Multiphoton parallel transmission (MP-pTx): Pulse design methods and numerical validation.

PURPOSE: We propose and evaluate multiphoton parallel transmission (MP-pTx) to mitigate flip angle inhomogeneities in high-field MRI. MP-pTx is an excitation method that utilizes a single, conventional birdcage coil supplemented with low-frequency (kHz) irradiation from a multichannel shim array and/or gradient channels. SAR analysis is simplified to that of a conventional birdcage coil, because only the radiofrequency (RF) field from the birdcage coil produces significant SAR. METHODS: MP-pTx employs an off-resonance RF pulse from a conventional birdcage coil supplemented with oscillating z $$ z $$ -directed fields from a multichannel shim array and/or the gradient coils. We simulate the ability of MP-pTx to create uniform nonselective brain excitations at 7 T using realistic B 1 + $$ {\mathrm{B}}_1^{+} $$ and Δ B 0 $$ \Delta {\mathrm{B}}_0 $$ field maps. The RF, shim array, and gradient waveform's amplitudes and phases are optimized using a genetic algorithm followed by sequential quadratic programming. RESULTS: A 1 ms MP-pTx excitation using a 32-channel shim array with current constrained to less than 50 Amp-turns reduced the transverse magnetization's normalized root-mean-squared error from 29% for a conventional birdcage excitation to 6.6% and was nearly 40% better than a 1 ms birdcage coil 5 kT-point excitation with optimized kT-point locations and comparable pulse power. CONCLUSION: The MP-pTx method resembles conventional pTx in its goals and approach but replaces the parallel RF channels with cheaper, low-frequency shim channels. The method mitigates high-field flip angle inhomogeneities to a level better than 3 T CP-mode and comparable to 7 T pTx while retaining the straightforward SAR characteristics of conventional birdcage excitations, as low-frequency shim array fields produce negligible SAR.

Chemerin Levels in Individuals with Type 2 Diabetes and a Normal Weight versus Individuals with Type 2 Diabetes and Obesity: An Observational, Cross-Sectional Study.

Chemerin acts as both a chemotactic agent and an adipokine that undergoes proteolytic cleavage, converting inactive precursors into their active forms before being subsequently inactivated. Elevated chemerin levels are linked to obesity and type 2 diabetes mellitus (T2D). This study aimed to elucidate the effects of T2D and obesity on chemerin levels by comparing plasma samples from individuals with a normal weight and T2D (BMI < 25; NWD group n = 22) with those from individuals who are overweight or obese and have T2D (BMI ≥ 25; OWD group n = 39). The total chemerin levels were similar in the NWD and OWD groups, suggesting that T2D may equalize the chemerin levels irrespective of obesity status. The cleavage of chemerin has been previously linked to myocardial infarction and stroke in NWD, with potential implications for inflammation and mortality. OWD plasma exhibited lower levels of cleaved chemerin than the NWD group, suggesting less inflammation in the OWD group. Here, we showed that the interaction between obesity and T2D leads to an equalization in the total chemerin levels. The cleaved chemerin levels and the associated inflammatory state, however, differ significantly, underscoring the complex relationship between chemerin, T2D, and obesity.

Experimental validation of a PNS-optimized whole-body gradient coil.

PURPOSE: Peripheral nerve stimulation (PNS) limits the usability of state-of-the-art whole-body and head-only MRI gradient coils. We used detailed electromagnetic and neurodynamic modeling to set an explicit PNS constraint during the design of a whole-body gradient coil and constructed it to compare the predicted and experimentally measured PNS thresholds to those of a matched design without PNS constraints. METHODS: We designed, constructed, and tested two actively shielded whole-body Y-axis gradient coil winding patterns: YG1 is a conventional symmetric design without PNS-optimization, whereas YG2's design used an additional constraint on the allowable PNS threshold in the head-imaging landmark, yielding an asymmetric winding pattern. We measured PNS thresholds in 18 healthy subjects at five landmark positions (head, cardiac, abdominal, pelvic, and knee). RESULTS: The PNS-optimized design YG2 achieved 46% higher average experimental thresholds for a head-imaging landmark than YG1 while incurring a 15% inductance penalty. For cardiac, pelvic, and knee imaging landmarks, the PNS thresholds increased between +22% and +35%. For abdominal imaging, PNS thresholds did not change significantly between YG1 and YG2 (-3.6%). The agreement between predicted and experimental PNS thresholds was within 11.4% normalized root mean square error for both coils and all landmarks. The PNS model also produced plausible predictions of the stimulation sites when compared to the sites of perception reported by the subjects. CONCLUSION: The PNS-optimization improved the PNS thresholds for the target scan landmark as well as most other studied landmarks, potentially yielding a significant improvement in image encoding performance that can be safely used in humans.

