Apparatus and method for ranging and noise reduction of low coherence interferometry LCI and optical coherence tomography OCT signals by parallel detection of spectral bands

Information

  • Patent Grant
  • 8054468
  • Patent Number
    8,054,468
  • Date Filed
    Thursday, December 13, 2007
    16 years ago
  • Date Issued
    Tuesday, November 8, 2011
    13 years ago
Abstract
Apparatus and method for increasing the sensitivity in the detection of optical coherence tomography and low coherence interferometry (“LCI”) signals by detecting a parallel set of spectral bands, each band being a unique combination of optical frequencies. The LCI broad bandwidth source is split into N spectral bands. The N spectral bands are individually detected and processed to provide an increase in the signal-to-noise ratio by a factor of N. Each spectral band is detected by a separate photo detector and amplified. For each spectral band the signal is band pass filtered around the signal band by analog electronics and digitized, or, alternatively, the signal may be digitized and band pass filtered in software. As a consequence, the shot noise contribution to the signal is reduced by a factor equal to the number of spectral bands. The signal remains the same. The reduction of the shot noise increases the dynamic range and sensitivity of the system.
Description
FIELD OF THE INVENTION

The present invention relates to apparatus and a method for dramatically increasing the sensitivity in the detection of optical coherence tomography and low coherence interferometry signals by detecting a parallel set of spectral bands, each band being a unique combination of optical frequencies.


BACKGROUND OF THE ART

Two methods currently exist to implement depth ranging in turbid media. The first method is known as Low Coherence Interferometry (“LCI”). This method uses a scanning system to vary the reference arm length and acquire the interference signal at a detector and demodulating the fringe pattern to obtain the coherence envelope of the source cross correlation function. Optical coherence tomography (“OCT”) is a means for obtaining a two-dimensional image using LCI. OCT is described by Huang et al. in U.S. Pat. No. 5,321,501. Multiple variations on OCT have been patented, but, many suffer from less than optimal signal to noise ratio (“SNR”), resulting in non-optimal resolution, low imaging frame rates, and poor depth of penetration.


A second method for depth ranging in turbid media is known in the literature as spectral radar. In spectral radar the real part of the cross spectral density of sample and reference arm light is measured with a spectrometer. Depth profile information is encoded on the cross-spectral density modulation. Prior art for spectral radar is primarily found in the literature. U.S. Pat. No. 5,491,552 discloses a spectral radar invention which employs a variation of this technique. The use of spectral radar concepts to increase the signal to noise ratio of LCI and OCT have been described earlier. However, in this description, only the real part of the complex spectral density is measured and the method requires a large number of detector elements (˜2,000) to reach scan ranges on the order of a millimeter. It would be desirable to have a method that would allow for an arbitrary number of detector elements. Secondly, the previously described method uses a charge coupled device (“CCD”) to acquire the data, which requires a reduction of the reference arm power to approximately the same level as the sample arm power. As a result, large integration times are needed to achieve the SNR improvement. Since no carrier is generated, the 1/f noise will dominate the noise in this system. Power usage is a factor in such imaging techniques. For example in ophthalmic uses, only a certain number of milliwatts of power is tolerable before thermal damage can occur. Thus, boosting power is not feasible to increase SNR in such environments. It would be desirable to have a method of raising the SNR without appreciably increasing power requirements.


SUMMARY OF THE INVENTION

The present invention increases the SNR of LCI and OCT by splitting the LCI broad bandwidth source into N spectral bands. The N spectral bands are individually detected and processed to provide an increase in the SNR by a factor of N. This increase in SNR enables LCI or OCT imaging by a factor of N times faster, or alternatively allows imaging at the same speed with a source that has N times lower power. As a result, the present invention overcomes two of the most important shortcomings of LCI and OCT, i.e., source availability and scan speed. The factor N may reach more than 1,000, and allows construction of OCT and LCI systems that can be more than three orders of magnitude improved from OCT and LCI technology currently in practice.


The present invention enables a breakthrough in current data acquisition speeds and availability of sources for OCT. The shot noise reduction allows for much lower source powers, or much higher acquisition rates than current systems. Limitations in current data acquisition rates (approximately 4 frames/sec) are imposed by available source power. An increase in the sensitivity of the detection by a factor of 8 would allow real time imaging at a speed of 30 frames per second. An increase of the sensitivity by a factor of 1,000-2,000 would allow for the use of sources with much lower powers and higher spectral bandwidths which are readily available, cheaper to produce, and can generate broader bandwidths.


For ophthalmic applications of OCT, the efficient detection would allow for a significant increase of acquisition speed. The limitation in ophthalmic applications is the power that is allowed to enter the eye according to the ANSI standards (approximately 700 microwatts at 830 nm). Current data acquisition speed in ophthalmic applications is approximately 100-500 A-lines per second. The power efficient detection would allow for A-line acquisition rates on the order of 100,000 A-lines per second, or video rate imaging at 3,000 A-lines per image.


In summary, the present invention represents a greatly improved means for performing LCI and OCT, and as a result, would be of great interest to entities considering developing LCI and OCT diagnostic technologies for medical and non-medical applications.


Other features and advantages of the present invention will become apparent upon reading the following detailed description of embodiments of the invention, when taken in conjunction with the appended claims.





BRIEF DESCRIPTION OF THE DRAWINGS

The invention is illustrated in the drawings in which like reference characters designate the same or similar parts throughout the figures of which:



FIG. 1 is a schematic view of a conventional system.



FIG. 2 is a schematic view of a preferred embodiment of the parallel detection scheme for LCI.



FIG. 3 is a schematic view of a system with one detector array according to one embodiment of the present invention.



FIG. 4 is a detail of a probe.



FIG. 5 is a schematic view of separating unit in combination with two integrating CCD arrays for detection of the dual-balanced wavelength demultiplexed signal.



FIG. 6 is a schematic view of a preferred embodiment of a standalone system



FIG. 7 is a schematic view showing spectral separating into 2 bands.



FIG. 8 is a schematic of spectral separating into 4 bands. The spectral resolution preferably used for each detector is twice as coarse as in the case of multiplexing into 2 bands.



FIG. 9 is a schematic view of using beam recombination to provide one dimension of interference information along one dimension of a two-dimensional detector array, while performing wavelength separating along the other dimension of the two dimensional array.



FIG. 10 is a schematic view of a phase tracking system according to one embodiment of the present invention.



FIG. 11 is a flowchart depicting the reconstruction of LCI or OCT signal from wavelength bands.



FIG. 12 is a schematic view of a spectral domain OCT interferometer design with a source combining the spectra of several superluminescent sources.



FIG. 13 is a schematic view of a system with a four detector array.



FIG. 14 is a graph of a typical interference patter as a function of path length difference between the sample arm and reference arm.



FIG. 15 is an embodiment of a phase tracker system with an extended phase lock range.



FIGS. 15A-C are flow diagrams of a method.



FIG. 16 is a graph of frequency versus OCT power spectrum.



FIG. 17 is a graph of frequency versus amplitude spectrum subtracted from the shot noise (experimental data) for the N=I (dotted line) and N=⅓ (solid line) cases.



FIG. 18 is a graph of power density for the full spectrum as a function of frequency.



FIG. 19 is a graph after subtraction of the shot noise levels.



FIG. 20 is a graph after processing the signals.



FIG. 21 is a graph of the coherence envelope for the coherently summed channels.





DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Background


The present invention describes a hybrid method that implements aspects of LCI and OCT where the reference arm is scanned, and spectral radar, which does not require reference arm scanning. The signal in the detection arm of an OCT system is split into more than one spectral band before detection. Each spectral band is detected by a separate photo detector and amplified. For each spectral band the signal is band pass filtered around the signal band by analog electronics and digitized, or, alternatively, the signal may be digitized and band pass filtered in software. As a consequence, the shot noise contribution to the signal is reduced by a factor equal to the number of spectral bands. The signal remains the same. The reduction of the shot noise increases the dynamic range and sensitivity of the system. In the limit of many detectors, no ranging or reference arm scanning is required and the method is similar to spectral radar except that phase information of the cross spectral density is preserved.


