High-density diffuse optical tomography for imaging human brain function

This review describes the unique opportunities and challenges for noninvasive optical mapping of human brain function. Diffuse optical methods offer safe, portable, and radiation free alternatives to traditional technologies like positron emission tomography or functional magnetic resonance imaging (fMRI). Recent developments in high-density diffuse optical tomography (HD-DOT) have demonstrated capabilities for mapping human cortical brain function over an extended field of view with image quality approaching that of fMRI. In this review, we cover fundamental principles of the diffusion of near infrared light in biological tissue. We discuss the challenges involved in the HD-DOT system design and implementation that must be overcome to acquire the signal-to-noise necessary to measure and locate brain function at the depth of the cortex. We discuss strategies for validation of the sensitivity, specificity, and reliability of HD-DOT acquired maps of cortical brain function. We then provide a brief overview of some clinical applications of HD-DOT. Though diffuse optical measurements of neurophysiology have existed for several decades, tremendous opportunity remains to advance optical imaging of brain function to address a crucial niche in basic and clinical neuroscience: that of bedside and minimally constrained high fidelity imaging of brain function

Brain Specificity of Diffuse Optical Imaging: Improvements from Superficial Signal Regression and Tomography

Functional near infrared spectroscopy (fNIRS) is a portable monitor of cerebral hemodynamics with wide clinical potential. However, in fNIRS, the vascular signal from the brain is often obscured by vascular signals present in the scalp and skull. In this paper, we evaluate two methods for improving in vivo data from adult human subjects through the use of high-density diffuse optical tomography (DOT). First, we test whether we can extend superficial regression methods (which utilize the multiple source–detector pair separations) from sparse optode arrays to application with DOT imaging arrays. In order to accomplish this goal, we modify the method to remove physiological artifacts from deeper sampling channels using an average of shallow measurements. Second, DOT provides three-dimensional image reconstructions and should explicitly separate different tissue layers. We test whether DOT's depth-sectioning can completely remove superficial physiological artifacts. Herein, we assess improvements in signal quality and reproducibility due to these methods using a well-characterized visual paradigm and our high-density DOT system. Both approaches remove noise from the data, resulting in cleaner imaging and more consistent hemodynamic responses. Additionally, the two methods act synergistically, with greater improvements when the approaches are used together

Maternal fluoxetine exposure alters cortical hemodynamic and calcium response of offspring to somatosensory stimuli

Epidemiological studies have found an increased incidence of neurodevelopmental disorders in populations prenatally exposed to selective serotonin reuptake inhibitors (SSRIs). Optical imaging provides a minimally invasive way to determine if perinatal SSRI exposure has long-term effects on cortical function. Herein we probed the functional neuroimaging effects of perinatal SSRI exposure in a fluoxetine (FLX)-exposed mouse model. While resting-state homotopic contralateral functional connectivity was unperturbed, the evoked cortical response to forepaw stimulation was altered in FLX mice. The stimulated cortex showed decreased activity for FLX versus controls, by both hemodynamic responses [oxyhemoglobin (Hb

High-density speckle contrast optical tomography (SCOT) for three dimensional tomographic imaging of the small animal brain

High-density speckle contrast optical tomography (SCOT) utilizing tens of thousands of source-detector pairs, was developed for in vivo imaging of blood flow in small animals. The reduction in cerebral blood flow (CBF) due to local ischemic stroke in a mouse brain was transcanially imaged and reconstructed in three dimensions. The reconstructed volume was then compared with corresponding magnetic resonance images demonstrating that the volume of reduced CBF agrees with the infarct zone at twenty-four hours.Peer ReviewedPostprint (author's final draft

Open-source statistical and data processing tools for wide-field optical imaging data in mice

SIGNIFICANCE: Wide-field optical imaging (WOI) can produce concurrent hemodynamic and cell-specific calcium recordings across the entire cerebral cortex in animal models. There have been multiple studies using WOI to image mouse models with various environmental or genetic manipulations to understand various diseases. Despite the utility of pursuing mouse WOI alongside human functional magnetic resonance imaging (fMRI), and the multitude of analysis toolboxes in the fMRI literature, there is not an available open-source, user-friendly data processing and statistical analysis toolbox for WOI data. AIM: To assemble a MATLAB toolbox for processing WOI data, as described and adapted to combine techniques from multiple WOI groups and fMRI. APPROACH: We outline our MATLAB toolbox on GitHub with multiple data analysis packages and translate a commonly used statistical approach from the fMRI literature to the WOI data. To illustrate the utility of our MATLAB toolbox, we demonstrate the ability of the processing and analysis framework to detect a well-established deficit in a mouse model of stroke and plot activation areas during an electrical paw stimulus experiment. RESULTS: Our processing toolbox and statistical methods isolate a somatosensory-based deficit 3 days following photothrombotic stroke and cleanly localize sensory stimulus activations. CONCLUSIONS: The toolbox presented here details an open-source, user-friendly compilation of WOI processing tools with statistical methods to apply to any biological question investigated with WOI techniques

Evaluation of rigid registration methods for whole head imaging in diffuse optical tomography

Functional brain imaging has become an important neuroimaging technique for the study of brain organization and development. Compared to other imaging techniques, diffuse optical tomography (DOT) is a portable and low-cost technique that can be applied to infants and hospitalized patients using an atlas-based light model. For DOT imaging, the accuracy of the forward model has a direct effect on the resulting recovered brain function within a field of view and so the accuracy of the spatially normalized atlas-based forward models must be evaluated. Herein, the accuracy of atlas-based DOT is evaluated on models that are spatially normalized via a number of different rigid registration methods on 24 subjects. A multileveled approach is developed to evaluate the correlation of the geometrical and sensitivity accuracies across the full field of view as well as within specific functional subregions. Results demonstrate that different registration methods are optimal for recovery of different sets of functional brain regions. However, the “nearest point to point” registration method, based on the EEG 19 landmark system, is shown to be the most appropriate registration method for image quality throughout the field of view of the high-density cap that covers the whole of the optically accessible cortex

Lightweight high-density diffuse optical tomography using sCMOS detection

The widespread adoption of optical neuroimaging has been restricted by the tradeoff between cap wearability and brain coverage [1]. Increased coverage requires more fibers and larger imaging consoles, however these changes drastically reduce the wearability of the imaging cap and the portability of the entire system. The size of the detection fibers, which is driven by signal-to-noise considerations, is the primary obstacle to fabricating more wearable and portable optical neuroimaging arrays. Here we report on a design that leverages the low-noise of scientific CMOS cameras, along with binning and noise reduction algorithms to use fibers with approximately 30x smaller cross-sectional area than current high-density diffuse optical tomography (HD-DOT) systems [2]. We have developed a Super-Pixel sCMOS Diffuse Optical Tomography (SP-DOT) system (Fig. 1a) that uses 200um diameter source and detector fibers, with a lightweight low-profile, wearable design. A super-pixel algorithm leverages pixel binning to provide dynamic range (DNR), Noise Equivalent Power (NEP), and cross- talk (CT) specifications comparable to previous HD-DOT [2]. We have demonstrated retinotopic mapping with a SP-DOT system (Fig. 1). The system has a high DNR (\u3e105), high frame rate (\u3e6Hz) and low NEP (\u3c 9fW/√Hz). Please click Additional Files below to see the full abstract