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High-resolution awake mouse functional magnetic resonance imaging (fMRI) remains challenging despite extensive efforts to address motion-induced artifacts and stress. This study introduces an implantable radio frequency (RF) surface coil design that minimizes image distortion caused by the air/tissue interface of mouse brains while simultaneously serving as a headpost for fixation during scanning. Furthermore, this study provides a thorough acclimation method used to accustom animals to the MRI environment minimizing motion-induced artifacts. Using a 14 T scanner, high-resolution fMRI enabled brain-wide functional mapping of visual and vibrissa stimulation at 100 µm×100 µm×200 µm resolution with a 2 s per frame sampling rate. Besides activated ascending visual and vibrissa pathways, robust blood oxygen level-dependent (BOLD) responses were detected in the anterior cingulate cortex upon visual stimulation and spread through the ventral retrosplenial area (VRA) with vibrissa air-puff stimulation, demonstrating higher-order sensory processing in association cortices of awake mice. In particular, the rapid hemodynamic responses in VRA upon vibrissa stimulation showed a strong correlation with the hippocampus, thalamus, and prefrontal cortical areas. Cross-correlation analysis with designated VRA responses revealed early positive BOLD signals at the contralateral barrel cortex (BC) occurring 2 s prior to the air-puff in awake mice with repetitive stimulation, which was not detected using a randomized stimulation paradigm. This early BC activation indicated a learned anticipation through the vibrissa system and association cortices in awake mice under continuous exposure of repetitive air-puff stimulation. This work establishes a high-resolution awake mouse fMRI platform, enabling brain-wide functional mapping of sensory signal processing in higher association cortical areas. 

Recent innovations in virtual and mixed-reality (VR/MR) technologies have enabled innovative hands-on training applications in high-risk/high-value fields such as medicine, flight, and worker-safety. Here, we present a detailed description of a novel VR/MR tactile user interactions/interface (TUI) hardware and software development framework that enables the rapid and cost-effective no-code development, optimization, and distribution of fully authentic hands-on VR/MR laboratory training experiences in the physical and life sciences. We applied our framework to the development and optimization of an introductory pipette calibration activity that is often carried out in real chemistry and biochemistry labs. Our approach provides users with nuanced real-time feedback on both their psychomotor skills during data acquisition and their attention to detail when conducting data analysis procedures. The cost-effectiveness of our approach relative to traditional face-to-face science labs improves access to quality hands-on science lab experiences. Importantly, the no-code nature of this Hands-On Virtual-Reality (HOVR) Lab platform enables faculties to iteratively optimize VR/MR experiences to meet their student’s targeted needs without costly software development cycles. Our platform also accommodates TUIs using either standard virtual-reality controllers (VR TUI mode) or fully functional hand-held physical lab tools (MR TUI mode). In the latter case, physical lab tools are strategically retrofitted with optical tracking markers to enable tactile, experimental, and analytical authenticity scientific experimentation. Preliminary user study data highlights the strengths and weaknesses of our generalized approach regarding student affective and cognitive student learning outcomes. 

Recently, there has been a growing interest in ultra-fast fMRI mapping. We are providing an optimized pulse sequence method for a 2D line-scanning technique, allowing for the detection of dynamic MRI signals with a high temporal resolution (6 ms). This work addresses an intriguing observation using MRI to directly detect neuronal activity in the brain; a topic that has been investigated by many scientists in the past few decades. This FLASH-based fMRI pulse sequence enables the ultrafast sampling of signals by reshuffling single k-space line acquisitions across multiple repetitions as a function of time for a given block design stimulation paradigm. 

Despite recent advances in deep learning, object detection and tracking still require considerable manual and computational effort. First, we need to collect and create a database of hundreds or thousands of images of the target objects. Next we must annotate or curate the images to indicate the presence and position of the target objects within those images. Finally, we must train a CNN (convolution neural network) model to detect and locate the target objects in new images. This training is usually computationally intensive, consists of thousands of epochs, and can take tens of hours for each target object. Even after the model training in completed, there is still a chance of failure if the real-time tracking and object detection phases lack sufficient accuracy, precision, and/or speed for many important applications. Here we present a system and approach which minimizes the computational expense of the various steps in the training and real-time tracking process outlined above of for applications in the development of mixed-reality science laboratory experiences by using non-intrusive object-encoding 2D QR codes that are mounted directly onto the surfaces of the lab tools to be tracked. This system can start detecting and tracking it immediately and eliminates the laborious process of acquiring and annotating a new training dataset for every new lab tool to be tracked. 

