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.

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.

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.

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.

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.

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.

Detection of mild traumatic brain injury in rodent models using shear wave elastography: preliminary studies.

OBJECTIVES: Traumatic brain injury (TBI) can cause adverse physiologic changes in fluid content within the brain, which may lead to changes in tissue elasticity (eg, stiffness). This study evaluated the ability of ultrasonic shear wave elastography to observe these changes in the brain after TBI in vivo. METHODS: Mice and rats received a mild TBI or sham surgery and were imaged acutely or 24 hours after injury using shear wave elastography, and the hemispheric stiffness values were compared. RESULTS: Stiffness values were consistent across brain hemispheres of sham TBI rodents. By 24 hours after TBI, relative brain tissue stiffness values for mice and rats each decreased ipsilaterally and increased contralaterally, both relative to each other and compared to sham TBI rodents (P < .05). The absolute tissue elasticity value increased for rats (P < .05) but not for mice. CONCLUSIONS: Differences between intrahemispheric stiffness values of rodent brains by 24 hours after mild TBI may reflect the observed edema and hemorrhage ipsilateral to TBI and the known reduction of cerebral blood flow in both brain hemispheres. If these hypotheses hold true, ultrasonic shear wave elastography may offer a method for detecting adverse changes in fluid content within the brain after mild TBI.

Does targeted nerve implantation reduce neuroma pain in amputees?

BACKGROUND: Symptomatic neuroma occurs in 13% to 32% of amputees, causing pain and limiting or preventing the use of prosthetic devices. Targeted nerve implantation (TNI) is a procedure that seeks to prevent or treat neuroma-related pain in amputees by implanting the proximal amputated nerve stump onto a surgically denervated portion of a nearby muscle at a secondary motor point so that regenerating axons might arborize into the intramuscular motor nerve branches rather than form a neuroma. However, the efficacy of this approach has not been demonstrated. QUESTIONS/PURPOSES: We asked: Does TNI (1) prevent primary neuroma-related pain in the setting of acute traumatic amputation and (2) reduce established neuroma pain in upper- and lower-extremity amputees? METHODS: We retrospectively reviewed two groups of patients treated by one surgeon: (1) 12 patients who underwent primary TNI for neuroma prevention at the time of acute amputation and (2) 23 patients with established neuromas who underwent neuroma excision with secondary TNI. The primary outcome was the presence or absence of palpation-induced neuroma pain at last followup, based on a review of medical records. The patients presented here represent 71% of those who underwent primary TNI (12 of 17) and 79% of those who underwent neuroma excision with secondary TNI (23 of 29 patients) during the period in question; the others were lost to followup. Minimum followup was 8 months (mean, 22 months; range, 8-60 months) for the primary TNI group and 4 months (mean, 22 months; range, 4-72 months) for the secondary TNI group. RESULTS: At last followup, 11 of 12 patients (92%) after primary TNI and 20 of 23 patients (87%) after secondary TNI were free of palpation-induced neuroma pain. CONCLUSIONS: TNI performed either primarily at the time of acute amputation or secondarily for the treatment of established symptomatic neuroma is associated with a low frequency of neuroma-related pain. By providing a distal target for regenerating axons, TNI may offer an effective strategy for the prevention and treatment of neuroma pain in amputees.

Intense focused ultrasound preferentially stimulates subcutaneous and focal neuropathic tissue: preliminary results.

OBJECTIVE: Potential peripheral sources of pain from subcutaneous tissue can require invasive evocative tests for their localization and assessment. Here, we describe studies whose ultimate goal is development of a noninvasive evocative test for subcutaneous, painful tissue. DESIGN: We used a rat model of a focal and subcutaneous neuroma to test the hypothesis that intense focused ultrasound can differentiate focal and subcutaneous neuropathic tissue from control tissue. To do so, we first applied intense focused ultrasound (2 MHz, with individual pulses of 0.1 second in duration) to the rat's neuroma while the rat was under light anesthesia. We started with low values of intensity, which we increased until intense focused ultrasound stimulation caused the rat to reliably flick its paw. We then applied that same intense focused ultrasound protocol to control tissue away from the neuroma and assayed for the rat's response to that stimulation. RESULTS: Intense focused ultrasound of sufficient strength (I(SATA) of 600 +/- 160 W/cm(2) ) applied to the neuroma caused the rat to flick its paw, while the same intense focused ultrasound applied millimeters to a centimeter away failed to induce a paw flick. CONCLUSION: Successful stimulation of the neuroma by intense focused ultrasound required colocalization of the neuroma and intense focused ultrasound supporting our hypothesis.