Influence of peripheral axon geometry and local anatomy on magnetostimulation chronaxie.

Objective.Rapid switching of magnetic resonance imaging (MRI) gradient fields induces electric fields that can cause peripheral nerve stimulation (PNS) and so accurate characterization of PNS is required to maintain patient safety and comfort while maximizing MRI performance. The minimum magnetic gradient amplitude that causes stimulation, the PNS threshold, depends on intrinsic axon properties and the spatial and temporal properties of the induced electric field. The PNS strength-duration curve is widely used to characterize simulation thresholds for periodic waveforms and is parameterized by the chronaxie and rheobase. Safety limits to avoid unwanted PNS in MRI rely on a single chronaxie value to characterize the response of all nerves. However, experimental magnetostimulation peripheral nerve chronaxie values vary by an order of magnitude. Given the diverse range of chronaxies observed and the importance of this number in MRI safety models, we seek a deeper understanding of the mechanisms contributing to chronaxie variability.Approach.We use a coupled electromagnetic-neurodynamic PNS model to assess geometric sources of chronaxie variability. We study the impact of the position of the stimulating magnetic field coil relative to the body, along with the effect of local anatomical features and nerve trajectories on the driving function and the resulting chronaxie.Main results.We find realistic variation of local axon and tissue geometry can modulate a given axon's chronaxie by up to two-fold. Our results identify the temporal rate of charge redistribution as the underlying determinant of the chronaxie.Significance.This charge distribution is a function of both intrinsic axon properties and the spatial stimulus along the nerve; thus, examination of the local tissue topology, which shapes the electric fields, as well as the nerve trajectory, are critical for better understanding chronaxie variations and defining more biologically informed MRI safety guidelines.

Edema progression in proximity to traumatic microbleeds: evolution of cytotoxic and vasogenic edema on serial MRI.

Introduction: Although cerebral edema is common following traumatic brain injury (TBI), its formation and progression are poorly understood. This is especially true for the mild TBI population, who rarely undergo magnetic resonance imaging (MRI) studies, which can pick up subtle structural details not visualized on computed tomography, in the first few days after injury. This study aimed to visually classify and quantitatively measure edema progression in relation to traumatic microbleeds (TMBs) in a cohort of primarily mild TBI patients up to 30 days after injury. Researchers hypothesized that hypointense lesions on Apparent Diffusion Coefficient (ADC) detected acutely after injury would evolve into hyperintense Fluid Attenuated Inversion Recover (FLAIR) lesions. Methods: This study analyzed the progression of cerebral edema after acute injury using multimodal MRI to classify TMBs as potential edema-related biomarkers. ADC and FLAIR MRI were utilized for edema classification at three different timepoints: ≤48 hours, ~1 week, and 30 days after injury. Hypointense lesions on ADC (ADC+) suggested the presence of cytotoxic edema while hyperintense lesions on FLAIR (FLAIR+) suggested vasogenic edema. Signal intensity Ratio (SIR) calculations were made using ADC and FLAIR to quantitatively confirm edema progression. Results: Our results indicated the presence of ADC+ lesions ≤48 hours and ~1 week were associated with FLAIR+ lesions at ~1 week and 30 days, respectively, suggesting some progression of cytotoxic edema to vasogenic edema over time. Ten out of 15 FLAIR+ lesions at 30 days (67%) were ADC+ ≤48 hours. However, ADC+ lesions ≤48 hours were not associated with FLAIR+ lesions at 30 days; 10 out of 25 (40%) ADC+ lesions ≤48 hours were FLAIR+ at 30 days, which could indicate that some lesions resolved or were not visualized due to associated atrophy or tissue necrosis. Quantitative analysis confirmed the visual progression of some TMB lesions from ADC+ to FLAIR+. FLAIR SIRs at ~1 week were significantly higher when lesions were ADC+ ≤48 hours (1.22 [1.08-1.32] vs 1.03 [0.97-1.11], p=0.002). Conclusion: Awareness of how cerebral edema can evolve in proximity to TMBs acutely after injury may facilitate identification and monitoring of patients with traumatic cerebrovascular injury and assist in development of novel therapeutic strategies.

