Preterm infants variability in cerebral near-infrared spectroscopy measurements in the first 72-h after birth.

BACKGROUND: Cerebral near-infrared spectroscopy is a non-invasive tool used to measure regional cerebral tissue oxygenation (rScO2) initially validated in adult and pediatric populations. Preterm neonates, vulnerable to neurologic injury, are attractive candidates for NIRS monitoring; however, normative data and the brain regions measured by the current technology have not yet been established for this population. METHODS: This study's aim was to analyze continuous rScO2 readings within the first 6-72 h after birth in 60 neonates without intracerebral hemorrhage born at ≤1250 g and/or ≤30 weeks' gestational age (GA) to better understand the role of head circumference (HC) and brain regions measured. RESULTS: Using a standardized brain MRI atlas, we determined that rScO2 in infants with smaller HCs likely measures the ventricular spaces. GA is linearly correlated, and HC is non-linearly correlated, with rScO2 readings. For HC, we infer that rScO2 is lower in infants with smaller HCs due to measuring the ventricular spaces, with values increasing in the smallest HCs as the deep cerebral structures are reached. CONCLUSION: Clinicians should be aware that in preterm infants with small HCs, rScO2 displayed may reflect readings from the ventricular spaces and deep cerebral tissue. IMPACT: Clinicians should be aware that in preterm infants with small head circumferences, cerebral near-infrared spectroscopy readings of rScO2 displayed may reflect readings from the ventricular spaces and deep cerebral tissue. This highlights the importance of rigorously re-validating technologies before extrapolating them to different populations. Standard rScO2 trajectories should only be established after determining whether the mathematical models used in NIRS equipment are appropriate in premature infants and the brain region(s) NIRS sensors captures in this population, including the influence of both gestational age and head circumference.

Surface Electromyography-Driven Therapeutic Gaming for Rehabilitation of Upper Extremity Weakness: A Pilot Study.

SUMMARY: In patients with severe upper extremity weakness that may result from peripheral nerve injuries, stroke, and spinal cord injuries, standard therapy in the earliest stages of recovery consists primarily of passive rather than active exercises. Adherence to prescribed therapy may be poor, which may contribute to suboptimal functional outcomes. The authors have developed and integrated a custom surface electromyography device with a video game to create an interactive, biofeedback-based therapeutic gaming platform. Sensitivity of the authors' custom surface electromyography device was evaluated with simultaneous needle electromyography recordings. Testing of this therapeutic gaming platform was conducted with a single 30-minute gameplay session in 19 patients with a history of peripheral nerve injury, stroke, spinal cord injury, and direct upper extremity trauma, including 11 patients who had undergone nerve and/or tendon transfers. The device was highly sensitive in detecting low levels of voluntary muscle activation and was used with 10 distinct muscles of the arm, forearm, and hand. Nerve and tendon transfer patients successfully activated the donor nerve/muscle and elicited the desired movement to engage in gameplay. On surveys of acceptability and usability, patients felt the system was enjoyable, motivating, fun, and easy to use, and their hand therapists expressed similar enthusiasm. Surface electromyography-based therapeutic gaming is a promising approach to rehabilitation that warrants further development and investigation to examine its potential efficacy, not only for building muscle strength and endurance but also for facilitating motor relearning after nerve and tendon transfer surgical procedures. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Repeated Application of Transcranial Diagnostic Ultrasound Towards the Visual Cortex Induced Illusory Visual Percepts in Healthy Participants.

Transcranial magnetic stimulation (TMS) of the visual cortex can induce phosphenes as participants look at a visual target. So can non-diagnostic ultrasound (nDU), delivered in a transcranial fashion, while participants have closed their eyes during stimulation. Here, we sought to determine if DU, aimed at the visual cortex, could alter the perception of a visual target. We applied a randomized series of actual or sham DU, transcranially and towards the visual cortex of healthy participants while they stared at a visual target (a white crosshair on a light-blue background), with the ultrasound device placed where TMS elicited phosphenes. These participants observed percepts seven out of ten times, which consisted of extra or extensions of lines relative to the original crosshair, and additional colors, an average of 53.7 ± 2.6% of the time over the course of the experiment. Seven out of ten different participants exposed to sham-only DU observed comparable percepts, but only an average of 36.3 ± 1.9% of the time, a statistically significant difference (p < 0.00001). Moreover, on average, participants exposed to a combination of sham and actual ultrasound reported a net increase of 47.9 percentage points in the likelihood that they would report a percept by the end of the experiment. Our results are consistent with the hypothesis that a random combination of sham-only and actual DU, applied directly over the visual cortex of participants, increased the likelihood that they would observe visual effects, but not the type of effects, with that likelihood increasing over the course of the experiment. From this, we conclude that repeated exposures by DU may make the visual cortex more responsive to stimulation of their visual cortex by the visual target itself. Future studies should identify the biophysical mechanism(s) and neural pathways by which DU, in our hands and others, can generate its observed effects on brain function. These observations, consistent with other's observation of effects of DU stimulation of the human motor cortex and amygdala, as well as the FDA approved nature of DU, may lead to increased use of DU as a means of altering brain function.

