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Understanding the cellular mechanisms of kHz electrical stimulation is of broad interest in neuromodulation including forms of transcranial electrical stimulation (tES), interferential stimulation, and high-rate spinal cord stimulation (SCS). Yet, the well-established low-pass filtering by neuronal membranes suggests minimal neuronal polarization in respond to charge-balanced kHz stimulation. The hippocampal brain slice model is among the most studied systems in neuroscience and exhaustively characterized in screening the effects of electrical stimulation. High-frequency electric fields of varied amplitudes (1-150 V/m), waveforms (sinusoidal, symmetrical pule, asymmetrical pulse) and frequencies (1 and10 kHz) were tested. Changes in single or paired-pulse field excitatory post-synaptic potentials (fEPSP) in CA1 were measured in response to radial- and tangential-directed electric fields, with brief (30 s) or long (30 min) application times. The effects of kHz stimulation on ongoing endogenous network activity were tested in carbachol-induced gamma oscillation of CA3a and CA3c. Across 23 conditions evaluated, no significant changes in fEPSP were resolved, while responses were detected for within-slice control DC fields. 1 kHz sinusoidal and pulse stimulation (≥60 V/m), but not 10 kHz induced changes in oscillating neuronal network. We thus report no responses to low-amplitude 1 kHz or any 10 kHz fields, suggesting that any brain sensitivity to these fields is via yet to be-determined mechanism(s) of action which were not identified in our experimental preparation.SIGNIFICANCE STATEMENT There a large mismatch between enthusiasm for clinical treatments using kHz frequency electrical stimulation and the understanding of kHz mechanisms of action. Indeed, the well-established low-pass properties of cell membranes should attenuate any response to kHz stimulation. This study presents the largest and broadest characterization of the cellular effects of kHz stimulation using the most established animal model to detect CNS sensitivity to electric fields: Our work systematically evaluated sensitivity of hippocampal synaptic function and oscillatory network activity in response to kHz. Only at low kHz (1 kHz but not 10 kHz) with high intensity and during oscillations responses were detected. This systematic and largely negative experimental series suggest kHz neuromodulation operates via yet to be determined mechanisms.

Characterizing the cellular targets of kHz (1–10 kHz) electrical stimulation remains a pressing topic in neuromodulation because expanding interest in clinical application of kHz stimulation has surpassed mechanistic understanding. The presumed cellular targets of brain stimulation do not respond to kHz frequencies according to conventional electrophysiology theory. Specifically, the low‐pass characteristics of cell membranes are predicted to render kHz stimulation inert, especially given the use of limited‐duty‐cycle biphasic pulses. Precisely because kHz frequencies are considered supra‐physiological, conventional instruments designed for neurophysiological studies such as stimulators, amplifiers and recording microelectrodes do not operate reliably at these high rates. Moreover, for pulsed waveforms, the signal frequency content is well above the pulse repetition rate. Thus, the very tools used to characterize the effects of kHz electrical stimulation may themselves be confounding factors. We illustrate custom equipment design that supports reliable electrophysiological recording during kHz‐rate stimulation. Given the increased importance of kHz stimulation in clinical domains and compelling possibilities that mechanisms of actions may reflect yet undiscovered neurophysiological phenomena, attention to suitable performance of electrophysiological equipment is pivotal. [Image: see text]

Objective Despite the high prevalence of chronic multisite pain, there is little consensus on methods to characterize it. Commonly used assessments report only one dimension of pain, that is, intensity, thus ignoring the spatial aspect of pain. We developed a novel pain quantification index, the Integrated Pain Quantification Index (IPQI), on a scale of 0 to 1 that integrates multiple distinct pain measures into a single value, thus representing multidimensional pain information with a single value. Design Single-visit, noninterventional, epidemiological study. Setting Fourteen outpatient multidisciplinary pain management programs. Patients Patients with chronic pain of the trunk and/or limbs for at least six months with average overall pain intensity of at least 5 on the numeric rating scale. Methods Development of IPQI was performed in a large population (N = 810) of chronic pain patients from the Multiple Areas of Pain (MAP) study. Results Prevalence of two or more noncontiguous painful areas was at 88.3% (95% confidence interval [CI] = 0.86-0.90), with a mean of 6.3 areas (SD = 5.57 areas). Prevalence of more than 10% body area in pain was at 52.8% (95% CI = 0.49-0.56), with a mean at 16.1% (17.16%). On average, IPQI values were near the middle of the scale, with mean and median IPQI at 0.52 (SD = 0.13) and 0.55, respectively. The IPQI was generalizable and clinically relevant across all domains recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials. Conclusions IPQI provided a single pain score for representing complex, multidimensional pain information on one scale and has implications for comparing pain populations across longitudinal clinical trials.

