Focused Ultrasound Neuromodulation of Human In Vitro Neural Cultures in Multi-Well Microelectrode Arrays.

The neuromodulatory effects of focused ultrasound (FUS) have been demonstrated in animal models, and FUS has been used successfully to treat movement and psychiatric disorders in humans. However, despite the success of FUS, the mechanism underlying its effects on neurons remains poorly understood, making treatment optimization by tuning FUS parameters difficult. To address this gap in knowledge, we studied human neurons in vitro using neurons cultured from human-induced pluripotent stem cells (HiPSCs). Using HiPSCs allows for the study of human-specific neuronal behaviors in both physiologic and pathologic states. This report presents a protocol for using a high-throughput system that enables the monitoring and quantification of the neuromodulatory effects of FUS on HiPSC neurons. By varying the FUS parameters and manipulating the HiPSC neurons through pharmaceutical and genetic modifications, researchers can evaluate the neural responses and elucidate the neuro-modulatory effects of FUS on HiPSC neurons. This research could have significant implications for the development of safe and effective FUS-based therapies for a range of neurological and psychiatric disorders.

Photoacoustic Lifetime Imaging of Hypoxia.

We present an approach based on photoacoustic lifetime imaging (PALI) to map the distribution of oxygen partial pressure (pO2) in tissue. This method utilizes methylene blue, a dye widely used in clinical applications, as an oxygen-sensitive imaging agent. PALI measurement of oxygen relies upon pO2-dependent excitation lifetime of the dye. The technique maps the excited triplet state of oxygen-sensitive dye, thus reflecting the spatial and temporal distributions of tissue oxygen.

Tethered spinal cord tension assessed via ultrasound elastography in computational and intraoperative human studies.

BACKGROUND: Tension in the spinal cord is a trademark of tethered cord syndrome. Unfortunately, existing tests cannot quantify tension across the bulk of the cord, making the diagnostic evaluation of stretch ambiguous. A potential non-destructive metric for spinal cord tension is ultrasound-derived shear wave velocity (SWV). The velocity is sensitive to tissue elasticity and boundary conditions including strain. We use the term Ultrasound Tensography to describe the acoustic evaluation of tension with SWV. METHODS: Our solution Tethered cord Assessment with Ultrasound Tensography (TAUT) was utilized in three sub-studies: finite element simulations, a cadaveric benchtop validation, and a neurosurgical case series. The simulation computed SWV for given tensile forces. The cadaveric model with induced tension validated the SWV-tension relationship. Lastly, SWV was measured intraoperatively in patients diagnosed with tethered cords who underwent treatment (spinal column shortening). The surgery alleviates tension by decreasing the vertebral column length. RESULTS: Here we observe a strong linear relationship between tension and squared SWV across the preclinical sub-studies. Higher tension induces faster shear waves in the simulation (R2 = 0.984) and cadaveric (R2 = 0.951) models. The SWV decreases in all neurosurgical procedures (p < 0.001). Moreover, TAUT has a c-statistic of 0.962 (0.92-1.00), detecting all tethered cords. CONCLUSIONS: This study presents a physical, clinical metric of spinal cord tension. Strong agreement among computational, cadaveric, and clinical studies demonstrates the utility of ultrasound-induced SWV for quantitative intraoperative feedback. This technology is positioned to enhance tethered cord diagnosis, treatment, and postoperative monitoring as it differentiates stretched from healthy cords.

Tethered spinal cord syndrome occurs when surrounding tissue attaches to and causes stretching across the spinal cord. People with a tethered cord can experience weakness, pain, and loss of bladder control. Although increased tension in the spinal cord is known to cause these symptoms, evaluating the amount of stretching remains challenging. We investigated the ability of an ultrasound imaging approach to measure spinal cord tension. We studied our method in a computer simulation, a benchtop validation model, and in six people with tethered cords during surgery that they were undergoing to reduce tension. In each phase, the approach could detect differences between stretched spinal cords and spinal cords in a healthy state. Our method could potentially be used in the future to improve the care of people with a tethered cord.

Unidirectional brain-computer interface: Artificial neural network encoding natural images to fMRI response in the visual cortex.

While significant advancements in artificial intelligence (AI) have catalyzed progress across various domains, its full potential in understanding visual perception remains underexplored. We propose an artificial neural network dubbed VISION, an acronym for "Visual Interface System for Imaging Output of Neural activity," to mimic the human brain and show how it can foster neuroscientific inquiries. Using visual and contextual inputs, this multimodal model predicts the brain's functional magnetic resonance imaging (fMRI) scan response to natural images. VISION successfully predicts human hemodynamic responses as fMRI voxel values to visual inputs with an accuracy exceeding state-of-the-art performance by 45%. We further probe the trained networks to reveal representational biases in different visual areas, generate experimentally testable hypotheses, and formulate an interpretable metric to associate these hypotheses with cortical functions. With both a model and evaluation metric, the cost and time burdens associated with designing and implementing functional analysis on the visual cortex could be reduced. Our work suggests that the evolution of computational models may shed light on our fundamental understanding of the visual cortex and provide a viable approach toward reliable brain-machine interfaces.

Disruption of the Blood-Spinal Cord Barrier using Low-Intensity Focused Ultrasound in a Rat Model.