Theory


In current OCT system, the recombined light of sample and reference arm is detected by a single detector. The signal is determined by the interference of light reflected from sample and reference arm. For a single object in the sample arm, the OCT signal is proportional to the real part of the Fourier transform of the source spectrum S(k),

R(Δz)∝Re∫exp(ikΔz)S(k)dk,  (1)

with k=2π/λ=ω/c the free space wave number and Δz=z−z′ the path length difference between reference and sample waves respectively. R(z) is the interference part of the signal detected at the photo detectors. The intensity I(z) backscattered from the sample arm at location z is proportional to the square of the envelope of R(z),

I(z)∝R2(z).


Converting path length difference Δz to time difference τ between arrival of reference and sample waves, τ=Δz/c and using that the time difference τ is given by measurement time t times twice the speed of the reference mirror v divided by the speed of light c, τ=2vt/c, we obtain,

R(t)∝Re∫exp(iωtv/c)S(ω)dω,  (2)

with t the measurement time.


Fourier transforming the depth profile R(t), the frequency spectrum of the signal is obtained,

|R(ω)|∝|S(ωc/v)|,  (3)


This demonstrates that each angular frequency of the light source or equivalently each wavelength of the source is represented at its own frequency in the measured interferometric signal. The depth profile information R(t) can be obtained from the complex cross spectral density R(ω) by a Fourier transform.


The complex cross spectral density can also be obtained by splitting the signal R(t) in several spectral bands by means of a dispersive or interferometric element. At each detector, only part of the complex cross spectral density is determined. Combining the cross spectral densities of each detector, the full spectral density of the signal is retrieved.


Thus, the same information can be obtained by separating spectral components to individual detectors. Combining the signal of all detectors in software or hardware would result in the same signal as obtained with a single detector. However, a careful analysis of the noise present at each frequency in the case of many individual detectors, reveals that the shot noise contribution is significantly lower, leading to a significant signal to noise improvement. The signal to noise improvement is linearly dependent on the number of spectral bands in which the signal is split. Thus, two spectral bands give a signal to noise improvement of a factor of 2, four spectral bands give a signal to noise improvement of a factor of 4, etc.


Signal to Noise Analysis of Optical Coherence Tomography Signals in the Frequency Domain.


For a single reflector in the sample arm, the interference fringe signal as a function of position is given by

R(Δz)∝Re∫exp(ikΔz)S(k)dk,

or equivalently as a function of time,

R(t)∝Re∫exp(iωtv/c)S(ω)dω


The coherence envelope peak value is found by setting Δz=0 or t=0;

Ipeak∝∫S(k)dk∝∫S(ω)dω


In the frequency domain, the Fourier transform of R(t) is given by

R(ω)=∫R(t)eiωtdt=∫Re∫exp(iω′tv/c)S(ω′)dω′eiωtdt=Sc/v)


The peak value is given by

Ipeak∝∫R(ω)dω=∫Sc/2v)


In terms of electrical power, the signal is defined as Ipeak2. In the frequency domain, the signal is,

Ipeak2∝[∫R(ω)dω]2=[∫Sc/2v)dω]2 or in terms of sample and reference arm power,
Ipeak2∝[∫√{square root over (Srefc/2v))}*√{square root over (Ssamplec/2v))}dω]2=a(z)[∫Srefc/2v)dω]2,

with Ssample(ωc/2v)=a(z)Sref(ωc/2v) and a(z) the reflectivity at z.


Thus, the signal is proportional to a(z)[∫Sref(ωc/2v)dω]2.


The total power Pref is given by Pref=∫Sref(ωc/2v)dω


The shot noise has a white noise distribution and the shot noise density is proportional to the total power on the detector

Nshot(ω)∝∫Srefc/2v)dω=Pref


The shot noise density is given in units [W2/Hz], [A2/Hz] or [V2/Hz]. The total shot noise that contributes to the noise is the Shot noise density multiplied with the bandwidth BW, Nshot=Pref*BW


Using the above expressions for the Signal and Noise, the SNR ratio for a single detector is given by

SNR∝a(z)[∫Srefc/2v)dω]2/Pref*BW=Psample/BW.


For a two detector configuration, where the spectrum is equally split over two detectors, the bandwidth BW per detector is half, as is the reference power. For an individual detector in the two detector configuration the signal is given by an integration over half the signal bandwidth,









a


(
z
)




[




0.5
*
BW






S
ref



(

ω






c
/
2






v

)





ω



]


2

.





The noise is given by 0.5*Pref*0.5*BW and the SNR is now








S





N





R







a


(
z
)




[




0.5





BW






S
ref



(

ω






c
/
2






v

)





ω



]


2

/
0.5







P
ref

*
0.5





BW


=


P
sample

/

BW
.






The SNR is the same as in the previous case where the full spectrum was detected by a single detector.


To evaluate the Signal to noise for two detectors simultaneously, the signals of both detectors are coherently added after digital or analog band pass filtering, i.e., after Fourier transforming of the signal R(t) the frequency components R(ω) within the signal band of each detector are added to form the total signal in the frequency domain. The signal is,









I
peak
2





a


(
z
)




[





0.5





BW






S
ref



(

ω






c
/
2






v

)





ω



+




0.5





BW






S
ref



(

ω






c
/
2






v

)





ω




]


2


=



a


(
z
)




[



BW





S
ref



(

ω






c
/
2






v

)





ω



]


2


,





which is equal to the signal if all the light was detected by a single detector.


The Noise is the sum of the noise at each detector. The individual detector noise was Nshot=0.5*Pref*0.5*BW. The sum of the noise of both detectors is Nshot=0.5*Pref*BW and the noise is half of what it was if the full spectrum or all the light was detected by a single detector. The SNR ratio in the case when each detector detects half the spectrum and the signal is coherently combined is,

SNR∝a(z)[∫Srefc/2v)dω]2/0.5*Pref*BW=2Psample/BW


Thus, the SNR is twice as high compared to if the full spectrum or all the light was detected by a single detector.


The gain in SNR is achieved because the shot noise has a white noise spectrum. An intensity present at the detector at frequency ω (or wavelength λ) contributes only to the signal at frequency ω, but the shot noise is generated at all frequencies. By narrowing the optical band width per detector, the shot noise contribution at each frequency is reduced, while the signal component remains the same.


Redundant SNR Arguments


The signal to noise can also be evaluated per frequency. The total SNR is given by,








S





N





R




[






S





N






R


(
ω
)












ω



]

2


=




a


(
z
)




P
ref

*
BW




[





S
ref



(

ω






c
/
2






v

)





ω



]


2






which defines a SNR density as

√{square root over (SNR(ω))}∝Sref(ωc/2v)√{square root over (a(z))}/√{square root over (Pref*BW)},

which demonstrates that the SNR density at a particular frequency depends on the total pass band (BW) and the reference power of the signal at the particular detector.


For two detectors, where the spectrum is equally split over two detectors, the bandwidth BW is half, as is the reference power. For an individual detector in the two detector configuration the SNR density is given by,

√{square root over (SNR(ω))}∝Sref(ωc/2v)√{square root over (a(z))}/√{square root over (0.5Pref*0.5BW)}


From the above equation, it is clear that the SNR density increases as the spectral bandwidth at the detector is decreased.


One embodiment of the system of the present invention is shown in FIG. 1. The basic embodiment is an interferometer with a source arm, a sample arm, a reference arm, and a detection arm with a spectral demultiplexing unit, multiple detectors, optional analog processing electronics, and A/D conversion of all signals. The processing and display unit has optionally digital band pass filtering, Digital Fast Fourier Transforms (“FFT's”), coherent combination of signals, and data processing and display algorithms. The detector array may be 1×N for simple intensity ranging and imaging, 2×N for dual balanced detection, 2×N for polarization and/or Doppler sensitive detection, or 4×N for combined dual balanced and polarization and/or Doppler sensitive detection. Alternatively, an M×N array may be used for arbitrary M to allow detection of transverse spatial information on the sample.