This article describes a six-point auricular acupuncture protocol to influence the neuroanatomical and psychoemotional targets of trauma. This protocol can be used immediately or years following the noxious experience. The article addresses the rationale for combining these points, their locations, and methods of stimulation, as well as briefly discussing anecdotal experience in military and civilian populations. The protocol is presented as a simple and safe intervention of potential value for addressing the multiple manifestations of the trauma spectrum.

The purpose of this investigation is to assess the potential interchangeability of key material response metrics as measured using quasi-static indentation (QSI) and low-velocity impact (LVI). This report compares the response of a S2/SC-15 glass /epoxy composite material subjected these two test methods. Specimens of 102 152 5.5 mm were quasi-statically indented at load rates in the range of 1.2 to 50 mm/min. Differences in material response over this range of loading rate were found to be negligible. The average value of peak input energy calculated from these QSI tests was used as the impact energy for subsequent LVI tests of identical specimens. Material tested using LVI (3.41 m/s velocity) exhibited higher initial stiffness and absorbed energy but with slightly lower maximum force and displacement values compared to material tested with QSI. Thirty QSI and LVI specimens were then evaluated with compression after impact (CAI) testing, and all specimens exhibited equivalent CAI strengths. Lightbox and cross-section analyses showed that material tested under LVI exhibited significantly less delamination and significantly more intralaminar fracture compared to QSI. For these reasons, LVI and QSI data are not interchangeable for this material system.

This report documents the fabrication and test of a woven glass/epoxy composite laminate that was reinforced in the through-thickness direction with aramid fibers using a needling process. The purpose of reinforcing laminated material in the through-thickness direction is to improve its delamination resistance/damage tolerance. The needled material was approximately 6.4-mm thick and was tested using American Standard Test Method ASTM standards to assess the improvements in impact response and any reductions in-plane strength, which is a typical tradeoff with 3D-reinforced stitched materials. Needled specimens exhibited 10-15% increase in effective stiffness (force-deflection response) under impact loading, and a 50% increase in compression-after-impact strength-a significant improvement in damage tolerance. Needled but non-impacted material exhibited a 9% increase in the in-plane compressive strength and a 17% increase in flexural strength, indicating at least that the needling process does not cause immediate tradeoffs in the in-plane strength of woven glass materials. Because the processing parameters were arbitrarily chosen, these experiments should be considered as proof-of-concept.

Four long-term captive adult rhinoceros iguanas (Cyclura cornuta) on display at the Dallas Zoo (Dallas, TX) were maintained for several years in an outdoor enclosure in the summer and in a smaller indoor enclosure in the winter. While fully exposed to sunlight and given the opportunity to supplement their diet with live vegetation each summer, they were deprived of the benefits of full sun exposure, including ultraviolet B (UVB) exposure, and they received no dietary vitamin D for several months each winter. Maintained with this protocol, the animals seemed healthy and they reproduced. However, increasing awareness of the important role of UVB in vitamin D–mediated calcium metabolism and the potential health risk of UVB and vitamin D deprivation stimulated us to focus more on seasonal changes in vitamin D status and possible subtle changes in health status throughout winter. From September 2008 to October 2010, an 85% decline in the serum 25-hydroxyvitamin D3 (calcidiol) concentrations was measur...