Towards a non-invasive cardiac arrest monitor: An in vivo pilot study.

INTRODUCTION: Hemodynamic-guided cardiopulmonary resuscitation (HGCPR) achieves better outcomes than standard resuscitation. Currently, HGCPR requires an invasive procedure, infeasible during resuscitation. Non-invasive measures of blood flow could provide useful hemodynamic guidance to rescuers. OBJECTIVE: We describe initial efforts to develop a device that detects, analyzes, and measures the velocity of carotid artery blood flow (CABF) towards the brain at pre-arrest baseline ('baseline') and during cardiopulmonary resuscitation, here tested in a swine model of cardiac arrest (CA). A key element of that device consists of non-imaging diagnostic ultrasound, due to its simplicity and small form factor, hence potential for deployment during HGCPR in a bandage placed on the neck. METHODS: Sixteen mixed-breed domestic swine were sedated, anesthetized and paralyzed, followed by endotracheal intubation and mechanical ventilation. Cardiac arrest was induced with a 3-s 100 mA transthoracic shock or bolus of fentanyl, after which all animals received mechanical CPR. A non-imaging ultrasound probe was manually applied to the neck over the carotid artery to capture CABF during baseline, as verified with diagnostic ultrasound imaging, and during mechanical resuscitation. RESULTS: We successfully collected CABF measurements at baseline in 14/16 swine and during attempted resuscitation with mechanical chest compression in 5/16 swine. Signal characteristics include peak blood flow both towards (90.4 +/-20.4 cm/s) and away from the brain (-44.2 +/-31.8 cm/s) during resuscitation, each larger than flow towards (41.7+/-14.8 cm/s) and away from brain (-3.0 +/-7.8 cm/s) during baseline. CONCLUSION: Measurement of CABF before and during CPR in swine with a non-imaging ultrasound probe is feasible before CA and informative when achieved during CPR. For example, observations of reverse flow within the carotid artery during CPR merits further study for its prevalence and effect on resuscitation outcomes. Also, tissue motion represents a significant obstacle for CABF measurement during CPR. Additional work will determine the feasibility and utility of non-imaging ultrasound measurements of CABF during resuscitation.

A Review of Recent Advances in Ultrasound, Placed in the Context of Pain Diagnosis and Treatment.

Ultrasound plays a significant role in the diagnosis and treatment of pain, with significant literature reaching back many years, especially with regard to diagnostic ultrasound and its use for guiding needle-based delivery of drugs. Advances in ultrasound over at least the last decade have opened up new areas of inquiry and potential clinical efficacy in the context of pain diagnosis and treatment. Here we offer an overview of the recent literature associated with ultrasound and pain in order to highlight some promising frontiers at the intersection of these two subjects. We focus first on peripheral application of ultrasound, for which there is a relatively rich, though still young, literature. We then move to central application of ultrasound, for which there is little literature but much promise.

Intense Focused Ultrasound Preferentially Stimulates Transected Nerves Within Residual Limbs: Pilot Study.

Objective: Identifying pain generators in tissue deep in the skin can require uncomfortable, complicated, and invasive tests. We describe pilot studies testing the hypothesis that ultrasound image-guided, intense focused ultrasound (ig-iFU) can noninvasively and differentially stimulate the end of transected nerves in the residual limbs of amputee patients. Design: We applied iFU to the transected nerve ending as individual pulses with a length of 0.1 seconds using a carrier frequency of 2.0 MHz. After targeting, we gradually increased the iFU intensity to reach consistent patient-reported stimulation of the transected nerve ending. We also stimulated the proximal nerve, tissue near the nerve ending, and the intact contralateral nerve. We described the resulting sensations and correlated the results of the study participant's pre-iFU study responses to phantom and residual limb pain questionnaires. Results: iFU spatial and temporal average intensity values between 16 W/cm2 and 433 W/cm2 that were applied to the transected nerve ending and proximal nerve elicited sensations, including phantom limb sensations, while the same intensity applied to control tissue centimeters away from the nerve ending, or to the intact nerve on the contralateral limb, did not. Two out of 11 study participants reported only mild and transient pain created by iFU stimulation. Successful iFU intensity values correlated with neither phantom nor residual limb pain scores. Conclusions: Transected nerves had greater sensitivity to iFU stimulation than ipsilateral and contralateral control tissue, including intact nerve. These results support the view that ig-iFU may one day help physicians identify deep, tender tissue in patients who report experiencing pain.

