entire cornea, anterior chamber, crystalline lens, posterior segment, and retina of an ocular system.
According to embodiments of the present invention, an intraocular imaging method is disclosed that includes receiving, with an optical coherence tomography system, image data of an ocular system at a first image depth range and a second image depth range, forming a first A-scan from the image data at the first image depth range, forming a second A-scan from the image data at the second image depth range, the second range overlapping the first image depth range across an overlap region, cropping said first and second A-scans at a location in the overlap region, and producing a composite image by combining the cropped first and second A-scans. Further A-scans may be combined to form the composite image. For example, three, four, or more A-scans at additional depths may be combined. These one or more further A-scans may overlap with the first or second A-scans or may be provided at a distinct non-overlapping depth range.
In a further embodiment, the present invention is directed to an intraocular imaging method that includes receiving, with an optical coherence tomography system, raw image data of an ocular system at an image depth range and forming an A-scan from the raw image data in a process that comprises removing artifacts from the raw data. The artifacts may be removed by performing a background subtraction to provide cleaned raw data. The background subtraction may include subtracting an array of values representing autocorrelation artifacts and fixed pattern noise. The method may further include, before the background subtraction, forming a plurality of A-scans and forming the array of values by averaging the plurality of A-scans.
In a further embodiment, the present invention is directed to an intraocular imaging method that includes receiving imaging data in the form of wavelength data and forming an A-scan from the wavelength data by converting the wavelength data into non-linear frequency domain data, resampling the frequency array to provide linearized data and processing the linearized data to provide the A-scan. The processing may include performing a Fourier transform on the linearized data to provide an intensity profile and a complex result, determining an absolute value of the complex result to provide magnitude data, and determining a logarithm of the magnitude data to provide a compressed dynamic range.
According to the present invention, in further embodiments of the imaging methods, the method includes forming a first B-scan comprising a plurality of said A-scans at a first image depth range, forming a second B-scan comprising a plurality of A-scans at the second image depth range and producing a composite image combining the first B-scan and the second B-scan. Further B-scans may be combined to form the composite image. A further B-scan may overlap with the first or second B-scans or may be provided at a distinct non-overlapping depth range.
Intraocular imaging methods, according to embodiments of the present invention, further comprise receiving image data using an optical coherence tomography system that includes an interferometer including a reference arm and a sample arm and providing a selected amount of dispersion compensating material in the reference arm.
Further intraocular imaging methods, according to embodiments of the present invention, further comprise receiving imaging data at a first image depth range and at a second image depth range, different from the first image depth range, wherein the location of the first and second image depth ranges is selected so that image data includes substantially no mirror-image artifacts. When the ocular system includes a cornea and a crystalline lens, the first image depth range may be selected so that a zero delay location of an optical coherence tomography system is located anterior to the cornea and the second image depth range is selected so that the zero delay location of the optical coherence tomography is located posterior to the crystalline lens. In this way an image of the anterior segment of an eye may be formed. An image of another portion of the posterior segment, or of the whole eye, may be formed using imaging data from one or more further image depth ranges.
Still further intraocular imaging methods, according to embodiments of the present invention, further comprise performing optical coherence tomography through an objective lens configured to provide a focal plane and imaging at imaging depths, so that the focal plane is located at a mid-point between a zero delay location at the imaging depths or in a region of overlap of the imaging depths. The optical coherence tomography system may include a first and a second lateral scanner for providing a B-scan and the optical coherence tomography system may be configured to have a back focal plane located between the first and the second lateral scanner.
The intraocular imaging methods described above may be implemented individually, or in any combination, each such combination being hereby incorporated herein as if individually set forth. The methods may also be varied or supplemented with other steps as described herein.
According to one embodiment of the present invention, an intraocular imaging system is disclosed, comprising a spectrometer, an interferometer comprising a sample arm and a reference arm, and an image processor. The interferometer is configured to comprise a plurality of optical paths of different path lengths along the reference arm and switch between the optical paths, the optical paths causing the imaging system to image at different imaging ranges. The intraocular system is arranged to operate said optical scanner and interferometer to provide the image processor B-scan data at said path lengths and wherein the image processor is arranged to combine the B-scan data to form a composite image extending over an imaging range longer than the imaging ranges formed by the individual path lengths.
According to further embodiments of the present invention, an objective lens of the intraocular imaging system is configured to provide a focal plane at a location in an overlap of overlapping imaging ranges. When the image processor is arranged to combine B-scan data, it may be arranged to do so by cropping the B-scan data at said path lengths at or around a location corresponding to the location of the focal plane of the objective lens. The intraocular imaging system may include lateral scanners for controlling a position of the imaging ranges to enable B-scans to be formed and a back focal plane of an objective lens of the imaging system may be located between the lateral scanners.
According to further embodiments, an intraocular imaging system of the present invention comprises a spectrometer, an interferometer comprising a sample arm and a reference arm, and an image processor. In the reference arm is a movable dispersion compensating material that is configured so that movement of the material varies the amount of said dispersion compensating material in the optical path of the reference arm.
Still further, according to embodiments of the present invention, an intraocular imaging system comprises a spectrometer, an interferometer comprising a sample arm and a reference arm, and an image processor. The interferometer includes a sensor that includes pixels distributed across individual pixel locations. The image processor processes image data from the sensor using a map of the individual pixel locations to their corresponding wavelength. The map is configured to calibrate for non-linear distribution of the wavelengths across the pixel locations.
According to further embodiments, an intraocular imaging system of the present invention may be formed using any combination of the features described above, each such combination being hereby incorporated herein as if individually set forth. The imaging systems may also be varied or supplemented with other integers described herein.



BRIEF DESCRIPTION OF DRAWINGS
The foregoing and other features and embodiments of the present invention may be better understood by referring to the description of preferred embodiments and claims which follow, taken together with the accompanying drawings wherein:
FIG. 1 is a schematic diagram of one embodiment of a combined ophthalmic surgical microscope and optical coherence tomography (OCT) apparatus.
FIG. 2 is a schematic diagram of the OCT apparatus shown in FIG. 1, comprising a light source, fiber optic interferometer, and detection unit including an imaging spectrometer, and reference arm incorporating fast scanning optical switch.
FIG. 3 is a schematic diagram of the imaging spectrometer used in the detection arm of the OCT system.
FIG. 4 is a schematic diagram of a signal processing algorithm used to process recorded interference data and convert the data to the depth dependent intensity profiles, or A-scans.
FIG. 5A is a schematic diagram of a cross-section of an eye and the location of three image frames.
FIG. 5B is a schematic diagram of a three-position fast scanning optical switch according to an embodiment of the invention.
FIG. 6 is a timing diagram showing operation of an optical switch of the apparatus shown in FIG. 2.
FIG. 7 shows a plot of sensitivity against frequency about a zero-delay location for an OCT system.
FIG. 8 shows a representation of an anterior segment of an eye and a location of two zero-delay locations provided by an optical switch of the apparatus shown in FIG. 2.
FIG. 9 shows a representation of two individual images from the extended depth spectrometer of FIG. 2, overlapped and summed to produce the single image with increased imaging depth and with improved sensitivity roll-off performance.
FIG. 10 shows examples of images captured at two zero-delay locations and a composite image formed from the two images.
FIG. 11A shows examples of images captured at three zero-delay locations.
FIG. 11B shows an example of a composite image formed using the images of FIG. 11A.
FIG. 11C shows a diagram of a corrected ocular interface positions.
FIG. 12 shows a schematic diagram of a ray-tracing algorithm used in one embodiment.