Background: With advances in spinal cord stimulation (SCS) technology, particularly rechargeable implantable, patients are now being offered a wider range of parameters to treat their pain. In particular, pulse width (PW) programming ranges of rechargeable implantable pulse generators now match that of radiofrequency systems (with programmability up to 1000µs). The intent of the present study was to investigate the effects of varying PW in SCS. Objective: To understand the effects of PW programming in spinal cord stimulation (SCS). Design: Single-center, prospective, randomized, single-blind evaluation of the technical and clinical outcomes of PW programming. Setting: Acute, outpatient follow-up. Methods: Subjects using fully-implanted SCS for > 3 months to treat chronic intractable low back and/or leg pain. Programming of a wide range (50-1000μs) of programmed PW settings using each patient’s otherwise unchanged ‘walk-in’ program. Outcome Measures: Paresthesia thresholds (perception, maximum comfortable, discomfort), paresthesia coverage and patient choice of tested programs. Results: We found strength-duration parameters of chronaxie and rheobase to be 295 (242 – 326) μs and 2.5 (1.3 – 3.3) mA, respectively. The median PW of all patients’ ‘walk-out’ programs was 400μs, approximately 48% higher than median chronaxie (P = 0.01), suggesting that chronaxie may not relate to patient-preferred stimulation settings. We found that 7/19 patients selected new PW programs, which significantly increased their paresthesia-pain overlap by 56% on average (P = 0.047). We estimated that 10/19 patients appeared to have greater paresthesia coverage, and 8/19 patients appeared to display a ‘caudal shift’ of paresthesia coverage with increased PW. Limitations: Small number of patients. Conclusions: Variable PW programming in SCS appears to have clinical value, demonstrated by some patients improving their paresthesia-pain overlap, as well as the ability to increase and even ‘steer’ paresthesia coverage. Key words: Spinal cord stimulation, pulse width, paresthesia, dermatome, implantable pulse generator, neurostimulation, chronic pain, neuropathic, dorsal column, dorsal root, chronaxie.

We developed BRISK–CON–VPS, a rapid phase-contrast cine approach that is a hybrid of the BRISK–VPS (Block Regional Interpolation Scheme for k-space) and conventional (CONV–VPS) scanning employing k-space views per segment (VPS). BRISK–CON–VPS allows data acquisition approximately four times faster than CONV–VPS imaging and has the advantage compared to BRISK–VPS that it can potentially be incorporated into real-time applications. In BRISK–CON–VPS contiguous regions of k-space are sampled using a views per segment factor that is varied as a function of distance from the k-space center. Computational fluid dynamics (CFD) data were used to simulate CONV–VPS, BRISK–VPS, and BRISK–CON–VPS. BRISK–CON–VPS was simulated by incrementing the VPS progressively with increasing distance from the k-space origin while BRISK–VPS was simulated using a uniform VPS applied to the sparse sampling scheme. Simulations showed that up to a base VPS of 5, both BRISK–CON–VPS and BRISK–VPS retained excellent axial-velocity accuracy. Secondary in-plane velocity flow fields were well represented with BRISK–CON–VPS and BRISK–VPS up to a base VPS of 3. CONV–VPS, BRISK–CON–VPS, and BRISK–VPS were applied in vivo and shown to provide comparable quantitative flow data. BRISK–CON–VPS accomplishes breath-hold acquisitions as efficiently as BRISK–VPS, but without requiring data interpolation or under-sampling k-space.

Purpose To evaluate different grades of in-stent stenosis in a nickel-titanium stent with MRI. Materials and Methods Magnetic resonance phase velocity mapping (MR-PVM) was used to measure flow velocity through a 9-mm NiTi stent with three different degrees of stenosis in a phantom study. The tested stenotic geometries were 1) axisymmetric 75%, 2) axisymmetric 90%, and 3) asymmetric 50%. The MR-PVM data were subsequently compared with the velocities from computational fluid dynamic (CFD) simulations of identical conditions. Results Good quantitative agreement in velocity distribution for the 50% and 75% stenoses was observed. The agreement was poor for the 90% stenosis, most likely due to turbulence and the high-velocity gradients found in the small luminal area relative to the pixel resolution in our imaging settings. Conclusion The accuracy of the MRI velocities inside the stented area renders MRI a modality that may be used to assess moderate to severe in-stent restenosis (ISR) in medium-sized vascular stents in peripheral vessels, such as the iliac, carotid, and femoral arteries. Advances in MR instrumentation may provide sufficient resolution to obtain adequate velocity information from smaller vessels, such as the coronary arteries, and allow MRI to substitute for invasive and expensive catheterization procedures currently in clinical use. J. Magn. Reson. Imaging 2005;22:248–257. © 2005 Wiley-Liss, Inc.

