Phase-resolved optical coherence tomography and optical Doppler tomography: technology and applications

A novel phase resolved optical coherence tomographic (OCT) and optical Doppler tomographic (ODT) system is developed for simultaneous imaging of tissue structure and physiology with high imaging speed and high spatial resolution.


I. INTRODUCTION
Direct visualization of tissue anatomy and physiology provides important information to the physician for 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 on biomedical research and clinical medicine.
Optical coherence tomography and optical Doppler tomography is a newly developed tomographic imaging modality that combines Doppler velocimetry with coherent gating of the partial coherence source to imaging in vivo tissue structure and blood flow velocity with high spatial resolution (2-10 tm) and high velocity sensitivity (10 jim/s) [1][2][3][4][5][6]. The technology is similar to ultrasound and Doppler ultrasound. However, it uses near infrared optical waves instead of sound waves and it has the advantage of noncontact and high spatial resolution. The exceptionally high spatial resolution of phase resolved OCT/ODT allows in vivo "optical biopsy" of tissue structure and physiology for tumor diagnosis. The noninvasive nature of this technique has many applications in the clinical management of patients in whom imaging tissue structure and monitoring blood flow dynamics is essential. Applications of this technique to imaging changes in tissue structure and hemodynamics following pharmacological intervention and photodynamic therapy, screening vasoactive drug, evaluating efficacy of laser treatment of port wine stain patient, and mapping cortical hemodynamics for brain research has been demonstrated. However, previously developed OCT/ODT systems were unable to achieve simultaneously both high imaging speed and high velocity sensitivity, which are essential for measuring blood flow in clinical applications [2,3,6].
In this report, we describe a novel phase resolved OCT/ODT system that uses phase information derived from a Hilbert transformation to image tissue structure and blood flow with fast-scanning speed and high velocity sensitivity.
Using phase change between sequential scans to construct flow velocity imaging, this technique decouples spatial resolution and velocity sensitivity in flow images and increases imaging speed by more than two orders of magnitude without compromising spatial resolution and velocity sensitivity. The minimum flow velocity that can be detected using an A-line scanning speed of 1 kHz is as low as 10 tm/s while maintaining a spatial resolution of 10 tm. The significant increases in scanning speed and velocity sensitivity made it possible for us to image in vivo blood flow in both normal and port wine stain human skin.
In addition to the regular structure and flow velocity images, the variance of blood flow velocity is used to map location and size of the microvasculature. This method has the advantage that it is less sensitive to the pulsatile nature of blood flow and does not depend on the flow direction. It provides better mapping of vessel size and location that are important for many clinical conditions. Furthermore, this method can also be used to study turbulence and separate Doppler shift due to biological flow from the background motion of the tissue under study.

II. METHODS
The schematic diagram of the phase resolved OCT/ODT system is shown in Figure 1 . A broadband 1 .3 m SLD from AFC, Inc. (Quebec, Canada) is used as the light source. Polarization control devices are inserted into the fibers to control the polarization states of the light. A rapidscanning optical delay (RSOD) line is used for group phase delay or depth scanning. RSOD is based on the principle that a linear phase ramp in the frequency domain produces a delay in the time domain [7]. A grating in the delay line is used to spread the spectrum of the source across a galvanometermounted mirror. Tilting the minor introduces an optical path delay that varies linearly with wavelength. Scanning speeds of a few kHz with a depth range of several mm have been achieved with the RSOD. Because RSOD can uncouple the group delay from the phase delay [7], an electro-optical phase modulator is introduced to produce a stable carrier frequency to improve the accuracy of the velocity measurements. where T is the time interval between sequential scans, and n is the number of sequential scans averaged. To increase the SNR in ODT images, 8 sequential A-line scans are averaged. The standard deviation of the Doppler frequency spectrum, 0 is calculated by the following: where P(co) is the Doppler power spectrum and Z3 is the centroid value of the Doppler frequency shift. Because the time interval (1) between each A-scan is much longer than the pixel time window, very small Doppler shifts can be detected using this technique. For example, in an OCT/ODT image with 100 x 100 pixels, if the data acquisition time at each pixel is 100 j.ts, using the phase difference between sequential A-line scans increases the time window from 100 .ts to lOOxlOO .ts = 10 ms. Therefore, frequency resolution improves from 10 kHz to 100 Hz, and the velocity sensitivity improves from 3 mm/s to 30 .tmIs. In addition, spatial resolution and velocity sensitivity is 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.

III. RESULTS AND DISCUSSIONS
(1) To demonstrate the ability of phase resolved ODT to image in vivo blood flow, we imaged the subsurface microcirculation in human skin. Figure 2 shows the images obtained from the ring finger of a human volunteer. Crosssectional structural ( Fig. 2A), velocity (Fig. 2B), and standard deviation of Doppler frequency spectrum (Fig. 2C) images are obtained simultaneously. In this experiment, the RSOD scanning rate is 400 Hz and the EOM modulation frequency is 800 kHz. The velocity image is color-coded where red represents blood flow moving towards the probe (positive Doppler shift) and blue represents flow in the opposite direction. In the OCT structure image ( Fig. 2A), one can clearly see the boundary between the stratum corneum and the epidermis. In the OCT velocity (Fig. 2B) and standard deviation (Fig. 2C) images, many vessels are detected in the dermis between 400 tm and 1 mm below the skin surface. As can be seen, it is much easier to identify the blood vessel dimension and location in the c image (Fig. 2C) to the velocity images (Fig. 2B). In many clinical applications, where the dimension and location of the microvasculature is more important than the absolute value of the flow velocity, c image has the advantage that it is less sensitive to the orientation of the flow direction and pulsatile nature of the blood flow. Vessels as small as 10 .tm diameter can be detected.
A typical velocity profile from a small vein in he human skin is shown in Fig. 3. The measured Doppler frequency shift in the center of the vein is 400 Hz, which corresponds to a blood flow velocity of approximately 3.0 mmls assuming that the angle between the direction of blood flow and the optical probe is 85 degrees. The background noise in the velocity image is very small and velocity