Traumatic brain injury induced by exposure to blast overpressure via ear canal.

Exposure to explosive shockwave often leads to blast-induced traumatic brain injury in military and civilian populations. Unprotected ears are most often damaged following exposure to blasts. Although there is an association between tympanic membrane perforation and TBI in blast exposure victims, little is known about how and to what extent blast energy is transmitted to the central nervous system via the external ear canal. The present study investigated whether exposure to blasts directed through the ear canal causes brain injury in Long-Evans rats. Animals were exposed to a single blast (0-30 pounds per square inch (psi)) through the ear canal, and brain injury was evaluated by histological and behavioral outcomes at multiple time-points. Blast exposure not only caused tympanic membrane perforation but also produced substantial neuropathological changes in the brain, including increased expression of c-Fos, induction of a profound chronic neuroinflammatory response, and apoptosis of neurons. The blast-induced injury was not limited only to the brainstem most proximal to the source of the blast, but also affected the forebrain including the hippocampus, amygdala and the habenula, which are all involved in cognitive functions. Indeed, the animals exhibited long-term neurological deficits, including signs of anxiety in open field tests 2 months following blast exposure, and impaired learning and memory in an 8-arm maze 12 months following blast exposure. These results suggest that the unprotected ear canal provides a locus for blast waves to cause TBI. This study was approved by the Institutional Animal Care and Use Committee at the University of Mississippi Medical Center (Animal protocol# 0932E, approval date: September 30, 2016 and 0932F, approval date: September 27, 2019).

Exposure to blast shock waves via the ear canal induces deficits in vestibular afferent function in rats.

The ears are air-filled structures that are directly impacted during blast exposure. In addition to hearing loss and tinnitus, blast victims often complain of vertigo, dizziness and unsteady posture, suggesting that blast exposure induces damage to the vestibular end organs in the inner ear. However, the underlying mechanisms remain to be elucidated. In this report, single vestibular afferent activity and the vestibulo-ocular reflex (VOR) were investigated before and after exposure to blast shock waves (∼20 PSI) delivered into the left external ear canals of anesthetized rats. Single vestibular afferent activity was recorded from the superior branch of the left vestibular nerves of the blast-treated and control rats one day after blast exposure. Blast exposure reduced the spontaneous discharge rates of the otolith and canal afferents. Blast exposure also reduced the sensitivity of irregular canal afferents to sinusoidal head rotation at 0.5-2Hz. Blast exposure, however, resulted in few changes in the VOR responses to sinusoidal head rotation and translation. To the best of our knowledge, this is the first study that reports blast exposure-induced damage to vestibular afferents in an animal model. These results provide insights that may be helpful in developing biomarkers for early diagnosis of blast-induced vestibular deficits in military and civilian populations.

Passive eye movements induced by electromagnetic force (EMF) in rats.

Accurate information on eye position in the orbit is available from visual feedback, efference copy of the oculomotor commands and proprioceptive signals from the extraocular muscles (EOM). Whereas visual feedback and oculomotor commands have been extensively studied, central processing of EOM proprioceptive signals remains to be elucidated. A challenge to the field is to develop an approach to induce passive eye movements without physically contacting the eyes. A novel method was developed to generate passive eye movements in rats. A small rare-earth magnet disk (0.7 mm diameter, 0.5 mm thickness) was attached to the surface of a rat's eyeball. A metal rod (5 mm diameter) wrapped with an electromagnetic (EM) coil was placed near the magnet (8-15 mm). By passing currents to the EM coil, electromagnetic force (EMF) was generated and acted upon the magnet and induced passive eye movements. The EMF induced well-defined passive eye movements, whose directions were dependent on current polarity and amplitudes and peak velocities were dependent on current intensity and duration. Peak velocities of the EMF-induced eye movements were linearly related to amplitudes, exhibiting main sequence relationships similar to that of saccades in awake rats and eye movements induced by electrical microstimulation of the abducens nucleus in anesthetized rats. Histological examination showed that repetitive EMF stimulations did not appear to result in damages in the EOM fibers. These results validated the EMF approach as a novel tool to investigate EOM proprioceptive signals and their roles in visual localization and gaze control.

Autonomic responses to blast overpressure can be elicited by exclusively exposing the ear in rats.

Blast overpressure has become an increasing cause of brain injuries in both military and civilian populations. Though blast's direct effects on the cochlea and vestibular organs are active areas of study, little attention has been given to the ear's contribution to the overall spectrum of blast injury. Acute autonomic responses to blast exposure, including bradycardia and hypotension, can cause hypoxia and contribute to blast-induced neurotrauma. Existing literature suggests that these autonomic responses are elicited through blast impacting the thorax and lungs. We hypothesize that the unprotected ear also provides a vulnerable locus for blast to cause autonomic responses. We designed a blast generator that delivers controlled overpressure waves into the ear canal without impacting surrounding tissues in order to study the ear's specific contribution to blast injury. Anesthetized adult rats' left ears were exposed to a single blast wave ranging from 0 to 110 PSI (0-758 kPa). Blast exposed rats exhibited decreased heart rates and blood pressures with increased blast intensity, similar to results gathered using shock tubes and whole-body exposure in the literature. While rats exposed to blasts below 50 PSI (345 kPa) exhibited increased respiratory rate with increased blast intensity, some rats exposed to blasts higher than 50 PSI (345 kPa) stopped breathing immediately and ultimately died. These autonomic responses were significantly reduced in vagally denervated rats, again similar to whole-body exposure literature. These results support the hypothesis that the unprotected ear contributes to the autonomic responses to blast.

Precision analysis of a quantitative CT liver surface nodularity score.

PURPOSE: To evaluate precision of a software-based liver surface nodularity (LSN) score derived from CT images. METHODS: An anthropomorphic CT phantom was constructed with simulated liver containing smooth and nodular segments at the surface and simulated visceral and subcutaneous fat components. The phantom was scanned multiple times on a single CT scanner with adjustment of image acquisition and reconstruction parameters (N = 34) and on 22 different CT scanners from 4 manufacturers at 12 imaging centers. LSN scores were obtained using a software-based method. Repeatability and reproducibility were evaluated by intraclass correlation (ICC) and coefficient of variation. Using abdominal CT images from 68 patients with various stages of chronic liver disease, inter-observer agreement and test-retest repeatability among 12 readers assessing LSN by software- vs. visual-based scoring methods were evaluated by ICC. RESULTS: There was excellent repeatability of LSN scores (ICC:0.79-0.99) using the CT phantom and routine image acquisition and reconstruction parameters (kVp 100-140, mA 200-400, and auto-mA, section thickness 1.25-5.0 mm, field of view 35-50 cm, and smooth or standard kernels). There was excellent reproducibility (smooth ICC: 0.97; 95% CI 0.95, 0.99; CV: 7%; nodular ICC: 0.94; 95% CI 0.89, 0.97; CV: 8%) for LSN scores derived from CT images from 22 different scanners. Inter-observer agreement for the software-based LSN scoring method was excellent (ICC: 0.84; 95% CI 0.79, 0.88; CV: 28%) vs. good for the visual-based method (ICC: 0.61; 95% CI 0.51, 0.69; CV: 43%). Test-retest repeatability for the software-based LSN scoring method was excellent (ICC: 0.82; 95% CI 0.79, 0.84; CV: 12%). CONCLUSION: The software-based LSN score is a quantitative CT imaging biomarker with excellent repeatability, reproducibility, inter-observer agreement, and test-retest repeatability.