A double-gaussian, percentile-based method for estimating maximum blood flow velocity.

OBJECTIVES: Transcranial Doppler sonography allows for the estimation of blood flow velocity, whose maximum value, especially at systole, is often of clinical interest. Given that observed values of flow velocity are subject to noise, a useful notion of "maximum" requires a criterion for separating the signal from the noise. All commonly used criteria produce a point estimate (ie, a single value) of maximum flow velocity at any time and therefore convey no information on the distribution or uncertainty of flow velocity. This limitation has clinical consequences especially for patients in vasospasm, whose largest flow velocities can be difficult to measure. Therefore, a method for estimating flow velocity and its uncertainty is desirable. METHODS: A gaussian mixture model is used to separate the noise from the signal distribution. The time series of a given percentile of the latter, then, provides a flow velocity envelope. This means of estimating the flow velocity envelope naturally allows for displaying several percentiles (e.g., 95th and 99th), thereby conveying uncertainty in the highest flow velocity. RESULTS: Such envelopes were computed for 59 patients and were shown to provide reasonable and useful estimates of the largest flow velocities compared to a standard algorithm. Moreover, we found that the commonly used envelope was generally consistent with the 90th percentile of the signal distribution derived via the gaussian mixture model. CONCLUSIONS: Separating the observed distribution of flow velocity into a noise component and a signal component, using a double-gaussian mixture model, allows for the percentiles of the latter to provide meaningful measures of the largest flow velocities and their uncertainty.

Evidence of changes in brain tissue stiffness after ischemic stroke derived from ultrasound-based elastography.

OBJECTIVES: Ischemia, edema, elevated intracranial pressure, and reduced blood flow can occur in the brain as a result of ischemic stroke, including contralateral to the stroke via a process known as diaschisis. In this study, ultrasound elastography, an imaging process sensitive to the stiffness of tissue, including its relative fluid content, was used to study changes in the stiffness of individual cerebral hemispheres after transient ischemic injury. METHODS: Elastographic images of mouse brains were collected 24 and 72 hours after middle cerebral artery occlusion. The shear moduli of both ipsilateral and contralateral brain hemispheres for these mice were measured and compared to corresponding values of control animals. RESULTS: At 24 hours (but not 72 hours) after induction of ischemic stroke, there was a significant decrease in the shear modulus in the ipsilateral hemisphere (P < .01) and a significant increase in the shear modulus in the contralateral hemisphere compared to that of control animals (P < .01). Significant differences were also evident between ipsilateral and contralateral shear modulus values at 24 and 72 hours after infarction (P < .01 for both). CONCLUSIONS: The differences between intrahemispheric averages of shear moduli of the brains of animals with stroke at 24 and 72 hours after stroke induction likely reflect the initial formation of edema and reduction of cerebral blood flow known to develop ipsilateral to ischemic infarction, the known transient increase in intracranial pressure, as well as the known initial reduction of blood flow and subsequent development of edema in the contralateral hemisphere (diaschisis). Thus, elastography offers a possible method to detect subtle changes in brain after ischemic stroke.

Rapid ultrasonic stimulation of inflamed tissue with diagnostic intent.