Abstract High-resolution awake mouse fMRI remains challenging despite extensive efforts to address motion-induced artifacts and stress. This study introduces an implantable radiofrequency (RF) surface coil design that minimizes image distortion caused by the air/tissue interface of mouse brains while simultaneously serving as a headpost for fixation during scanning. Using a 14T scanner, high-resolution fMRI enabled brain-wide functional mapping of visual and vibrissa stimulation at 100x100x200µm resolution with a 2s per frame sampling rate. Besides activated ascending visual and vibrissa pathways, robust BOLD responses were detected in the anterior cingulate cortex upon visual stimulation and spread through the ventral retrosplenial area (VRA) with vibrissa air-puff stimulation, demonstrating higher-order sensory processing in association cortices of awake mice. In particular, the rapid hemodynamic responses in VRA upon vibrissa stimulation showed a strong correlation with the hippocampus, thalamus, and prefrontal cortical areas. Cross-correlation analysis with designated VRA responses revealed early positive BOLD signals at the contralateral barrel cortex (BC) occurring 2 seconds prior to the air-puff in awake mice with repetitive stimulation, which was not detectable with the randomized stimulation paradigm. This early BC activation indicated learned anticipation through the vibrissa system and association cortices in awake mice under continuous training of repetitive air-puff stimulation. This work establishes a high-resolution awake mouse fMRI platform, enabling brain-wide functional mapping of sensory signal processing in higher association cortical areas. Significance StatementThis awake mouse fMRI platform was developed by implementing an advanced implantable radiofrequency (RF) coil scheme, which simultaneously served as a headpost to secure the mouse head during scanning. The ultra-high spatial resolution (100x100x200µm) BOLD fMRI enabled the brain-wide mapping of activated visual and vibrissa systems during sensory stimulation in awake mice, including association cortices, e.g. anterior cingulate cortex and retrosplenial cortex, for high order sensory processing. Also, the activation of barrel cortex at 2 s prior to the air-puff indicated a learned anticipation of awake mice under continuous training of the repetitive vibrissa stimulation. 

Abstract The perivascular space (PVS) plays a crucial role in facilitating the clearance of waste products and the exchange of cerebrospinal fluid and interstitial fluid in the central nervous system. While optical imaging methods identify the glymphatic transport of fluorescent tracers through PVS of surface-diving arteries, their limited depth penetration impedes the study of glymphatic dynamics in deep brain regions. In this study, we introduced a novel high-resolution dynamic contrast-enhanced MRI mapping approach based on single-vessel multi-gradient-echo methods. This technique allowed the differentiation of penetrating arterioles and venules from adjacent parenchymal tissue voxels and enabled the detection of Gd-enhanced signals coupled to PVS of penetrating arterioles in the deep cortex and hippocampus. By directly infusing Gd into the lateral ventricle, we eliminated delays in cerebrospinal fluid flow and focused on PVS Gd transport through PVS of hippocampal arterioles. The study revealed significant PVS-specific Gd signal enhancements, shedding light on glymphatic function in deep brain regions. These findings advance our understanding of brain-wide glymphatic dynamics and hold potential implications for neurological conditions characterized by impaired waste clearance, warranting further exploration of their clinical relevance and therapeutic applications. 

Abstract High‐field preclinical functional MRI (fMRI) is enabled the high spatial resolution mapping of vessel‐specific hemodynamic responses, that is single‐vessel fMRI. In contrast to investigating the neuronal sources of the fMRI signal, single‐vessel fMRI focuses on elucidating its vascular origin, which can be readily implemented to identify vascular changes relevant to vascular dementia or cognitive impairment. However, the limited spatial and temporal resolution of fMRI is hindered hemodynamic mapping of intracortical microvessels. Here, the radial encoding MRI scheme is implemented to measure BOLD signals of individual vessels penetrating the rat somatosensory cortex. Radial encoding MRI is employed to map cortical activation with a focal field of view (FOV), allowing vessel‐specific functional mapping with 50 × 50 µm²in‐plane resolution at a 1 to 2 Hz sampling rate. Besides detecting refined hemodynamic responses of intracortical micro‐venules, the radial encoding‐based single‐vessel fMRI enables the distinction of fMRI signals from vessel and peri‐vessel voxels due to the different contribution of intravascular and extravascular effects.