High-Density Diffuse Optical Tomography (HD-DOT) is an emerging modality that uses a dense array of overlapping measurements that provides image quality validated against fMRI. Here, we doubled the optode density of our previously reported HD-DOT system, expanded the field of view and achieve higher resolution and image quality. Task-based and movie viewing activation maps reveal strong contrast to noise of cortical function across these tasks. Additionally, we show the expanded field of view covers functional networks not available with our previously reported HD-DOT system. This system is promising for future studies using resting state functional connectivity, decoding, and naturalistic paradigms.

Previous work established that optical properties (absorption (μa) and reduced scattering (μs’) coefficients) can affect speckle contrast, and hence blood-flow measurements. Here, we introduce a cerebral metabolic imaging system that combines laser speckle imaging and spatial frequency domain imaging for rodents. Using measured optical properties and speckle contrast values, we developed a method of achieving absolute measurements of cerebral blood flow (CBF) using the correlation diffusion. We tested our approach with a mouse hindpaw stimulation model and observed a more substantial increase in peak CBF than conventional speckle contrast analysis.

Functional MRI has decoded complex information about naturalistic stimuli using brain responses, but other non-invasive technologies have not achieved similar decoding capabilities. To evaluate feasibility of naturalistic visual decoding with Diffuse Optical Tomography (DOT), a 6.5-mm-spaced optode grid was employed to decode which of four 90-second movies was viewed by human subjects. >90% and >80% average decoding accuracy were achieved using a template-matching decoder within and between sessions, respectively. Average accuracy remained >60% and above chance using a model-based decoder to identify four and 40 clips outside the decoder's training set, respectively. DOT therefore has potential for more-complex neural decoding.

High-Density Speckle Contrast Optical Tomography (HD-SCOT) is an optical technique with the potential to address the limitations of current techniques for imaging Cerebral Blood Flow (CBF). To evaluate HD-SCOT’s performance, we developed an anatomical-head-based simulation to obtain HD-SCOT measurements and reconstructed images. We observed that including longer source-detector distances can reduce localization errors. Even though speckle contrast decreases with increased exposure times, the System-to-Noise Ratio (SNR) can increase dramatically. For instrumentation, we evaluated statistics of speckles through a multi-mode fiber (MMF) bundle and demonstrated the feasibility of tracking pulsatile blood flow in a human subject using MMFs.

Psychedelics, which effects appear to be mediated via seratonin-2A receptors(5-HT2AR), are a promising therapeutic. Recent human studies have shown drastic changes in functional network organization but may be confounded due to Serotonin’s vasoconstriction effects. We aimed to determine if 5-HT2AR agonism (via Lisuride), alone, differentially affect cortical neuronal and hemodynamic activity, functional connectivity (FC), and neurovascular coupling (NVC). Eight Thy1-jRGECO1a mice were imaged for 60-minutes under awake, resting-state conditions using wide-field optical imaging. Lisuride significantly reduced neuronal and hemodynamic bilateral FC and activity in a region- and frequency-band-specific manner. Furthermore, delayed NVC was observed. Results suggest 5-HT2AR agonism alters hemodynamic activity, FC and NVC. Future work will evaluate acute effects of commonly used psychedelics on brain function and differentiate hallucinatory vs non-hallucinatory 5-HT2A receptor activation.

Cerebral microhemorrhages (CMH) are the accumulation of hemosiderin-iron deposits which are associated with cognitive impairments. CMH are suspected to be the result of the deterioration of cerebral microvessels. Despite the clinical significance of CMH, our understanding of CMH formation remains limited. Standard histology for CMH visualization is constrained by thin planar views obtained sparsely throughout brain tissue. This limitation can misrepresent the true size and extent of CMH. Here we incorporate tissue clearing to capture a complete view of CMH and compare it to that of a two-dimensional approach.

Neurovascular coupling, the interplay between neurons and the vasculature, is thought be essential to sustain brain function. This coupling mechanism can be very sensitive to pathologies that Increase Intracranial Pressure (ICP). Head Fixed Body Tilt (HFBT) experiments were conducted in awake mice to induce changes in ICP. Images sensitive to neuronal and vascular responses were acquired during whisker stimulation and rest before, during and after body tilting. Resting state data was used to extract Hemodynamic Responses Functions (HRF) using a double gamma model. Changes in the shape of the HRF were used to assess the impact of potential changes in ICP. We also analyzed resting state imaging data to characterize the potential effects of ICP on hemodynamic responses across brain regions.

There are currently no evidence-based methods to detect cannabis-impaired driving, and current field sobriety tests with gold-standard, drug recognition evaluations are resource-intensive and may be prone to bias. This study evaluated the capability of a simple, portable imaging method to accurately detect individuals with Δ9-tetrahydrocannabinol (THC) impairment. Comparing resting state connectivity of post-dose THC and post-dose placebo in impaired participants, we identified decreased connectivity after THC. Furthermore, using standard machine learning algorithms, we were able to predict impairment with >70% accuracy.

