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 (0.4mm) detection of a scientific complementary metal-oxide-semiconductor camera with the rapid (2Hz) imaging of a few ([Formula: see text]) 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.
Highlights
As advances in functional magnetic resonance imaging have transformed the study of human brain function, they have widened the divide between standard research techniques used in humans and those used in mouse models
We developed a structured illumination (SI) approach to Diffuse optical tomography (DOT) for noninvasive imaging of brain function in mice
The SI-DOT system combined the dense spatial sampling of camera-based DOT systems, finite element light modeling, and the rapid scanning afforded by SI
Summary
As advances in functional magnetic resonance imaging (fMRI) have transformed the study of human brain function, they have widened the divide between standard research techniques used in humans and those used in mouse models. Both task-based evoked responses[1,2] and resting state networks[3,4] have recently been observed in mice using fMRI, high signalto-noise ratio (SNR) and resolution remain challenging due to the small volume of the mouse brain, and the logistics of fMRI hinder widespread application to high-throughput mouse studies. OIS requires, at the least, a minimally invasive procedure of scalp reflection, making longitudinal imaging difficult or even impossible in some populations, such as infant mice
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