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. 2023 May 31;13(1):8803.
doi: 10.1038/s41598-023-36074-8.

Portable, high speed blood flow measurements enabled by long wavelength, interferometric diffuse correlation spectroscopy (LW-iDCS)

Affiliations

Portable, high speed blood flow measurements enabled by long wavelength, interferometric diffuse correlation spectroscopy (LW-iDCS)

Mitchell B Robinson et al. Sci Rep. .

Abstract

Diffuse correlation spectroscopy (DCS) is an optical technique that can be used to characterize blood flow in tissue. The measurement of cerebral hemodynamics has arisen as a promising use case for DCS, though traditional implementations of DCS exhibit suboptimal signal-to-noise ratio (SNR) and cerebral sensitivity to make robust measurements of cerebral blood flow in adults. In this work, we present long wavelength, interferometric DCS (LW-iDCS), which combines the use of a longer illumination wavelength (1064 nm), multi-speckle, and interferometric detection, to improve both cerebral sensitivity and SNR. Through direct comparison with long wavelength DCS based on superconducting nanowire single photon detectors, we demonstrate an approximate 5× improvement in SNR over a single channel of LW-DCS in the measured blood flow signals in human subjects. We show equivalence of extracted blood flow between LW-DCS and LW-iDCS, and demonstrate the feasibility of LW-iDCS measured at 100 Hz at a source-detector separation of 3.5 cm. This improvement in performance has the potential to enable robust measurement of cerebral hemodynamics and unlock novel use cases for diffuse correlation spectroscopy.

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Conflict of interest statement

M.A.F had a financial interest in 149 Medical, Inc., a company developing DCS technology for assessing and monitoring cerebral blood flow in newborn infants. M.A.F.’s interests are managed by Mass General Hospital, and Mass General Brigham in accordance with their conflict-of-interest policies. M.B.R, M.R., N.N.O., A.N.M, N.O., and S.A.C. have nothing to report.

Figures

Figure 1
Figure 1
Optical instrumentation used in this work. A long coherence, 1064 nm laser was coupled to a 90%/10% fused fiber coupler to split the light into a reference arm for the interferometer (90%) and the seed source for the fiber amplifier (10%). The amplified source light was split by a 50%/50% fused fiber coupler to supply two MPE limited sources. Single mode fibers were placed at 5 mm (1) and at 35 mm (4) to bring the light to the SPAD detector and the SNSPDs, respectively. The single photon detection events were time tagged at 6.67 ns resolution and transferred to the computer via USB 3.0. Multimode fibers were also placed at 35 mm (7), which brought light to the sample arm of the interferometer. Light from both the reference and sample arms was shaped to match the size of the linescan camera array (12.5 µm × 25.6 mm), and the intensity signals from the camera were digitized at 300 kHz.
Figure 2
Figure 2
Comparison of the BFi fit from simulated multilayer DCS measurements. (A) The BFi fit from the baseline simulations with different fitting functions can be seen. The discrepancy between the fits of g1τ and g1τ2 would be observed as discrepancies between the fits of iDCS and DCS, respectively. (B) The change in BFi measured in response to a 50% increase in the brain BFi is shown. Without the weighted fitting, the iDCS measurement resolves ~ 50% of the changes that DCS does, reducing the sensitivity to the cerebral signal. With weighted fitting, the fit based on g1τ is seen to be equivalent to the fit based on g1τ2.
Figure 3
Figure 3
Comparison of the characteristics of BFi time traces measured at 100 Hz from the LW-iDCS and LW-DCS instruments. (A) An example of a single subject, pulsatile cardiac signal is shown for both instruments, demonstrating equivalency in the measured blood flow index as well as the reduced noise of the blood flow trace measured by the LW-iDCS instrument. (B) The coefficient of variation σBFi/μBFi was computed for each point in the cardiac cycle, and the results for each subject for each measurement modality are shown in violin plots. On average, the reduction in coefficient of variation provided by the LW-iDCS instrument is ~ 2.25× when compared to the 4 channel LW-DCS instrument. Equivalency of the measured BFi values beyond the pulsatile signals between the two instruments is also shown across subjects and tasks using the cardiac filtered, BFi signals. (C) The measured BFi values are plotted against each other, and cluster nicely around the line of unity. (D) The Bland–Altman plot shows a narrow distribution of the differences in the measured BFi, characterized by a mean difference of 4.27 × 10−10 cm2/s and a standard deviation of 8.39 × 10−10 cm2/s, demonstrating good agreement between the two blood flow measurements.
Figure 4
Figure 4
Subject averaged responses to breath holding. (A) Comparison of the measured blood flow responses to the 30 s breath hold. The relative change in flow in the long separation measurements is seen to be slightly lower than the change observed at the short separation, which has been previously observed. (B) Comparison of relative changes in blood pressure and heart rate, respectively in response to the 30 s breath hold. A progressive increase in blood pressure was observed throughout the breath holding period, while the heart rate remains relatively constant.
Figure 5
Figure 5
Subject averaged response to hyperventilation maneuver. (A) Measured hemodynamic response to 60 s of hyperventilation. As in the breath holding task, the short separation measurement shows a more exaggerated response to the physiologic manipulation, exhibiting a decrease of 30% in BFi after the onset of hyperventilation. The matching long separation responses show a lesser degree of BFi reduction, and all blood flow can be seen to return to the baseline before the end of the hyperventilation trial. (B) For this maneuver, the heart rate increased significantly following the start of the trial, while the blood pressure was seen to reduce.
Figure 6
Figure 6
Subject averaged response to the pressure modulation maneuver. (A) Measured hemodynamic response to 30 s of tourniquet tightening. Using the ratio of the relative decrease between the long channel (39.2%) and the short channel (85.3%), the sensitivity of the long channel to the scalp blood flow can be estimated to be 46%. For long separation DCS measurements, brain sensitivity has been shown to be inversely proportional to scalp sensitivity, and we can estimate that the 35 mm separation measurement has a brain sensitivity > 50%. (B) For this maneuver, as expected, the systemic physiology was not significantly affected by the tightening of the tourniquet on the forehead.

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