The present invention relates generally to imaging using optical coherence tomography (“OCT”), and more particularly to processes, systems and software arrangements which are capable of determining at least one location in a sample using OCT technique(s).
Optical coherence tomography (“OCT”) is an imaging technique that can measure an interference between a reference beam of light and a detected beam reflected back from a sample. A detailed system description of convention time-domain OCT has been provided in Huang et al. “Optical coherence tomography,” Science 254 (5035), 1178-81 (1991). The spectral-domain variant of optical coherence tomography (“OCT”), called spectral-domain optical coherence tomography (“SD-OCT”), is a technique is a technology that is suitable for ultrahigh-resolution ophthalmic imaging. This technique has been described in Cense, B. et al., “Ultrahigh-resolution high-speed retinal imaging using spectral-domain optical coherence tomography”, Optics Express, 2004 and in International Patent Publication No. WO 03/062802. In addition, U.S. patent application Ser. No. 10/272,171 filed on Oct. 16, 2002, Wojtkowski et al., “In Vivo Human Retinal Imaging by Fourier Domain Optical Coherence Tomography”, Journal of Biomedical Optics, 2002, 7(3), pp. 457-463, Nassif, N. et al., “In Vivo Human Retinal Imaging by Ultrahigh-Speed Spectral Domain Optical Coherence Tomography,” Optics Letters, 2004, 29(5), pp. 480-482, also relates to this subject matter. In addition, optical frequency domain interferometry (“OFDI”) setup (as described in Yun, S. H. et al., “High-Speed Optical Frequency-Domain Imaging, Optics Express, 2003, 11(22), pp. 2953-2963, International Publication No. WO 03/062802 and U.S. Patent Application Ser. No. 60/514,769 filed on Oct. 27, 2004 further relate to the subject matter of the present invention.
The imaging range (e.g., a depth of the image), in SD-OCT and OFDI are generally fixed by parameters of a spectrometer. The imaging range in conventional time-domain OCT systems can be determined by the magnitude of the sweep in a reference arm length. In such systems, the overall reference arm length generally determines the position of the imaging region of a sample. By increasing the reference arm length or by moving a reference arm sweep to deeper lengths, the imaging region may be made deeper, while reducing the reference arm length can moves the imaging region to a more shallow area of the sample.
These technologies have been successfully applied to imaging biological sample. However, such biological samples may often contain irregular surfaces and structures that can make imaging problematic. For example, a curved topology of a retina generally indicates that retinal surface may appear at one depth for a particular scan, while appearing at a different depth for a scan at a different lateral location. In addition, a motion of the sample may further compounds this problem. One of the advantages of the above-referenced imaging techniques and systems employing such techniques is that they do not contact the sample and that they are non-invasive. However, this means that it is often impossible to eliminate or significantly reduce the motion of the sample relative to the imaging device. Referring to the example of retinal imaging, any slight motion on the part of the subject whose retina is being imaged would likely result in undesirable variations in position of the entire eye, in addition to the topological variations inherent in the eye itself. It should be understood that techniques to stabilize and account for motion and topological variations may significantly facilitate the application of these imaging technologies by addressing the motion problem described above.
One possible approach to address for these variations may be to increase the imaging range so as to accommodate these variations due to motion or topology. Again, using the retinal sample as an example, if the range in position of the retinal surface is 10 mm, it is possible to use a system which provides an overall imaging depth of 12 mm. With such system, the consideration for the movement of the surface from image to image are not essential since the retina would likely always be within the proper range. However, using this approach may have the effect of degrading the signal-to-noise ratio and sensitivity of the image.
Accordingly, a method to track the location of features within the sample for the purpose of determining the most appropriate imaging position and range is likely desirable. Previous techniques typically used the position of the surface of the sample as determined from a structural (intensity) image (e.g., using a cross-correlation technique or a peak signal), and provided to adapt a ranging location. (See U.S. Pat. Nos. 6,191,862 and 6,552,796). However, the detection of such prior techniques was not robust.