Previous studies have observed that individual pulses of intense focused ultrasound (iFU) applied to inflamed and normal tissue can generate sensations, where inflamed tissue responds at a lower intensity than normal tissue. It was hypothesized that successively applied iFU pulses will generate sensation in inflamed tissue at a lower intensity and dose than application of a single iFU pulse. This hypothesis was tested using an animal model of chronic inflammatory pain, created by injecting an irritant into the rat hind paw. Ultrasound pulses were applied in rapid succession or individually to rats' rear paws beginning at low peak intensities and progressing to higher peak intensities, until the rats withdrew their paws immediately after iFU application. Focused ultrasound protocols consisting of successively and rapidly applied pulses elicited inflamed paw withdrawal at lower intensity and estimated tissue displacement values than single pulse protocols. However, both successively applied pulses and single pulses produced comparable threshold acoustic dose values and estimates of temperature increases. This raises the possibility that temperature increase contributed to paw withdrawal after rapid iFU stimulation. While iFU-induction of temporal summation may also play a role, electrophysiological studies are necessary to tease out these potential contributors to iFU stimulation.

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.

Evaluation of the use of ultrasound within a power toothbrush to dislodge oral bacteria using an in vitro Streptococcus mutans biofilm model.

PURPOSE: To investigate in vitro the use of ultrasound in a power toothbrush to aid in the removal of dental plaque biofilm without bristle contact. METHODS: Dental plaque was modeled using Streptococcus mutans biofilm adherent to hydroxyapatite disks. Treatment arms included positive and negative controls, disks with and without biofilm, respectively. Power toothbrush modes of action tested included a toothbrush with sonic and ultrasonic action (ULT), the same toothbrush with only sonic action (ULN), a sonic toothbrush (SON) and a rotating/oscillating toothbrush (OSC). The active element of the toothbrushes (bristles or point of ultrasound emission) was immersed in toothpaste slurry and held 3 mm away from the disk surface. Treatment included activation of the toothbrush mode of action for 5 seconds. Control disks were exposed to the same fluid environment but not exposed to a power toothbrush. After treatment, biofilm present on the disks was stained using a red dental plaque disclosing solution. Photographs were then taken and the presence of biofilm assessed using digital image analysis. For each disk a normalized pixel volume, related to the presence of biofilm corrected for lighting, was determined. Statistical testing was done with a one-way ANOVA and a Bonferroni post hoc test. RESULTS: Normalized pixel volumes (mean +/- standard deviation) were 0.428 (0.010) for the negative control and 1.022 (0.040) for the positive control. Normalized pixel volumes for the power toothbrush modes of action were 0.641 (0.075) for ULT, 0.972 (0.027) for ULN, 0.921 (0.010) for SON and 0.955 (0.025) for OSC. Statistical analysis showed a significant treatment effect (P<0.001). All power toothbrush modes of action exhibited some biofilm removal without bristle contact in this in vitro assay. Of the modes of action tested, the combined sonic and ultrasonic mode of action (ULT) removed the greatest amount of biofilm from the disk surfaces. The same toothbrush when tested with (ULT) and without (ULN) ultrasound showed a greater amount of biofilm removed when ultrasound was present.

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.

Synergistic use of ultrasound and sonic motion for removal of dental plaque bacteria.

Proving that an idea has merit for further investigation is one of the earliest steps in product development. This proof of concept can be effectively studied in a dynamic, multidisciplinary environment where ideas can be quickly tested in a manner related to final product use. In this article, the authors demonstrate the fecundity of a multidisciplinary environment by reviewing their early work that shows that ultrasound could be added to a power toothbrush to enhance the removal of dental plaque bacteria. They hypothesized that sonic brush head motion would generate bubbles in a dentifrice so that ultrasound beamed into that slurry would cause those bubbles to expand and contract in a manner that would dislodge the plaque bacteria adherent to the tooth surfaces. In this work, Streptococcus mutans bacteria adherent to various surfaces was used as a model of dental plaque on human teeth. Prototype power toothbrushes were created using commercially available and custom components so that the ultrasound and sonic processes could be individually modified and applied. Research demonstrated that the combination of sonic and ultrasound processes could synergistically remove S mutans biofilm. This finding established the proof of concept that eventually led to the development of a power toothbrush that uses both ultrasound and sonic activity.

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.

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.