Sources


The source arm contains a spatially coherent source that is used to illuminate the interferometer with low-coherence light. The source temporal coherence length is preferably shorter than a few microns (range is about 0.5 μm-30 μm). Examples of sources include, but are not limited to, semiconductor optical amplifier, superluminescent diodes, light-emitting diodes, solid-state femtosecond sources, amplified spontaneous emission, continuum sources, thermal sources, combinations thereof and the like.


Interferometer


The sample arm collects light reflected from the specimen and is combined with the light from the reference arm to form interference fringes. The reference arm reflects light back to be combined with the reference arm. This action of beam splitting/recombining may be performed using a beam splitter (Michelson), or circulator(s) (Mach-Zehnder) or other means known to those skilled in the art for separating a beam into multiple paths and recombining these multiple beams in a manner that interference between the beams may be detected. The splitting may be accomplished in free space or by using passive fiber optic or waveguide components.


Sample Arm


For LCI applications, the sample arm may be terminated by an optical probe comprising an cleaved (angled, flat, or polished) optical fiber or free space beam. A lens (aspherical, gradient index, spherical, diffractive, ball, drum) may be used to focus the beam on or within the sample. Beam directing elements may also be contained within the probe (mirror, prism, diffractive optical element) to direct the focused beam to a desired position on the sample for OCT applications, the position of the beam may be changed on the sample as a function of time, allowing reconstruction of a two-dimensional image. Altering the position of the focused beam on the sample may be accomplished by a scanning mirror (such as, but not limited to, a galvanometer or piezoelectric actuator), electrooptic actuator, moving the optical fiber (rotating the optical fiber, or linearly translating the optical fiber). The sample arm probe may be a fiber optic probe that has an internally moving element where the motion is initiated at a proximal end of the probe and the motion is conveyed by a motion transducing means (such as, but not limited to, wire, guidewire, speedometer cable, spring, optical fiber and the like) to the distal end. The fiber optic probe may be enclosed in a stationary sheath which is optically transparent where the light exits the probe at the distal end.


Reference Arm Delay


A delay mechanism in the reference arm allows for scanning the length or the group velocity of the reference arm. This delay is produced by stretching ah optical fiber, free space translational scanning using a piezoelectric transducer, or via a grating based pulse shaping optical delay line. As opposed to traditional LCI or OCT systems described in prior art, the reference arm in the present invention does not necessarily need to scan over the full ranging depth in the sample, but is required to scan over at least a fraction of the ranging depth equal to one over the number of detectors. This feature of the present invention is fundamentally different from delay scanning schemes used in LCI and OCT systems disclosed in prior art. The delay line optionally has a mechanism for generating a carrier frequency such as an acoustooptic modulator, electrooptic phase modulator or the like. In order to reduce the scan range of the reference arm, the spectrum needs to be split into spectral bands according to a method that will be explained below.


Detection


In the detection arm a spectral demultiplexing unit demultiplexes the spectral components to separate detectors. The detectors may consist of photodiodes (such as, but not limited to, silicon, InGaAs, extended InGaAs, and the like). Alternatively, a one or two dimensional array of detectors (such as, but not limited to, photodiode array, CCD, CMOS array, active CMOS array, CMOS “smart pixel” arrays, combinations thereof and the like) may be employed for detection. Two detectors for each spectral band may be used for polarization sensitive detection following separation of the recombined light into orthogonal polarization eigenstates. Detector arrays may be 1×N for simple intensity ranging and imaging, 2×N for dual balanced detection, 2×N for polarization and/or Doppler sensitive detection, or 4×N for combined dual balanced and polarization and/or Doppler sensitive detection. Alternatively, an M×N array may be used for arbitrary M to allow detection of transverse spatial information on the sample.


Detector signals are amplified by Trans Impedance Amplifiers (“TIA's”), band pass filtered (digitally or using analog circuitry) and digitized by A/D converters and stored in a computer for further processing. Each detector is preferably configured to be shot noise limited. Shot noise limited detection is achieved by adjusting the intensity of light returned from the reference arm so that the shot noise dominates over the thermal noise of the resistor in the TIA and is higher than the relative intensity noise (“RIN”). Each detector is balanced for such dual noise reduction.


In a broad aspect of the present invention, the number of detectors, N, can range from 2-10,000 or more. A preferred range of N is about 8-10,000 detectors. In one preferred embodiment, eight detectors (or a number in that area) can provide real time, or close to real time, imaging. When more than about one hundred detectors are used, it is likely that a custom array would need to be constructed.


Alternatively, another means for detection includes an integrating one-dimensional or two-dimensional CCD array which is capable of obtaining images at a rate greater than 1/f noise (approximately 10 kHz) (see FIG. 8). In this case the TIA is not needed and the BPF can be implemented discretely following digitization. An additional modification to this method includes using a second CCD for balanced detection which allows increased reference arm power and acquisition speed due to reduction of RIN. This method could be implemented using a single CCD with dual-balanced detection enabled by either interleaving dual balanced rows of the array detector or by placing two similar CCD detectors adjacent to one another.


Processing


The signal of each detector is band pass filtered around the signal frequency, such as by FFT's. The signal of all detectors can be combined as explained hereinabove to obtain the complex cross spectral density in the frequency domain. By Fourier transform, the complex cross spectral density can be converted to a depth profile in the tissue. Several methods to process the complex spectral density to obtain depth profile information are included by reference.


System Integration


Processing of the multiple signals may be performed using an imaging or diagnostic console which performs basic operations including, mathematical image reconstruction, display, data storage. Alternatively, another embodiment, shown in FIG. 2, envisions a standalone detection and processing system that may be connected to OCT and/or LCI systems already in use. In this case, the detector and digitization may be performed in the standalone unit. The input to the standalone unit would be the light combined from both reference and sample arms. The output of the system would be an interferometric signal similar to previous OCT or LCI console inputs, but with increased SNR. The standalone unit would contain the means for splitting the wavelengths into spectral bands, multiple detectors, analog electronics, including TIA's and means for reconstructing the interferometric signal. The means for reconstructing the interferometric signal would include either analog or digital means where the analog means includes band pass filters (“BPF's”), and analog means for adding the individual interferograms from each wavelength band. Digital means would include an analog to digital converter, CPU capable of recombining the interferograms from each spectral band into a single full bandwidth interferometric signal. The reconstructed interferogram may be then the output of the standalone system or alternatively, the reconstructed interferograms demodulated signal may be used as the input to the pre-existing system console.


Scan Range of the Reference Arm.


The ranging depth in the sample is determined by the resolution with which the cross spectral density can be determined. In a method using a single detector the spectral resolution of the complex spectral density is determined by the scan range of the reference arm. The larger the scan range, the higher the spectral resolution and the larger the ranging depth in the sample. In a system with a spectral demultiplexing unit and multiple detectors, the resolution of the cross spectral density is a combination of reference arm scan range and spectral demultiplexing characteristics.


Any suitable wavelength band shape may be used for demultiplexing. For arbitrary spectral band shapes, the scan range of the reference arm is determined by the maximum path length delay that is needed to completely resolve the spectral components in each band. In cases where the wavelength band is determined by successive non-overlapping optical bandpass filters, a full scan length is needed and the SNR improvement is achieved by decreasing the width of the BPF for each spectral bands.


For instance, in one preferred embodiment, as depicted in FIG. 3, the spectral demultiplexing unit can split the spectrum into two bands where each band consists of a set of narrow spectra in a comb-like structure. Interleaving the comb-like spectral bands of each detector gives back a continuous spectrum. The resolution needed to resolve the spectrum at an individual detector is half of what it would need to be in a single detector system, and thus the scan range of the reference arm can be reduced by a factor of two, while maintaining the same ranging depth in the sample. In an alternative embodiment, the spectral demultiplexing unit can be in the reference arm. In FIG. 4 an example is shown for splitting up the spectrum in four spectral bands. In this example the scan range of the reference arm can be reduced by a factor of four while maintaining the same ranging depth in the sample.


