Sensitivity of laser speckle contrast imaging to flow perturbations in the cortex

Abstract

Laser speckle contrast imaging has become a ubiquitous tool for imaging blood flow in a variety of tissues. However, due to its widefield imaging nature, the measured speckle contrast is a depth integrated quantity and interpretation of baseline values and the depth dependent sensitivity of those values to changes in underlying flow has not been thoroughly evaluated. Using dynamic light scattering Monte Carlo simulations, the sensitivity of the autocorrelation function and speckle contrast to flow changes in the cerebral cortex was extensively examined. These simulations demonstrate that the sensitivity of the inverse autocorrelation time, 1 /τ c , varies across the field of view: directly over surface vessels 1 /τ c is strongly localized to the single vessel, while parenchymal ROIs have a larger sensitivity to flow changes at depths up to 500 µm into the tissue and up to 200 µm lateral to the ROI. It is also shown that utilizing the commonly used models the relate 1 /τ c to flow resulted in nearly the same sensitivity to the underlying flow, but fail to accurately relate speckle contrast values to absolute 1 /τ c . Mandeville, J. Cohen-Adad et al., "Quantifying the microvascular origin of bold-fmri from first principles with two-photon microscopy and an oxygen-sensitive nanoprobe," J. Neurosci. 35, 3663-3675 (2015). 26. P. S. Tsai, J. P. Kaufhold, P. Blinder, B. Friedman, P. J. Drew, H. J. Karten, P. D. Lyden, and D. Kleinfeld, "Correlations of neuronal and microvascular densities in murine cortex revealed by direct counting and colocalization of nuclei and vessels,"

Acute simvastatin treatment restores cerebral functional capillary density and attenuates angiotensin II‐induced microcirculatory changes in a model of primary hypertension

“…68 Thus, LSCI approach offers a rapid real-time characterization of cortical flow dynamics for functional monitoring of the microcirculation. [69][70][71] Nevertheless, without detailed characterization of the specimen-specific three-dimensional microvascular network, 70 the exact physical relationship of inverse correlation times to both blood volume and absolute blood flow may remain unclear during LSCI assessments. [69][70][71] More elaborated implementations and calibrations (i.e., multiexposure imaging) may enhance the accurate extraction of blood flow dynamics from imaged speckles.…”

“…[69][70][71] Nevertheless, without detailed characterization of the specimen-specific three-dimensional microvascular network, 70 the exact physical relationship of inverse correlation times to both blood volume and absolute blood flow may remain unclear during LSCI assessments. [69][70][71] More elaborated implementations and calibrations (i.e., multiexposure imaging) may enhance the accurate extraction of blood flow dynamics from imaged speckles. 72 In the present study, hypertensive rats presented a reduction in relative basal mCBF compared to normotensive WKY rats, and SIM treatment normalized relative mCBF in hypertensive rats.…”

Vessel packaging effect in laser speckle contrast imaging and laser Doppler imaging

“…[17][18][19][20] This paper is a continuation of that work that will ultimately lead to a better understanding and refined methods to translate the measured contrast into accurate perfusion measures.…”

Dynamic Laser Speckle Imaging

“…the value of n, depends on the amount of dynamic scattering, i.e. single or multiple light scattering, and on whether the dynamics are ordered or unordered [15][16][17] . The amount of dynamic scattering of light for the measurement geometries of LDF and LSCI has typically been assumed to be on average much less than one dynamic scattering event per detected photon 23 , but recent studies have suggested that at least for brain that this number is on average greater than 1 16 .…”

“…single or multiple light scattering, and on whether the dynamics are ordered or unordered [15][16][17] . The amount of dynamic scattering of light for the measurement geometries of LDF and LSCI has typically been assumed to be on average much less than one dynamic scattering event per detected photon 23 , but recent studies have suggested that at least for brain that this number is on average greater than 1 16 . For DCS, the amount of dynamic light scattering is clearly in the multiple scattering regime as the separation between the source and detector on the surface of the tissue is much larger than the scattering length of light within the tissue 6 .…”