In contrast to the conventional techniques, an exemplary embodiment of a system, process and software arrangement according to the present invention is capable of using real time dynamic feedback to detect an axial location of features within a sample, and adjust the scan position and range accordingly. For example, an approximate location of a surface in a depth profile of an Optical Coherence Tomography scan may be located. The determination of the approximate location of the surface can be used to generate a feedback signal to, e.g., a ranging device in the reference arm. In addition, a dynamically-adjustable parameter can be used to determine the responsiveness of the feedback loop.
For example, the exemplary embodiments of the present invention, in contrast with the previously implemented systems, provide techniques for locating different types of features in the sample. These include, but are not limited to, structural (or intensity) features traditionally used in tracking techniques, as well as features of flow, birefringence, or spectroscopic data, and combinations thereof. For example, flow is described in Z. Chen et al., “Noninvasive imaging of in vivo blood flow velocity using optical Doppler tomography,” Opt. Lett. 22, 1119-21 (1997), and Y. Zhao et al., “Phase-Resolved Optical Coherence Tomography and Optical Doppler Tomography for Imaging blood flow in human skin with fast scanning speed and high velocity sensitivity,” Opt. Lett. 25, 114-6 (2000). The birefringence is described in J. F. de Boer et al., “Two dimensional birefringence imaging in biological tissue by polarization-sensitive optical coherence tomography,” Opt. Lett. 22, 934-6 (1997). J. F. de Boer et al., “Determination of the depth-resolved Stokes parameters of light backscattered from turbid media by use of polarization-sensitive optical coherence tomography,” Opt. Lett. 24, 300-2 (1999), C. E. Saxer et al., “High-speed fiber-based polarization-sensitive optical coherence tomography of in vivo human skin,” Opt. Lett. 25, 1355-7 (2000), and B. H. Park et al., “Real-time multi-functional optical coherence tomography,” Optics Express 11, 782 (2003). Further, the spectroscopic data is described in U. Morger et al., “Spectroscopic optical coherence tomography,” Opt. Lett. 25(2), 111-3 (2000), and B. Hermann et al., “Precision of extracting absorption profiles from weakly scattering media with spectroscopic time-domain optical coherence tomography,” Opt. Express 12(8), 1677-88 (2004). In addition, a reactivity parameter that affects how the evolution of these features can be used to alter system acquisition parameters e.g., (imaging location, window, range) during the acquisition.
According to one exemplary embodiment of the present invention, a system, process and software arrangement are provided to determine at least one position of at least one portion of a sample. In particular, information associated with the portion of the sample is obtained. Such portion may be associated with an interference signal that includes a first electromagnetic radiation received from the sample and a second electromagnetic radiation received from a reference. In addition, depth information and/or lateral information of the portion of the sample, may be obtained. At least one weight function can be applied to the depth information and/or the lateral information so as to generate resulting information. Further, a surface position, a lateral position and/or a depth position of the portion of the sample may be ascertained based on the resulting information.
In another exemplary embodiment of the present invention, the depth information can include (i) flow information within the at least one portion of the sample, (ii) birefringence information and polarization information associated with the at least one portion of the sample, (iii) spectroscopic information of the at least one portion of the sample, and/or (iv) intensity information of the portion of the sample. In addition, a length of the reference can be modified based on the surface position and/or the depth position. After the length is modified, the depth information and/or the lateral information may be obtained based on a new position of the reference. In addition, the length of the reference can be modified using a controllable parameter. The controllable parameter may be a responsiveness parameter which is used to dynamically control a level of modification of the length of the reference.
According to a further exemplary embodiment of the present invention, after ascertaining the particular information, at least further one of the surface position, the lateral position and/or the depth position is estimated and/or predicted as a function of the particular information. Further, the procedure can be performed a number of times to obtain a set of data associated with the particular information; and the estimation and/or prediction can be based on (or using) the set of data.
