Neurophotonics最新文献

Significance: Parkinson's disease (PD) is diagnosed when 50% neurodegeneration has occurred. The retina could provide biomarkers that would allow for earlier diagnosis. Retinal spectroscopy is a technique that could be used to find such biomarkers.

Aim: We aimed to find new diagnostic biomarkers for PD following detailed spectral examinations of the retina.

Approach: The newly developed Zilia Ocular device was used to perform spectrometric scans of the optic nerve head (ONH) and the retina of four cynomolgus monkeys (Macaca fascicularis) before and after the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin used to produce the gold-standard animal model of PD. From the spectrometric data, the blood oximetry was calculated, and the diffuse reflectance spectra (DRS) were analyzed to find variations between the two experimental conditions. Post-mortem analyses were also performed on the retina of the four parkinsonian monkeys and four additional control animals.

Results: The analysis of the DRS indicated a lower slope between the 480- and 525-nm wavelengths in both the ONH and the retina. Post-mortem measurements of the retinal layer thicknesses showed that the outer nuclear layer was significantly thinner in MPTP-intoxicated monkeys, compared with controls. Altogether, these results indicate that MPTP altered the optical properties of the ONH and the retina and show that these variations might be explained by MPTP-induced structural changes in the eye fundus, as observed post-mortem.

Conclusions: Overall, our results indicate that spectroscopy could be used as a noninvasive method to detect changes in the retina that occur in PD and that such changes could represent retinal biomarkers for improved diagnosis.

Significance: Mapping the spatial distribution of specific neurons across the entire brain is essential for understanding the neural circuits associated with various brain functions, which in turn requires automated and reliable neuron detection and mapping techniques.

Aim: To accurately identify somatic regions from 3D imaging data and generate reliable soma locations for mapping to diverse brain regions, we introduce NeuronMapper, a brain-wide 3D neuron detection and mapping approach that leverages the power of deep learning.

Approach: NeuronMapper is implemented as a four-stage framework encompassing preprocessing, classification, detection, and mapping. Initially, whole-brain imaging data is divided into 3D sub-blocks during the preprocessing phase. A lightweight classification network then identifies the sub-blocks containing somata. Following this, a Video Swin Transformer-based segmentation network delineates the soma regions within the identified sub-blocks. Last, the locations of the somata are extracted and registered with the Allen Brain Atlas for comprehensive whole-brain neuron mapping.

Results: Through the accurate detection and localization of somata, we achieved the mapping of somata at the one million level within the mouse brain. Comparative analyses with other soma detection techniques demonstrated that our method exhibits remarkably superior performance for whole-brain 3D soma detection.

Conclusions: Our approach has demonstrated its effectiveness in detecting and mapping somata within whole-brain imaging data. This method can serve as a computational tool to facilitate a deeper understanding of the brain's complex networks and functions.

Significance: The imaging of cerebral blood flow in small rodents is crucial for a better understanding of brain functions in healthy and diseased conditions. Existing methods often struggle to provide both superficial and deep tissue blood flow measurements in a non-invasive, flexible, and reliable manner, creating a need for an integrated platform that addresses these limitations.

Aim: We aim to design and develop a multi-modal laser speckle-based imaging platform and associated algorithms to image superficial and deep tissue cerebral blood flow in small rodents.

Approach: A modular design has been adopted to integrate laser speckle contrast imaging and multi-speckle diffuse correlation tomography to a single cerebral blood flow imaging platform for small rodents with an independent module for animal holding and handling. A topographic imaging method, equipped with a filter to remove surface artifacts, was incorporated to image cerebral blood flow changes in response to forepaw and olfactory stimuli activations, with the skull and scalp kept intact.

Results: A significant increase in blood flow was found in the olfactory bulbs of mice post-stimulation by various odors ( $p<0.01$ ). Similarly, forepaw stimulation resulted in a significant increase in blood flow in the contralateral side of the somatosensory cortex with the application of the filter for skull and scalp intact, skull intact, and skull removed cases ( $p<0.01$ ).