In the drawings, like reference numerals refer to equivalent features.
DETAILED DESCRIPTION
One embodiment of an intraocular imaging system comprises at least two main components: 1) an optical coherence tomography (OCT) system capable of generating a cross-sectional view of at least substantially the entire portion of the crystalline lens not hidden by the iris, and 2) a delivery system capable of interfacing the OCT system to an operation microscope, such that, for example, a surgeon can visualize the crystalline lens while surgical instruments are in the field of view. The following description is provided primarily with reference to intraocular imaging systems of this form, which will have other applications in addition to visualization of a crystalline lens.
In other embodiments the intraocular imaging system is integrated in a slit-lamp biomicroscope or a handheld device, such as a handheld microscope and in some embodiments the intraocular imaging system may stand alone.
As implemented in embodiments of the present invention, the novel OCT system provides a substantially real-time, cross-sectional image enabling the surgeon to visualize a cross-section of a whole eye (cornea through to retina) or of a part of an eye, for example, a crystalline lens, cornea and crystalline lens, or cornea, crystalline lens and retina while performing surgery. This is accomplished by providing an OCT video image of the eye or a part of the eye in at least one of the operation microscope oculars, to an external display, or both. The human crystalline lens is, on average, approximately 5 mm in maximum physical thickness. For the scan depth (axial) to be large enough to image the entire crystalline lens, this requires that the scan depth of the OCT system be greater than the optical thickness of the lens (7-8 mm). The long-range depth scanning requirement can be satisfied using a number of techniques, including, for example, 1) a high spectral-resolution imaging spectrometer designed to achieve the required depth range, 2) an optical switching method implemented in the reference arm of the interferometer, or 3) both.
One component of the OCT system that contributes to achieving the extended depth range is the high spectral-resolution imaging spectrometer. The spectrometer described herein preferably employs a single line camera and a single transmission grating to achieve long axial range (approximately 10 mm in air, approximately 7-8 mm in tissue, including tissue that may be up to 99% water when used with FD-OCT with a fixed group delay). The design parameters define the spectral resolution of the spectrometer, which is related to the detectable depth range of a SD-OCT through the following formula (Eq. 1):




  
    
      
        
          Δ
          ⁢
          
            
          
          ⁢
          z
        
        =
        
          
            1
            
              4
              ⁢
              
                
              
              ⁢
              n
            
          
          ⁢
          
            
              
                (
                
                  λ
                  0
                
                )
              
              2
            
            
              δ
              ⁢
              
                
              
              ⁢
              λ
            
          
        
      
    
    
      
        Eq
        .
        
          
        
        ⁢
        
          (
          1
          )
        
      
    
  




