Relative retinal flow velocity detection using optical coherence tomography angiography imaging

Abstract

Optical coherence tomography angiography (OCTA) imaging is a valuable tool for the visualization of retinal vasculature at an unprecedented level of details. However, due to relatively long time-interval between repeated scans in the conventional OCTA scanning protocol, the OCTA flow signal suffers from low dynamic range and loss of velocity-intensity correlation. The ability to distinguish fast and slow flow in the retina may provide a powerful tool for the assessment of early-stage retinal diseases such as vein occlusion. Here, we report a method to detect relative flow velocity in human retina using a 67.5 kHz spectral-domain OCTA device. By adapting the selection of A-scan time-intervals within a single OCTA acquisition and combining the resulting OCTA images, we expand the detectable velocity range. After a quantitative validation of this method performing microchannel flow experiments with varying flow velocities, we demonstrate this approach on human eyes using CIRRUS HD-OCT 5000 with AngioPlex (ZEISS, Dublin, CA) through a prototype scanning pattern.

Fig. 1.

(A) Illustration of the scanning algorithm. A-scans performed n times (ΔT = time-interval between A-Scans considered for decorrelation) at the same location before beam was moved to the next position. (B) Schematic of the experimental setup. For microchannel experiments, a mixture of milk and distilled water (1:10 mixing ratio) was introduced into phantom through a syringe pump. Red area: the scanning area. (C) OCT cross-section through microfluidic phantom. Dotted line: detected rear surface. Microchannel expresses strong signal. (D) OCT cross-section through human eye. Data averaging was performed between ILM and RPE (yellow dotted lines). Inserts show OCTA signal from region of interest (yellow) and the Choroid layer (red). Scalebars: 200 μm, Inset: 500 μm

Fig. 2.

Representative flow calibration table for microchannel experiments. For different interval-times ΔT the OCTA signal was measured at various flow rates. The OCTA signal increases with longer interval-times ΔT at constant flow rates. Similarly, the OCTA signal gets stronger with higher flow rates at constant interval-times ΔT. Arrow represents the flow direction. Note: Here, images have not been corrected for background.

Fig. 3.

(A) Calibration graphs obtained by microchannel experiments for different interval-times ΔT. Note, that for ΔT=75 μs and ΔT=90 μs the flow signal saturates at low flow speeds and therefore does not contribute to the calibration. (B) Calibration graphs at two different interval-times ΔT=60 μs and 45 μs taken at two different microchannels (light green/blue=60 μm and dark green/blue=240 μm). (C) Representative calibration measurement for ΔT=60 μs. Input flow velocities in mm/s. Influx (red arrow) detected only for flow velocities beyond v>3 mm/s and cannot be distinguished for v>16 mm/s. Scalebar: 500μm.

Fig. 4.

(A) Idealized OCTA intensity (normalized) profiles for different interval-times ΔT. Underlying color marks the sensitive flow range of each ΔT setting. (B) Signal sensitivity at different flow velocities for different interval-times ΔT. (C) Normalized OCT signal intensity at most sensitive flow ranges for different time-intervals ΔT. Each flow velocity range can be efficiently detected by different time-intervals ΔT. By combining all four parts the flow velocity can be measured over a larger range.

Fig. 5.

OCTA images of a micro-channel with different interval-times ΔT and constant flow (v = 8 mm/s) and the combined image forming a velocity map. Blue: v<10 mm/s, green: v=10-25 mm/s, red: v>25 mm/s. Arrow indicates flow direction. Scalebar: 500μm.

Fig. 6.

(A) Blood flow maps at three different regions of a healthy human subject. Red, green and blue areas correspond to fast (ΔT=15 μs), moderate (ΔT=45 μs) and slow blood flow (ΔT=60 μs) which were most sensitive at different ΔT-settings, respectively. Insert: Cross-section through retinal vessel (pink line). Yellow color represents fast flow. Blue color indicates slow flow. Scalebars: 250 μm Inset: 50 μm. (B) Combined image of the velocity map and a standard angiography image. Hot-color bar indicates the flow velocity. (C) Left: OCTA signal maps at time-interval ΔT=15 μs, ΔT=45 μs and ΔT=60 μs, respectively. right: Color-coded relative flow velocity map of the same vascular network visualized by the simultaneous representation of slow (blue, ΔT=60 μs), moderate (green, ΔT=45 μs) and fast (red, ΔT=15 μs) flow regimes. Scalebars: 250 μm