In another exemplary embodiment of the present invention, a delay arrangement can be provided which is associated with the sample and/or the reference, and facilitates variable transmissive optical paths therein. Further, at least a section of a particular path of the sample and/or the reference may be non-reciprocal. The reference can receive radiation via a path that is different from a path along which the radiation is transmitted from the reference.
According to still another exemplary embodiment of the present invention, the portion can include a feature of the sample, and the lateral position of the feature may be determined. The lateral information can include (i) flow information within the at least one portion of the sample, (ii) birefringence information and polarization information associated with the at least one portion of the sample, (iii) spectroscopic information of the at least one portion of the sample, and/or (iv) intensity information of the portion of the sample. A lateral scan range of the sample can be modified based on the lateral position. After modifying the lateral scan range, the depth information and/or the lateral information may be obtained based on a new lateral scan range. The lateral scan range may be modified using a controllable parameter (e.g., a responsiveness parameter which is used to dynamically control a level of modification of the lateral scan range).
These and other objects, 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.
Further objects, features and advantages of the invention will become apparent from the following detailed description taken in conjunction with the accompanying figures showing illustrative embodiments of the invention, in which:
In general, a relative intensity noise (“RIN”) of the received light signal may be proportional to a reciprocal of the linewidth, and the relatively high RIN can be reduced by dual balanced detection (e.g., using a dual balanced receiver 170). The differential current of two InGaAs detectors D1 and D2 in the receiver 170 may be amplified using trans-impedance amplifiers (“TIA”) having a total gain of 56 dB, and passed through a low pass filter (“LPF”) with a 3-dB cutoff frequency at approximately half the sampling rate. The common-noise rejection efficiency of the receiver 170 may be typically greater than 20 dB. In addition to the RIN reduction, the balanced detection may provide other significant benefits—a suppression of a self-interference noise originating from multiple reflections within the sample and optical components; an improvement in the dynamic range; and a reduction of a fixed-pattern noise by greatly reducing the strong background signal from the reference light. Thereafter, a detecting arrangement 180 receives such signals, and forward them to a processing arrangement 190 (e.g., a computer) which implements the exemplary embodiments of the system, process and software arrangement according to the present invention to reduce dispersion, and assist in displaying a resultant image that is based on the original image and the reduction of the dispersion.
Both of these exemplary arrangements, e.g., the SD-OCT arrangement described above with reference to
For example, 2.5 mW of source light may be incident onto the surface of the sample in a focused spot of, e.g., 30-mm diameter. A grating-based rapid scanning optical delay line 520 (“RSOD”) can be used with the source spectrum offset on the scanning mirror to provide both group and phase delay scanning so as to generating a carrier frequency at about 800 kHz. A two-step voltage function may be used to drive the polarization modulator 505 such that it is synchronized with the 1-kHz triangular scanning waveform of the RSOD 520, such that the polarization states that are incident upon the sample during inward and outward A-line scans can be orthogonal in the Poincaré sphere representation. A polarizing cube can be inserted into the reference arm to ensure that light in the RSOD 520 is provided in substantially the same linear state, regardless of the polarization state at the sample. Static polarization controllers in the detection and reference arms may be aligned for an equal distribution of the reference arm light over both the horizontal and vertical detection channels for both input polarization states. Electronic signals from each detector can be amplified, filtered and digitized with a 12-bit 5-Msample_s analog-to-digital board (e.g., National Instruments NI 6110).
The exemplary techniques that are described herein below (e.g., adaptive ranging techniques) according to the present invention can be implemented using the exemplary systems described above with reference to
A position function, e.g., a weighted first moment, may be calculated according to the following:
where d and n is a depth scan and point within the depth scan, respectively, and thus Wd,n represents a weight for a particular position in the image. For example, this weight may be equal to the reflected light intensity on either a linear or logarithmic scale, depending on user preference during software initialization. In most cases, using the logarithm of the intensity gives more intuitive results, as the intensity image itself is shown on a logarithmic scale as well.