Conclusions: We have validated our system through functional studies, demonstrating its capability to detect enhanced blood flow changes across the olfactory bulbs and somatosensory cortex in rodents with potential for broad applications in preclinical research.

Significance: Abnormal gait of children with cerebral palsy (CP) is caused by brain damage or developmental defects, exploring the brain's functional characteristics and regulatory mechanisms is essential for rehabilitation.

Aim: We aim to study the brain function characteristics in children with CP during walking.

Approach: The cortical activation, functional connectivity, information flow, and dynamic state transitions of 17 children with CP and 13 healthy children (HC) were analyzed in the resting and walking states.

Results: The motor cortex (MC) of HC is significantly activated in the walking state, whereas both the prefrontal cortex (PFC) and MC of children with CP are significantly activated. The resting brain functional connectivity of children with CP decreased and showed higher global efficiency and modularity and lower clustering coefficients and local efficiency. During walking, the brain network of children with CP was difficult to maintain a stable global high-connectivity state so the local high-connectivity state became the main connectivity state. For children with CP, more brain resources were allocated to the non-dominant MC during walking, whereas more brain resources were allocated to the dominant MC in HC.

Conclusions: These indicators reflect the characteristics of brain activation, network connectivity, and information regulation in children with CP, which provide the theoretical basis for targeted rehabilitation treatment.

Visible-light optical coherence tomography (vis-OCT) is an emerging OCT technology that uses visible rather than near-infrared illumination and is useful for pre-clinical and clinical imaging. It provides one-micron level axial resolution and distinct scattering and absorption contrast that enables oximetry but requires additional considerations in system implementation and practical settings. We review the development of vis-OCT and demonstrated applications. We also provide insights into prospects and possible technological improvements that may address current challenges.

Significance: Neuroscience of the everyday world requires continuous mobile brain imaging in real time and in ecologically valid environments, which aids in directly translating research for human benefit. Combined functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) studies have increased in demand, as the combined systems can provide great insights into cortical hemodynamics, neuronal activity, and neurovascular coupling. However, fNIRS-EEG studies remain limited in modularity and portability due to restrictions in combined cap designs, especially for high-density (HD) fNIRS measurements.

Aim: We have built and tested custom fNIRS sources that attach to electrodes without decreasing the overall modularity and portability of the probe.

Approach: To demonstrate the design's utility, we screened for any potential interference and performed a HD-fNIRS-EEG measurement with co-located opto-electrode positions during a modified Stroop task.

Results: No observable interference was present from the fNIRS source optodes in the EEG spectral analysis. The performance, fNIRS, and EEG results of the Stroop task supported the trends from previous research. We observed increased activation with both fNIRS and EEG within the regions of interest.

Conclusion: Overall, these results suggest that the co-localization method is a promising approach to multimodal imaging.

Significance: Miniature multiphoton microscopy has revolutionized neuronal imaging in freely behaving animals. However, its shallow depth of field-a result of high axial resolution-combined with a limited field of view (FOV), makes it challenging for researchers to identify regions of interest in three-dimensional space across multimillimeter cranial windows, thereby reducing the system's ease of use.

Aim: We aimed to develop a multimodal imaging platform with enhanced guidance and a standardized workflow tailored for efficient imaging of freely behaving animals.

Approach: We present a wide-field fluorescence navigation system (WF-Nav) featuring a 90-mm working distance, a 4-mm FOV, and single-cell resolution, enabling rapid and precise localization of designated regions. By seamlessly integrating this navigation system with our prior miniature multiphoton microscopes, we established a multimodal platform that supports versatile imaging modalities and seamless transitions to two- or three-photon imaging. Building on this integration, we developed a streamlined workflow for efficient, user-friendly imaging in freely behaving mice.

Results: We validated the system through large-FOV imaging (4 mm), dual-color imaging (920 and 1030 nm), and deep-brain neuronal imaging (up to 1 mm) in either awake mice or freely moving mice. The entire experimental procedure was completed in $\sim 20\min$ , achieving a 100% success rate ( $n=15$ ).

