Acute brain injury (ABI) is a complex disease process that begins with an initial insult followed by secondary injury resulting from disturbances in cerebral physiology. In the metabolically active brain, early recognition of physiologic derangements is critical in enabling clinicians with the insight to adjust therapeutic interventions and reduce risk of ischemia and permanent injury. Current established approaches for monitoring cerebral physiology include the neurologic physical examination, traditional brain imaging such as computed tomography (CT) and magnetic resonance imaging (MRI), electroencephalography (EEG), and bedside modalities such as invasive parenchymal probes and transcranial doppler ultrasound. Diffuse optical spectroscopy (DOS), diffuse correlation spectroscopy (DCS), and optical coherence tomography (OCT) are non-invasive optical techniques that have shown promise in measuring clinically relevant changes in cerebral physiology. These new modalities may offer clinicians significant benefits as they are safe, can be utilized at the point-of-care, and provide continuous measurements. This paper reviews major causes of primary and secondary ABI encountered in neurocritical care units, conventional measures of cerebral physiology during ABI, and emerging non-invasive optical techniques that have significant potential for translation to the bedside.

Rapid sub-nanometer neuronal deformations have been shown to occur as a consequence of action potentials in vitro, allowing for optical registration of discrete axonal and synaptic depolarizations. Such optically-measured deformations are a novel signature for recording neural activity. We demonstrate this signature can be extended to in vivo measurements through recording of rapid neuronal deformations on the population level with holographic, optical phase-based recordings. Our system demonstrates, for the first time, non-invasive recordings of in vivo tissue deformation associated with population level neuronal activity, including through-skull. We confirmed this technique across a range of neural activation models, including direct epidural focal electrical stimulation, anesthetic-induced cortical deactivation, activation of primary somatosensory cortex via whisker barrel stimulation, and pharmacologically-induced seizures. Collectively, we show holographic imaging provides a pathway for high-resolution, label-free, non-invasive recording of transcranial in vivo neural activity at depth, making it highly advantageous for studying neural function and signaling.

Rapid sub-nanometer neuronal deformations have been shown to occur as a consequence of action potentials in vitro , allowing for registration of discrete axonal and synaptic depolarizations and thus providing a novel signature for recording neural activity (1–3). We demonstrate that this signature can be extended to in vivo measurements through recording of rapid neuronal deformations on the population level with optical phase-based recordings. Complicating these measurements is the optical phase noise due to microvascular flow as well as the presence of significant tissue clutter (deformation) associated with physiologic processes (e.g., heart and respiratory rate). These recordings were acquired using a full-field holographic imaging system with spatiotemporal resolutions of less than 1 ms and 0.1 mm 3 over a 3 mm diameter field of view (FOV). Our system demonstrates, for the first time, the ability to non-invasively record in vivo tissue deformation associated with population level neuronal activity. We confirmed this technique across a range of neural activation models, including direct epidural focal electrical stimulation (FES), activation of primary somatosensory cortex via whisker barrel stimulation, and pharmacologically-induced seizures. Calibrated displacement measurements of the associated tissue deformations provided additional insight into the underlying neural activation mechanisms. Collectively, we show that holographic imaging provides a pathway for high-resolution, label-free, non-invasive recording of transcranial in vivo neural activity at depth, making it highly advantageous for studying neural function and signaling.

The Defense Advanced Research Projects Agency's Revolutionizing Prosthetics program demonstrated the potential for neural interface technologies, enabling patients to control and feel a prosthetic arm and hand, and even pilot an aircraft in simulation. These landmark achievements required invasive, chronically implanted penetrating electrode arrays, which are fundamentally incompatible with applications for the able-bodied warfighter or for long-term clinical applications. Noninvasive neural recording approaches have not been as effective, suffering from severe limitations in temporal and spatial resolution, signal-to-noise ratio, depth penetration, portability, and cost. To help close these gaps, researchers at the Johns Hopkins University Applied Physics Laboratory (APL) are exploring optical techniques that record correlates of neural activity through either hemodynamic signatures or neural tissue motion as represented by the fast optical signal. Although these two signatures differ in terms of spatiotemporal resolution and depth at which the neural activity is recorded, they provide a path to realizing a portable, low-cost, high-performance brain-computer interface. If successful, this work will help usher in a new era of computing at the speed of thought.

A combination of experimental lidar results and shape-dependent scatter amplitude matrix calculations are used to explore the utility of polarimetric lidars for aerosol characterization. Solutions are developed for the induced polarization vector response of skewed spheroidal particles and the scatter is then computed using an improved anomalous diffraction approximation method. Experimental data was collected on biological simulant, chemical simulant, and interferent aerosol clouds using a 1047 nm micropulse lidar designed to measure the simultaneous depolarization using a linearly polarized source. Depolarization signatures obtained during testing show a clear difference between wet and dry biological simulant aerosols, wet chemical simulant releases, and some interferents. Combining these measurements with the shape-dependent model calculations help us understand the unique polarimetric signatures that may be exploited for aerosol characterization using stand-off lidar techniques.

Optical neuroimaging technologies aim to observe neural tissue structure and function by detecting changes in optical signals (scatter, absorption, etc…) that accompany a range of anatomical and functional properties of brain tissue. At present, there is a tradeoff between spatial and temporal resolution that is not currently optimized in a single imaging modality. We have developed a coherent optical imaging approach that begins to remove this trade-off and have demonstrated high spatiotemporal (<100µm and >100Hz) in-vivo recordings of neural activity over large 20mm2 areas.