Structured illumination diffuse optical tomography for noninvasive functional neuroimaging in mice

Abstract

Abstract. Optical intrinsic signal (OIS) imaging has been a powerful tool for capturing functional brain hemodynamics in rodents. Recent wide field-of-view implementations of OIS have provided efficient maps of functional connectivity from spontaneous brain activity in mice. However, OIS requires scalp retraction and is limited to superficial cortical tissues. Diffuse optical tomography (DOT) techniques provide noninvasive imaging, but previous DOT systems for rodent neuroimaging have been limited either by sparse spatial sampling or by slow speed. Here, we develop a DOT system with asymmetric source-detector sampling that combines the high-density spatial sampling (0.4 mm) detection of a scientific complementary metal-oxide-semiconductor camera with the rapid (2 Hz) imaging of a few (<50) structured illumination (SI) patterns. Analysis techniques are developed to take advantage of the system's flexibility and optimize trade-offs among spatial sampling, imaging speed, and signal-to-noise ratio. An effective source-detector separation for the SI patterns was developed and compared with light intensity for a quantitative assessment of data quality. The light fall-off versus effective distance was also used for in situ empirical optimization of our light model. We demonstrated the feasibility of this technique by noninvasively mapping the functional response in the somatosensory cortex of the mouse following electrical stimulation of the forepaw. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

Effective Connectivity Measured Using Optogenetically Evoked Hemodynamic Signals Exhibits Topography Distinct from Resting State Functional Connectivity in the Mouse

“…Given the relatively low laser power delivered to the tissue surface, and the large extinction coefficient of blue light in biological tissue ( Prahl 2002 ), Thy1-EC patterns primarily result from stimulation of superficial dendritic processes of deeper layer 5 neurons and downstream (orthodromic) synaptic targets. As with other planar imaging methods, connectivity information between stimulated cortical sites and deeper brain structures (e.g., thalamus) cannot be determined, and will require whole-brain mapping with fMRI or other tomographic approaches ( Bauer et al 2011 ; Eggebrecht et al 2014 ; Nasiriavanaki et al 2014 ; Reisman et al 2017 ). Previous studies in rodents demonstrating optogenetically defined connectivity using fMRI ( Lee et al 2010 ; Desai et al 2011 ) were limited to stimulating single sites and required craniotomies for implanting fiber optics ( Desai et al 2011 ).…”

Review of structured light in diffuse optical imaging

“…The use of FRET with structured-light tomography has pushed this limit further and has been demonstrated as a nanoscale proximity assay in small animals 148 , 165 . Endogenous sensing continues to improve with structured light, as real-time tomographic maps of cerebral hemodynamics in a mouse (through the scalp and skull) 171 are possible and mammogram reconstructions improve 176 …”

“…The paw of the mouse was stimulated at the beginning of the imaging session, and (b) the distribution of total hemoglobin HbT within the brain was seen to change according to activation of various areas of the brain. (c) The time-course response in terms of total hemoglobin, oxygenated hemoglobin (HbO2), and deoxygenated hemoglobin (HbR) 171 …”

“…This is a nascent application with great promise. Recently, Reisman et al., 171 following the pioneering developments highlighted above, implemented structured-light tomography for functional brain imaging of the intact mouse brain (through the scalp and skull). The researchers collected the data by projecting sinusoidal patterns of different spatial frequencies, phases, and orientations.…”

Spatial frequency domain imaging in 2019: principles, applications, and perspectives

“…SFDI also has the unique ability to provide the additional depth section capability for tomographic localization of hemodynamic signals during functional activation imaging. 117,125 Lin et al [126][127][128] have also done work to characterize SFDI optical signatures in degenerative diseases like Alzheimer's and characterized baseline properties while measuring vascular impairment due to neuronal death and amyloid-beta plaques. Due to continuous noninvasive imaging capability, treatments and disease can be tracked much more efficiently in preclinical research.…”