Conclusions: We have developed a comprehensive imaging platform that integrates a single-photon wide-field navigation system with miniature two-photon and three-photon microscopy, leveraging the strengths of each modality. Building on this platform, we established a streamlined workflow tailored for imaging freely behaving animals, markedly expanding its applicability and improving efficiency.

Significance: Multiphoton microscopy serves as an essential tool for high-resolution imaging of the living mouse brain. To facilitate optical access to the brain during imaging, cranial window surgery is commonly used. However, this procedure restricts physical access above the imaging area and hinders the direct delivery of imaging agents and chemical compounds to the brain.

Aim: We aim to develop a method that allows the repeated administration of imaging agents and compounds to the mouse brain while performing in vivo imaging with multiphoton microscopy.

Approach: We have developed a cannula delivery system that enables the implantation of a low-profile cannula nearly parallel to the brain surface at angles as shallow as 8 deg while maintaining compatibility with multiphoton microscopy.

Results: To validate our shallow-angle cannula approach, we performed direct infusion and imaging of various fluorescent cell markers in the brain. In addition, we successfully demonstrated tracking of degenerating neurons over time in Alzheimer's disease mice using Fluoro-Jade C. Furthermore, we showed longitudinal imaging of the partial pressure of oxygen in brain tissue using a phosphorescent oxygen sensor.

Conclusions: Our developed technique should enable a wide range of longitudinal imaging studies in the mouse brain.

Optical neuroimaging has significantly advanced our understanding of brain function, particularly through techniques such as two-photon microscopy, which captures three-dimensional brain structures with sub-cellular resolution. However, traditional methods struggle to record fast, complex neuronal interactions in real time, which are crucial for understanding brain networks and developing treatments for neurological diseases such as Alzheimer's, Parkinson's, and chronic pain. Recent advancements in ultrafast imaging technologies, including kilohertz two-photon microscopy, light field microscopy, and event-based imaging, are pushing the boundaries of temporal resolution in neuroimaging. These techniques enable the capture of rapid neural events with unprecedented speed and detail. This review examines the principles, applications, and limitations of these technologies, highlighting their potential to revolutionize neuroimaging and improve the diagnose and treatment of neurological disorders. Despite challenges such as photodamage risks and spatial resolution trade-offs, integrating these approaches promises to enhance our understanding of brain function and drive future breakthroughs in neuroscience and medicine. Continued interdisciplinary collaboration is essential to fully leverage these innovations for advancements in both basic and clinical neuroscience.

Significance: Cerebral blood flow (CBF) and cerebral blood volume (CBV) are key metrics for regional cerebrovascular monitoring. Simultaneous, non-invasive measurement of CBF and CBV at different brain locations would advance cerebrovascular monitoring and pave the way for brain injury detection as current brain injury diagnostic methods are often constrained by high costs, limited sensitivity, and reliance on subjective symptom reporting.

Aim: We aim to develop a multi-channel non-invasive optical system for measuring CBF and CBV at different regions of the brain simultaneously with a cost-effective, reliable, and scalable system capable of detecting potential differences in CBF and CBV across different regions of the brain.

Approach: The system is based on speckle contrast optical spectroscopy and consists of laser diodes and board cameras, which have been both tested and investigated for safe use on the human head. Apart from the universal serial bus connection for the camera, the entire system, including its battery power source, is integrated into a wearable headband and is powered by 9-V batteries.

Results: The temporal dynamics of both CBF and CBV in a cohort of five healthy subjects were synchronized and exhibited similar cardiac period waveforms across all six channels. The potential use of our six-channel system for detecting the physiological sequelae of brain injury was explored in two subjects, one with moderate and one with significant structural brain damage, where the six-point CBF and CBV measurements were referenced to structural magnetic resonance imaging (MRI) scans.

Conclusions: We pave the way for a viable multi-point optical instrument for measuring CBF and CBV. Its cost-effectiveness allows for baseline metrics to be established prior to injury in populations at risk for brain injury.