Faculty Bibliography

The production and perception of music is preferentially mediated by cortical areas within the right hemisphere, but little is known about how these brain regions individually contribute to this process. In an experienced singer undergoing awake craniotomy, we demonstrated that direct electrical stimulation to a portion of the right posterior superior temporal gyrus (pSTG) selectively interrupted singing but not speaking. We then focally cooled this region to modulate its activity during vocalization. In contrast to similar manipulations in left hemisphere speech production regions, pSTG cooling did not elicit any changes in vocal timing or quality. However, this manipulation led to an increase in the pitch of speaking with no such change in singing. Further analysis revealed that all vocalizations exhibited a cooling-induced increase in the frequency of the first formant, raising the possibility that potential pitch offsets may have been actively avoided during singing. Our results suggest that the right pSTG plays a key role in vocal sensorimotor processing whose impact is dependent on the type of vocalization produced.

Objective: To determine if administration of a muscarinic agonist can stimulate the secretion of tears in patients with familial dysautonomia (FD). Background: FD is frequently referred to as a disease with no tears, but the underlying reason for this alacrima is unknown. Normally, nerves in the cornea stimulate the production of tears from lacrimal glands in the eye. Whether the absent/reduced tears in FD is due to denervation or an abnormality in the lacrimal glands themselves is unclear. Design/Methods: We applied pilocarpine (4%, a parasympathetic M3 receptor agonist), topically to the eyes of 16 patients with genetically confirmed FD to stimulate the tear secretion directly in the lacrimal glands bypassing the nerve pathways. We assessed corneal sensitivity using a Cochet-Bonnet esthesiometer. Tear volume was estimated with the Schirmer test (a scaled paper strip placed in the lower eyelid and the length of moisture measured after 5 minutes). Schirmer's test was performed four times: at baseline; 30-minutes after instillation of normal saline (placebo, 2 drops); at 30-minutes; and 3-hours after pilocarpine instillation (2 drops). Results: Basal tear secretion was 6.3 +/- 2.6 mm (mean +/- SD), and 6.9 +/- 3.0 mm 30 min after placebo (p=0.395). Thirty minutes after the instillation of piloparpine, tear volume more than doubled to 19.6 +/- 8.3 mm (p<0.001); and the increased tear production persisted at 3 hours (12.6 +/- 5.1 mm; p<0.001). There was a significant positive correlation between corneal sensitivity and tear secretion at baseline (p<0.0001; R2=0.74). Conclusions: Patients with FD have functional lacrimal glands, which can be stimulated with an M3 agonist to produce tears. Basal tear secretion was directly related to corneal sensitivity. The findings suggest for the first time that tear production in patients with FD can be restored pharmacologically

The introduction of compressed sensing for increasing imaging speed in magnetic resonance imaging (MRI) has raised significant interest among researchers and clinicians, and has initiated a large body of research across multiple clinical applications over the last decade. Compressed sensing aims to reconstruct unaliased images from fewer measurements than are traditionally required in MRI by exploiting image compressibility or sparsity. Moreover, appropriate combinations of compressed sensing with previously introduced fast imaging approaches, such as parallel imaging, have demonstrated further improved performance. The advent of compressed sensing marks the prelude to a new era of rapid MRI, where the focus of data acquisition has changed from sampling based on the nominal number of voxels and/or frames to sampling based on the desired information content. This article presents a brief overview of the application of compressed sensing techniques in body MRI, where imaging speed is crucial due to the presence of respiratory motion along with stringent constraints on spatial and temporal resolution. The first section provides an overview of the basic compressed sensing methodology, including the notion of sparsity, incoherence, and nonlinear reconstruction. The second section reviews state-of-the-art compressed sensing techniques that have been demonstrated for various clinical body MRI applications. In the final section, the article discusses current challenges and future opportunities. LEVEL OF EVIDENCE: 5 J. Magn. Reson. Imaging 2016.