Embodiments of the Demultiplexing Filter


Several techniques are known to demultiplex or disperse the spectrum. One method would use a grating and a micro lens array to focus spectral components onto individual detectors. A second method would use prisms instead of a grating. A third method would use a grating and an addressable mirror array (such as, but not limited to, a “MEMS” mirror or digital light processing “DLP” apparatus or the like) to direct spectral components to individual detectors. A fourth method would use a linear array of optical filters prior to the array of individual detectors. A fifth method would use waveguides etched into a material or manufactured from fiber optic components to generate a pattern with the desired filter action. As an example, in FIG. 4 an embodiment of a wave guide filter is drawn that will split the spectrum into bands. A sixth method would use arrayed waveguide gratings (“AWG”) to create the interleaved or arbitrary spectral bands.


Relative Intensity Noise


One of the noise terms that are present at the detectors is relative intensity noise (“RIN”) or Bose-Einstein noise. For a system where the sample arm optical power is negligible compared to the reference arm optical power at the detectors, RIN will become dominant for spectral widths less than a few nanometers at trans impedance amplifier bandwidths of 1 MHz. For many detector configurations, the spectral width at each detector will be smaller than a few nanometers, and the relative intensity noise will dominate the overall system noise. Thus, balanced detection needs to be implemented to eliminate the RIN. Several methods known in the art exist to implement balanced detection. One method will be discussed in more detail. Light from the reference arm and sample arm is incident on a grating at slightly different angles and reflected and focused onto a linear N×M photo detector array. Along the N direction (column) of the array, wavelength is encoded. Along the M direction (row) of the array, the interference pattern of the sample and reference arm at a particular wavelength is recorded. Since sample and reference arm light were incident at slightly different angles, a pattern of interference maxima and minima will be present in the column direction. Balanced detection can be implemented by subtracting diode signals that are exactly out of phase with respect to the maxima and minima pattern. Alternatively, balanced detection can be implemented by measuring the amplitude of the interference pattern in the column direction which may be accomplished by subtracting the maxima or the interference pattern from the minima of the interference pattern along the column.


Signal Processing to Reconstruct the Signal after Spectral Demultiplexing and Detection.


Two cases will be discussed as nonlimiting illustrations of the present invention, firstly the case of continuous spectral bands (blocks), and secondly the comb-like spectral bands as depicted in FIGS. 2 and 3.


Case A: Continuous Spectral Bands.


The detection arm light is split into N spectral blocks, where each spectral block contains the intensity between two optical frequencies,







B
N

=




ω
N


ω

N
+
1







S
ref



(

ω






c
/
2






v

)





ω







The signal for the full spectral width is obtained by an FFT of the signal in each band, an optional compensation of dispersion and other corrections to the phase and amplitude of each Fourier component to optimize the signal and to correct the spectral density for side lobe reduction, addition of the complex FFT spectra, and inverse FFT on the added complex FFT spectrum, optionally with data reduction before the inverse FFT, to obtain the optionally demodulated function R(t), which is the interferometric response for a depth scan with the full source spectrum.


Case B: Comb Like Spectral Bands and the Reconstruction of the Full Depth Range in the Sample Arm from Reduced Reference Arm Scans.


The following discussion describes the principle of reconstruction of the full depth range in the sample arm from reduced reference arm scans. The procedure will be explained in the case of demultiplexing the spectrum in two spectral bands. The method can be expanded for demultiplexing into many spectral bands.


The signal at the detector for a single detector system is given by R(t). The depth range in the sample is given by the measurement time T of a single A-line (depth profile) times the group velocity generated by the reference arm delay line,

zrange=vgT


The smallest resolvable frequency after an FFT is given by 1/T, which gives a smallest resolvable angular frequency Δω=2π/T. The filter as depicted in FIG. 4 splits the signal into two bands with peaks at ω=ω0, ω0+2Δω, ω0+4Δω, etc. and ω=ω0+Δω, ω0+3Δω, etc., respectively.


B1(t) and B2 (t) are the signals in band one and two respectively. The signal in spectral bands one and two after Fourier transform are given by B1(ω)=R(ω)cos2(ωT/4) and B2(ω)=R(ω)sin2(ωT/4).


This product in the Fourier domain can also be written as a convolution in the time domain. Assuming the signals periodic with time T, the signals B1(t) and B2(t) are given by B1(t)=R(t)+R(t+T/2) and B2 (t)=R(t)−R(t+T/2).


Using the above equations, the signal R(t) from t=0 to t=T can be reconstructed from the signals B1(t) and B2 (t) recorded from t=0 to t=T/2 by writing, R(t)=B1(t)+B2 (t) and R(t+T/2=B1(t)−B2(t) for 0<t<T/2. For higher N>2, the identical procedure is performed such that R(t) is reconstructed from B1 to BN.


This demonstrates that the signals B1(t) and B2 (t) only need to be recorded over half the depth range zrange. Thus, the depth ranging in the reference arm can be reduced by a factor of 2 while the ranging depth in the sample remains the same. If the signal is split into more spectral bands, like shown in FIG. 3, a similar procedure as described above allows reduction of the depth scan in the reference arm by a factor of N, while the ranging depth in the sample remains the same, and N the number of spectral bands.


A flow diagram of the procedure described above is given in FIG. 7.


Case B2. Limit of Large Number of Spectral Bands


In the limit of a large number of spectral bands,







N


L
λ


,





the optical path length change in the reference arm approaches that of a wavelength, λ. In this limit, only a phase change across one wavelength is needed for reconstructing the entire axial scan over length L. In this case, the reference arm path delay may be accomplished by using any of the aforementioned means for scanning the reference arm delay. Other preferred methods include insertion of an electrooptic modulator, acoustooptic modulator or phase control rapidly scanning optical delay line (“RSOD”) in the reference arm path to impart the path length delay of one wavelength. Also in this case, the wavelength demultiplexing unit does not separate the wavelengths into a comb pattern, but demultiplexes the spectrum into unique optical frequencies, with each frequency detected by a single detector.


Case C. Fourier Domain Reconstruction for Arbitrary Wavelength Patterns


As opposed to reconstruction of the LCI or OCT signal in the time or space domains, the signal may be reconstructed in the Fourier domain by adding the complex spectral components for each wavelength band to compose the Fourier transform of the LCI or OCT signal. Alterations of the phase for each Fourier component may be needed in some circumstances to correct for minimization of reference arm delay length.


Reconstruction of the Image or One Dimensional Axial Scan


Following reconstruction of the LCI or OCT signal in the real domain, the axial reflectivity may be determined by demodulating the reconstructed LCI or OCT signal. Means for demodulation include, multiplication by a sinusoid and low pass filtering, envelope demodulation using envelope detection, square law demodulation and low pass filtering, quadrature demodulation followed by FIR, IIR filtering, or low pass filtering. In addition, known to those skilled in the art, is reconstruction of Stokes vectors (polarization) and flow from these LCI or OCT signals. Following reconstruction and demodulation, the data may be displayed in one or two-dimensional format (image) for interpretation and ultimately diagnosis of a tissue condition or defect in a medium. If one reconstructs the LCI or OCT signal in the Fourier domain, the reconstructed signal in the Fourier domain can be demodulated in the Fourier domain by shifting the Fourier spectrum and performing an inverse Fourier transform. As a result, the complex signal in the real domain (quadrature signal) is then reconstructed into axial reflectivity information by computing the amplitude of the real portion of the quadrature signal. The complex component is used for computing polarization or flow information. Alternatively, if the signal is reconstructed in the Fourier domain, it can be directly inverse Fourier transformed into the real domain and undergo the aforementioned processing described for the reconstructed real domain signals.


Advantages


The present invention reduces shot noise which allows for much lower source powers, or much higher acquisition rates than current systems. The increased detection sensitivity allows for real time imaging. Such imaging speed can help practitioners where motion artifacts are a continuing problem, such as in gastrointestinal, ophthalmic and arterial imaging environments. By increasing the frame rate while maintaining or improving the signal to noise ratio such artifacts can be minimized.


The invention will be further described in connection with the following examples, which are set forth for purposes of illustration only.


EXAMPLE

The method was verified in the lab by the following experiment.