Chemerin in Participants with or without Insulin Resistance and Diabetes.

Chemerin is a chemokine/adipokine, regulating inflammation, adipogenesis and energy metabolism whose activity depends on successive proteolytic cleavages at its C-terminus. Chemerin levels and processing are correlated with insulin resistance. We hypothesized that chemerin processing would be higher in individuals with type 2 diabetes (T2D) and in those who are insulin resistant (IR). This hypothesis was tested by characterizing different chemerin forms by specific ELISA in the plasma of 18 participants with T2D and 116 without T2D who also had their insulin resistance measured by steady-state plasma glucose (SSPG) concentration during an insulin suppression test. This approach enabled us to analyze the association of chemerin levels with a direct measure of insulin resistance (SSPG concentration). Participants were divided into groups based on their degree of insulin resistance using SSPG concentration tertiles: insulin sensitive (IS, SSPG ≤ 91 mg/dL), intermediate IR (IM, SSPG 92-199 mg/dL), and IR (SSPG ≥ 200 mg/dL). Levels of different chemerin forms were highest in patients with T2D, second highest in individuals without T2D who were IR, and lowest in persons without T2D who were IM or IS. In the whole group, chemerin levels positively correlated with both degree of insulin resistance (SSPG concentration) and adiposity (BMI). Participants with T2D and those without T2D who were IR had the most proteolytic processing of chemerin, resulting in higher levels of both cleaved and degraded chemerin. This suggests that increased inflammation in individuals who have T2D or are IR causes more chemerin processing.

Investigating the Relevance of Maximal Speed and Acceleration in Varsity-Level Female Ice Hockey Players.

PURPOSE: To characterize and compare female ice hockey players' peak skating speed and acceleration ability during linear sprints and gameplay. We also sought to quantify the time spent at various speeds and the frequency of accelerations at different thresholds during games. METHODS: Seventeen varsity-level female ice hockey players (20 [1.4] y, 68.9 [4.9] kg, 167.6 [4.7] cm) participated in an on-ice practice session (performing 3 × 40-m linear sprints) and 4 regular-season games while being monitored using a local positioning system. Speed and acceleration were recorded from the sprint and within-game monitoring. Time on ice spent in relative skating speed zones and the frequency of accelerations at different intensities were recorded. RESULTS: Players' greatest peak speeds (29.5 [1.3] vs 28.3 [1.1] km/h) and accelerations (4.39 [0.48] vs 3.34 [0.36] m/s2) reached during gameplay were higher than those reached in linear sprinting (both P < .01). Peak in-game values were moderately predicted by linear sprint values for speed (r = .69, P < .01) but not for acceleration (r < .01, P = .95). Players spent little time at near-peak linear sprint speeds (≥80% [22.7 km/h], ∼3% time on ice; ≥90% [25.5 km/h], <1% of time on ice) during gameplay. However, 26% to 35% of accelerations recorded during the 4 games were ≥90% of linear sprint acceleration. CONCLUSIONS: Although skating speed may be advantageous in specific game situations, our results suggest that players spend little time at near-maximal speeds while accelerating frequently during games. This warrants further investigation of direction changes, skating transitions, repeated sprints, and other determinant variables potentially related to on-ice success and the implementation of training strategies to improve repeated acceleration or qualities beyond maximal skating speed.

Late lesion growth following endovascular therapy: is 24 hours too early to assess acute infarct size including the effects of secondary injury?