Evaluating a Targeted Bedside Measure of Cerebral Perfusion in a Nonhuman Primate Model of Neonatal Hypoxic-Ischemic Encephalopathy.

OBJECTIVES: To compare ultrasound-derived resistive indices (RIs) obtained at the level of the thalamus via fast Doppler ultrasound with traditional anterior cerebral artery measures in a model of neonatal hypoxic-ischemic encephalopathy and to correlate each with clinical outcomes. METHODS: Nine nonhuman primate neonates underwent no umbilical cord occlusion (n = 3), umbilical cord occlusion without hypothermia (n = 3), or umbilical cord occlusion with hypothermia (n = 3). The RI was measured in the anterior cerebral artery and thalamus on days 0, 1, and 4 of life. Magnetic resonance imaging with spectroscopy was performed on day 4. RESULTS: Mean thalamus and anterior cerebral artery RI values in the first 36 hours of life were statistically different in neonates who died (+0.13; P = .019) or developed cerebral palsy (-0.08; P = .003). Thalamic RI values showed stronger associations with serum and spectroscopic lactate values than those in the anterior cerebral artery. The umbilical cord occlusion-with-hypothermia group showed a significant increase in the RI in the thalamus but not the anterior cerebral artery. CONCLUSIONS: Resistive index measurements in the thalamus may eventually supplement other bedside measures for predicting outcomes in the HIE population, but further studies need to differentiate the effect of hypothermia from illness severity on thalamic perfusion.

Temporal and Spatial Evolution of Raised Intraspinal Pressure after Traumatic Spinal Cord Injury.

Traumatic spinal cord injury (SCI) often leads to permanent neurological impairment. Currently, the only clinically effective intervention for patients with acute SCI is surgical decompression by removal of impinging bone fragments within 24 h after injury. Recent clinical studies suggest that elevated intraparenchymal spinal pressure (ISP) limits functional recovery following SCI. Here, we report on the temporal and spatial patterns of elevated ISP following a moderate rodent contusion SCI. Compared with physiological ISP in the intact cord (2.7 ± 0.5 mm Hg), pressures increase threefold 30 min following injury (8.9 ± 1.1 mm Hg, p < 0.001) and remain elevated for up to 7 days (4.3 ± 0.8 mm Hg). Measurements of rostrocaudal ISP distribution reveal peak pressures in the injury center and in segments rostral to the injury during the acute phase(≤ 24 h). During the subacute phase(≥ 72 h), peak ISP decreases while a 7.5 mm long segment of moderately elevated ISP remains, centered on the initial contusion site. Interestingly, the contribution of the dural and pial compartments toward increased ISP changes with time after injury: Dural and pial linings contribute almost equally to increased ISP during the acute phase, whereas the dural lining is primarily responsible for elevated ISP during the subacute phase (78.9%). Our findings suggest that a rat contusion SCI model in combination with novel micro-catheters allows for direct measurement of ISP after SCI. Similarly to traumatic brain injury, raised tissue pressure is likely to have detrimental effects on spontaneous recovery following SCI.

Severity of ASD symptoms and their correlation with the presence of copy number variations and exposure to first trimester ultrasound.

