Mesoscopic and microscopic imaging of sensory responses in the same animal

Abstract

Imaging based on blood flow dynamics is widely used to study sensory processing. Here we investigated the extent to which local neuronal and capillary responses (two-photon microscopy) are correlated to mesoscopic responses detected with fast ultrasound (fUS) and BOLD-fMRI. Using a specialized chronic olfactory bulb preparation, we report that sequential imaging of the same mouse allows quantitative comparison of odour responses, imaged at both microscopic and mesoscopic scales. Under these conditions, functional hyperaemia occurred at the threshold of neuronal activation and fUS-CBV signals could be detected at the level of single voxels with activation maps varying according to blood velocity. Both neuronal and vascular responses increase non-linearly as a function of odour concentration, whereas both microscopic and mesoscopic vascular responses are linearly correlated to local neuronal calcium. These data establish strengths and limits of mesoscopic imaging techniques to report neural activity.

Differential effects of aquaporin-4 channel inhibition on BOLD fMRI and Diffusion fMRI responses in rat visual cortex

“…BOLD contrast results from the magnetic susceptibility balance between oxy-and deoxy-hemoglobin in circulating erythrocytes [29] which reflects the activation induced increase in blood oxygen consumption and blood flow in cerebral blood vessels [8]. Hence, BOLD fMRI primarily reflects changes in hemodynamics and oxygenation in large and small blood vessels, not directly neural activity, resulting in known limitations, namely its limited spatial and temporal resolution with regards to underlying neural activity [9,30], its sensitivity to underlying local organizational structure of the vascular network (which may not always covariate with local neural networks [30,31]) and to any confound interfering with the neurovascular mechanism (underlying pathology, presence of drugs) [9].…”

Correlated Multimodal Imaging in Life Sciences: Expanding the Biomedical Horizon

“…Several workflows have so far been established that solved the above-mentioned challenges on sample preparation, relocalization of ROIs, and data correlation. Recent examples for multiscale combinations of in-vivo and ex-vivo imaging include the correlation of intravital microscopy, CT and EM to study single tumor cells in the cerebral vasculature [81]; correlation of X-ray holographic nano-tomography, EM and FM to disentangle dense neuronal circuitry in Drosophila melanogaster and mammalian central and peripheral nervous tissue [82]; correlation of local neuronal and capillary responses by two-photon microscopy with mesoscopic responses detected by ultrasound (US) and BOLD-fMRI [83]; or extended CMI pipelines that include the correlation of a variety of imaging technologies, such as non-invasive US, CT and highresolution episcopic microscopy (HREM) for phenotyping left/right asymmetries of all visceral organs in a mouse model of heterotaxy or combined OCT, PAI and HREM of chick embryos at multiple development stages [8,84,85]. Further examples of novel CMI pipelines that uncover biophysical or chemical information include the correlation of FM, molecular (MALDI MSI) and elemental imaging [X-ray fluorescence (XRF)] to analyze lipids and elements relevant to bone structures in the very same sample section of a chicken phalanx without tissue decalcification at the µm scales [86].…”

Ultrafast ultrasound imaging pattern analysis reveals distinctive dynamic brain states and potent sub-network alterations in arthritic animals

“…Our study aimed at studying alterations of brain FC and brain states in a clinically-relevant animal model of chronic inflammatory pain, Adjuvant-Induced Arthritis (AIA), by using a new ultrasound-based neuroimaging technique, functional ultrasound (fUS) imaging. By exploiting the hemodynamic impulse response to neural events 17 , this technique allows imaging of cerebral blood volume (CBV) 18,19 in the rat 20 and infant brain 21 with a large field of view and high spatial (10-100 μm) and temporal (2 msec) resolution 20 , allowing detection in single trials and at the level of a voxel 22 . Due to neurovascular coupling, fUS imaging measures with high sensitivity both the cortical hemodynamic changes induced by olfactory 23 , visual 24 and auditory 25 stimuli.…”