In the existing OCT system, the shot noise power spectrum as determined from the spectral density due to the reference arm optical power was measured. Then ⅔ of the spectrum from the reference arm was blocked, and experimentally it was verified that the shot noise power spectrum was reduced by a factor of three, thus demonstrating that the shot noise is reduced by a factor of 3 if the spectrum is split in three spectral bands (see FIG. 5). The upper curve (gray dotted line) shows the power spectrum for the OCT signal with one detector. For the lower curve (solid line), the spectrum was limited by ⅓ with a corresponding factor of 3 improvement in signal to noise ratio. This data was generated by experiment, blocking ⅔ of the spectrum in a grating-based double-passed pulse shaping rapidly scanning optical delay line.


An object with low reflectivity was inserted in the sample arm. Using the full spectral width of the source, the power spectrum of the interference between sample and reference arm light was determined in the lower half of the spectral density. Then the upper part of the source spectrum was blocked in the reference arm, and it was verified that the lower ⅓ of the power spectrum of the interference between sample and reference arm light had the same magnitude as in the previous measurement (see FIG. 6). This figure demonstrates that the signal amplitude is equal for the N=1 and N=⅓ cases where they overlap. The result of equal amplitude signal for N=⅓ case and the 3-fold lower noise for the N=⅓ case (see FIG. 2) demonstrates that splitting into N wavelength bands increases the SNR by a factor of N.


This demonstrates that when the light in the detection arm is split in two spectral bands, the spectral density of the interference between sample and reference arm light within the spectral bandwidth of a single detector is unchanged. Combined with the measurement that showed a reduction in the shot noise power spectrum, the conclusion is that a reduction of shot noise can be realized by splitting the detection arm light in separate spectral bands.


Although only a few exemplary embodiments of this invention have been described in detail above, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. Accordingly, all such modifications are intended to be included within the scope of this invention as defined in the following claims. It should further be noted that any patents, applications and publications referred to herein are incorporated by reference in their entirety.

Claims
  • 1. An apparatus for optical imaging, comprising: a) an interferometer;b) a first arrangement providing at least one electro-magnetic radiation to the interferometer and a first signal, and generating a path length difference that is a fraction of a ranging depth of the interferometer;c) a spectral separating second arrangement that receives a second signal from the interferometer and splits the second signal into a further signal having a plurality of optical frequencies, wherein the spectral separating unit obtains the second signal based on information provided by the first signal; andd) a plurality of detectors, each detector configured to detect at least a portion of the optical frequencies received from the spectral separating second arrangement.
  • 2. The apparatus according to claim 1, wherein the first arrangement comprises a fiber stretching arrangement.
  • 3. The apparatus according to claim 1, wherein the first arrangement comprises a piezoelectric transducer configured to perform free space translational scanning.
  • 4. The apparatus according to claim 1, wherein the first arrangement comprises a phase control optical delay line.
  • 5. The apparatus according to claim 1, wherein the first arrangement scans over at least a fraction of the ranging depth equal to one over the number of detectors.
  • 6. The apparatus according to claim 1, wherein the first arrangement further comprises a carrier frequency generator which is configured to facilitate carrier frequencies for the second signal.
  • 7. The apparatus according to claim 1, wherein the first arrangement comprises an acoustic modulator.
  • 8. The apparatus according to claim 1, wherein the first arrangement comprises an electro-optic modulator.
  • 9. The apparatus according to claim 1, wherein the first arrangement comprises a phase control RSOD.
  • 10. The apparatus according to claim 1, wherein the first arrangement produces a delay that has a distance that is less than a range of a sample arm.
  • 11. The apparatus according to claim 1, wherein the spectral separating second arrangement comprises the at least one of (i) the addressable mirror array or (ii) the waveguide filter.
  • 12. The apparatus according to claim 1, wherein the spectral separating second arrangement splits the signal into the bands.
  • 13. The apparatus according to claim 1, wherein the detectors are provided in a form of a two-dimensional array.
  • 14. The apparatus according to claim 1, wherein the sample is scanned in a series of simultaneous illuminations of substantially all areas of the sample.
  • 15. The apparatus according to claim 1, wherein the spectral separating second arrangement comprises a polarization separating unit.
  • 16. The apparatus according to claim 1, wherein the spectral separating second arrangement at least one of: i. comprises at least one of (i) an addressable mirror array, or (ii) a waveguide filter, orii. splits the signal into a plurality of bands, whereby at least one of the bands comprises spectra that has a comb-like structure.
  • 17. The apparatus according to claim 1, wherein the sample is scanned in a series of simultaneous illuminations of less than all of areas of the sample.
  • 18. The apparatus according to claim 1, wherein the detectors include at least three detectors.
CROSS-REFERENCE TO RELATED APPLICATION(S)

The present application is a divisional of U.S. Patent application Ser. No. 10/501,276, filed Jul. 9, 2004, which issued as U.S. Pat. No. 7,355,716 on Apr. 8, 2008, which is U.S. National Phase of International Application No. PCT/US03/02349 filed Jan. 24, 2003. This application also claims benefit of copending U.S. provisional patent application No. 60/351,904, filed Jan. 24, 2002, entitled APPARATUS AND METHOD FOR RANGING AND SHOT NOISE REDUCTION OF LOW COHERENCE INTERFEROMETRY (LCI) AND OPTICAL COHERENCE TOMOGRAPHY (OCT) SIGNALS BY PARALLEL DETECTION OF SPECTRAL BANDS, and copending U.S. application Ser. No. 10/136,813, filed Apr. 30, 2002, entitled METHOD AND APPARATUS FOR IMPROVING IMAGE CLARITY AND SENSITIVITY IN OPTICAL COHERENCE TOMOGRAPHY USING DYNAMIC FEEDBACK TO CONTROL FOCAL PROPERTIES AND COHERENCE GATING, both commonly assigned to the assignee of the present application. The disclosures of all these applications are incorporated herein by reference in their entireties.