where n is the refractive index of the sample examined with the OCT system and λ0 is the central wavelength of the light source used in the OCT system.
According to preferred embodiments of the present invention, the optical scanning system is preferably fixed to the operation microscope since the surgeon's hands are often occupied with surgical instruments. This can be accomplished by two methods: 1) an external fixation and delivery of the OCT beam, or 2) an internal OCT beam delivery system that uses the operation microscope's primary objective to focus the OCT beam on the patient. For the external delivery method, the transverse optical scanners, scan lens, and optionally a dichroic beam splitter are positioned and mounted on the operation microscope, preferably positioned beneath the microscope objectives.
According to embodiments of the present invention, combining the two components of a long depth range OCT system with a delivery system integrated with the operation microscope produces a system that allows a surgeon to visualize the eye in cross-section. This is advantageous for example when the lens is visualized for a lens-refilling procedure, for example after capsulorhexis, so that the surgeon has visual feedback during refilling regarding the effect of the amount of material that is being injected into the lens capsule. Such a system would also be useful for femtosecond crystalline lens and cataract surgery. Furthermore, by employing a high-speed line scan camera utilizing either CCD or CMOS technology in the imaging spectrometer, fast acquisition rates are possible. The high acquisition rates enable either up to or higher than video-rate 2D cross-sectional imaging or recording of entire 3D volumes, for example 3D images of substantially entire ocular components such as, for example, lenses and components for which 2D cross-sectional imaging is possible, or selected portions thereof as desired. From either data source, quantitative analysis is possible to perform biometric measurements of the lens both before and after surgical procedures, including, for example, thickness, surface curvatures, diameter, eye length etc.
Embodiments of the spectrometer described herein may have free-space scan depths of approximately 10 mm, or approximately 7-8 mm in tissue. This depth range is required for in vivo imaging of the crystalline lens during surgery, where tissue manipulation during surgery would otherwise move the object out of the imaging frame. When such a spectrometer is combined with the optical switching methods described herein utilizing two switching arms, the free-space scan depth may be extended to be greater than 9 mm in tissue, for example to 12.7 mm. When such a spectrometer is combined with the optical switching methods described herein utilizing three or more switching arms, the free-space scan depth may be extended to be greater still, for example to 40 mm in air or 25-30 mm in the eye, which may be continuous or in two or more separate scan depths.
The depth range may be increased beyond 40 mm if the depth of focus of the beam is increased by changing the optical elements of the beam delivery probe. For instance if the beam delivery probe is designed to produce a larger focused spot diameter in the eye, then the depth of focus is increased by the square of the increase in the focused spot diameter (if the spot diameter is increased by a factor 2, the depth of focus increases by a factor 4). In practice, however, there is a trade-off between depth of focus and lateral resolution (spot diameter). For instance, if the OCT system uses a light source emitting at 840 nm, a depth of focus (defined as twice the Rayleigh range) of 20 mm in air corresponds to a lateral resolution (defined as the focused spot diameter) of 0.10 mm, whereas a depth of focus of 40 mm corresponds to a lateral resolution of 0.15 mm.
This depth range is sufficient to image at least the whole anterior segment of the human eye, from the anterior surface of the cornea to the posterior surface of the crystalline lens. The depth range facilitates lens-refilling surgical procedures, where the location and orientation of the lens capsular bag with respect to the other anterior segment structures, such as the cornea, would greatly benefit the surgeon. The depth range also allows at least the portion of the vitreous located beneath the eye pupil that does not lie beneath the iris to be imaged. The method may therefore be used to provide images useful in diagnosis and treatment of diabetic retinopathy and similar diseases. The images may be used to view fibrous membranes that can develop in Cloquet's space following laser capsulotomy, vitreous condensates beneath the lens that might occur following vitrectomy with injection of a silicone oil tamponade as well as very small bubbles of silicone oil that emulsify with time and that may locates itself in Cloquet's channel. The depth range also allows the eye to be imaged up to the retina, e.g. for the measurement of the eye length from the cornea outer surface to the retinal surface.
The imaging system described herein can also be used for quantitative analyses of tissue shape, including the radii of curvature, as well as thickness of both the cornea and lens, even during surgery. Such ability would have utility during lens refilling procedures as a practitioner would be able to “view” the procedure and reduce the risk of under- or over-filling the lens capsular bag. Other surgeries in which embodiments of the intraocular imaging system may have utility include, but are not limited to, DALK, DSEAK and KPro procedures, cataract surgery with IOL implantation, surgical removal of fibrous membranes situated at a distance beneath the crystalline or artificial lens posterior surface, surgical removal of emulsified silicone oil beneath the lens, and removal of foreign bodies in Cloquet's space and beneath.
Other applications include intraoperative biometry of the eye in the implantation of an anterior chamber lens (ACIOL) (for example, the Verisyse IOL from AMO or the Artisan iris-claw IOL from Ophtec BV), an intraocular contact lens (ICL) implanted in front of the crystalline lens (for example the Intraocular Collamer Lens from Staar Inc), an intraocular lens implanted in the sulcus (SIOL) or in the lens capsule (PIOL), and a vitreous tamponade (or vitreous replacement) using silicone oils, perfluorocarbon liquids, or a combination of polymeric fluids that have a density higher than water.
FIG. 1 shows a schematic diagram of an embodiment of an intraocular imaging system, which comprises operation microscope 100 and optical coherence tomography (OCT) system 300.
The operation microscope 100 consists of objective lens 110, which has a long working distance (100-200 mm) for focusing on a patient's eye 900 during a surgical procedure such as femtosecond laser surgery. Light from the focal plane is collected and collimated by objective lens 110 and directed to magnifier 120. Magnifier 120 is a beam expander with multiple lens sets, or a zoom lens system to provide multiple magnifications to the observer. The collimated beam is focused by relay lens 130 to form an intermediate image of the object which is located at the object plane of eyepieces 140. Eyepieces 140 then provide collimated light output, forming a magnified image of the patient's eye 900.
The operation microscope 100 shown in FIG. 1 is understood to be in a fundamental form. It is to be understood by those skilled in the art that other elements may be included in the optical path to add greater functionality. Other embodiments of the ocular imaging system include integrating it with a slit-lamp biomicroscope or with a stand-alone hand-held delivery system.
As shown in FIG. 1, a primary objective lens of the surgical microscope (not shown) has been removed and has been replaced with an assembly consisting of beamcombiner 250 and the objective lens 110 with focal length chosen to optimize the beam delivery characteristics of the OCT system, to be described below.
