Simultaneous High-Frame-Rate Acoustic Plane-Wave and Optical Imaging of Intracranial Cavitation in Polyacrylamide Brain Phantoms during Blunt Force Impact.

Blunt and blast impacts occur in civilian and military personnel, resulting in traumatic brain injuries necessitating a complete understanding of damage mechanisms and protective equipment design. However, the inability to monitor in vivo brain deformation and potential harmful cavitation events during collisions limits the investigation of injury mechanisms. To study the cavitation potential, we developed a full-scale human head phantom with features that allow a direct optical and acoustic observation at high frame rates during blunt impacts. The phantom consists of a transparent polyacrylamide material sealed with fluid in a 3D-printed skull where windows are integrated for data acquisition. The model has similar mechanical properties to brain tissue and includes simplified yet key anatomical features. Optical imaging indicated reproducible cavitation events above a threshold impact energy and localized cavitation to the fluid of the central sulcus, which appeared as high-intensity regions in acoustic images. An acoustic spectral analysis detected cavitation as harmonic and broadband signals that were mapped onto a reconstructed acoustic frame. Small bubbles trapped during phantom fabrication resulted in cavitation artifacts, which remain the largest challenge of the study. Ultimately, acoustic imaging demonstrated the potential to be a stand-alone tool, allowing observations at depth, where optical techniques are limited.

Measuring vibrations on a biofidelic brain using ferroelectret nanogenerator.

Our knowledge of traumatic brain injury has been fast growing with the emergence of new markers pointing to various neurological changes that the brain undergoes during an impact or any other form of concussive event. In this work, we study the modality of deformations on a biofidelic brain system when subject to blunt impacts, highlighting the importance of the time-dependent behavior of the resulting waves propagating through the brain. This study is carried out using two different approaches involving optical (Particle Image Velocimetry) and mechanical (flexible sensors) in the biofidelic brain. Results show that the system has a natural mechanical frequency of [Formula: see text] 25 oscillations per second, which was confirmed by both methods, showing a positive correlation with one another. The consistency of these results with previously reported brain pathology validates the use of either technique, and establishes a new, simpler mechanism to study brain vibrations by using flexible piezoelectric patches. The visco-elastic nature of the biofidelic brain is validated by observing the the relationship between both methods at two different time intervals, by using the information of the strain and stress inside the brain from the Particle Image Velocimetry and flexible sensor, respectively. A non-linear stress-strain relationship was observed and justified to support the same.

Characterization of material properties and deformation in the ANGUS phantom during mild head impacts using MRI.

Traumatic brain injury (TBI) is a major health concern affecting both military and civilian populations. Despite notable advances in TBI research in recent years, there remains a significant gap in linking the impulsive loadings from a blast or a blunt impact to the clinical injury patterns observed in TBI. Synthetic head models or phantoms can be used to establish this link as they can be constructed with geometry, anatomy, and material properties that match the human brain, and can be used as an alternative to animal models. This study presents one such phantom called the Anthropomorphic Neurologic Gyrencephalic Unified Standard (ANGUS) phantom, which is an idealized gyrencephalic brain phantom composed of polyacrylamide gel. Here we mechanically characterized the ANGUS phantom using tagged magnetic resonance imaging (MRI) and magnetic resonance elastography (MRE), and then compared the outcomes to data obtained in healthy volunteers. The direct comparison between the phantom's response and the data from a cohort of in vivo human subjects demonstrate that the ANGUS phantom may be an appropriate model for bulk tissue response and gyral dynamics of the human brain under small amplitude linear impulses. However, the phantom's response differs from that of the in vivo human brain under rotational impacts, suggesting avenues for future improvements to the phantom.

Understanding Primary Blast Injury: High Frequency Pressure Acutely Disrupts Neuronal Network Dynamics in Cerebral Organoids.

Blast exposure represents a common occupational risk capable of generating mild to severe traumatic brain injuries (TBI). During blast exposure, a pressure shockwave passes through the skull and exposes brain tissue to complex pressure waveforms. The primary neurophysiological response to blast-induced pressure waveforms remains poorly understood. Here, we use a computer-controlled table-top pressure chamber to expose human stem cell-derived cerebral organoids to varied frequency of pressure waves and characterize the neurophysiological response. Pressure waves that reach a maximum amplitude of 250 kPa were used to model a less severe TBI and 350 kPa for a more severe blast TBI event. With each amplitude, a frequency range of 500 Hz, 3000 Hz, and 5000 Hz was tested. Following the 250 kPa overpressure a multi-electrode array recorded organoid neural activity. We observed an acute suppression neuronal activity in single unit events, population events, and network oscillations that recovered within 24 h. Additionally, we observed a network desynchronization after exposure higher frequency waveforms. Conversely, organoids exposed to higher amplitude pressure (350k Pa) displayed drastic neurophysiological differences that failed to recover within 24 h. Further, lower amplitude "blast" (250 kPa) did not induce cellular damage whereas the higher amplitude "blast" (350 kPa) generated greater apoptosis throughout each organoid. Our data indicate that specific features of pressure waves found intracranially during blast TBI have varied effects on neurophysiological activity that can occur even without cellular damage.

Sulcal Cavitation in Linear Head Acceleration: Possible Correlation With Chronic Traumatic Encephalopathy.