US Referenced Citations (472)
Number Name Date Kind
2339754 Brace Jan 1944 A
3090753 Matsuszak et al. May 1963 A
3601480 Randall Aug 1971 A
3856000 Chikama Dec 1974 A
3872407 Hughes Mar 1975 A
3941121 Olinger Mar 1976 A
3973219 Tang et al. Aug 1976 A
3983507 Tang et al. Sep 1976 A
4030827 Delhaye et al. Jun 1977 A
4030831 Gowrinathan Jun 1977 A
4140364 Yamashita et al. Feb 1979 A
4141362 Wurster Feb 1979 A
4224929 Furihata Sep 1980 A
4295738 Meltz et al. Oct 1981 A
4300816 Snitzer et al. Nov 1981 A
4303300 Pressiat et al. Dec 1981 A
4428643 Kay Jan 1984 A
4479499 Alfano Oct 1984 A
4533247 Epworth Aug 1985 A
4585349 Gross et al. Apr 1986 A
4601036 Faxvog et al. Jul 1986 A
4607622 Fritch et al. Aug 1986 A
4631498 Cutler Dec 1986 A
4639999 Daniele Feb 1987 A
4650327 Ogi Mar 1987 A
4734578 Horikawa Mar 1988 A
4744656 Moran et al. May 1988 A
4751706 Rohde et al. Jun 1988 A
4763977 Kawasaki et al. Aug 1988 A
4770492 Levin et al. Sep 1988 A
4827907 Tashiro et al. May 1989 A
4834111 Khanna et al. May 1989 A
4868834 Fox et al. Sep 1989 A
4890901 Cross, Jr. Jan 1990 A
4892406 Waters Jan 1990 A
4905169 Buican et al. Feb 1990 A
4909631 Tan et al. Mar 1990 A
4925302 Cutler May 1990 A
4928005 Lefèvre et al. May 1990 A
4940328 Hartman Jul 1990 A
4965441 Picard Oct 1990 A
4965599 Roddy et al. Oct 1990 A
4966589 Kaufman Oct 1990 A
4984888 Tobias et al. Jan 1991 A
4993834 Carlhoff et al. Feb 1991 A
4998972 Chin et al. Mar 1991 A
5039193 Snow et al. Aug 1991 A
5040889 Keane Aug 1991 A
5045936 Lobb et al. Sep 1991 A
5046501 Crilly Sep 1991 A
5065331 Vachon et al. Nov 1991 A
5085496 Yoshida et al. Feb 1992 A
5120953 Harris Jun 1992 A
5121983 Lee Jun 1992 A
5127730 Brelje et al. Jul 1992 A
5197470 Helfer et al. Mar 1993 A
5202745 Sorin et al. Apr 1993 A
5202931 Bacus et al. Apr 1993 A
5208651 Buican May 1993 A
5212667 Tomlinson et al. May 1993 A
5214538 Lobb May 1993 A
5217456 Narciso, Jr. Jun 1993 A
5228001 Birge et al. Jul 1993 A
5241364 Kimura et al. Aug 1993 A
5248876 Kerstens et al. Sep 1993 A
5250186 Dollinger et al. Oct 1993 A
5251009 Bruno Oct 1993 A
5262644 Maguire Nov 1993 A
5275594 Baker Jan 1994 A
5281811 Lewis Jan 1994 A
5283795 Fink Feb 1994 A
5291885 Taniji et al. Mar 1994 A
5293872 Alfano et al. Mar 1994 A
5293873 Fang Mar 1994 A
5302025 Kleinerman Apr 1994 A
5304173 Kittrell et al. Apr 1994 A
5304810 Amos Apr 1994 A
5305759 Kaneko et al. Apr 1994 A
5317389 Hochberg et al. May 1994 A
5318024 Kittrell et al. Jun 1994 A
5321501 Swanson et al. Jun 1994 A
5348003 Caro Sep 1994 A
5353790 Jacques et al. Oct 1994 A
5383467 Auer et al. Jan 1995 A
5394235 Takeuchi et al. Feb 1995 A
5404415 Mori et al. Apr 1995 A
5411016 Kume et al. May 1995 A
5419323 Kittrell et al. May 1995 A
5424827 Horwitz et al. Jun 1995 A
5439000 Gunderson et al. Aug 1995 A
5441053 Lodder et al. Aug 1995 A
5450203 Penkethman Sep 1995 A
5454807 Lennox et al. Oct 1995 A
5459325 Hueton et al. Oct 1995 A
5459570 Swanson et al. Oct 1995 A
5465147 Swanson Nov 1995 A
5486701 Norton et al. Jan 1996 A
5491524 Hellmuth et al. Feb 1996 A
5491552 Knuttel Feb 1996 A
5522004 Djupsjobacka et al. May 1996 A
5526338 Hasman et al. Jun 1996 A
5555087 Miyagawa et al. Sep 1996 A
5562100 Kittrell et al. Oct 1996 A
5565983 Barnard et al. Oct 1996 A
5565986 Knüttel Oct 1996 A
5566267 Neuberger Oct 1996 A
5583342 Ichie Dec 1996 A
5590660 MacAulay et al. Jan 1997 A
5600486 Gal et al. Feb 1997 A
5601087 Gunderson et al. Feb 1997 A
5621830 Lucey et al. Apr 1997 A
5623336 Raab et al. Apr 1997 A
5635830 Itoh Jun 1997 A
5649924 Everett et al. Jul 1997 A
5697373 Richards-Kortum et al. Dec 1997 A
5698397 Zarling et al. Dec 1997 A
5710630 Essenpreis et al. Jan 1998 A
5716324 Toida Feb 1998 A
5719399 Alfano et al. Feb 1998 A
5730731 Mollenauer et al. Mar 1998 A
5735276 Lemelson Apr 1998 A
5740808 Panescu et al. Apr 1998 A
5748318 Maris et al. May 1998 A
5748598 Swanson et al. May 1998 A
5752518 McGee et al. May 1998 A
5784352 Swanson et al. Jul 1998 A
5785651 Kuhn et al. Jul 1998 A
5795295 Hellmuth et al. Aug 1998 A
5801826 Williams Sep 1998 A
5801831 Sargoytchev et al. Sep 1998 A
5803082 Stapleton et al. Sep 1998 A
5807261 Benaron et al. Sep 1998 A
5810719 Toida Sep 1998 A
5817144 Gregory Oct 1998 A
5836877 Zavislan et al. Nov 1998 A
5840023 Oraevsky et al. Nov 1998 A
5840075 Mueller et al. Nov 1998 A
5842995 Mahadevan-Jansen et al. Dec 1998 A
5843000 Nishioka et al. Dec 1998 A
5843052 Benja-Athon Dec 1998 A
5847827 Fercher Dec 1998 A
5862273 Pelletier Jan 1999 A
5865754 Sevick-Muraca et al. Feb 1999 A
5867268 Gelikonov et al. Feb 1999 A
5871449 Brown Feb 1999 A
5872879 Hamm Feb 1999 A
5877856 Fercher Mar 1999 A
5887009 Mandella et al. Mar 1999 A
5892583 Li Apr 1999 A
5910839 Erskine et al. Jun 1999 A
5912764 Togino Jun 1999 A
5920373 Bille Jul 1999 A
5920390 Farahi et al. Jul 1999 A
5921926 Rolland et al. Jul 1999 A
5926592 Harris et al. Jul 1999 A
5949929 Hamm Sep 1999 A
5951482 Winston et al. Sep 1999 A
5955737 Hallidy et al. Sep 1999 A
5956355 Swanson et al. Sep 1999 A
5968064 Selmon et al. Oct 1999 A
5975697 Podoleanu et al. Nov 1999 A
5983125 Alfano et al. Nov 1999 A
5987346 Benaron et al. Nov 1999 A
5991697 Nelson et al. Nov 1999 A
5994690 Kulkarni et al. Nov 1999 A
5995223 Power Nov 1999 A
6002480 Izatt et al. Dec 1999 A
6004314 Wei et al. Dec 1999 A
6006128 Izatt et al. Dec 1999 A
6007996 McNamara et al. Dec 1999 A
6010449 Selmon et al. Jan 2000 A
6014214 Li Jan 2000 A
6016197 Krivoshlykov Jan 2000 A
6020963 DiMarzio et al. Feb 2000 A
6025956 Nagano et al. Feb 2000 A
6033721 Nassuphis Mar 2000 A
6037579 Chan et al. Mar 2000 A
6044288 Wake et al. Mar 2000 A
6045511 Ott et al. Apr 2000 A
6048742 Weyburne et al. Apr 2000 A
6053613 Wei et al. Apr 2000 A
6069698 Ozawa et al. May 2000 A
6078047 Mittleman et al. Jun 2000 A
6091496 Hill Jul 2000 A
6091984 Perelman et al. Jul 2000 A
6094274 Yokoi Jul 2000 A
6107048 Goldenring et al. Aug 2000 A
6111645 Tearney et al. Aug 2000 A
6117128 Gregory Sep 2000 A
