Doppler flow imaging using optical coherence tomography

Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation

Reexamination Certificate

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Reexamination Certificate

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06735463

ABSTRACT:

BACKGROUND
Optical coherence tomography (OCT) is a technology that allows for non-invasive, cross-sectional optical imaging of biological media with hi high sensitivity. OCT is an extension of low-coherence or white-light interferometry, in which a low temporal coherence light source is utilized to obtain precise localization of reflections internal to a probed structure along an optic axis. In OCT, this technique is extended to enable scanning of the probe beam in the direction perpendicular to the optic axis, building up a two-dimensional reflectivity data set, used to create a cross-sectional gray-scale or false-color image of internal tissue backscatter.
OCT has been applied to imaging of biological tissue in vitro and in vivo, although the primary applications of OCT developed to date have been for high resolution imaging of transparent tissues, such as ocular tissues. U.S. patent application Ser. No. 09/040,128, filed Mar. 17, 1998, provides a system and method for substantially increasing the resolution of OCT and also for increasing the information content of OCT images through coherent signal processing of the OCT interferogram data. This system is capable of providing cellular resolution (i.e., in the order of 5 micrometers). Accordingly, OCT can be adapted for high fidelity diagnosis of pre-cancerous lesions, cancer, and other diseases of the skin, bladder, lung, GI tract and reproductive tract using non-invasive medical diagnostics.
In such diagnostic procedures utilizing OCT, it would also be desirable to monitor the flow of blood and/or other fluids, for example, to detect peripheral blood perfusion, to measure patency in small vessels, and to evaluate tissue necrosis. Another significant application would be in retinal perfusion analysis. Monitoring blood-flow in the retina and choroid may have significant applications in diagnosis and monitoring macular degeneration and other retinal diseases. Accordingly, it would be advantageous to combine Doppler flow monitoring with the above micron-scale resolution OCT imaging in tissue.
Wang, et al., “Characterization of Fluid Flow Velocity by Optical Doppler Tomography,”
Optics Letters
, Vol. 20, No. 11, Jun. 1, 1995, describes an Optical Doppler Tomography system and method which uses optical low coherence reflectrometry in combination with the Doppler effect to measure axial profiles of fluid flow velocity in a sample. A disadvantage of the Wang system is that it does not provide a method to determine direction of flow within the sample and also does not provide a method for generating a two-dimensional color image of the sample indicating the flow velocity and directions within the image.
U.S. Pat. No. 5,549,114 to Petersen, et al. also provides an optical coherence tomography system capable of measuring the Doppler shift of backscattered light from flowing fluid within a sample. However, similar to Wang, et al., Petersen, et al. does not disclose a system or method for displaying the direction of flow within the sample, nor does Petersen, et al. disclose a system or method for providing a two-dimensional color image of the sample which indicates the velocity and directions of flow of fluids within the sample.
SUMMARY
The present invention involves an advancement in OCT technology that provides for quantitative measurements of flow in scattering media by implementing systems for increased interferogram acquisition accuracy, coherent signal processing and display. The present invention provides a combination of micron-scale resolution tomographic optical imaging of a tissue sample simultaneously with Doppler flow monitoring of blood and other body fluids within the sample volume.
The present invention utilizes an OCT data acquisition system to obtain precise localization of reflections internal to the sample along the optic axis. Scanning the OCT probe beam in a direction perpendicular to the optic axis builds up a two-dimensional data set comprising a gray-scale cross-sectional image of internal tissue backscatter. The data acquisition system may also utilize a calibration interferometer for providing sub-100 nm accuracy calibration of the reference arm position during interferogram acquisition. In combination with the production of the cross-sectional gray-scale image internal tissue backscatter, the present invention also provides a two-dimensional color data image representing the Doppler flow velocity and directions of moving scatterers within the sample. The method for generating the two-dimensional, color, Doppler image is generally as follows:
For each axial reference arm scan (“A-scan”), interferometric data is acquired. This interferometric data corresponds to a cross-correlation measurement of the light returning from the reference arm and the light backscattered from the volume of potentially moving scatterers illuminated by the sample arm probe beam. The acquired interferometric data is first band-pass filtered for noise reduction. Next, the filtered data is coherently demodulated at a frequency corresponding to the Doppler shift induced by the reference mirror of the interferometer to produce an array of in-phase data values vs. time and an array of quadrature data values vs. time. As those of ordinary skill in the art will realize, the time element in these arrays is directly proportional to the reference arm length, and in turn, is directly proportional to the scanning depth into the sample.
Next, a starting time and a time window is selected. The selected starting time corresponds to a starting depth and the selected time window corresponds to a depth-range that is preferably longer than or equal to the coherence length of the light source of the low-coherence interferometer. At the selected starting time, the values of the in-phase array and the quadrature array corresponding to the selected time window are extracted from the in-phase and quadrature arrays and passed into a Fourier transform (FT) circuit or algorithm to obtain a power spectrum (localized Doppler spectrum) for that particular time window (depth range).
From this power spectrum, a central velocity estimate is calculated to obtain an estimate of the mean scatter velocity for that particular time window. In one embodiment, the central velocity estimate is obtained by calculating a centroid for the power spectrum. This velocity estimate will have a sign and a magnitude. Next, one of two colors is assigned for to the velocity estimate, the particular one of two colors assigned being determined according to the sign of the velocity estimate (i.e., blue for positive values and red for negative values). The brightness, intensity or density of the color to assign to the window is determined by the magnitude of the velocity estimate. The resultant color and brightness is applied to an image pixel, or to a plurality of image pixels in a velocity profile (which is an array of image pixels corresponding to the particular A-scan). The particular pixel(s) to which the color and brightness is applied is the pixel(s) corresponding to the particular depth range of the selected window.
Next, at a predetermined point past the starting time, another time window of in-phase and quadrature data is extracted from the in-phase an time window, a velocity estimate is calculated as described above, a color is assigned for this velocity estimate, and the color is applied to the velocity profile corresponding to the particular depth range of this next time window. New windows will thereafter be repeatedly extracted and processed to generate a complete velocity profile for the particular A-scan. In one embodiment of the invention, this complete velocity profile is a one-dimensional array of colorized image pixels corresponding to the lateral position of the sample probe.
Preferably, multiple A-scans are performed for a sample, each A-scan corresponding to a particular lateral position of the sample arm with respect to the sample. Alternatively, for angular scanning implementations of OCT, subsequent A-scans are arranged into a radial array. It is to be understood

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