Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation
Reexamination Certificate
2000-05-19
2003-04-15
Lateef, Marvin M. (Department: 3737)
Surgery
Diagnostic testing
Detecting nuclear, electromagnetic, or ultrasonic radiation
C600S473000, C600S476000, C250S363020, C250S368000, C250S350000, C250S385200, C250S483100
Reexamination Certificate
active
06549801
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The field of the invention relates to in vivo scanning of tissue using optical coherence tomography.
2. Description of the Prior Art
Direct visualization of tissue physiology and anatomy provides important information to the physician for the diagnosis and management of disease. High spatial resolution noninvasive techniques for imaging in vivo tissue structure and blood flow dynamics are currently not available as a diagnostic tool in clinical medicine. Such techniques could have a significant impact for biomedical research and patient treatment. Techniques such as Doppler ultrasound (DUS) and laser Doppler flowmetry (LDF) are currently used for blood flow velocity determination. DUS is based on the principle that the frequency of ultrasonic waves backscattered by moving particles are Doppler shifted. However, the relatively long acoustic wavelengths required for deep tissue penetration limits the spatial resolution of DUS to approximately 200 &mgr;m. Although LDF has been used to measure mean blood perfusion in the peripheral microcirculation, high optical scattering in biological tissue limits spatial resolution.
Optical Doppler tomography (ODT), also termed Doppler optical coherence tomography, is a recently developed optical technique for imaging both the tissue structure and the flow velocity of moving particles in highly scattering media. The noninvasive nature and exceptionally high spatial resolution of ODT have many potential applications in the clinical management of patients in whom the imaging of tissue structure and the monitoring of blood-flow dynamics are essential. Examples include burn-depth determination, evaluation of the efficiency of laser treatment of port wine stains, photodynamic therapy monitoring, and brain injury evaluation.
An example of an in vivo ODT imaging system with high spatial resolution and accurate blood-flow velocity measurements in vessels in rodent skin as been described by the present inventors, see Z. Chen, T. E. Milner, D. Dave, and J. S. Nelson, Opt. Left. 22, 64 (1997); and Z. Chen, T. E. Milner, S. Srinivas, X. Wang, A. Malekafzali, M. J. C. van Gemert, and J. S. Nelson, Opt. Lett. 22,1119 (1997).
However, previously developed ODT systems were unable to achieve simultaneously both high imaging speed and high velocity sensitivity, which are essential for measuring blood flow in human skin.
ODT combines the Doppler principle with optical coherence tomography (OCT) to yield high-resolution tomographic images of static and moving constituents simultaneously in highly scattering biological tissues. The flow velocity of moving particles in the sample can be determined by measurement of the Doppler shift of the fringe frequency with a short-time Fourier transform. Since detection of the Doppler shift requires sampling the interference fringe intensity over at least one oscillation cycle, the minimum detectable Doppler frequency shift (&Dgr;f
D
) varies inversely with the short-time Fourier transform window size (&Dgr;t
p
) at each pixel (i.e., &Dgr;f
D
≈1/&Dgr;t
p
). For a given time-window size at each pixel, the velocity sensitivity (v
min
) is given by
v
min
=
λ
0
2
n
cos
(
θ
)
Δ
t
p
where &lgr;
0
is the light-source center wavelength, n is the sample's refractive index, and &thgr; is the angle between the probing beam and the direction of flow. Therefore, the higher the value of &Dgr;t
p
, the higher the velocity sensitivity. However, spatial resolution, &Dgr;x
p
, is proportional to the short-time Fourier transform window size and is given by
&Dgr;
x
p
=V
&Dgr;t
p
,
where V is the one-dimensional scanning speed of the ODT system. Consequently, velocity sensitivity and spatial resolution are coupled. A large pixel time-window size increases velocity sensitivity while decreasing spatial resolution. Increasing the image frame rate also decreases velocity sensitivity. For example, for a rate of one frame per second for an image with 100×100 pixels, the maximum data-acquisition time for each pixel (&Dgr;t
p
) is 1/10,000 s. Accordingly, the minimum resolvable Doppler frequency shift is 10 kHz, which corresponds to a velocity sensitivity of approximately 25 mm/s for &lgr;
0
=1300 nm and &thgr;=80°. To measure blood flow in small vessels in which red blood cells are moving at low velocity, one must reduce the imaging frame rate if the spectrogram method is used. When ODT goes to real-time imaging, the time for each axial scan (A scan) is very short. As a result, the velocity sensitivity decreases dramatically, because the window time for each pixel is so short that a fast Fourier transform algorithm cannot detect any large Doppler frequency shift.
BRIEF SUMMARY OF THE INVENTION
The invention is a fast-scanning ODT system that uses phase information derived from a Hilbert transformation to increase the sensitivity of flow velocity measurements while maintaining high spatial resolution. The significant increases in scanning speed and velocity sensitivity realized by the invention make it possible to image in vivo blood flow in human skin. Signal processing according to the invention can be performed in a computer, a digital signal processor, in a phase lock-in amplifier, in a polarized optical system or any device now known or later devised which is equivalent thereto.
The method of the invention overcomes the inherent limitations of the prior art ODT by using a phase change between sequential line scans for velocity image reconstruction. The ODT signal phase can be determined from the complex function, {tilde over (&Ggr;)}
ODT
(t), which is determined through analytic continuation of the measured interference fringes function, &Ggr;
ODT
(t), by use of a Hilbert transformations, namely:
Γ
~
ODT
(
t
)
=
Γ
ODT
(
t
)
+
ⅈ
π
P
∫
-
∞
∞
Γ
ODT
(
τ
)
τ
-
t
ⅆ
τ
=
A
(
t
)
exp
[
ⅈ
ϕ
(
t
)
]
where P denotes the Cauchy principle value and A(t) and &psgr;(t) are the amplitude and the phase of {tilde over (&Ggr;)}
ODT
(t) respectively. The phase change in each pixel between sequential A-line scans is then used to calculate the Doppler frequency shift:
&ohgr;=&Dgr;&psgr;/
T
where T is the time interval between successive A scans. Because T is much longer than the pixel time window, very small Doppler shifts can be detected with this technique. For example, in an OCT/ODT image with 100×100 pixels, if the data-acquisition time at each pixel is 100 &mgr;s, using the phase difference between sequential A-line scans increases the time window from 100 &mgr;s to 100×100 &mgr;s=10 ms. Therefore, the frequency resolution improves from 10 kHz to 100 Hz, and the velocity sensitivity improves from 3 mm/s to 30 &mgr;m/s. In addition, spatial resolution and velocity sensitivity are decoupled. Furthermore, because two sequential A-line scans are compared at the same location, speckle modulations in the fringe signal cancel each other and, therefore, will not affect the phase-difference calculation. Consequently, the phase-resolved method reduces speckle noise in the velocity image. Finally, if the phase difference between sequential frames is used, then the velocity sensitivity can be increased further.
The invention now having been briefly summarized, turn to the following drawings wherein the invention and its operation may be more easily visualized.
REFERENCES:
patent: 5991697 (1999-11-01), Nelson et al.
patent: 6208415 (2001-03-01), De Boer et al.
Chen Zhongping
DeBoer Johannes F.
Nelson J. Stuart
Zhao Yonghua
Dawes Daniel L.
Lateef Marvin M.
Lin Jeoyuh
Myers Dawes & Andras LLP
The Regents of the University of California
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