Traumatic Brain Injury (TBI) is a significant public health and financial concern that is affecting tens of thousands of people in the United States annually. There were over a million hospital visits related to TBI in 2017. Along with immediate and short-term morbidity from TBI, chronic traumatic encephalopathy (CTE) can have life-altering, chronic morbidity, yet the direct linkage of how head impacts lead to this pathology remains unknown. A possible clue is that chronic traumatic encephalopathy appears to initiate in the depths of the sulci. The purpose of this study was to isolate the injury mechanism/s associated with blunt force impact events. To this end, drop tower experiments were performed on a human head phantom. Our phantom was fabricated into a three-dimensional extruded ellipsoid geometry made out of Polyacrylamide gelatin that incorporated gyri-sulci interaction. The phantom was assembled into a polylactic acid 3D-printed skull, surrounded with deionized water, and enclosed between two optical windows. The phantom received repetitive low-force impacts on the order of magnitude of an average boxing punch. Intracranial pressure profiles were recorded in conjunction with high-speed imaging, 25 k frames-per-second. Cavitation was observed in all trials. Cavitation is the spontaneous formation of vapor bubbles in the liquid phase resulting from a pressure drop that reaches the vapor pressure of the liquid. The observed cavitation was predominately located in the contrecoup during negative pressure phases of local intracranial pressure. To further investigate the cavitation interaction with the brain tissue phantom, a 2D plane strain computational model was built to simulate the deformation of gyrated tissue as a result from the initiation of cavitation bubbles seen in the phantom experiments. These computational experiments demonstrated a focusing of strain at the depths of the sulci from bubble expansion. Our results add further evidence that mechanical interactions could contribute to the development of chronic traumatic encephalopathy and also that fluid cavitation may play a role in this interaction.

Localizing Clinical Patterns of Blast Traumatic Brain Injury Through Computational Modeling and Simulation.

Blast traumatic brain injury is ubiquitous in modern military conflict with significant morbidity and mortality. Yet the mechanism by which blast overpressure waves cause specific intracranial injury in humans remains unclear. Reviewing of both the clinical experience of neurointensivists and neurosurgeons who treated service members exposed to blast have revealed a pattern of injury to cerebral blood vessels, manifested as subarachnoid hemorrhage, pseudoaneurysm, and early diffuse cerebral edema. Additionally, a seminal neuropathologic case series of victims of blast traumatic brain injury (TBI) showed unique astroglial scarring patterns at the following tissue interfaces: subpial glial plate, perivascular, periventricular, and cerebral gray-white interface. The uniting feature of both the clinical and neuropathologic findings in blast TBI is the co-location of injury to material interfaces, be it solid-fluid or solid-solid interface. This motivates the hypothesis that blast TBI is an injury at the intracranial mechanical interfaces. In order to investigate the intracranial interface dynamics, we performed a novel set of computational simulations using a model human head simplified but containing models of gyri, sulci, cerebrospinal fluid (CSF), ventricles, and vasculature with high spatial resolution of the mechanical interfaces. Simulations were performed within a hybrid Eulerian-Lagrangian simulation suite (CTH coupled via Zapotec to Sierra Mechanics). Because of the large computational meshes, simulations required high performance computing resources. Twenty simulations were performed across multiple exposure scenarios-overpressures of 150, 250, and 500 kPa with 1 ms overpressure durations-for multiple blast exposures (front blast, side blast, and wall blast) across large variations in material model parameters (brain shear properties, skull elastic moduli). All simulations predict fluid cavitation within CSF (where intracerebral vasculature reside) with cavitation occurring deep and diffusely into cerebral sulci. These cavitation events are adjacent to high interface strain rates at the subpial glial plate. Larger overpressure simulations (250 and 500kPa) demonstrated intraventricular cavitation-also associated with adjacent high periventricular strain rates. Additionally, models of embedded intraparenchymal vascular structures-with diameters as small as 0.6 mm-predicted intravascular cavitation with adjacent high perivascular strain rates. The co-location of local maxima of strain rates near several of the regions that appear to be preferentially damaged in blast TBI (vascular structures, subpial glial plate, perivascular regions, and periventricular regions) suggest that intracranial interface dynamics may be important in understanding how blast overpressures leads to intracranial injury.

Materials Characterization of Cranial Simulants for Blast-Induced Traumatic Brain Injury.

INTRODUCTION: The mechanical response of brain tissue to high-speed forces in the blast and blunt traumatic brain injury is poorly understood. Object-to-object variation and interspecies differences are current limitations in animal and cadaver studies conducted to study damage mechanisms. Biofidelic and transparent tissue simulants allow the use of high-speed optical diagnostics during a blast event, making it possible to observe deformations and damage patterns for comparison to observed injuries seen post-mortem in traumatic brain injury victims. METHODS: Material properties of several tissue simulants were quantified using standard mechanical characterization techniques, that is, shear rheometric, tensile, and compressive testing. RESULTS: Polyacrylamide simulants exhibited the best optical and mechanical property matching with the fewest trade-offs in the design of a cranial test object. Polyacrylamide gels yielded densities of ~1.04 g/cc and shear moduli ranging 1.3-14.55 kPa, allowing gray and white matter simulant tuning to a 30-35% difference in shear for biofidelity. CONCLUSIONS: These materials are intended for use as layered cranial phantoms in a shock tube and open field blasts, with focus on observing phenomena occurring at the interfaces of adjacent tissue simulant types or material-fluid boundaries. Mechanistic findings from these studies may be used to inform the design of protective gear to mitigate blast injuries.