An exemplary graphic user interface 700 according to the present invention with can be used with this technique during acquisition has two controls related to adaptive ranging, as shown in
ΔVoffset=−R·(P−PL) (2)
This value can be added to the offset voltage, and the updated value may be transmitted to the RSOD between the acquisition of the data chunks. Equation (2) is similar to Hooke's law governing a spring, where R can be equated to a spring constant. The fact that R can be dynamically controlled during acquisition then allows for a determination of the appropriate parameters for optimal damping of patient movement. The ranging procedure continues for each data chunk until the check mark control is deactivated, and the software relocks on to a new position when it is activated again.
It should be understood that the above description is merely an exemplary implementation of an exemplary embodiment of the technique according to the present invention. On having ordinary skill in the are can easily modify and customize it according to the concepts described herein. For example, depending on the application, it is possible to constantly (e.g., periodically) update the scanning range within an image. Alternatively or in addition, it may be beneficial to only update the position between images or between sets of images. These exemplary variations can be easily accomplished by altering the size of the data chunk to be anywhere from a single depth profile, to a particular fraction of an image, to several images.
As described above, the weight function can be based on the reflected intensity on either a linear or logarithmic scale, depending on the type of tissue being scanned. A wide array of other functions based on intensity can also be used, such as, e.g., an exponential, a (fractional) power of the intensity or a higher order polynomial could be used to enhance weakly reflecting features that use tracking. Indeed, it may be beneficial for certain situations to base the weight function on something entirely different. Various extensions of OCT, such as polarization-sensitive OCT (“PS-OCT”) and optical Doppler tomography (“ODT”), can enhance contrast by providing images of phase retardation and flow, respectively.
Multi-functional techniques that are capable of measuring intensity, flow, the full gamut of polarization properties, and even spectroscopy of a sample have also been demonstrated. It is also possible to base the above-described weighting function on any of such features. For example, it is possible to base the weight function on a flow if it is particularly important to track the location of blood vessels. The flexibility in the type of weighting function can even allow us to combine the various types of data at our disposal. A weight that is a combination of some function involving flow and some other function involving phase retardation may allow for the tracking of vessels surrounded by a muscular sheath. The fact that different mathematical functions can be used further enables for an emphasis or de-emphasis of certain information as. For example, it is possible to use a combination of spectroscopic data and flow, with an emphasis on the latter, so as to distinguish and lock on blood containing certain features, and would preferentially focus on those with a flow component.
The position function, P, can also be configured to the type of tissue being analyzed. For example, it is possible to focus the tracking on the position of superficial or deeper structures by changing to what power the depth, n, of a point is raised, e.g.,
Increasing x can put more emphasis on deeper structures of interest whereas decreasing x would emphasize more superficial layers. Alternatively, it is possible to utilize linear combinations of higher order moments, e.g., using the second moment of position combined with a weight based on flow could track the location of a changing flow profile. Another potentially useful application is with tracking locations where features might have phase wrapping. Some examples of this are with flow determined by phase shifts or birefringence as determined by cumulative phase retardation. In both these cases, the mere presence of the source of contrast can potentially be misleading and only by observing their spatial distribution can we ascertain a more accurate description of the tissue. It can easily be seen that the combination of position and weight functions can be adapted to track the location of a wide variety of features, both in terms of their inherent properties (intensity, phase retardation, flow, etc.) and in terms of their spatial properties.
Further, the nature of the feedback loop can be configured to a particular application as well. One way of visualizing the feedback loop can be as a potential well. Equation (2) described above can be equated to Hooke's law governing the motion of a spring, which acts a quadratic potential well. Altering the responsivity parameter generally alters the width of the well, and enable a quick correction for under- or over-damping of motion artifact. It is also possible to modify the nature of the potential well itself, e.g., creating a square well or using another function based on the difference between the current position as the locked position. Indeed, it is possible to use higher order polynomials of not only the difference in position, but also the derivatives of the position as well to design the feedback loop to respond to velocity or acceleration of the tissue in question. Further, instead of using such functions to modify the change in offset voltage, the functions can modify other statistic of the offset voltage such as acceleration. In addition, a locking scheme can be used where the exemplary technique according to the present invention may lock on to a tissue displacement in response to acoustic, photothermal or other external stimuli to the tissue.