6120516 Selmon et al. Sep 2000 A
6134003 Tearney et al. Oct 2000 A
6134010 Zavislan Oct 2000 A
6134033 Bergano et al. Oct 2000 A
6141577 Rolland et al. Oct 2000 A
6151522 Alfano et al. Nov 2000 A
6159445 Klaveness et al. Dec 2000 A
6160826 Swanson et al. Dec 2000 A
6161031 Hochman et al. Dec 2000 A
6166373 Mao Dec 2000 A
6174291 McMahon et al. Jan 2001 B1
6175669 Colston et al. Jan 2001 B1
6185271 Kinsinger Feb 2001 B1
6191862 Swanson et al. Feb 2001 B1
6193676 Winston et al. Feb 2001 B1
6198956 Dunne Mar 2001 B1
6201989 Whitehead et al. Mar 2001 B1
6208415 De Boer et al. Mar 2001 B1
6208887 Clarke Mar 2001 B1
6245026 Campbell et al. Jun 2001 B1
6249349 Lauer Jun 2001 B1
6249381 Suganuma Jun 2001 B1
6249630 Stock et al. Jun 2001 B1
6263234 Engelhardt et al. Jul 2001 B1
6264610 Zhu Jul 2001 B1
6272376 Marcu et al. Aug 2001 B1
6274871 Dukor et al. Aug 2001 B1
6282011 Tearney et al. Aug 2001 B1
6297018 French et al. Oct 2001 B1
6301048 Cao et al. Oct 2001 B1
6308092 Hoyns Oct 2001 B1
6324419 Guzelsu et al. Nov 2001 B1
6341036 Tearney et al. Jan 2002 B1
6353693 Kano et al. Mar 2002 B1
6359692 Groot Mar 2002 B1
6374128 Toida et al. Apr 2002 B1
6377349 Fercher Apr 2002 B1
6384915 Everett et al. May 2002 B1
6393312 Hoyns May 2002 B1
6394964 Sievert, Jr. et al. May 2002 B1
6396941 Bacus et al. May 2002 B1
6421164 Tearney et al. Jul 2002 B2
6437867 Zeylikovich et al. Aug 2002 B2
6441892 Xiao et al. Aug 2002 B2
6441959 Yang et al. Aug 2002 B1
6445485 Frigo et al. Sep 2002 B1
6445939 Swanson et al. Sep 2002 B1
6445944 Ostrovsky Sep 2002 B1
6459487 Chen et al. Oct 2002 B1
6463313 Winston et al. Oct 2002 B1
6469846 Ebizuka et al. Oct 2002 B2
6475159 Casscells et al. Nov 2002 B1
6475210 Phelps et al. Nov 2002 B1
6477403 Eguchi et al. Nov 2002 B1
6485413 Boppart et al. Nov 2002 B1
6485482 Belef Nov 2002 B1
6501551 Tearney et al. Dec 2002 B1
6501878 Hughes et al. Dec 2002 B2
6516014 Sellin et al. Feb 2003 B1
6517532 Altshuler et al. Feb 2003 B1
6538817 Farmer et al. Mar 2003 B1
6540391 Lanzetta et al. Apr 2003 B2
6549801 Chen et al. Apr 2003 B1
6552796 Magnin et al. Apr 2003 B2
6556305 Aziz et al. Apr 2003 B1
6556853 Cabib et al. Apr 2003 B1
6558324 Von Behren et al. May 2003 B1
6564087 Pitris et al. May 2003 B1
6564089 Izatt et al. May 2003 B2
6567585 Harris May 2003 B2
6593101 Richards-Kortum et al. Jul 2003 B2
6611833 Johnson et al. Aug 2003 B1
6615071 Casscells, III et al. Sep 2003 B1
6622732 Constantz Sep 2003 B2
6654127 Everett et al. Nov 2003 B2
6657730 Pfau et al. Dec 2003 B2
6658278 Gruhl Dec 2003 B2
6680780 Fee Jan 2004 B1
6685885 Nolte et al. Feb 2004 B2
6687007 Meigs Feb 2004 B1
6687010 Horii et al. Feb 2004 B1
6687036 Riza Feb 2004 B2
6692430 Adler Feb 2004 B2
6701181 Tang et al. Mar 2004 B2
6721094 Sinclair et al. Apr 2004 B1
6738144 Dogariu et al. May 2004 B1
6741355 Drabarek May 2004 B2
6757467 Rogers Jun 2004 B1
6790175 Furusawa et al. Sep 2004 B1
6806963 Wälti et al. Oct 2004 B1
6816743 Moreno et al. Nov 2004 B2
6831781 Tearney et al. Dec 2004 B2
6839496 Mills et al. Jan 2005 B1
6882432 Deck Apr 2005 B2
6900899 Nevis May 2005 B2
6903820 Wang Jun 2005 B2
6909105 Heintzmann et al. Jun 2005 B1
6949072 Furnish et al. Sep 2005 B2
6961123 Wang et al. Nov 2005 B1
6980299 de Boer Dec 2005 B1
6996549 Zhang et al. Feb 2006 B2
7006231 Ostrovsky et al. Feb 2006 B2
7006232 Rollins et al. Feb 2006 B2
7019838 Izatt et al. Mar 2006 B2
7027633 Foran et al. Apr 2006 B2
7061622 Rollins et al. Jun 2006 B2
7072047 Westphal et al. Jul 2006 B2
7075658 Izatt et al. Jul 2006 B2
7099358 Chong et al. Aug 2006 B1
7113288 Fercher Sep 2006 B2
7113625 Watson et al. Sep 2006 B2
7130320 Tobiason et al. Oct 2006 B2
7139598 Hull et al. Nov 2006 B2
7142835 Paulus Nov 2006 B2
7148970 De Boer Dec 2006 B2
7177027 Hirasawa et al. Feb 2007 B2
7190464 Alphonse Mar 2007 B2
7230708 Lapotko et al. Jun 2007 B2
7231243 Tearney et al. Jun 2007 B2
7236637 Sirohey et al. Jun 2007 B2
7242480 Alphonse Jul 2007 B2
7267494 Deng et al. Sep 2007 B2
7272252 De La Torre-Bueno et al. Sep 2007 B2
7304798 Izumi et al. Dec 2007 B2
7330270 O'Hara et al. Feb 2008 B2
7336366 Choma et al. Feb 2008 B2
7342659 Horn et al. Mar 2008 B2
7355716 De Boer et al. Apr 2008 B2
7355721 Quadling et al. Apr 2008 B2
7359062 Chen et al. Apr 2008 B2
7366376 Shishkov et al. Apr 2008 B2
7382809 Chong et al. Jun 2008 B2
7391520 Zhou et al. Jun 2008 B2
7458683 Chernyak et al. Dec 2008 B2
7530948 Seibel et al. May 2009 B2
7539530 Caplan et al. May 2009 B2
7609391 Betzig Oct 2009 B2
7630083 de Boer et al. Dec 2009 B2
7643152 de Boer et al. Jan 2010 B2
7643153 de Boer et al. Jan 2010 B2
7646905 Guittet et al. Jan 2010 B2
7649160 Colomb et al. Jan 2010 B2
7664300 Lange et al. Feb 2010 B2
7733497 Yun et al. Jun 2010 B2
7782464 Mujat et al. Aug 2010 B2
7805034 Kato et al. Sep 2010 B2
20010036002 Tearney et al. Nov 2001 A1
20010047137 Moreno et al. Nov 2001 A1
20020016533 Marchitto et al. Feb 2002 A1
20020024015 Hoffmann et al. Feb 2002 A1
20020048025 Takaoka Apr 2002 A1
20020048026 Isshiki et al. Apr 2002 A1
20020052547 Toida May 2002 A1
20020057431 Fateley et al. May 2002 A1
20020064341 Fauver et al. May 2002 A1
20020076152 Hughes et al. Jun 2002 A1
20020085209 Mittleman et al. Jul 2002 A1
20020086347 Johnson et al. Jul 2002 A1
20020091322 Chaiken et al. Jul 2002 A1
20020093662 Chen et al. Jul 2002 A1
20020109851 Deck Aug 2002 A1
20020122182 Everett et al. Sep 2002 A1
20020122246 Tearney et al. Sep 2002 A1
20020140942 Fee et al. Oct 2002 A1
20020158211 Gillispie Oct 2002 A1
20020161357 Anderson et al. Oct 2002 A1
20020163622 Magnin et al. Nov 2002 A1
20020168158 Furusawa et al. Nov 2002 A1
20020172485 Keaton et al. Nov 2002 A1
20020183623 Tang et al. Dec 2002 A1
20020188204 McNamara et al. Dec 2002 A1
20020196446 Roth et al. Dec 2002 A1
20020198457 Tearney et al. Dec 2002 A1
20030001071 Mandella et al. Jan 2003 A1
20030013973 Georgakoudi et al. Jan 2003 A1
20030023153 Izatt et al. Jan 2003 A1
20030026735 Nolte et al. Feb 2003 A1