Introduction Stroke lesion volume on MRI or CT provides objective evidence of tissue injury as a consequence of ischemic stroke. Measurement of "final" lesion volume at 24hr following endovascular therapy (post-EVT) has been used in multiple studies as a surrogate for clinical outcome. However, despite successful recanalization, a significant proportion of patients do not experience favorable clinical outcome. The goals of this study were to quantify lesion growth during the first week after treatment, identify early predictors, and explore the association with clinical outcome. Methods This is a prospective study of stroke patients at two centers who met the following criteria: i) anterior large vessel occlusion (LVO) acute ischemic stroke, ii) attempted EVT, and iii) had 3T MRI post-EVT at 24hr and 5-day. We defined "Early" and "Late" lesion growth as ≥10mL lesion growth between baseline and 24hr DWI, and between 24hr DWI and 5-day FLAIR, respectively. Complete reperfusion was defined as >90% reduction of the volume of tissue with perfusion delay (Tmax>6sec) between pre-EVT and 24hr post-EVT. Favorable clinical outcome was defined as modified Rankin scale (mRS) of 0-2 at 30 or 90 days. Results One hundred twelve patients met study criteria with median age 67 years, 56% female, median admit NIHSS 19, 54% received IV or IA thrombolysis, 66% with M1 occlusion, and median baseline DWI volume 21.2mL. Successful recanalization was achieved in 87% and 68% had complete reperfusion, with an overall favorable clinical outcome rate of 53%. Nearly two thirds (65%) of the patients did not have Late lesion growth with a median volume change of -0.3mL between 24hr and 5-days and an associated high rate of favorable clinical outcome (64%). However, ~1/3 of patients (35%) did have significant Late lesion growth despite successful recanalization (87%: 46% mTICI 2b/ 41% mTICI 3). Late lesion growth patients had a 27.4mL change in Late lesion volume and 30.1mL change in Early lesion volume. These patients had an increased hemorrhagic transformation rate of 68% with only 1 in 3 patients having favorable clinical outcome. Late lesion growth was independently associated with incomplete reperfusion, hemorrhagic transformation, and unfavorable outcome. Conclusion Approximately 1 out of 3 patients had Late lesion growth following EVT, with a favorable clinical outcome occurring in only 1 out of 3 of these patients. Most patients with no Early lesion growth had no Late lesion growth. Identification of patients with Late lesion growth could be critical to guide clinical management and inform prognosis post-EVT. Additionally, it can serve as an imaging biomarker for the development of adjunctive therapies to mitigate reperfusion injury.

Single-shot Echo Planar Time-resolved Imaging for multi-echo functional MRI and distortion-free diffusion imaging.

Purpose: To develop EPTI, a multi-shot distortion-free multi-echo imaging technique, into a single-shot acquisition to achieve improved robustness to motion and physiological noise, increased temporal resolution, and high SNR efficiency for dynamic imaging applications. Methods: A new spatiotemporal encoding was developed to achieve single-shot EPTI by enhancing spatiotemporal correlation in k-t space. The proposed single-shot encoding improves reconstruction conditioning and sampling efficiency, with additional optimization under various accelerations to achieve optimized performance. To achieve high SNR efficiency, continuous readout with minimized deadtime was employed that begins immediately after excitation and extends for an SNR-optimized length. Moreover, k-t partial Fourier and simultaneous multi-slice acquisition were integrated to further accelerate the acquisition and achieve high spatial and temporal resolution. Results: We demonstrated that ss-EPTI achieves higher tSNR efficiency than multi-shot EPTI, and provides distortion-free imaging with densely-sampled multi-echo images at resolutions ~1.25-3 mm at 3T and 7T-with high SNR efficiency and with comparable temporal resolutions to ss-EPI. The ability of ss-EPTI to eliminate dynamic distortions common in EPI also further improves temporal stability. For fMRI, ss-EPTI also provides early-TE images (e.g., 2.9ms) to recover signal-intensity and functional-sensitivity dropout in challenging regions. The multi-echo images provide TE-dependent information about functional fluctuations, successfully distinguishing noise-components from BOLD signals and further improving tSNR. For diffusion MRI, ss-EPTI provides high-quality distortion-free diffusion images and multi-echo diffusion metrics. Conclusion: ss-EPTI provides distortion-free imaging with high image quality, rich multi-echo information, and enhanced efficiency within comparable temporal resolution to ss-EPI, offering a robust and efficient acquisition for dynamic imaging.