The optical output of OCT system 300 is delivered to the surgical microscope 100 via transverse scanning unit 200 in the interferometer's sample arm 202 (shown in FIG. 2). The output of optical fiber 210 is collimated by lens 220 and directed to optical scanners 230 and 240. Optical scanners 230 and 240 are optical mirrors typically mounted on pivoting galvanometers. The galvanometer's positions are controlled by computer 150. The collimated OCT beam is delivered to the surgical microscope and is combined with the optical path by beam-combiner 250. Beam-combiner 250 is a dichroic filter, such as a hot mirror that reflects wavelengths higher than about 750 nm and transmits wavelengths that are lower than about 750 nm. The OCT beam is focused by surgical microscope objective lens 110. Objective lens 110 also focuses the collimated light from the operation microscope, ensuring that the focal plane of operation microscope 100 and the focal plane of the OCT beam are the same. The location of objective lens 110 is such that the back focal plane (BFP) is located at the midpoint between optical scanners 230 and 240. This ensures that the OCT beam is scanned across objective lens 110 in a manner to be described in detail below. The selection of the focal length is described below with reference to Eq. 9.
FIG. 2 shows a schematic diagram of a SD-OCT system 300 with an optical switch 400 in the reference arm 342, transverse scanning unit 200 that interfaces to the surgical microscope 100, and high-resolution imaging spectrometer 354 in the detection arm 352.
The OCT system employs a low-coherence light source 301, which may be a light emitting diode (LED), super-luminescent diode (SLD), femtosecond laser source or other white light source. In one embodiment the light source 301 has a center wavelength in the near infrared (NIR) spectral region, centered near 800-850 nm. In other embodiments, different wavelength regions are possible, including, but not limited to the 900, 1060, and 1300 nm spectral bands. Sources with longer wavelengths, such as 1.0 μm and 1.3 μm sources have a deeper penetration depth in highly scattering (translucent or relatively opaque) and vascularized tissues like the fibrovascular membranes in Persistent Hyperplastic Primary Vitreous (PHPV) occurring in babies. The deeper penetration may allow imaging thick membranes in the eye that are quasi opaque to 840 nm but more transparent at 1.0 or 1.3 μm. Such membranes occur in the anterior and posterior chambers of the eye. A longer penetration depth may also be useful in imaging dense cataracts, such those where a broken posterior capsule is suspected. If one is not aware of a broken posterior capsule, a broken capsule can lead to problems in cataract surgery: vitreous will end up in the anterior chamber, an emergency vitrectomy may be needed and the intraocular implant may have to be sutured in the sulcus. Visual outcome is not very good for these patients. Using longer wavelengths may also be useful for imaging the choroid and the inner surface of the sclera.
The source bandwidth may be in the range from 30 nm to 200 nm, depending on the resolution required. A higher resolution may require a configuration with more scanning mirrors due to the small area that is imaged at a time. In one embodiment the FWHM bandwidth of the light source is 50 μm. This bandwidth provides a resolution of approximately 7 μm. In another embodiment the FWHM bandwidth of the light source is 150 nm, providing a resolution of approximately 3 μm. Higher resolution may be useful to image small inclusions in the cornea (e.g. acanthamobea cysts), in cases of posterior capsule opacification and phemosis, for DSEAK surgery, as well as to image the posterior capsule and fine structures in Cloquet's space.
The radiation emitted by source 301 is coupled into input optical fiber 320 of single mode fiber optic coupler 330. In the embodiment shown the interferometer includes a 2×2 fiber optic coupler 330. Light coupled into the input optical fiber 320 is split into reference arm optical fiber 340 and optical fiber 210. The output of reference arm optical fiber 340 is reflected by fast-scanning optical switch 400 described below, and coupled back to the reference arm optical fiber 340. The output of optical fiber 210 is directed to transverse scanning unit 200 described above and interfaces to a surgical microscope at beamcombiner 250 shown in FIG. 1. Objective lens 110 focuses the optical output of transverse scanning unit 200. The radiation that is backscattered from the patient's eye 900 is collected by the optical fiber 210 and combined with the radiation collected by optical fiber 340 returning from fast-scanning optical switch 400. Fiber optic coupler 330 combines the reflected light and a portion of the optical output, which includes the image information for detection, and the combined light is directed to the detection arm optical fiber 350.
The output of the optical fiber 350 is collimated by lens 360 and directed to diffraction grating 370.
Light dispersed by diffraction grating 370 is collected by imaging lens 380 and the individual wavelength components of light source 301 are focused onto a linear array detector 390 which may be a CCD or CMOS sensor. The digitized electronic output of detector 390 is collected by a dedicated capture card (not shown) and sent to computer 150150 for processing and display. The line density of diffraction grating 370 and the focal length and aperture of imagine lens 380 are selected to spread adequately the bandwidth of light source 301 over the sensitive length of sensor 390.
Interference between light backscattered by the delivery arm object and the light reflected by the reference arm 342 fast scanning optical switch 400 occurs only when the optical path length difference between the reference and sample arms of the interferometer is within the coherence length of light source 301.
Under this condition, spectral interference fringes at different spatial frequencies illuminate sensor 390. The spatial frequency of the interference fringes encodes the axial position of scatterers in the sample. Increasing optical frequency corresponds to larger optical path length differences, that is, longer axial lengths, or deeper sample depths.
In the specific OCT system embodiment shown in FIG. 2, the imaging spectrometer 354 in the detection arm 352 is designed to have an extended depth range, according to the criteria described above. The specific design parameters of the spectrometer 354 that are required to achieve the extended depth range are dependent on the specific light source used in the OCT system.
In one embodiment, light source 301 is a superluminescent diode (SLD) with center wavelength λ0=836 nm, full-width, half-maximum (FWHM) bandwidth of ΔλFWHM=50 nm, and full bandwidth at the 1% output power level of Δλ1%=68 nm, with a spectral range from λ1=802 nm to λ2=870 nm. It is to be understood that while the design details of the extended depth spectrometer are matched to the specifications of the light source employed, other light sources can be used to achieve the required depth range.
Referring to FIG. 3 showing a schematic of the spectrometer 354, the light emitting from optical fiber 350 consists of the individual wavelength components of light source 301 and is incident on the transmission grating 370 at an angle θi and is dispersed at an angle equal to θi+θ. The angle θi is calculated using the grating equation (Eq. 2):

λ=d sin(θi)+d sin(θi+θ),  Eq. (2)

where d is the grating period. Grating 370 is a transmission grating, such as a volume phase holographic (VPH) transmission grating with a spatial frequency of 1800 lines/mm, which is equal to a grating period of d=5.56×10−4 mm.