20030028114 Casscells, III et al. Feb 2003 A1
20030030816 Eom et al. Feb 2003 A1
20030043381 Fercher Mar 2003 A1
20030053673 Dewaele et al. Mar 2003 A1
20030067607 Wolleschensky et al. Apr 2003 A1
20030082105 Fischman et al. May 2003 A1
20030097048 Ryan et al. May 2003 A1
20030108911 Klimant et al. Jun 2003 A1
20030120137 Pawluczyk et al. Jun 2003 A1
20030135101 Webler Jul 2003 A1
20030137669 Rollins et al. Jul 2003 A1
20030164952 Deichmann et al. Sep 2003 A1
20030165263 Hamer et al. Sep 2003 A1
20030171691 Casscells, III et al. Sep 2003 A1
20030174339 Feldchtein et al. Sep 2003 A1
20030199769 Podoleanu et al. Oct 2003 A1
20030216719 Debenedictis et al. Nov 2003 A1
20030220749 Chen et al. Nov 2003 A1
20030236443 Cespedes et al. Dec 2003 A1
20040002650 Mandrusov et al. Jan 2004 A1
20040039298 Abreu Feb 2004 A1
20040054268 Esenaliev et al. Mar 2004 A1
20040072200 Rigler et al. Apr 2004 A1
20040075841 Van Neste et al. Apr 2004 A1
20040076940 Alexander et al. Apr 2004 A1
20040077949 Blofgett et al. Apr 2004 A1
20040085540 Lapotko et al. May 2004 A1
20040086245 Farroni et al. May 2004 A1
20040100631 Bashkansky et al. May 2004 A1
20040100681 Bjarklev et al. May 2004 A1
20040110206 Wong et al. Jun 2004 A1
20040126048 Dave et al. Jul 2004 A1
20040126120 Cohen et al. Jul 2004 A1
20040133191 Momiuchi et al. Jul 2004 A1
20040150829 Koch et al. Aug 2004 A1
20040150830 Chan Aug 2004 A1
20040152989 Puttappa et al. Aug 2004 A1
20040165184 Mizuno Aug 2004 A1
20040166593 Nolte et al. Aug 2004 A1
20040189999 De Groot et al. Sep 2004 A1
20040212808 Okawa et al. Oct 2004 A1
20040239938 Izatt Dec 2004 A1
20040246490 Wang Dec 2004 A1
20040246583 Mueller et al. Dec 2004 A1
20040254474 Seibel et al. Dec 2004 A1
20040263843 Knopp et al. Dec 2004 A1
20050018133 Huang et al. Jan 2005 A1
20050018201 De Boer Jan 2005 A1
20050035295 Bouma et al. Feb 2005 A1
20050036150 Izatt et al. Feb 2005 A1
20050046837 Izumi et al. Mar 2005 A1
20050057680 Agan Mar 2005 A1
20050057756 Fang-Yen et al. Mar 2005 A1
20050059894 Zeng et al. Mar 2005 A1
20050065421 Burckhardt et al. Mar 2005 A1
20050075547 Wang Apr 2005 A1
20050083534 Riza et al. Apr 2005 A1
20050119567 Choi et al. Jun 2005 A1
20050128488 Yelin et al. Jun 2005 A1
20050165303 Kleen et al. Jul 2005 A1
20050171438 Chen et al. Aug 2005 A1
20050190372 Dogariu Sep 2005 A1
20050254061 Alphonse et al. Nov 2005 A1
20060033923 Hirasawa et al. Feb 2006 A1
20060093276 Bouma et al. May 2006 A1
20060103850 Alphonse et al. May 2006 A1
20060146339 Fujita et al. Jul 2006 A1
20060155193 Leonardi et al. Jul 2006 A1
20060164639 Horn et al. Jul 2006 A1
20060171503 O'Hara et al. Aug 2006 A1
20060184048 Saadat et al. Aug 2006 A1
20060193352 Chong et al. Aug 2006 A1
20060244973 Yun et al. Nov 2006 A1
20070013002 Wax et al. Jan 2007 A1
20070019208 Toida et al. Jan 2007 A1
20070038040 Cense et al. Feb 2007 A1
20070070496 Gweon et al. Mar 2007 A1
20070076217 Baker et al. Apr 2007 A1
20070086013 De Lega et al. Apr 2007 A1
20070086017 Buckland et al. Apr 2007 A1
20070091317 Freischlad et al. Apr 2007 A1
20070188855 Shishkov et al. Aug 2007 A1
20070223006 Tearney et al. Sep 2007 A1
20070236700 Yun et al. Oct 2007 A1
20070258094 Izatt et al. Nov 2007 A1
20070291277 Everett et al. Dec 2007 A1
20080002197 Sun et al. Jan 2008 A1
20080007734 Park et al. Jan 2008 A1
20080049220 Izzia et al. Feb 2008 A1
20080094613 de Boer et al. Apr 2008 A1
20080094637 de Boer et al. Apr 2008 A1
20080097225 Tearney et al. Apr 2008 A1
20080097709 de Boer et al. Apr 2008 A1
20080100837 de Boer et al. May 2008 A1
20080152353 de Boer et al. Jun 2008 A1
20080154090 Hashimshony Jun 2008 A1
20080204762 Izatt et al. Aug 2008 A1
20080265130 Colomb et al. Oct 2008 A1
20080308730 Vizi et al. Dec 2008 A1
20090011948 Unlu et al. Jan 2009 A1
20090196477 Cense et al. Aug 2009 A1
20090273777 Yun et al. Nov 2009 A1
20090290156 Popescu et al. Nov 2009 A1
20100086251 Xu et al. Apr 2010 A1
20100094576 de Boer et al. Apr 2010 A1
20100150467 Zhao et al. Jun 2010 A1
Foreign Referenced Citations (85)
Number Date Country
1550203 Dec 2004 CN
4105221 Sep 1991 DE
4309056 Sep 1994 DE
19542955 May 1997 DE
10351319 Jun 2005 DE
0110201 Jun 1984 EP
0251062 Jan 1988 EP
0617286 Feb 1994 EP
0590268 Apr 1994 EP
0728440 Aug 1996 EP
0933096 Aug 1999 EP
1426799 Jun 2004 EP
2738343 Aug 1995 FR
1257778 Dec 1971 GB
2030313 Apr 1980 GB
2209221 May 1989 GB
2298054 Aug 1996 GB
6073405 Apr 1985 JP
20040056907 Feb 1992 JP
4135550 May 1992 JP
4135551 May 1992 JP
5509417 Nov 1993 JP
2002214127 Jul 2002 JP
20030035659 Feb 2003 JP
2007271761 Oct 2007 JP
7900841 Oct 1979 WO
9201966 Feb 1992 WO
9216865 Oct 1992 WO
9219930 Nov 1992 WO
9303672 Mar 1993 WO
9219865 Oct 1993 WO
9533971 Dec 1995 WO
9628212 Sep 1996 WO
9732182 Sep 1997 WO
9800057 Jan 1998 WO
9801074 Jan 1998 WO
9814132 Apr 1998 WO
9835203 Aug 1998 WO
9838907 Sep 1998 WO
9846123 Oct 1998 WO
9848838 Nov 1998 WO
9848846 Nov 1998 WO
9905487 Feb 1999 WO
9944089 Sep 1999 WO
9957507 Nov 1999 WO
0058766 Oct 2000 WO
0101111 Jan 2001 WO
0108579 Feb 2001 WO
0127679 Apr 2001 WO
0138820 May 2001 WO
0142735 Jun 2001 WO
0236015 May 2002 WO
0237075 May 2002 WO
0238040 May 2002 WO
02053050 Jul 2002 WO
02054027 Jul 2002 WO
02084263 Oct 2002 WO
03020119 Mar 2003 WO
03046495 Jun 2003 WO
03046636 Jun 2003 WO
03052478 Jun 2003 WO
1324051 Jul 2003 WO
03062802 Jul 2003 WO
03105678 Dec 2003 WO
2004034869 Apr 2004 WO
2004057266 Jul 2004 WO
2004066824 Aug 2004 WO
2004088361 Oct 2004 WO
2004105598 Dec 2004 WO
2005000115 Jan 2005 WO
2005047813 May 2005 WO
2005054780 Jun 2005 WO
2005082225 Sep 2005 WO
20050082225 Sep 2005 WO
2006004743 Jan 2006 WO
2006014392 Feb 2006 WO
2006038876 Apr 2006 WO
2006039091 Apr 2006 WO
2006059109 Jun 2006 WO
2006124860 Nov 2006 WO
2006130797 Dec 2006 WO
2007028531 Mar 2007 WO
2007038787 Apr 2007 WO
2007083138 Jul 2007 WO
2007084995 Jul 2007 WO
Related Publications (1)
Number Date Country
20080094613 A1 Apr 2008 US
Divisions (1)
Number Date Country
Parent 10501276 US
Child 11955961 US