Romer-EPTI: rotating-view motion-robust super-resolution EPTI for SNR-efficient distortion-free in-vivo mesoscale dMRI and microstructure imaging.

Purpose: To overcome the major challenges in dMRI acquisition, including low SNR, distortion/blurring, and motion vulnerability. Methods: A novel Romer-EPTI technique is developed to provide distortion-free dMRI with significant SNR gain, high motion-robustness, sharp spatial resolution, and simultaneous multi-TE imaging. It introduces a ROtating-view Motion-robust supEr-Resolution technique (Romer) combined with a distortion/blurring-free EPTI encoding. Romer enhances SNR by a simultaneous multi-thick-slice acquisition with rotating-view encoding, while providing high motion-robustness through a motion-aware super-resolution reconstruction, which also incorporates slice-profile and real-value diffusion, to resolve high-isotropic-resolution volumes. The in-plane encoding is performed using distortion/blurring-free EPTI, which further improves effective spatial resolution and motion robustness by preventing not only T2/T2*-blurring but also additional blurring resulting from combining encoded volumes with inconsistent geometries caused by dynamic distortions. Self-navigation was incorporated to enable efficient phase correction. Additional developments include strategies to address slab-boundary artifacts, achieve minimal TE for SNR gain at 7T, and achieve high robustness to strong phase variations at high b-values. Results: Using Romer-EPTI, we demonstrate distortion-free whole-brain mesoscale in-vivo dMRI at both 3T (500-µm-iso) and 7T (485-µm-iso) for the first time, with high SNR efficiency (e.g., 25×), and high image quality free from distortion and slab-boundary artifacts with minimal blurring. Motion experiments demonstrate Romer-EPTI's high motion-robustness and ability to recover sharp images in the presence of motion. Romer-EPTI also demonstrates significant SNR gain and robustness in high b-value (b=5000s/mm2) and time-dependent dMRI. Conclusion: Romer-EPTI significantly improves SNR, motion-robustness, and image quality, providing a highly efficient acquisition for high-resolution dMRI and microstructure imaging.

Incidence of Tether Breakage in Anterior Vertebral Body Tethering.

BACKGROUND: Thoracic anterior vertebral body tethering (TAVBT) is an emerging treatment for adolescent idiopathic scoliosis. Tether breakage is a known complication of TAVBT with incompletely known incidence. We aim to define the incidence of tether breakage in patients with adolescent idiopathic scoliosis who undergo TAVBT. The incidence of tether breakage in TAVBT is hypothesized to be high and increase with time postoperatively. METHODS: All patients with right-sided, thoracic curves who underwent TAVBT with at least 2 and up to 3 years of radiographic follow-up were included. Tether breakage between 2 vertebrae was defined a priori as any increase in adjacent screw angle >5 degrees from the minimum over the follow-up period. The presence and timing of tether breakage were noted for each patient. A Kaplan-Meier survival analysis was performed to calculate expected tether breakage up to 36 months. χ 2 analysis was performed to examine the relationship between tether breakage and reoperations. Independent t test was used to compare the average final Cobb angle between cohorts. RESULTS: In total, 208 patients from 10 centers were included in our review. Radiographically identified tether breakage occurred in 75 patients (36%). The initial break occurred at or beyond 24 months in 66 patients (88%). Kaplan-Meier survival analysis estimated the cumulative rate of expected tether breakage to be 19% at 24 months, increasing to 50% at 36 months. Twenty-one patients (28%) with a radiographically identified tether breakage went on to require reoperation, with 9 patients (12%) requiring conversion to posterior spinal fusion. Patients with a radiographically identified tether breakage went on to require conversion to posterior spinal fusion more often than those patients without identified tether breakage (12% vs. 2%; P =0.004). The average major coronal curve angle at final follow-up was significantly larger for patients with radiographically identified tether breakage than for those without tether breakage (31 deg±12 deg vs. 26 deg±12 deg; P =0.002). CONCLUSIONS: The incidence of tether breakage in TAVBT is high, and it is expected to occur in 50% of patients by 36 months postoperatively. LEVEL OF EVIDENCE: Level IV.