Current research suggests that incidence and heterogeneity of autism spectrum disorder (ASD) symptoms may arise through a variety of exogenous and/or endogenous factors. While subject to routine clinical practice and generally considered safe, there exists speculation, though no human data, that diagnostic ultrasound may also contribute to ASD severity, supported by experimental evidence that exposure to ultrasound early in gestation could perturb brain development and alter behavior. Here we explored a modified triple hit hypothesis [Williams & Casanova, ] to assay for a possible relationship between the severity of ASD symptoms and (1) ultrasound exposure (2) during the first trimester of pregnancy in fetuses with a (3) genetic predisposition to ASD. We did so using retrospective analysis of data from the SSC (Simon's Simplex Collection) autism genetic repository funded by the Simons Foundation Autism Research Initiative. We found that male children with ASD, copy number variations (CNVs), and exposure to first trimester ultrasound had significantly decreased non-verbal IQ and increased repetitive behaviors relative to male children with ASD, with CNVs, and no ultrasound. These data suggest that heterogeneity in ASD symptoms may result, at least in part, from exposure to diagnostic ultrasound during early prenatal development of children with specific genetic vulnerabilities. These results also add weight to on-going concerns expressed by the FDA about non-medical use of diagnostic ultrasound during pregnancy. Autism Res 2017, 10: 472-484. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Toward Deep Brain Monitoring with Superficial EEG Sensors Plus Neuromodulatory Focused Ultrasound.

Noninvasive recordings of electrophysiological activity have limited anatomic specificity and depth. We hypothesized that spatially tagging a small volume of brain with a unique electroencephalography (EEG) signal induced by pulsed focused ultrasound could overcome those limitations. As a first step toward testing this hypothesis, we applied transcranial ultrasound (2 MHz, 200-ms pulses applied at 1050 Hz for 1 s at a spatial peak temporal average intensity of 1.4 W/cm(2)) to the brains of anesthetized rats while simultaneously recording EEG signals. We observed a significant 1050-Hz electrophysiological signal only when ultrasound was applied to a living brain. Moreover, amplitude demodulation of the EEG signal at 1050 Hz yielded measurement of gamma band (>30 Hz) brain activity consistent with direct measurements of that activity. These results represent preliminary support for use of pulsed focused ultrasound as a spatial tagging mechanism for non-invasive EEG-based mapping of deep brain activity with high spatial resolution.

Towards use of MRI-guided ultrasound for treating cerebral vasospasm.

Cerebral vasospasm is a major cause of morbidity and mortality in patients with subarachnoid hemorrhage (SAH), causing delayed neurological deficits in as many as one third of cases. Existing therapy targets induction of cerebral vasodilation through use of various drugs and mechanical means, with a range of observed efficacy. Here, we perform a literature review supporting our hypothesis that transcranially delivered ultrasound may have the ability to induce therapeutic cerebral vasodilation and, thus, may one day be used therapeutically in the context of SAH. Prior studies demonstrate that ultrasound can induce vasodilation in both normal and vasoconstricted blood vessels in peripheral tissues, leading to reduced ischemia and cell damage. Among the proposed mechanisms is alteration of several nitric oxide (NO) pathways, where NO is a known vasodilator. While in vivo studies do not point to a specific physical mechanism, results of in vitro studies favor cavitation induction by ultrasound, where the associated shear stresses likely induce NO production. Two papers discussed the effects of ultrasound on the cerebral vasculature. One study applied clinical transcranial Doppler ultrasound to a rodent complete middle cerebral artery occlusion model and found reduced infarct size. A second involved the application of pulsed ultrasound in vitro to murine brain endothelial cells and showed production of a variety of vasodilatory chemicals, including by-products of arachidonic acid metabolism. In sum, nine reviewed studies demonstrated evidence of either cerebrovascular dilation or elaboration of vasodilatory compounds. Of particular interest, all of the reviewed studies used ultrasound capable of transcranial application: pulsed ultrasound, with carrier frequencies ranging between 0.5 and 2.0 MHz, and intensities not substantially above FDA-approved intensity values. We close by discussing potential specific treatment paradigms of SAH and other cerebral ischemic disorders based on MRI-guided transcranial ultrasound.

Microbubbles and ultrasound increase intraventricular polyplex gene transfer to the brain.

Neurons in the brain can be damaged or lost from neurodegenerative disease, stroke, or traumatic injury. Although neurogenesis occurs in mammalian adult brains, the levels of natural neurogenesis are insufficient to restore function in these cases. Gene therapy has been pursued as a promising strategy to induce differentiation of neural progenitor cells into functional neurons. Non-viral vectors are a preferred method of gene transfer due to potential safety and manufacturing benefits but suffer from lower delivery efficiencies compared to viral vectors. Since the neural stem and progenitor cells reside in the subventricular zone of the brain, intraventricular injection has been used as an administration route for gene transfer to these cells. However, the choroid plexus epithelium remains an obstacle to delivery. Recently, transient disruption of the blood-brain barrier by microbubble-enhanced ultrasound has been used to successfully improve drug delivery to the brain after intravenous injection. In this work, we demonstrate that microbubble-enhanced ultrasound can similarly improve gene transfer to the subventricular zone after intraventricular injection. Microbubbles of different surface charges (neutral, slightly cationic, and cationic) were prepared, characterized by acoustic flow cytometry, and evaluated for their ability to increase the permeability of immortalized choroid plexus epithelium monolayers in vitro. Based on these results, slightly cationic microbubbles were evaluated for microbubble and ultrasound-mediated enhancement of non-viral gene transfer in vivo. When coupled with our previously reported gene delivery vehicles, the slightly cationic microbubbles significantly increased ultrasound-mediated transfection of the murine brain when compared to commercially available Definity® microbubbles. Temporary disruption of the choroid plexus by microbubble-enhanced ultrasound is therefore a viable way of enhancing gene delivery to the brain and merits further research.