Solving Eq. (2) for the angle θi using the light source central wavelength λ0=836 nm and setting the diffraction angle θ=0:




  
    
      
        
          θ
          i
        
        =
        
          
            
              sin
              
                -
                1
              
            
            ⁡
            
              (
              
                
                  λ
                  0
                
                
                  2
                  ⁢
                  
                    
                  
                  ⁢
                  d
                
              
              )
            
          
          =
          
            48.80
            ∘
          
        
      
    
    
      
        Eq
        .
        
          
        
        ⁢
        
          (
          3
          )
        
      
    
  




According to the grating equation (Eq. 2), the dispersion angles for SLD light source 301 span from θ1=48.80°−5.07° to θ2=48.80°+5.65°.
As shown in the spectrometer schematic, the position x of a wavelength component on the sensor array is estimated from the following equation (Eq. 4):

x=f tan θ  Eq. (4)

where f is the focal length of imaging lens 380 of the spectrometer. The focal length of the lens is chosen to fill as many of the pixels on the sensor 390 as possible. Using a sensor array with N=4096 pixels and a pixel size of p=10 μm and an imaging lens with f=210 mm, the pixels on the sensor that are illuminated from the dispersed spectrum span from:

x1=f tan(θ1−θi)=−18.63 mm

to

x2=f tan(θ2−θi)=+20.78 mm

and x0=0 mm is the position of the central wavelength λ0=836 nm. The spectral resolution can be approximately calculated using the following equation:




  
    
      
        
          δ
          ⁢
          
            
          
          ⁢
          λ
        
        ≈
        
          
            Δ
            ⁢
            
              
            
            ⁢
            
              λ
              
                1
                ⁢
                %
              
            
          
          
            
              
                x
                2
              
              -
              x
            
            p
          
        
      
    
    
      
        Eq
        .
        
          
        
        ⁢
        
          (
          5
          )
        
      
    
  




Here,




  
    
      
        x
        2
      
      -
      
        x
        1
      
    
    p
  
  =
  3942




px is me number of pixels illuminated on the sensor by the spectrum at the 1% power level, giving an estimated spectral resolution of δλ=0.017 nm/px From the spectral resolution of the spectrometer, the estimated detectable free-space depth range is calculated using the following equation:





  
    
      
        
          Δ
          ⁢
          
            
          
          ⁢
          z
        
        =
        
          
            
              1
              
                4
                ⁢
                
                  
                
                ⁢
                n
              
            
            ⁢
            
              
                
                  (
                  
                    λ
                    0
                  
                  )
                
                2
              
              
                δ
                ⁢
                
                  
                
                ⁢
                λ
              
            
          
          =
          
            10.129
            ⁢
            
              
            
            ⁢
            mm
          
        
      
    
    
      
        Eq
        .
        
          
        
        ⁢
        
          (
          6
          )
        
      
    
  




One requirement in order to achieve a high sensitivity OCT system is that the spectrometer must have high efficiency, i.e. optical losses in the device must be minimized. One method of reducing optical losses is by maximizing the coupling of the collected light to the individual camera pixels. This can be accomplished by ensuring that the focused beam spot size is smaller than the size of a single pixel in detector 390, which is 10×10 μm, or is reduced as much as the optical assemblies allow.
Assuming a Gaussian beam profile, the beam waist diameter 2ω at the focal plane of the imaging lens 380 is given by the following equation:




  
    
      
        
          2
          ⁢
          
            
          
          ⁢
          ω
        
        =
        
          
            2
            ⁢
            
              
            
            ⁢
            λ
            ⁢
            
              
            
            ⁢
            f
          
          
            π
            ⁢
            
              
            
            ⁢
            
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        .
        
          
        
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          7
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where f=210 mm is the focal length of the imaging lens and ω0=14 mm is the collimated beam diameter incident on the imaging lens. Using these examples of values for f and ω0, over the spectral band incident on the sensor from λ1=820 nm to λ2=870 nm, the calculated beam waist at the focal plane of the imaging lens varies from 15.12 μm (802 nm) to 16.62 μm (870 nm).
In one embodiment the sensor used is a line scan camera which detects the spectral interferogram, and it has a linear array of N=4096 pixels. The individual pixel locations are mapped to their corresponding wavelength of the detected spectral interferogram, which is determined primarily through the grating equation (Eq. 2). The distribution of wavelengths over the array is non-linear, so a calibration is performed to accurately map the pixel number to its corresponding wavelength. An imprecise spectrometer calibration may lead to errors when converting the spectral data to the depth-dependent reflectivity profiles that are used to construct a cross-sectional image, resulting in poor image quality. The non-linear distribution is approximated with a fourth-order polynomial, which maps the wavelength to the pixel location across the array:

λ=a0+a1x1+a2x2+a3x3+a4x4  Eq. (8)

where a0, a1, a2, a3, a4 are the polynomial coefficients.
Calibration of the spectrometer is performed with a gas discharge spectral calibration Neon lamp. The Neon lamp emits multiple spectral lines at known wavelengths over the spectral range of the spectrometer. A multimode optical fiber cable (50 μm core) couples the light output from the Neon lamp to the spectrometer. The spectral lines are dispersed across the detector array and the exposure time of the camera is adjusted so that the low intensity light emitting from the calibration source can be detected. Several spectral lines of known wavelength are selected from the recorded spectrum, for example 8 spectral lines (λ1, . . . , λN, N<8) may be used. Their corresponding pixel positions x0 . . . xN, N<8 are recorded and a plot of the wavelength as a function of pixel number is obtained, which is used to calculate the polynomial coefficients a0, a1, a2, a3, a4 from Eq. (8). Any suitable number of spectral lines may be used, for example N<3. Using more spectral lines may improve the accuracy of the calibration, for example using N=15 or N<15.
Other models of the non-linear distribution of wavelengths over the array may be used, including for example higher order polynomials.
An “A-scan” is a map of the reflectivity of the sample versus depth and is provided by the envelope of the measured interferogram pattern. A “B-scan” is a two-dimensional map of reflectivity versus depth and lateral extent that is built up using multiple A-scans that are acquired when a sample beam is scanned across the tissue surface.
Referring to FIG. 4, the flowchart describes one embodiment of the present invention, a process 600 to convert raw image data acquired from the sensor (detector 390 in FIG. 2) to a depth-dependent reflectivity profile, or A-scan.
Raw image data is acquired at step 602. Spectral domain OCT systems typically suffer from several signal and noise sources that manifest as artifacts in the processed B-scan. Two common sources are the autocorrelation artifacts, which is the DC component of the spectral interferogram, and the so-called fixed pattern noise, which is typical of CMOS sensors in the detector. Both of these sources are corrected by performing a background subtraction 604 as the first step in the signal processing pipeline. This is done by capturing the first B-scan in an acquisition sequence, which typically has 1000 A-lines, and averaging all of the A-lines in the B-scan. This results in a 1-D array of values 606 that contain the autocorrelation (DC signal) and fixed-pattern noise components. At step 604 this array 606 is subtracted from each subsequent A-line acquired. Next, at step 608, the pixel data is converted from pixel number to wavelength by applying the calibration curve from Eq. (8).
The spectral interferogram is Fourier transformed to frequency space in order to calculate the depth-dependent intensity, therefore the wavelength data is converted to frequency at step 610 by taking the inverse:




  f
  =
  
    
      1
      λ
    
    .
  