Penile Strangulation: Analysis of Postextrication Follow-Up, Sequelae, and a Review of Literature.

Numerous case reports exist on penile strangulation injuries and extrication methods; however, the care and long-term consequences of penile strangulation injuries have been under-reported. Our aim is to investigate the long-term outcomes and sequalae following penile strangulation injuries. The PubMed Medline database was searched using the keyword string "penile strangulation," "penis strangulation," and "constriction" for all studies reporting outcomes of published penile strangulation injuries. Articles were evaluated for follow-up after strangulation injury, strangulating agent, extricating agent, and sequelae of injury. Fifty-six studies resulted with reports of 100 cases of penile strangulation and extrication from January 2000 to December 2019. The mean patient age was 41 (range: 3-86) years. Twenty-four (24/100) cases reported sequalae following extrication. Follow-up ranged from 2 weeks to 7 years with median follow-up time in the 7- to 12-month grouping. Metal rings comprised 36% (36/100) of strangulation agents and 50% of reported incidents were attributed to sexual activity. To our knowledge, this is the only study focusing on long-term outcomes after penile strangulation. This review provides a summary of 56 studies that document penile strangulation injuries over the last 20 years. Although a wide array of penile strangulation injuries have been documented in the literature, reports lack secondary management and long-term outcomes after removal of the strangulation device. We recommend that providers report long-term penile strangulation outcomes for future urologic evaluations after extrication.

The effects of osteopathic manipulative treatment on pain and disability in patients with chronic low back pain: a single-blinded randomized controlled trial.

CONTEXT: The evidence for the efficacy of osteopathic manipulative treatment (OMT) in the management of low back pain (LBP) is considered weak by systematic reviews, because it is generally based on low-quality studies. Consequently, there is a need for more randomized controlled trials (RCTs) with a low risk of bias. OBJECTIVES: The objective of this study is to evaluate the efficacy of an OMT intervention for reducing pain and disability in patients with chronic LBP. METHODS: A single-blinded, crossover, RCT was conducted at a university-based health system. Participants were adults, 21-65 years old, with nonspecific LBP. Eligible participants (n=80) were randomized to two trial arms: an immediate OMT intervention group and a delayed OMT (waiting period) group. The intervention consisted of three to four OMT sessions over 4-6 weeks, after which the participants switched (crossed-over) groups. The primary clinical outcomes were average pain, current pain, Patient-Reported Outcomes Measurement Information System (PROMIS) 29 v1.0 pain interference and physical function, and modified Oswestry Disability Index (ODI). Secondary outcomes included the remaining PROMIS health domains and the Fear Avoidance Beliefs Questionnaire (FABQ). These measures were taken at baseline (T0), after one OMT session (T1), at the crossover point (T2), and at the end of the trial (T3). Due to the carryover effects of OMT intervention, only the outcomes obtained prior to T2 were evaluated utilizing mixed-effects models and after adjusting for baseline values. RESULTS: Totals of 35 and 36 participants with chronic LBP were available for the analysis at T1 in the immediate OMT and waiting period groups, respectively, whereas 31 and 33 participants were available for the analysis at T2 in the immediate OMT and waiting period groups, respectively. After one session of OMT (T1), the analysis showed a significant reduction in the secondary outcomes of sleep disturbance and anxiety compared to the waiting period group. Following the entire intervention period (T2), the immediate OMT group demonstrated a significantly better average pain outcome. The effect size was a 0.8 standard deviation (SD), rendering the reduction in pain clinically significant. Further, the improvement in anxiety remained statistically significant. No study-related serious adverse events (AEs) were reported. CONCLUSIONS: OMT intervention is safe and effective in reducing pain along with improving sleep and anxiety profiles in patients with chronic LBP.

Food for thought: Physiological considerations for nutritional ergogenic efficacy.