Mixture Models for Estimating Maximum Blood Flow Velocity.

OBJECTIVES: A gaussian mixture model (GMM) was recently developed for estimating the probability density function of blood flow velocity measured with transcranial Doppler ultrasound data. In turn, the quantiles of the probability density function allow one to construct estimators of the "maximum" blood flow velocity. However, GMMs assume gaussianity, a feature that is not omnipresent in observed data. The objective of this work was to develop mixture models that do not invoke the gaussian assumption. METHODS: Here, GMMs were extended to a skewed GMM and a nongaussian kernel mixture model. All models were developed on data from 59 patients with closed head injuries from multiple hospitals in the United States, with ages ranging from 13 to 81 years and Glasgow Coma Scale scores ranging from 3 to 11. The models were assessed in terms of the log likelihood (a goodness-of-fit measure) and via visual comparison with the underlying spectrograms. RESULTS: Among the models examined, the skewed GMM showed a significantly (P< .05) higher log likelihood for 56 of the 59 patients and produced maximum flow velocity estimates consistent with the observed spectrograms for all patients. Kernel mixture models are generally less "robust" in that their quality is inconsistent across patients. CONCLUSIONS: Among the models examined, it was found that the skewed GMM provided a better model of the data both in terms of the quality of the fit and in terms of visual comparison of the underlying spectrogram and the estimated maximum blood flow velocity. Nongaussian mixture models have potential for even higher-quality assessment of blood flow, but further development is called for.

Fast Doppler as a novel bedside measure of cerebral perfusion in preterm infants.

BACKGROUND: Altered cerebral perfusion from impaired autoregulation may contribute to the morbidity and mortality associated with premature birth. We hypothesized that fast Doppler imaging could provide a reproducible bedside estimation of cerebral perfusion and autoregulation in preterm infants. METHODS: This is a prospective pilot study using fast Doppler ultrasound to assess blood flow velocity in the basal ganglia of 19 subjects born at 26-32 wk gestation. Intraclass correlation provided a measure of test-retest reliability, and linear regression of cerebral blood flow velocity and heart rate or blood pressure allowed for estimations of autoregulatory ability. RESULTS: The intraclass correlation when imaging in the first 48 h of life was 0.634. We found significant and independent correlations between the systolic blood flow velocity and both systolic blood pressure and heart rate (P = 0.015 and 0.012 respectively) only in the 26-28 wk gestational age infants in the first 48 h of life. CONCLUSION: Our results suggest that fast Doppler provides reliable bedside measurements of cerebral blood flow velocity at the tissue level in premature infants, acting as a proxy for cerebral tissue perfusion. Additionally, autoregulation appears to be impaired in the extremely preterm infants, even within a normal range of blood pressures.

Ultrasound stylet for non-image-guided ventricular catheterization.

OBJECT Urgent ventriculostomy placement can be a lifesaving procedure in the setting of hydrocephalus or elevated intracranial pressure. While external ventricular drain (EVD) insertion is common, there remains a high rate of suboptimal drain placement. Here, the authors seek to demonstrate the feasibility of an ultrasound-based guidance system that can be inserted into an existing EVD catheter to provide a linear ultrasound trace that guides the user toward the ventricle. METHODS The ultrasound stylet was constructed as a thin metal tube, with dimensions equivalent to standard catheter stylets, bearing a single-element, ceramic ultrasound transducer at the tip. Ultrasound backscatter signals from the porcine ventricle were processed by custom electronics to offer real-time information about ventricular location relative to the catheter. Data collected from the prototype device were compared with reference measurements obtained using standard clinical ultrasound imaging. RESULTS A study of porcine ventricular catheterization using the experimental device yielded a high rate of successful catheter placement after a single pass (10 of 12 trials), despite the small size of pig ventricles and the lack of prior instruction on porcine ventricular architecture. A characteristic double-peak signal was identified, which originated from ultrasound reflections off of the near and far ventricular walls. Ventricular dimensions, as obtained from the width between peaks, were in agreement with standard ultrasound reference measurements (p < 0.05). Furthermore, linear ultrasound backscatter data permitted in situ measurement of the stylet distance to the ventricular wall (p < 0.05), which assisted in catheter guidance. CONCLUSIONS The authors have demonstrated the ability of the prototype ultrasound stylet to guide ventricular access in the porcine brain. The alternative design of the device makes it potentially easy to integrate into the standard workflow for bedside EVD placement. The availability of a fast, easy-to-use, inexpensive guidance system can play a role in reducing the complication rate for EVD placement.