After taking the inverse, the frequency array has generally a non-linear interval, so it is resampled to linearize the frequency data at step 612. The frequency interval is calculated based on the spectral span of the detector and the number of elements in the array, and the new frequency spectrum is interpolated with a cubic spline algorithm, resulting in an array of elements that contains the spectral interferogram that is linear in frequency.

Once the frequency data has been scaled and linearized, the following signal processing is performed at step 614:

    
    
        the intensity profile is obtained by a Fast-Fourier Transform (FFT);
        the absolute value of the complex result of the FFT is taken to return the magnitude of the signal;
        the log of the signal is taken to compress its dynamic range, resulting in a depth-dependent intensity profile (A-scan).
    
    


This type of signal processing contributes to providing a usable A-scan quickly so that an image can be provided to the output of the system (e.g. in the ocular of the operation microscope) in substantially real-time. Other types and combinations of signal processing may also be used to provide usable A-scans as will be understood by a person skilled in the art. The A-scan is displayed at step 616.
A cross-sectional image of the sample is generated by OCT system 300 by recording a series of adjacent depth scans (A-scans) that are scanned across the sample by transverse scanning unit 200. At each lateral position of the OCT beam, one line of data is read from linear array detector 390 and processed by computer 150, described above, to create one depth-dependent intensity profile of the backscattered signal (A-scan). A series of A-scans are recorded while the transverse scanning unit scans the OCT beam across the sample in one cross-sectional plane (x-direction). Optical scanners 230 and 240 are driven by linear ramp signals to ensure the lateral scan velocity of the beam is constant. Additionally, objective lens 110 is positioned so that its back focal plane is located at the midpoint of optical scanners 230 and 240. This configuration assures that the chief rays of the OCT beam remain substantially parallel to the optical axis of surgical microscope 100, and normal to the sample or patient's eye 900. Normally incident rays are important to reduce image distortions due to refraction at individual surfaces.
The recorded series of adjacent A-scans, typically 100-1000, are then combined in computer 150 to create a 2-dimensional map of the backscattered intensity (B-scan), thereby revealing the internal structures of the patient's eye. The lateral length of the scan is limited by the aperture of objective lens 110, but can be large enough to cover the entire lateral dimension of a patient's eye.
As is shown in FIG. 2, OCT system 300 uses optical fiber 340 to direct its output to reference arm switch 400. Lens 410 collimates the output of the fiber and directs it through optical wedges 420 and 430. Optical wedge 420 is mounted in a fixed position and optical wedge 430 is mounted on a stage that translates the element laterally with respect to the optical beam, which is used to compensate for dispersion mismatch in the two arms of the interferometer, described below. The reference arm optical switch 400 comprises a pivoting mirror mounted on optical scanner 440, typically a galvanometer motor whose position is computer controlled.
A galvanometer-mounted mirror is the preferred embodiment for the reference arm switch due to its simple operation and fast response time, however other implementations of the optical switch are possible, including micro-electromechanical (MEMs) mirrors, integrated optical devices, and fiber-optic switches, all of which are capable of performing a similar function as will be understood by those skilled in the art. As described herein, the reference arm optical switch is used generally for extending the imaging depth range in an OCT system.
In its nominal state optical scanner 440 deflects the reference arm beam toward a retro-reflector comprising focusing lens 450 and fixed mirror 460. The optical path length between optical element 410 and 460 determines the zero-delay location, which corresponds to the location in the sample where interference can be detected. The zero-delay location determines the initial location of a single depth scan from the OCT system.
By applying a fixed voltage to optical scanner 440, the mirror pivots and directs the reference arm beam to lens 470, which focuses the beam on fixed mirror 480. The optical path length between elements 410 and 480 is chosen to be longer than the optical path length between elements 410 and 460 by an amount that is determined by the desired overlap of the top and bottom imaging windows, described below. Switching optical scanner 440 between the two optical paths 410 to 460 and 410 to 480 permits two distinct zero-delay locations to be scanned in rapid succession.
Other embodiments of the reference arm optical switch can be implemented by, for example, incorporating more than two optical paths to increase the scan depth further.
FIG. 5A is a schematic diagram of a cross-section of an eye 500 comprising a cornea 501, an anterior chamber 502, a crystalline lens 504, a vitreous humor 506 and a retina 508. Three image frames (FRAME 1-3) are shown. The image frames may be obtained using the configuration of a three-position fast scanning optical switch 520 shown schematically in FIG. 5B. FRAME 1 and 2 combine into a 12 mm (in air) frame that covers the entire anterior segment. The method by which this is done is described in further detail below with reference to FIG. 6. FRAME 3 covers 10 mm (in air) over the retina and it is positioned at 24 mm (in air) from FRAME 2.
Referring to FIG. 5B, the switch 520 uses a mirror mounted on a galvanometer 522 scanner that rapidly switches the reference beam between three delay lines (D1, D2 and D3). The switching speed, Tswitch, is between 200 and 400 μs, for example Tswitch=300 μs. The delay lines D1-D3 have a calibrated optical path length difference, the paths stretching between the galvanometer 522 and the respective mirrors M1, M2, M3 associated with each of the delay lines D1-D3. The calibrated optical path length difference allows the three frames (FRAME 1-3) to be recorded within 60-100 ms, for example within 75 ms. The optical path difference of the delay lines represents the axial offset between the frames that are alternately recorded.
As shown in FIG. 5B the mirrors are spaced apart as follows: M2 12 mm further than M1, and M3 another 24 mm further. This results in the spacing of the frames as shown in FIG. 5A with FRAME 1 and FRAME 2 overlapping across the area containing the cornea 501, anterior chamber 502 and crystalline lens 504, and with FRAME 3 used to image the retina 508.
It will be understood that more than 3 delay lines may be used if more frames are required for imaging other areas of the eye. For example, a fourth mirror may be added to image the anterior vitreous and a fifth mirror may be added to image the posterior vitreous and retina. In this way multiple delay lines may be used to image a cross section of the whole or substantially the whole eye. One or more frames providing images of the vitreous humor may be obtained by using delay lines with different lengths to those shown in FIG. 5B, for example mirror M3 could be placed 12 mm further than M2 (instead of the 24 mm shown) to produce two overlapping images (i.e. Image 2 showing the posterior part of the lens and anterior vitreous and Image 3 showing the anterior vitreous as well as deeper regions of the vitreous).
For the two switch position embodiment shown in FIG. 2, FIG. 6 shows a timing diagram of the operation of the fast optical switch when implemented in the reference arm of a SD-OCT system. The top trace 702 is the line sync signal, which is used to control the exposure of the line-scan camera and synchronize the other control signals in the OCT system. The line sync can be generated either internally by the camera, or externally and supplied to the camera. Each rising edge 704 of the line sync triggers one acquisition of a spectrum from the camera, which corresponds to one A-line of data. This signal is repeated until the required number of A-lines have been recorded to construct one B-scan.
During the acquisition of one B-scan, the transverse scanners (optical scanners 230, 240 in FIG. 1), X or Y or both, are driven with a drive waveform to laterally scan the beam in the desired pattern. For a cross-sectional image in a single meridian, it is sufficient to drive either the X or Y scanners with a linear ramp function 706, from −V to +V so the beam scans across the sample at a constant velocity. At the completion of the first ramp 708 (X or Y) the scanner returns to its starting location −V 710.
During the first cycle, the Z scanner, which controls the optical switch 400, is held constant at its starting location 712, corresponding to the initial zero-delay location. At time T1, the transverse scanner (X or Y) returns to its initial location and the fast optical switch scanner (Z) is activated, deflecting the reference arm beam to a longer optical path, thereby shifting the zero-delay location to a new depth in the sample. For embodiments with three or more optical paths, then the Z scanner has corresponding three or more positions, so as to implement scanning at three or more scan depths.
There is a delay τ between the time the optical switch 400 is activated and the time that it settles at its new location. This delay is on the order of 100-20 μs, which includes the settling time of the galvanometer and the time it takes the scanner to traverse the necessary angle. At time T2, the zero-delay has been shifted to its new location, and the acquisition of the second B-scan commences. The X or Y transverse scan pattern is repeated during the acquisition of the second B-scan, ensuring that the two frames are scanned in the same plane parallel to the optical axis. The two B-scans that have been recorded are then stitched together, for example in a manner described below. By alternating the acquisition between a top and bottom frame, the amount of time in shifting the zero-delay location is minimized, thereby maximizing the total acquisition speed and reducing possible motion artifacts.
In other embodiments, the transverse scanners, X or Y or both do not return to the start configuration when the fast optical switch scanner (Z) is activated. For example, referring to FIG. 6, at time T1 the transverse scanner control would remain at +V while the scanner control changes from 0 to +V and after the delay τ the transverse scanner control would ramp down to −V.
Dispersion imbalance between the sample and reference arms (202, 342) of the interferometer degrades the axial resolution in OCT by broadening the signal peaks that are generated from reflections in the sample. First-order dispersion, or group-delay dispersion (GDD) is the result of a difference in the amount of dispersive optics in the sample and reference arm. Referring to FIG. 2, optical wedges 420 and 430 are used to compensate for the additional dispersion present in the sample arm 202 of the OCT system, which can be due to, for example, differences in fiber-optic lead lengths, or the dispersion of surgical microscope objective 110. By translating optical wedge 430 laterally with respect to the optical axis, a variable amount of glass in the optical path can be introduced, thereby adding the additional dispersion required. The opposing configuration of the wedges assures that the beam remains collinear and does not deviate from its optical axis while wedge 430 is translated to adjust the dispersion compensation.
The amount of dispersion compensation required is determined empirically, by minimizing the FWHM of the point spread function from a first-surface reflection in the sample arm as a function of the offset of optical wedge 430. Balancing the amount of dispersion in the sample and reference arms of the OCT system will optimize the axial resolution of the system at only one sample depth, the zero-delay location.
If the sample is a dispersive medium, like the human eye, then a second-order dispersion, or group-velocity dispersion (GVD), introduces a depth-dependent reduction in the axial resolution. GVD can be compensated for using numerical techniques, such as those described in U.S. Pat. No. 7,719,692 B2, hereby incorporated by reference herein, as if made a part of this specification, where the GVD is automatically removed from the spectral interferogram during signal processing.