Top-class athletes have optimized their athletic performance largely through adequate training, nutrition, recovery, and sleep. A key component of sports nutrition is the utilization of nutritional ergogenic aids, which may provide a small but significant increase in athletic performance. Over the last decade, there has been an exponential increase in the consumption of nutritional ergogenic aids, where over 80% of young athletes report using at least one nutritional ergogenic aid for training and/or competition. Accordingly, due to their extensive use, there is a growing need for strong scientific investigations validating or invalidating the efficacy of novel nutritional ergogenic aids. Notably, an overview of the physiological considerations that play key roles in determining ergogenic efficacy is currently lacking. Therefore, in this brief review, we discuss important physiological considerations that contribute to ergogenic efficacy for nutritional ergogenic aids that are orally ingested including (1) the impact of first pass metabolism, (2) rises in systemic concentrations, and (3) interactions with the target tissue. In addition, we explore mouth rinsing as an alternate route of ergogenic efficacy that bypasses the physiological hurdles of first pass metabolism via direct stimulation of the central nervous system. Moreover, we provide real-world examples and discuss several practical factors that can alter the efficacy of nutritional ergogenic aids including human variability, dosing protocols, training status, sex differences, and the placebo effect. Taking these physiological considerations into account will strengthen the quality and impact of the literature regarding the efficacy of potential ergogenic aids for top-class athletes.

Comparison of tight-fitting 7T parallel-transmit head array designs using excitation uniformity and local specific absorption rate metrics.

PURPOSE: We model the performance of parallel transmission (pTx) arrays with 8, 16, 24, and 32 channels and varying loop sizes built on a close-fitting helmet for brain imaging at 7 T and compare their local specific absorption rate (SAR) and flip-angle performances to that of birdcage coil (used as a baseline) and cylindrical 8-channel and 16-channel pTx coils (single-row and dual-row). METHODS: We use the co-simulation approach along with MATLAB scripting for batch-mode simulation of the coils. For each coil, we extracted B1 + maps and SAR matrices, which we compressed using the virtual observation points algorithm, and designed slice-selective RF shimming pTx pulses with multiple local SAR and peak power constraints to generate L-curves in the transverse, coronal, and sagittal orientations. RESULTS: Helmet designs outperformed cylindrical pTx arrays at a constant number of channels in the flip-angle uniformity at a constant local SAR metric: up to 29% for 8-channel arrays, and up to 34% for 16-channel arrays, depending on the slice orientation. For all helmet arrays, increasing the loop diameter led to better local SAR versus flip-angle uniformity tradeoffs, although this effect was more pronounced for the 8-channel and 16-channel systems than the 24-channel and 32-channel systems, as the former have more limited degrees of freedom and therefore benefit more from loop-size optimization. CONCLUSION: Helmet pTx arrays significantly outperformed cylindrical arrays with the same number of channels in local SAR and flip-angle uniformity metrics. This improvement was especially pronounced for non-transverse slice excitations. Loop diameter optimization for helmets appears to favor large loops, compatible with nearest-neighbor decoupling by overlap.

Commentary: On measurement error, PSA doubling time, and prostate cancer.

Exposure measurement error is a pervasive problem for epidemiology research projects designed to provide valid and precise statistical evidence supporting postulated exposure-disease relationships of interest. The purpose of this commentary is to highlight an important real-life example of this exposure measurement error problem and to provide a simple and useful diagnostic tool for physicians and their patients that corrects for the exposure measurement error. More specifically, prostate-specific antigen doubling time (PSADT) is a widely used measure for guiding future treatment options for patients with biochemically recurrent prostate cancer. Numerous papers have been published claiming that a low calculated PSADT value (denoted PSADT^) is predictive of metastasis and premature death from prostate cancer. Unfortunately, none of these papers have adjusted for the measurement error in PSADT^, an estimator that is typically computed using the popular Memorial Sloan Kettering website very often visited by both physicians and their patients. For this website, the estimator PSADT^ of the true (but unknown) PSADT for a patient (denoted PSADT∗) is computed as the natural log of 2 (i.e., 0.6931) divided by the estimated slope of the straight-line regression of the natural log of PSA (in ng/mL) on time. We utilize PSADT^ to derive an expression for the probability that the unknown PSADT∗ for a patient is below a specified value C (>0) of concern to both the physician and the patient. This probability is easy to interpret and takes into account the fact that PSADT^ is a statistical estimator with variability. This variability introduces measurement error, namely, the difference between a computed value PSADT^ and the true, but unknown, value PSADT∗. We have developed an Excel calculator that, once the [time, ln(PSA)] values are entered, outputs both the value of PSADT^ and the desired probability. In addition, we discuss problematic statistical issues attendant with PSADT∗ estimation typically based on at most three or four PSA values. We strongly recommend the use of this probability when physicians are discussing PSADT^ values and associated treatment options with their patients. And, we stress that future epidemiology research projects involving PSA doubling time should take into account the measurement error problem highlighted in this Commentary.