Laser scanning two-photon fluorescence microscopy is widely used for in vivo neural recordings. Commercially available imaging systems can support an imaging rate of up to tens of Hz. With the emergence of faster function indicators, an imaging rate of hundreds of Hz is needed, which is beyond the capability of the widely used systems. To broadly enable such high-speed imaging capabilities in neuroscience research, we have developed an optical gearbox system that is compatible with the commonly available hardware systems. We employed the gearbox-based two-photon system for high-speed recording of neuronal and vascular dynamics in the animal brain.

Direct imaging of metabolism at sub-cellular resolution provides insights to understand single-cell physiology at spatially resolved manner. Here, we presented a metabolic profiling platform based on Optical Photothermal Infrared (OPTIR) spectroscopic imaging that enables in situ lipid metabolism characterization at sub-cellular resolution. We applied the developed metabolic imaging platform to study lipid synthesis from azide-labeled fatty acids across various systems including neuroglioma cells, human-induced pluripotent stem cells (iPSCs), iPSC-derived microglia cells, and iPSC-derived brain organoids. The specificity of the developed platform was further improved by coupling a fluorescence module that enables cell type specific-metabolic profiling. Collectivity, the proposed metabolic imaging platform opens a vast potential for in situ metabolism characterization at the single-cell level.

Our wearable, modular, high-density diffuse optical tomography system addresses the gap for safe, portable, high-resolution neuroimaging technologies. Miniaturized optoelectronics, improved mechanical design, and Wi-Fi connectivity fit into small modules connected to portable power, allowing free movement. Previous systems have sparse grids, retain mobility-restricting tethers, and/or lack spring-loaded optodes. Our high dynamic range, sensitivity, and SNR at a range of source-detector distances improves resolution compared to sparse arrays. In vivo tests show good benchmark metrics as well as retinotopic mapping. The lightweight system has been tested under different ambulatory conditions. Our wearable system addresses the need for portable, high-resolution, noninvasive neuroimaging modalities.

Traditional Bivariate Functional Connectivity (BFC) computes correlations between two target brain regions (ROIs), which has the potential weakness of ignoring associations with other ROIs. Multivariate functional connectivity (MFC) solves for weights between one target ROI and the rest of the brain; thereby changing the question of correlation to a question of prediction, which is potentially more powerful. The fundamental difference lies essentially in multiplying the seed region time-course by the transpose of the data matrix (BFC) vs. multiplying it by the pseudoinverse of the data matrix (MFC). Human resting-state DOT data was analyzed for homotopic contralateral FC using both approaches.

Optical calcium imaging has been widely used in neuroscience. However, a major limitation of optical measurement is the limited imaging depth in live mammalian brain tissue. Although miniature optical imaging probes have been employed to access the deep brain regions, their imaging field-of-view is very limited, resulting in low measurement throughput and success rate. Recently, we have developed the Clear Optically Matched Panoramic Access Channel Technique (COMPACT), which can improve the tissue access volume by two to three orders of magnitude. Here, we present our latest results of 0.5 mm diameter COMPACT systems.

We report a two-photon excitation fluorescence microscopy imager that uses a fiber-delivered fs supercontinuum (SC) generation source to achieve simultaneous dual-wavelength imaging. The SC generation is based on pumping a polarization-maintaining photonic crystal fiber with a fiber laser. The SC is then delivered to the imaging head through a broadband hollow-core fiber. Excitation wavelengths centered at 920 nm and 1180 nm were selected, which enabled simultaneous imaging of neurons transfected with GCaMP6 and administrated with muscimol-conjugated BODIPY. Imaging results of calcium dynamics of in vivo mouse brain and cultured primary neurons were collected to demonstrate the technology feasibility.

One of the challenges in indirect measurements of electrical activity is its representation as biologically-relevant features. Non-invasive techniques for controlling neural activity, such as optogenetics with simultaneous optical imaging, have emerged as powerful and versatile tools. We demonstrated Superfast Polarization-sensitive Off-axis Full-field (SPoOF) OCM to image changes to both the optical phase and birefringence from the electrical activity of neurons at cellular resolution for an entire network at a millisecond scale. Here, we demonstrate all-optical neurophysiology with SPoOF OCM and optical excitation as a non-invasive versatile technique for studying neural circuits at high throughput, and a method to convert optical metrics to biologically relevant electrical features.

We suggest the multi-functions of nanodiamond (ND) as a neuritogenesis promoter and super-resolution imaging probe. Owing to the photoblinking property of ND, bioimages were visualized in super-resolution using the direct stochastic optical reconstruction microscopy process, which resolved the ambiguity in the distinction of nearby particles. In this study, NDs were endocytosed by HT-22 hippocampal neuronal cells and promoted a spontaneous neuritogenesis without any differentiation factor, which was visualized by NDs as super-resolution imaging probes without toxicity. In conclusion, it is suggested that ND has excellent neuritogenic capability and potential as a super-resolution neural imaging probe with its outstanding biocompatibility.