Another manner of visualizing the effect of the dynamic responsivity parameter is that the user can use such parameter to control how the system reacts to and anticipates any changes in the position of features being imaged. The example of the usefulness of such exemplary feature is as follows: assume a feature is moving at a constant velocity. An autoranging procedure that merely takes the position from time point to time point will likely be at least slightly behind the true position of an object. This is due to the time the procedure has reacted to a specific position, and thus the object will likely have already moved to a new one. Using the exemplary reactivity parameter in accordance with the present invention, the system can overcompensate for the difference between the current and locked positions, and thus predict where the feature of interest would likely appear. Due to the fact that this is a dynamically controllable parameter, the user may use it to quickly tailor the response to fit the imaging subject.
The exemplary tracking technique according to the present invention described above is not limited to axial degrees of freedom. By providing a feedback loop to the lateral motion controllers, e.g., an x-y galvo set, the exemplary tracking technique can also provide a transversal lock on blood vessels or other structures that can be distinguished through their structure, polarization properties or velocity through, e.g., a Doppler shift. Similar feedback loops can be applied for controlling the range of the image by tracking the boundaries of the region of interest.
Then, the position function, P, can be evaluated in step 640. If tracking is not active, then the program updates the value of a locking position PL in step 660. Otherwise, the procedure is continued to step 670 in which a reactivity/reaction parameter, R, is obtained from the interface. One of the goals of the tracking procedure, when activated, is to maintain the position of the most recently acquired data chunk as close to this locking value as possible. This is done by determining the change in the RSOD offset voltage most appropriate for the given value of the responsivity in step 680, and offset voltage, Voffset, is updated in step 690. Finally, the new voltage is transmitted in step 695, and the process returns to step 630. Thus, this exemplary technique facilitates the most current evaluation of the position function.
The foregoing merely illustrates the principles of the invention. Various modifications and alterations to the described embodiments will be apparent to those skilled in the art in view of the teachings herein. For example, the invention described herein is usable with the exemplary methods, systems and apparatus described in U.S. patent application Ser. No. 60/514,769. It will thus be appreciated that those skilled in the art will be able to devise numerous systems, arrangements and methods which, although not explicitly shown or described herein, embody the principles of the invention and are thus within the spirit and scope of the present invention. In addition, all publications, patents and patent applications referenced above are incorporated herein by reference in their entireties.
The present application claims priority from U.S. Patent Application Ser. No. 60/599,809 filed Aug. 6, 2004, the entire disclosure of which is incorporated herein by reference. This application also relates to U.S. Patent Publication No. 2002/0198457, the entire disclosure of which is incorporated herein by reference.