Clinical use of cardiac synchronized Magnetic Resonance Imaging has been limited because of long unacceptable acquisition times. BRISK (Block Regional Interpolation Scheme for k-space) is a rapid MRI technique, which employs temporal sparse sampling scheme that varies the sampling rate as a function of distance from the k-space center. Using combination of conventional segmentation and BRISK approach, a new rapid phase contrast cine approach named FAST was investigated. FAST technique samples contiguous regions of k-space using a segmentation factor, just as in conventional segmentation, with the difference that the segmentation factor (SF) is varied as a function of distance from the k-space center. FAST and BRISK can be performed in nearly equally scan times. Both retained excellent axial-velocity accuracy. However secondary velocities, which were two orders of magnitude lower than the primary, suffered from comparable inaccuracies and distortion in conventional segmentation, BRISK and FAST.Copyright © 2004 by ASME

The development of Intimal Hyperplasia (IH) in saphenons vein coronary artery bypass grafts (SV-CABG) is responsible for the short-term patency of these grafts. Previous studies of SV-CABG models were performed on rigid anastomotic vessels. However, the effects of compliance, bulging and curvature at the anastomosis on the general hemodynamic field, due to compliance and geometric mismatch between the vein and the artery have not been evaluated. We studied axial and transverse velocities by Laser Doppler Velocimetry on a compliant; in vitro, anatomical model of an end-to-side saphenous vein graft (SVG) to left anterior descending (LAD). The model incorporated a bulge at the sinus and curvature at the graft-host junction. Physiologic pressure and flow conditions pertaining to SV-CABG were applied. The presence of the bulge and curvature showed differences in the velocity profiles in comparison with previous rigid model studies. Dynamic separation zones were temporally augmented at the flow divider. The moving stagnation point at the floor of the host vessel was observed to move past the toe of the model during the accelerating portion of the cycle. These findings suggest that the presence of the bulge curvature and compliance may further favor conditions for the development of intimal hyperplasia (IH) at the floor of a CABG.

The effects of lithium dialkylamide structure, mixed aggregate formation, and solvation on the stereoselectivity of ketone enolization were examined. Of the lithium dialkylamides examined, lithium tetramethylpiperidide (LiTMP) in THF resulted in the best enolization selectivity. The stereoselectivity was further improved in the presence of a LiTMP-butyllithium mixed aggregate. The use of less polar solvents reduced the enolization stereoselectivity. Ab initio calculations predict LDA and LiTMP to form mixed cyclic dimers in ethereal solvents. The calculations also predict LiTMP-alkyllithium mixed aggregates to competitively inhibit the formation of less stereoselective LiTMP-lithium enolate mixed aggregates.

Cardiac synchronized magnetic resonance imaging of flowfields has suffered due to the relatively long acquisition times required. We developed a rapid MRI approach, BRISK PCA (Block Regional Interpolation Scheme for k-space Phase Contrast Angiography) which was simulated here using data generated by computational fluid dynamics to investigate the role of interpolation and segmentation on the accuracy and efficiency of the method. BRISK differs from other sparse sampling schemes in that the sampling rate is a function of the position in k-space and interpolation is used to generate data points not directly acquired. Combined with conventional segementation, this allows more efficient use of time, resulting in rapid acquisitions with good spatial and temporal resolution. FAST (Fourier AcquiSition in Time) is a similar sparse sampling strategy that varies the segmentation factor, rather than the sampling rate, as a function of k-space position. BRISK and FAST can be performed in nearly equally scan times. However, deviation from ideal in the FAST data was highly dependant on the starting phase of the flow waveform, while BRISK was immune to such variation. Simulations showed that BRISK (up to segmentation factor 5) and FAST 5 retained excellent axial-velocity accuracy, but the accuracy of FAST was variable and dependent on waveform characteristics.Copyright © 2003 by ASME

To understand the theoretical effects of pulse width (PW) programming in spinal cord stimulation (SCS), we implemented a mathematical model of electrical fields and neural activation in SCS to gain insight into the effects of PW programming. The computational model was composed of a finite element model for structure and electrical properties, coupled with a nonlinear double-cable axon model to predict nerve excitation for different myelinated fiber sizes. Mathematical modeling suggested that mediolateral lead position may affect chronaxie and rheobase values, as well as predict greater activation of medial dorsal column fibers with increased PW. These modeling results were validated by a companion clinical study. Thus, variable PW programming in SCS appears to have theoretical value, demonstrated by the ability to increase and even ‘steer’ spatial selectivity of dorsal column fiber recruitment. It is concluded that the computational SCS model is a valuable tool to understand basic mechanisms of nerve fiber excitation modulated by stimulation parameters such as PW and electric fields.