15-year survivorship of a unique dual-modular femoral stem in primary hip arthroplasty.

BACKGROUND: Hip offset, version, and length are interdependent femoral variables which determine stability and leg length. Balancing these competing variables remains a core challenge in hip arthroplasty. The potential benefits of modular femoral stems have been overshadowed by higher rates of failure. The objective of this study was to assess the survivorship of a unique dual-modular femoral stem at an average 15-year follow-up period. METHODS: The records of all patients with osteoarthritis who underwent primary total hip arthroplasty with this device between 2004-2009 were reviewed. There were no exclusions for BMI or other factors. We examined the data with Kaplan-Meier survival analysis. The primary endpoint for survival was mechanical failure of the modular neck-body junction. RESULTS: The survivorship of this device in 172 subjects was 100% with none experiencing mechanical failure of the modular junction at an average of 15 years. 60 patients died of causes unrelated to their THA and 9 patients were lost to follow-up. There were three early (≤ 12 months) dislocations (1.7%), and seven total dislocations (4.1%). 16 patients underwent reoperations during the follow-up period, none for any complication of the modular junction. Radiographic results showed well-fixed femoral stems in all cases. There were no leg length discrepancies of greater than 10 mm, and 85% were within 5 mm. CONCLUSION: There were no mechanical failures of the modular junction in any of the subjects over the average 15-year period, demonstrating that this dual-modular design is not associated with increased failure rates. We achieved a 1.7% early dislocation rate and a 4.1% total dislocation rate without any clinically significant leg length discrepancies.

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.

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.

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.

Increased anatomical specificity of neuromodulation via modulated focused ultrasound.

Transcranial ultrasound can alter brain function transiently and nondestructively, offering a new tool to study brain function now and inform future therapies. Previous research on neuromodulation implemented pulsed low-frequency (250-700 kHz) ultrasound with spatial peak temporal average intensities (ISPTA) of 0.1-10 W/cm(2). That work used transducers that either insonified relatively large volumes of mouse brain (several mL) with relatively low-frequency ultrasound and produced bilateral motor responses, or relatively small volumes of brain (on the order of 0.06 mL) with relatively high-frequency ultrasound that produced unilateral motor responses. This study seeks to increase anatomical specificity to neuromodulation with modulated focused ultrasound (mFU). Here, 'modulated' means modifying a focused 2-MHz carrier signal dynamically with a 500-kHz signal as in vibro-acoustography, thereby creating a low-frequency but small volume (approximately 0.015 mL) source of neuromodulation. Application of transcranial mFU to lightly anesthetized mice produced various motor movements with high spatial selectivity (on the order of 1 mm) that scaled with the temporal average ultrasound intensity. Alone, mFU and focused ultrasound (FUS) each induced motor activity, including unilateral motions, though anatomical location and type of motion varied. Future work should include larger animal models to determine the relative efficacy of mFU versus FUS. Other studies should determine the biophysical processes through which they act. Also of interest is exploration of the potential research and clinical applications for targeted, transcranial neuromodulation created by modulated focused ultrasound, especially mFU's ability to produce compact sources of ultrasound at the very low frequencies (10-100s of Hertz) that are commensurate with the natural frequencies of the brain.

Blast exposure causes early and persistent aberrant phospho- and cleaved-tau expression in a murine model of mild blast-induced traumatic brain injury.

Mild traumatic brain injury (mTBI) is considered the 'signature injury' of combat veterans that have served during the wars in Iraq and Afghanistan. This prevalence of mTBI is due in part to the common exposure to high explosive blasts in combat zones. In addition to the threats of blunt impact trauma caused by flying objects and the head itself being propelled against objects, the primary blast overpressure (BOP) generated by high explosives is capable of injuring the brain. Compared to other means of causing TBI, the pathophysiology of mild-to-moderate BOP is less well understood. To study the consequences of BOP exposure in mice, we employed a well-established approach using a compressed gas-driven shock tube that recapitulates battlefield-relevant open-field BOP. We found that 24 hours post-blast a single mild BOP provoked elevation of multiple phospho- and cleaved-tau species in neurons, as well as elevating manganese superoxide-dismutase (MnSOD or SOD2) levels, a cellular response to oxidative stress. In hippocampus, aberrant tau species persisted for at least 30 days post-exposure, while SOD2 levels returned to sham control levels. These findings suggest that elevated phospho- and cleaved-tau species may be among the initiating pathologic processes induced by mild blast exposure. These findings may have important implications for efforts to prevent blast-induced insults to the brain from progressing into long-term neurodegenerative disease processes.