Testing a computational model for aural detection of aircraft in ambient noise.

Computational models are used to predict the performance of human listeners for carefully specified signal and noise conditions. However, there may be substantial discrepancies between the conditions under which listeners are tested and those used for model predictions. Thus, models may predict better performance than exhibited by the listeners, or they may "fail" to capture the ability of the listener to respond to subtle stimulus conditions. This study tested a computational model devised to predict a listener's ability to detect an aircraft in various soundscapes. The model and listeners processed the same sound recordings under carefully specified testing conditions. Details of signal and masker calibration were carefully matched, and the model was tested using the same adaptive tracking paradigm. Perhaps most importantly, the behavioral results were not available to the modeler before the model predictions were presented. Recordings from three different aircraft were used as the target signals. Maskers were derived from recordings obtained at nine locations ranging from very quiet rural environments to suburban and urban settings. Overall, with a few exceptions, model predictions matched the performance of the listeners very well. Discussion focuses on those differences and possible reasons for their occurrence.

Next-generation MRI scanner designed for ultra-high-resolution human brain imaging at 7 Tesla.

To increase granularity in human neuroimaging science, we designed and built a next-generation 7 Tesla magnetic resonance imaging scanner to reach ultra-high resolution by implementing several advances in hardware. To improve spatial encoding and increase the image signal-to-noise ratio, we developed a head-only asymmetric gradient coil (200 mT m-1, 900 T m-1s-1) with an additional third layer of windings. We integrated a 128-channel receiver system with 64- and 96-channel receiver coil arrays to boost signal in the cerebral cortex while reducing g-factor noise to enable higher accelerations. A 16-channel transmit system reduced power deposition and improved image uniformity. The scanner routinely performs functional imaging studies at 0.35-0.45 mm isotropic spatial resolution to reveal cortical layer functional activity, achieves high angular resolution in diffusion imaging and reduces acquisition time for both functional and structural imaging.

Cell-type expression and activation by light of neuropsins in the developing and mature Xenopus retina.

Photosensitive opsins detect light and perform image- or nonimage-forming tasks. Opsins such as the "classical" visual opsins and melanopsin are well studied. However, the retinal expression and functions of a novel family of neuropsins are poorly understood. We explored the developmental time-course and cell-type specificity of neuropsin (opn5, 6a, 6b, and 8) expression in Xenopus laevis by in situ hybridization and immunohistochemistry. We compared the Xenopus results with publicly available single cell RNA sequencing (scRNA-seq) data from zebrafish, chicken, and mouse. Additionally, we analyzed light-activation of neuropsin-expressing cells through induction of c-fos mRNA. opn5 and opn8 expression begins at stage 37/38 when the retinal circuits begin to be activated. Once retinal circuits connect to the brain, opn5 mRNA is distributed across multiple retinal cell types, including bipolar (~70%-75%), amacrine (~10%), and retinal ganglion (~20%) cells, with opn8 present in amacrine (~70%) and retinal ganglion (~30%) cells. opn6a and opn6b mRNAs emerge in newborn-photoreceptors (stage 35), and are colocalized in rods and cones by stage 37/38. Interestingly, in the mature larval retina (stage 43/44), opn6a and opn6b mRNAs become preferentially localized to rods and cones, respectively, while newborn photoreceptors bordering the proliferative ciliary marginal zone express both genes. In zebrafish, opn6a and opn6b are also expressed in photoreceptors, while Müller glia and amacrine cells express opn8c. Most neuropsin-expressing retinal ganglion cells display c-fos expression in response to light, as do over half of the neuropsin-expressing interneurons. This study gave a better understanding of retinal neuropsin-expressing cells, their developmental onset, and light activation.