One feature of GVD is that its impact on degrading image quality increases with increasing source bandwidth. By limiting the source bandwidth to approximately 70 nm or less, the depth-dependent loss of axial resolution is kept within acceptable limits. Furthermore, for the case when only the anterior segment of the human eye is imaged, the length of dispersive medium is limited to approximately 10-12 mm, which in turn, limits the impact of GVD.
The depth range of conventional SD-OCT is limited by the spectral resolution of the spectrometer in the detection arm. Reflections from longer axial lengths are encoded as higher fringe frequencies in the spectral interferogram. As the fringe frequency increases beyond the spatial dimension of the individual pixels in the detector array, the spectral interferogram becomes under-sampled according to the Nyquist criterion, which leads to the theoretical depth range limit in Eq. (1).
FIG. 7 shows an example plot of sensitivity against frequency about a zero-delay location for an OCT system showing the fall off in sensitivity at longer axial lengths, the scan ranging from position (DC−Z) to position (DC+Z).
In practice, several factors contribute to the depth range limit, which lead to a depth dependent falloff in the sensitivity profile. That is, the interference signal is stronger at the zero-delay location than it is at the deepest part of its range. This reduces the useable depth range for imaging by as much as one-half.
For typical retinal imaging where only about 2 mm of imaging range is required, this does not pose a serious problem. However, for imaging where >10 mm of range is required, this imposes limitations on the system performance due to the design trade-offs of the spectrometer. For a linear array sensor with a finite number of pixels, increasing the spectral resolution of the spectrometer reduces the light source spectral span on the array, thereby reducing the source bandwidth, and reducing the axial resolution of the OCT system. For a given required axial resolution, the imaging depth may be increased by employing a linear array sensor with a larger number of pixels. However, this increases cost and complexity. Alternatively, a method to capture multiple frames in rapid succession, as described herein, can be used.
For imaging the anterior segment of the eye, the imaging depth in tissue may be extended beyond approximately 10 mm by employing the two position reference arm optical switch described above and shown in FIG. 2. Referring to FIGS. 2 and 8, a method to use both the positive and negative sides of the complex scan with the reference arm optical switch is described.
FIG. 8 shows a representation of an anterior segment of an eye and a location of two zero-delay locations provided by the optical switch 400. Reference arm mirror 460 is positioned such that its zero-delay location (ZD1) is slightly anterior to the cornea surface 810, as in FIG. 8. Reference arm mirror 480 is positioned such that its zero-delay location (ZD2) is slightly posterior to the posterior crystalline lens surface 820, as in FIG. 8. The first frame recorded 830 stretches from the cornea down through the anterior chamber 840, which is captured on the positive side of the top half-scan.
When the reference arm optical switch 400 is activated, the zero-delay location shifts to ZD2, and the second frame 860 captures the crystalline lens 850, which is recorded on the negative side of the bottom half-scan. After the two frames are captured, they are combined in the computer 150 by cropping the low-sensitivity end of each scan and creating a new image, where the two half-frames are joined together at the crop line 870. In some embodiments the cropping results in a switch from one half-frame to another half-frame at the crop line. In other embodiments, the two half-frames may be combined, for example by averaging the image in a region before switching to use of only one of the half-frames, or using another method of transitioning between the half frames. Where the zero-delay locations and the imaging depth are such that there is no or substantially no overlap between the imaging depths, then the cropping may be omitted, for example for an embodiment where a third image of the retina is taken as described above with reference to FIGS. 5A and 5B. When scanning the retina, or any other additional component of the eye, the zero delay line is adjusted so as to avoid the presence of the mirror image and minimize the sensitivity fall-off. When imaging the retina for instance, the zero delay would be placed near to the vitreo-retinal boundary.
FIG. 9 shows a representation of the two individual images from first frame 830 and second frame 860, overlapped and summed to produce a single image with increased imaging depth and with improved sensitivity roll-off performance. The amount of distance that the two images overlap 890 is adjustable using software processing methods and is chosen based on image quality.
A normal calibrated free-space depth range of approximately 10.6 mm can be achieved with the spectrometer described herein. By applying the two position reference arm optical switch, the free-space depth range can be extended to at least 12.7 mm, which is sufficient to image substantially the entire anterior segment of a human eye, from anterior cornea surface to the posterior crystalline lens surface, with increased sensitivity. Note that any technical improvements to the sensitivity falloff will immediately extend the imaging range further by reducing the frame overlap that is required to construct the final B-scan. Because the high-sensitivity end of each frame is used to create the image, the deleterious effects of the sensitivity falloff inherent in FD-OCT are reduced.
For multiple switch positions such as the three position embodiment shown in FIG. 5B, the depth range can be extended to at least 40 mm in air (approximately 25-30 mm in the eye) for imaging substantially the entire cross section of a human eye (from infants to adults, including myopes). This depth range is also suitable for imaging parts of or the whole eye of animals such as rabbits, cats, dogs and horses.
In some embodiments that incorporate the stitching together of overlapping frames, all the image data can be measured from a first switch position to form a first composite image. This is followed by measuring all the image data from a second switch position to form a second composite image. The two composite images are then stitched together to form a final composite image. For example, all the A-scans are taken from the first switch position to foul′ a first B-scan. This is followed by taking all the A-scans from the second switch position to form a second B-scan. Following this, the two B-scans are stitched together.
In other embodiments, image data (e.g. a first A-scan) is acquired from the first switch position, followed by acquiring further image data (e.g. a second A-scan) from the second switch position. These two are then stitched together. This can be repeated until multiple stitched data pairs have been acquired, and these can then be combined into a single stitched composite image.
In embodiments that include frames that do not overlap, for example if there is a frame of the anterior segment and a frame of the retina, then the frames are stitched together without overlap. This is done by taking into account the distance between the zero delays produced by the mirrors of the optical switch thereby determining a relative position of the frames.
The method and system with which a composite image is produced does not rely on taking individual images sequentially. From the operator's point of view the process is seamless and the operator does not have to manage the process by which the images are acquired at multiple depths. Furthermore, no active focusing is required. In other words, the objective does not need to be moved to focus it at different depths. The entire length is imaged using the same fixed beam delivery system.
A limitation in known FD-OCT, both for SS-OCT and SD-OCT, is the so-called complex conjugate artifact, which arises as a result of the symmetry properties of the Fourier Transform of real signals, which produces identical signal peaks at both positive and negative frequencies. The complex conjugate artifact is manifested as a mirror image of the sample being scanned. Methods exist for removing the complex conjugate artifacts and using the full range of the complex spectrum and are described in, for example U.S. Pat. App. Pub. US 2011/0102802 A1. However, they generally suffer from reduced imaging speeds, as multiple frames of data (3-5) are required to construct a single B-scan and additional signal processing is required to eliminate the mirror image after the multiple acquisitions have been completed. The optical switching method described herein can create an entire B-scan from just 2 frames of data in real time and there is very little imaging time lost during the switching process. In addition, no additional signal processing steps are required.
During regular ophthalmic OCT scanning, the zero-delay location is positioned such that the structure of interest is completely located on one half side of the imaging frame, either the positive frequency (+Z) or negative frequency (−Z) side.
For typical retinal imaging, this poses no problem since the zero-delay location will be positioned slightly anterior to the retinal boundary, so that the negative frequency side (−Z) of the scan is completely located in the vitreous, where there are no significant structures to generate mirror-image artifacts. For typical corneal imaging, this is also not a problem for the same reason, since the negative frequency side of the scan is located outside the eye in air, where no mirror-image artifacts can be seen.
However, for crystalline lens imaging in the eye, this is problematic since if one were to position the zero-delay location near the anterior surface of the crystalline lens, a mirror-image artifact would be created from the reflections of the cornea, which would be superimposed on the image of the crystalline lens. In order to image the crystalline lens without mirror-image artifacts, the zero-delay location is located near the posterior lens boundary, such that the back-half, or negative frequency side of the scan is used for imaging. In this situation, the front-half, or positive frequency side of the scan is located in the vitreous where no significant structures can generate artifacts. This method of imaging the crystalline lens in real time is feasible with only the spectrometer described in this invention because it is possible to have an imaging depth in tissue of approximately 7.6 mm or more.
Therefore, in the system described herein no mirror-image artifacts are created when imaging the crystalline lens since the complex conjugate of the scan is always located in a region without significant structure. For the top frame including the cornea, the negative side of the scan is located outside the eye, where the air medium will not create artifacts. For the bottom frame including the crystalline lens, the positive side of the scan is located in the vitreous, where normally there is no significant structure to generate artifacts.
On the other hand, the vitreous can be imaged, for example for use in diabetic retinopathy, by adjusting the scan depth using the optical switch to switch to delay lines of an appropriate length.
Referring to FIG. 1, the focal length of objective 110 is chosen to provide sufficient depth of focus to image the eye within the complete scan depth range of the OCT system. The depth of focus of the scan is closely matched to the required scan depth. Known OCT systems use objective lenses that produce a small probe beam focal spot size. Typically, for limited range depth scanning of 2-3 mm, a short depth of focus with small focal spot size is desired to maximize the lateral resolution of the image. As described herein, however, a long depth of focus of approximately 5-10 mm is used to image substantially the entire crystalline lens during surgery, or even more depending on the number of switch positions used and the lengths of the delay lines. For extended depth imaging, a longer depth of focus in the order of the total scan depth range is required to ensure that the reflected signal strength is sufficient to maintain good image contrast throughout the scan range.
For anterior segment imaging with a required 12 mm free-space scan depth, the depth of focus, or confocal parameter, defined as twice the Rayleigh range (zr) for a Gaussian beam is approximately 12 mm as well. To achieve this depth of focus at NIR wavelengths near 830 nm, the f-number (f/# f/D) for a given objective focal length (f) and beam diameter (D) is:




