Statistical parametric mapping of stimuli evoked changes in total blood flow velocity in the mouse cortex obtained with extended-focus optical coherence microscopy

Abstract

Functional magnetic resonance (fMRI) imaging is the current gold-standard in neuroimaging. fMRI exploits local changes in blood oxygenation to map neuronal activity over the entire brain. However, its spatial resolution is currently limited to a few hundreds of microns. Here we use extended-focus optical coherence microscopy (xfOCM) to quantitatively measure changes in blood flow velocity during functional hyperaemia at high spatio-temporal resolution in the somatosensory cortex of mice. As optical coherence microscopy acquires hundreds of depth slices simultaneously, blood flow velocity measurements can be performed over several vessels in parallel. We present the proof-of-principle of an optimised statistical parametric mapping framework to analyse quantitative blood flow timetraces acquired with xfOCM using the general linear model. We demonstrate the feasibility of generating maps of cortical hemodynamic reactivity at the capillary level with optical coherence microscopy. To validate our method, we exploited 3 stimulation paradigms, covering different temporal dynamics and stimulated limbs, and demonstrated its repeatability over 2 trials, separated by a week.

Measurement and visualization of stimulus-evoked tissue dynamics in mouse barrel cortex using phase-sensitive optical coherence tomography

“…Cerebral hemodynamics, in particular, attracts tremendous interests as it is spatially and temporally regulated with neural activity through neurovascular coupling. The previous studies of optical neural activity imaging mainly use the optical methods such as laser speckle contrast imaging (LSCI) [1][2][3][4][5], laser doppler flowmetry (LDF) [6][7][8], near-infrared (NIR) spectroscopy [9,10], and optical coherence tomography [11][12][13][14][15][16][17][18] to detect the vascular responses to brain such as the changes in cerebral blood flow (CBF) [1,5], cerebral blood volume (CBV) [3,4], deoxyhemoglobin concentration (HbR) and oxyhemoglobin (Hb-O2) [1,2,4]. These hemodynamic-related changes are used as the markers to reveal the neural response regions.…”

Standard-unit measurement of cellular viability using dynamic light scattering optical coherence microscopy

“…By analyzing light scattered from cells, quantities such as frequency fluctuations and mean square displacement have been suggested to represent intracellular movements [13][14][15][16][17][18]. Recently, optical coherence tomography (OCT) was tested to detect ICM via the signal fluctuation amplitude, autocorrelation decay time [21], signal contrast [22], and decorrelation [23].…”

“…Label-free measurement of ICM has a potential to enable non-destructive assessment of cellular viability without any chemical injection or genetic manipulation and thereby facilitating longitudinal studies of drug effects or environmental cytotoxicity. The potential, however, has not been fully realized; previous label-free methods mostly measured ICM in an arbitrary unit such as the decorrelation of OCT signals [23,24], which is less suitable for quantitative comparison across different samples or systems than a standard unit-represented measurement, and/or have not sufficiently shown that the measured ICM indeed represents the cellular viability by testing if it varies with a change in viability [19,20,[25][26][27]. Previously, we used dynamic light scattering optical coherence tomography (DLS-OCT) [19] and found that neurons exhibit high diffusion coefficients [20], but have not tested if they vary with viability changes.…”

1700 nm broadband laser source enables deep brain optical biopsy

“…By combining the high-resolution optical microscopy technique (~1 μm) with OCT, OCM has been previously demonstrated to provide brain images at the individual neuron level 3 , 14 . Traditional OCM performed with a 1310 nm laser source requires invasive preparations in which overlying turbid tissues, such as the skull and dura, are removed to enable deep-brain imaging.…”