Intense focused ultrasound stimulation of the rotator cuff: evaluation of the source of pain in rotator cuff tears and tendinopathy.

The objective of this preliminary study was to evaluate the ability of individual 0.1-s long pulses of intense focused ultrasound (iFU) emitted with a carrier frequency of 2 MHz to evoke diagnostic sensations when applied to patients whose shoulders have rotator cuff tears or tendinopathy. Patients were adults with painful shoulders and clinical and imaging findings consistent with rotator cuff disease. iFU stimulation of the shoulder was performed using B-mode ultrasound coupled with a focused ultrasound transducer that allowed image-guided delivery of precisely localized pulses of energy to different anatomic areas around the rotator cuff. The main outcome measure was iFU spatial average-temporal average intensity (I_SATA), and location required to elicit sensation. In control patients, iFU produced no sensation throughout the range of stimulation intensities (≤2000 W/cm(2) I_SATA). In patients with rotator cuff disease, iFU was able to induce sensation in the tendons of the rotator cuff, the subacromial bursa, and the subchondral bone in patients with chronic shoulder pain and rotator cuff disease, with an average ± standard deviation intensity equaling 680 ± 281 W/cm(2) I_SATA. This result suggests a primary role for these tissues in the pathogenesis of shoulder pain related to rotator cuff tendinopathy.

Paclitaxel improves outcome from traumatic brain injury.

Pharmacologic interventions for traumatic brain injury (TBI) hold promise to improve outcome. The purpose of this study was to determine if the microtubule stabilizing therapeutic paclitaxel used for more than 20 years in chemotherapy would improve outcome after TBI. We assessed neurological outcome in mice that received direct application of paclitaxel to brain injury from controlled cortical impact (CCI). Magnetic resonance imaging was used to assess injury-related morphological changes. Catwalk Gait analysis showed significant improvement in the paclitaxel group on a variety of parameters compared to the saline group. MRI analysis revealed that paclitaxel treatment resulted in significantly reduced edema volume at site-of-injury (11.92 ± 3.0 and 8.86 ± 2.2mm(3) for saline vs. paclitaxel respectively, as determined by T2-weighted analysis; p ≤ 0.05), and significantly increased myelin tissue preservation (9.45 ± 0.4 vs. 8.95 ± 0.3, p ≤ 0.05). Our findings indicate that paclitaxel treatment resulted in improvement of neurological outcome and MR imaging biomarkers of injury. These results could have a significant impact on therapeutic developments to treat traumatic brain injury.

Transcranial vibro-acoustography can detect traumatic brain injury, in-vivo: Preliminary studies.

Vibro-acoustography (VA) uses two or more beams of confocal ultrasound to generate local vibrations within their target tissue through induction of a time-dependent radiation force whose frequency equals that of the difference of the applied frequencies. While VA has proven effective for assaying the mechanical properties of clinically relevant tissue such as breast lesions and tissue calcifications, its application to brain remains unexplored. Here we investigate the ability of VA to detect acute and focal traumatic brain injury (TBI) in-vivo through the use of transcranially delivered high-frequency (2 MHz) diagnostic focused ultrasound to rat brain capable of generating measurable low-frequency (200-270 kHz) acoustic emissions from outside of the brain. We applied VA to acute sham-control and TBI model rats (sham N=6; TBI N=6) and observed that acoustic emissions, captured away from the site of TBI, had lower amplitudes for TBI as compared to sham-TBI animals. The sensitivity of VA to acute brain damage at frequencies currently transmittable across human skulls, as demonstrated in this preliminary study, supports the possibility that the VA methodology may one day serve as a technique for detecting TBI.