Low-intensity focused ultrasound (LIFU) uses ultrasonic pulsations at lower intensities than ultrasound and is being tested as a reversible and precise neuromodulatory technology. Although LIFU-mediated blood-brain barrier (BBB) opening has been explored in detail, no standardized technique for blood-spinal cord barrier (BSCB) opening has been established to date. Therefore, this protocol presents a method for successful BSCB disruption using LIFU sonication in a rat model, including descriptions of animal preparation, microbubble administration, target selection and localization, as well as BSCB disruption visualization and confirmation. The approach reported here is particularly useful for researchers who need a fast and cost-effective method to test and confirm target localization and precise BSCB disruption in a small animal model with a focused ultrasound transducer, evaluate the BSCB efficacy of sonication parameters, or explore applications for LIFU at the spinal cord, such as drug delivery, immunomodulation, and neuromodulation. Optimizing this protocol for individual use is recommended, especially for advancing future preclinical, clinical, and translational work.

Oxygen Imaging for Non-Invasive Metastasis Detection.

Sentinel lymph node (SLN) biopsy is an integral part of treatment planning for a variety of cancers as it evaluates whether a tumor has metastasized, an event that significantly reduces survival probability. However, this invasive procedure is associated with patient morbidity, and misses small metastatic deposits, resulting in the removal of additional nodes for tumors with high metastatic probability despite a negative SLN biopsy. To prevent this over-treatment and its associated morbidities for patients that were truly negative, we propose a tissue oxygen imaging method called Photoacoustic Lifetime Imaging (PALI) as an alternative or supplementary tool for SLN biopsy. As the hyper-metabolic state of cancer cells significantly depresses tissue oxygenation compared to normal tissue even for small metastatic deposits, we hypothesize that PALI can sensitively and specifically detect metastases. Before this hypothesis is tested, however, PALI's maximum imaging depth must be evaluated to determine the cancer types for which it is best suited. To evaluate imaging depth, we developed and simulated a phantom composed of tubing in a tissue-mimicking, optically scattering liquid. Our simulation and experimental results both show that PALI's maximum imaging depth is 16 mm. As most lymph nodes are deeper than 16 mm, ways to improve imaging depth, such as directly delivering light to the node using penetrating optical fibers, must be explored.

Virtual fluoroscopy for intraoperative C-arm positioning and radiation dose reduction.

Positioning of an intraoperative C-arm to achieve clear visualization of a particular anatomical feature often involves repeated fluoroscopic views, which cost time and radiation exposure to both the patient and surgical staff. A system for virtual fluoroscopy (called FluoroSim) that could dramatically reduce time- and dose-spent "fluoro-hunting" by leveraging preoperative computed tomography (CT), encoded readout of C-arm gantry position, and automatic 3D-2D image registration has been developed. The method is consistent with existing surgical workflow and does not require additional tracking equipment. Real-time virtual fluoroscopy was achieved via mechanical encoding of the C-arm motion, C-arm geometric calibration, and patient registration using a single radiograph. The accuracy, time, and radiation dose associated with C-arm positioning were measured for FluoroSim in comparison with conventional methods. Five radiology technologists were tasked with acquiring six standard pelvic views pertinent to sacro-illiac, anterior-inferior iliac spine, and superior-ramus screw placement in an anthropomorphic pelvis phantom using conventional and FluoroSim approaches. The positioning accuracy, exposure time, number of exposures, and total time for each trial were recorded, and radiation dose was characterized in terms of entrance skin dose and in-room scatter. The geometric accuracy of FluoroSim was measured to be [Formula: see text]. There was no significant difference ([Formula: see text]) observed in the accuracy or total elapsed time for C-arm positioning. However, the total fluoroscopy time required to achieve the desired view decreased by 4.1 s ([Formula: see text] for conventional, compared with [Formula: see text] for FluoroSim, [Formula: see text]), and the total number of exposures reduced by 4.0 ([Formula: see text] for conventional, compared with [Formula: see text] for FluoroSim, [Formula: see text]). These reductions amounted to a 50% to 78% decrease in patient entrance skin dose and a 55% to 70% reduction in in-room scatter. FluoroSim was found to reduce the radiation exposure required in C-arm positioning without diminishing positioning time or accuracy, providing a potentially valuable tool to assist technologists and surgeons.

Defining Optimal Head-Tilt Position of Resuscitation in Neonates and Young Infants Using Magnetic Resonance Imaging Data.

Head-tilt maneuver assists with achieving airway patency during resuscitation. However, the relationship between angle of head-tilt and airway patency has not been defined. Our objective was to define an optimal head-tilt position for airway patency in neonates (age: 0-28 days) and young infants (age: 29 days-4 months). We performed a retrospective study of head and neck magnetic resonance imaging (MRI) of neonates and infants to define the angle of head-tilt for airway patency. We excluded those with an artificial airway or an airway malformation. We defined head-tilt angle a priori as the angle between occipito-ophisthion line and ophisthion-C7 spinous process line on the sagittal MR images. We evaluated medical records for Hypoxic Ischemic Encephalopathy (HIE) and exposure to sedation during MRI. We analyzed MRI of head and neck regions of 63 children (53 neonates and 10 young infants). Of these 63 children, 17 had evidence of airway obstruction and 46 had a patent airway on MRI. Also, 16/63 had underlying HIE and 47/63 newborn infants had exposure to sedative medications during MRI. In spontaneously breathing and neurologically depressed newborn infants, the head-tilt angle (median ± SD) associated with patent airway (125.3° ± 11.9°) was significantly different from that of blocked airway (108.2° ± 17.1°) (Mann Whitney U-test, p = 0.0045). The logistic regression analysis showed that the proportion of patent airways progressively increased with an increasing head-tilt angle, with > 95% probability of a patent airway at head-tilt angle 144-150°.