Abstract
Noninvasive microvascular imaging using optical coherence Doppler tomography (ODT) has shown great promise in brain studies; however, high-speed microcirculatory imaging in deep brain remains an open quest. A high-speed 1.3 μm swept-source ODT (SS-ODT) system is reported which was based on a 200 kHz vertical-cavity-surface-emitting laser. Phase errors induced by sweep-trigger desynchronization were effectively reduced by spectral phase encoding and instantaneous correlation among the A-scans. Phantom studies have revealed a significant reduction in phase noise, thus an enhancement of minimally detectable flow down to 268.2 μm/s. Further in vivo validation was performed, in which 3D cerebral-blood-flow (CBF) networks in mouse brain over a large field-of-view (FOV: 8.5 × 5 × 3.2 mm3) was scanned through thinned skull. Results showed that fast flows up to 3 cm/s in pial vessels and minute flows down to 0.3 mm/s in arterioles or venules were readily detectable at depths down to 3.2 mm. Moreover, the dynamic changes of the CBF networks elicited by acute cocaine such as heterogeneous responses in various vessel compartments and at different cortical layers as well as transient ischemic events were tracked, suggesting the potential of SS-ODT for brain functional imaging that requires high flow sensitivity and dynamic range, fast frame rate and a large FOV to cover different brain regions.
Highlights
Common-path schemes with one mirror to minimize phase errors near a certain depth[15,16] or double mirrors for multiple depths after phase unwrapping[14]
In 0.5% intralipid suspension with no pump flow, the flow noise floor of optical Doppler tomography (ODT) after phase correction is very low (301.27 μm/s) and comparable to the noise background (295.7 μm/s), but that of optical coherence angiography (OCA) is significantly increased to σOCA = 12 k counts due to non-directional Brownian motion
The comparison clearly shows that our phase correction approach can effectively enhance the detection of minimal flow rate from 957.1 μm/s without phase correction down to 301.2 μm/s, which is crucial for quantitative imaging of blood flow in biological systems, such as cerebral blood flows for brain functional studies
Summary
Common-path schemes with one mirror to minimize phase errors near a certain depth[15,16] or double mirrors for multiple depths after phase unwrapping[14] These methods required sophisticated hardware modification and intensive computation. A recent interesting method used a fiber Bragg grating (FBG) in one of the balanced detection arms to track each spectral sweeping and correct the phase jittering between A-scans for ODT reconstruction[17]. Much simpler, this method involved accurately matching the pathlengths between the two arms, but improved OCA image quality was shown[18,19]. Brain functional changes such as the CBF network dynamics in response to a pharmacological challenge (e.g., acute cocaine administration) was acquired[20], which clearly demonstrated the capability of our SS-ODT to enable 3D quantitative imaging of 3D blood flow network dynamics with markedly improved flow detection sensitivity, at high spatiotemporal resolutions, and over a large FOV
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