Number | Name | Date | Kind |
---|---|---|---|
2339754 | Brace | Jan 1944 | A |
3090753 | Matuszak 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 |
4650327 | Ogi | Mar 1987 | 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 | Lefevre et al. | May 1990 | A |
4965441 | Picard | Oct 1990 | A |
4965599 | Roddy et al. | 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 et al. | May 1993 | A |
5212667 | Tomlinson et al. | May 1993 | A |
5214538 | Lobb | May 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 |
5262644 | Maguire | Nov 1993 | A |
5275594 | Baker | Jan 1994 | A |
5291885 | Taniji et al. | Mar 1994 | A |
5293872 | Alfano et al. | Mar 1994 | A |
5293873 | Fang | Mar 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 | Kittrell | Feb 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 |
5784352 | Swanson et al. | Jul 1998 | A |
5785651 | Baker 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 et al. | 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 |
6033721 | Nassuphis | 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 |
6091496 | Hill | Jul 2000 | A |
6091984 | Perelman et al. | 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 |
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 |
6517532 | Altshuler et al. | Feb 2003 | B1 |
6538817 | Farmer et al. | Mar 2003 | B1 |
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 |
6680780 | Fee | Jan 2004 | B1 |
6685885 | Varma et al. | Feb 2004 | B2 |
6687007 | Meigs | Feb 2004 | B1 |
6687010 | Horii et al. | Feb 2004 | B1 |
6687036 | Riza | 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 |
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 |
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 |
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 |
7190464 | Alphonse | Mar 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 |
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 |
7391520 | Zhou et al. | Jun 2008 | B2 |
7458683 | Chernyak et al. | Dec 2008 | B2 |
7530948 | Seibel et al. | May 2009 | B2 |
7609391 | Betzig | Oct 2009 | B2 |
7646905 | Guittet et al. | Jan 2010 | B2 |
7664300 | Lange et al. | Feb 2010 | B2 |
7805034 | Kato et al. | Sep 2010 | B2 |
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 |
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 |
20030013973 | Georgakoudi et al. | Jan 2003 | A1 |
20030023153 | Izatt et al. | Jan 2003 | A1 |
20030026735 | Nolte et al. | Feb 2003 | A1 |
20030028114 | Casscells, III | Feb 2003 | A1 |
20030030816 | Eom et al. | Feb 2003 | A1 |
20030053673 | Dewaele et al. | Mar 2003 | A1 |
20030082105 | Fischman | 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 |
20040054268 | Esenaliev et al. | Mar 2004 | A1 |
20040072200 | Rigler et al. | Apr 2004 | A1 |
20040075841 | Van Neste et al. | Apr 2004 | A1 |
20040077949 | Blofgett et al. | Apr 2004 | A1 |
20040086245 | Farroni et al. | May 2004 | A1 |
20040100631 | Bashkansky et al. | May 2004 | A1 |
20040100681 | Bjarklev et al. | May 2004 | A1 |
20040126048 | Dave 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 |
20040212808 | Okawa et al. | Oct 2004 | A1 |
20040239938 | Izatt | 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 |
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 |
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 |
20060184048 | Saadat et al. | Aug 2006 | A1 |
20060193352 | Chong et al. | Aug 2006 | A1 |
20060244973 | Yun et al. | Nov 2006 | A1 |
20070019208 | Toida et al. | Jan 2007 | A1 |
20070038040 | Cense et al. | Feb 2007 | A1 |
20070070496 | Gweon et al. | Mar 2007 | A1 |
20070086013 | De Lega et al. | Apr 2007 | A1 |
20070133002 | Wax et al. | Jun 2007 | A1 |
20070188855 | Shishkov et al. | Aug 2007 | A1 |
20070223006 | Tearney et al. | Sep 2007 | A1 |
20070236700 | Yun et al. | Oct 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 |
20080097225 | Tearney et al. | Apr 2008 | A1 |
20090273777 | Yun et al. | Nov 2009 | A1 |
Number | Date | Country |
---|---|---|
4105221 | Sep 1991 | DE |
4309056 | Sep 1994 | DE |
19542955 | May 1997 | 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 |
1324051 | Jul 2003 | EP |
1426799 | Jun 2004 | EP |
2728343 | 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 |
9216865 | 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 | Sep 1998 | WO |
9838907 | Sep 1998 | WO |
9846123 | Oct 1998 | WO |
9848838 | Nov 1998 | WO |
9848846 | Nov 1998 | WO |
9905487 | Feb 1999 | WO |
9944089 | 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 |
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 |
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 |
2006004743 | Jan 2006 | WO |
2006014392 | Feb 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 |
Number | Date | Country | |
---|---|---|---|
20060039004 A1 | Feb 2006 | US |
Number | Date | Country | |
---|---|---|---|
60599809 | Aug 2004 | US |