  
    
      
        
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          ⁢
          
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          ⁢
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The location of the focal plane in the eye with respect to the two or more zero-delay locations impacts on the reference arm optical switching method because every image is preferably nearly in focus at all times. For two images, the focal plane is ideally located in a plane that corresponds approximately to the mid-point of the two zero-delay locations. For whole anterior segment imaging, this location is in the anterior chamber of the eye, close to the anterior surface of the crystalline lens. By locating a single beam focus with relatively long depth of focus, this eliminates the need for so-called dynamic focusing methods where multiple focal planes are scanned in succession and synchronized with the acquisition of the individual frames from the OCT system. Such methods have been described in U.S. Patent Application Publication US 2011/0102802 A1 in the application of switching scanning modes from a telecentric anterior segment scan to a retinal imaging scan with iris pivot. While dynamic focusing methods may improve the image quality for extended depth OCT, they require the physical movement of optical components in the delivery path, which typically have large inertia, and will generally have very slow response times, precluding them from high-speed imaging. The single, long depth of focus method described above allows the two frames acquired using the reference arm optical switch to be acquired at high-speed, without any additional delay between frames.
FIG. 10 shows an example of an image 910 captured at a first zero-delay location ZD1 and an example of an image 912 captured at a second zero-delay location ZD2. These two images are used to form a composite image 914 using the stitching method described above.
As shown in FIG. 11A-C the two switch position method used to provide the composite image 914 shown in FIG. 10 has been expanded on by using a switch with three positions as shown in FIG. 5B. As shown in FIG. 11A quantitative information of the entire eye may be obtained by sequentially recording 3 frames, two over the anterior segment and one over the retina. Low-coherence light from a superluminescent diode with center wavelength=835 nm and FWHM bandwidth=50 nm, which produces 7 μm axial resolution (in air) was used to achieve the results shown in FIG. 11A. The spectrometer of the system allows single frame imaging with an axial range of about 10 mm (in air) at a speed of 40,000 A-lines/s. The eye was imaged with 3 consecutive frames recorded at different depths so as to encompass within the imaging frames the anterior segment and the retina. Each frame had an axial length of 10 mm (in air). Each frame is composed of 1000 A-scans, and FRAME 1 covers a lateral width of 16 mm.
The sample light was delivered to the eye by a beam delivery system providing a telecentric scan with flat field. A modified commercial software package was used for the real-time acquisition and display of the OCT data (Bioptigen Inc, Research Triangle Park, NC). In post processing, the 3 frames were combined in a single OCT image and processed with a ray-tracing algorithm for correcting image distortions and obtaining biometric information. The ray-tracing algorithm was applied to a 10 mm wide rectangular region positioned at the center of FRAME 1 and FRAME 2.
Referring to FIG. 12, the ray-tracing algorithm works as follows. The images are first segmented at step 1202 to find the positions of the boundaries of the different ocular surfaces along each A-line (e.g. the anterior and posterior corneal surfaces, and the anterior and posterior lens surfaces). Ray-tracing is performed on each segment. The anterior corneal surface is undistorted, because the incident beam is parallel to the optical axis of the surface. No correction is therefore required for the anterior corneal surface. The anterior cornea is fit with a spherical or aspheric function at step 1204. Using the known incident beam direction 1206, measured undistorted curve fit of the anterior corneal surface as determined at step 1204, and the known group refractive index of the cornea 1208, the direction of the ray after refraction at the anterior corneal surface is calculated for each A-line by applying Snell's law (at step 1210). The posterior surface lies along that refracted ray. To find the true position of the posterior surface along this ray, the optical path length between the anterior and posterior corneal boundaries along the A-line (1207), obtained from the segmented image, is divided by the group refractive index of the cornea (1208). The resulting distance (determined at step 1209) is the length of the ray from the anterior corneal surface to the posterior corneal surface. At step 1214 the direction of the refracted ray (1206) and the length of the ray are used to determine the true position of the point of intersection of the ray with the posterior corneal surface. As shown by arrow 1212 this process is repeated for each A-line in the image to produce the corrected posterior corneal shape. The number of A-lines can be down-sampled to speed up the process. The posterior cornea is then fit a spherical or aspheric function, and the same ray-tracing method is repeated to determine the direction of the ray after refraction by the posterior corneal surface and the intersection of the ray with the anterior lens surface. This process (1204 to 1214) is repeated until all surfaces are corrected.
As shown in FIG. 11B, FRAME 1 and FRAME 2 were stitched together to form the composite image 920 while FRAME 3 is retained as is to provide an image 922 of the retina. The frames were precisely registered in depth according to the optical path difference of the delay lines. The black region 924 between the anterior segment and the retina is part of the vitreous cavity that was not imaged.
The light curves (930, 932, 934, 936, 038) in FIG. 11C represent the segmented surface and the dark curves (940, 942, 944, 946) represent the corrected ocular surfaces were calculated using the ray tracing procedure described above.
The method and system as described above can also be implemented using a swept-source (SS)-OCT instead of a spectral-domain (SD)-OCT. In such an embodiment, the nominal scan depth range of the SS-OCT system can be extended by the reference arm switch in a manner similar to that depicted in the timing diagram of FIG. 6, where the rising edge (704) of the line sync signal corresponds to the acquisition of one A-scan and the reference arm switch (712) is operated in the same manner as that described above for a SD-OCT system.
While the present invention has been described in detail with reference to specific embodiments thereof, it will be apparent to one skilled in the field that various changes, modifications and substitutions can be made, and equivalents employed without departing from, and are intended to be included within, the scope of the claims presented herein, as well as the claims presented in any subsequent US Utility Application based upon, and claiming priority from, the present US Provisional Application.
It will be understood that the invention disclosed and defined in this specification extends to all alternative combinations of two or more of the individual features mentioned or evident from the text or drawings. All of these different combinations constitute various alternative aspects of the invention.

## Claims

1. An intraocular imaging method comprising:
receiving image data representing image information of an ocular system from a plurality of images having a corresponding plurality of depth ranges, wherein at least two of the plurality of depth ranges overlap;
identifying a portion of at least one image that overlaps with a portion of at least one other image;
cropping said portion of at least one image; and
generating a composite image from the remainder of the plurality of images;
wherein at least one of the plurality of images is a subsurface image; and
wherein generating a composite image comprises forming from the image data a single image for the overlapping portion of the depth ranges.

2. The method of claim 1 wherein the plurality of depth ranges is three or more depth ranges.

3. The method of claim 2, wherein said at least two of the depth ranges that overlap are over an anterior segment of the ocular system and at least one of said depth ranges is over a retina of the ocular system.

4. The method of claim 3, wherein the plurality of depth ranges is at least four depth ranges, and at least one depth range is over a vitreous humor of the ocular system.

5. The method of claim 3, wherein said forming from the image data a single image for the overlapping portion of the depth range comprises removing artifacts from the image data.

6. The method of claim 3, wherein a first of said depth ranges that overlap has a zero delay location anterior to the cornea and a second one of said depth ranges that overlap has a zero delay location posterior to the crystalline lens.

7. The method of claim 6, wherein the first and second depth ranges overlap with each other.

8. The method of claim 3, wherein the depth range over the retina has a zero delay location near to the vitreo-retinal boundary.

9. An intraocular imaging system comprising:
imaging optics configured to obtain a plurality of images at a corresponding plurality of imaging ranges, at least two of the plurality of imaging ranges overlapping;
image processor circuitry configured in at least one of hardware and software to receive and process images to form, from the received plurality of images, a composite image comprising a single image for the overlapping portion of the imaging ranges;
wherein said single image is obtained by identifying a portion of at least one image corresponding to an overlapping depth range and cropping said portion; and
wherein at least one of the plurality of images is a subsurface image.

10. The intraocular imaging system of claim 9, wherein the plurality of different imaging ranges comprises at least three optical paths.

11. The intraocular imaging system of claim 10, wherein said overlapping image ranges comprise a first and a second image range and the plurality of images ranges comprises a third image range posterior to the first and second image ranges and spaced apart from the first and second image ranges a distance enabling the first and second image ranges to include a crystalline lens of a human eye and the third image range to include a retina of the eye.

12. The intraocular imaging system of claim 10, wherein said overlapping image ranges comprise a first and a second image range and the plurality of images ranges comprises a third image range posterior to the first and second image ranges and spaced apart from the first and second image ranges a distance enabling the first and second image ranges to include a cornea and crystalline lens of a human eye and the third image range to include a retina of the eye.

13. An intraocular imaging system comprising:
imaging optics forming an optical coherence tomography system configured to obtain a plurality of images at a corresponding plurality of different imaging ranges about respective zero delay locations, at least two of the plurality of imaging ranges overlapping;
an image output configured to receive image information at the plurality of different image ranges and output the image information in a machine readable form;
wherein said image output comprises identifying a portion of at least one image corresponding to overlapping depth ranges;
cropping said portion; and
wherein at least one of the plurality of images is a subsurface image.

14. The intraocular imaging system of claim 13, wherein the machine readable form comprises light signals and the image output is a connection suitable for transmitting said light signals of an optical fiber.

15. The intraocular imaging system of claim 13, configured so that the imaging ranges of said overlapping imaging ranges are locatable so that a zero delay location of a first of the overlapping imaging ranges is anterior to a cornea of a human eye and a zero delay location of a second of the overlapping imaging ranges is posterior to the crystalline lens of the eye.

16. The intraocular imaging system of claim 15, configured to image at a third imaging range, the third imaging range located so as to include the retina of the eye.

17. The intraocular imaging system of claim 16, configured to switch between the imaging ranges in about 300 microseconds.

18. The intraocular imaging system of claim 17, wherein the imaging optics comprises a light source with a center wavelength between 835 nm and 1300 nm and a full-width, half-maximum bandwidth between 50 nm and 200 run.

19. The intraocular imaging system of claim 13, wherein each imaging range is about 10 to 12 mm in air.