PURPOSE:To propose and validate a method for accurately quantifying renal plasma flow (RPF) with arterial spin labeling (ASL). MATERIALS AND METHODS:The proposed method employs a tracer-kinetic approach and derives perfusion from the slope of the ASL difference signal sampled at multiple inversion-times (TIs). To validate the method's accuracy, we performed a HIPAA-compliant and IRB-approved study with 15 subjects (9 male, 6 female; age range 24-73) to compare RPF estimates obtained from ASL to those from a more established dynamic contrast-enhanced (DCE) MRI method. We also investigated the impact of TI-sampling density on the accuracy of estimated RPF. RESULTS:Good agreement was found between ASL- and DCE-measured RPF, with a mean difference of 9±30ml/min and a correlation coefficient R=0.92 when ASL signals were acquired at 16 TIs and a mean difference of 9±57ml/min and R=0.81 when ASL signals were acquired at 5 TIs. RPF estimated from ASL signals acquired at only 2 TIs (400 and 1200ms) showed a low correlation with DCE-measured values (R=0.30). CONCLUSION:The proposed ASL method is capable of measuring RPF with an accuracy that is comparable to DCE MRI. At least 5 TIs are recommended for the ASL acquisition to ensure reliability of RPF measurements.

OBJECTIVE: Paresthesias can result from metabolic disorders, nerve entrapment following repetitive motions, hyperventilation pursuant to anxiety, or exposure to neurotoxins. We analyzed data from community members exposed to the World Trade Center (WTC) disaster of September 11, 2001, to evaluate whether exposure to the disaster was associated with paresthesias. METHODS: Analysis of data from 3141 patients of the WTC Environmental Health Center. RESULTS: Fifty-six percent of patients reported paresthesias at enrollment 7 to 15 years following the WTC disaster. After controlling for potential confounders, paresthesias were associated with severity of exposure to the WTC dust cloud and working in a job requiring cleaning of WTC dust. CONCLUSIONS: This study suggests that paresthesias were commonly associated with WTC-related exposures or post-WTC cleaning work. Further studies should objectively characterize these paresthesias and seek to identify relevant neurotoxins or paresthesia-inducing activities.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.

PURPOSE: Kidney stone prevention relies on the 24-hour urine collection to diagnose metabolic abnormalities and direct dietary and pharmacologic therapy. While its use is guideline-supported for high risk and interested patients, evidence that the test can accurately predict recurrence or treatment response is limited. We sought to critically reassess the role of the 24-hour urine collection in stone prevention. MATERIALS AND METHODS: In addition to a MEDLINE(R) search to identify controlled studies of dietary and pharmacologic interventions, evidence supporting the AUA and EAU guidelines for metabolic stone prevention were evaluated. Additionally, placebo-arms of these studies were examined to assess the stone clinic effect: the impact of regular office visits without specific treatment on stone recurrence. RESULTS: The 24-hour urine test has several limitations including the complexity of interpretation, need for repeat collections, inability to predict stone recurrence with individual parameters and supersaturation values, unclear rationale of laboratory cutoff values, and difficulty with determining collection adequacy. Only one prospective trial has compared selective dietary recommendations based on 24-hour urine collection results versus general dietary instructions. While the trial supported the intervention arm, significant limitations to the study were found. Placebo arms of intervention trials have noted a 0-61% decrease in stone recurrence rate and a remission rate during the study of 20-86%. CONCLUSIONS: Whether all recurrent stone formers benefit from 24-hour urine collection has not been established. Additional comparative effectiveness trials are needed to determine which stone former benefits from selective therapy, as guided by the 24-hour urine collection.

PURPOSE: Free-breathing whole-heart coronary MR angiography (MRA) commonly uses navigators to gate respiratory motion, resulting in lengthy and unpredictable acquisition times. Conversely, self-navigation has 100% scan efficiency, but requires motion correction over a broad range of respiratory displacements, which may introduce image artifacts. We propose replacing navigators and self-navigation with a respiratory motion-resolved reconstruction approach. METHODS: Using a respiratory signal extracted directly from the imaging data, individual signal-readouts are binned according to their respiratory states. The resultant series of undersampled images are reconstructed using an extradimensional golden-angle radial sparse parallel imaging (XD-GRASP) algorithm, which exploits sparsity along the respiratory dimension. Whole-heart coronary MRA was performed in 11 volunteers and four patients with the proposed methodology. Image quality was compared with that obtained with one-dimensional respiratory self-navigation. RESULTS: Respiratory-resolved reconstruction effectively suppressed respiratory motion artifacts. The quality score for XD-GRASP reconstructions was greater than or equal to self-navigation in 80/88 coronary segments, reaching diagnostic quality in 61/88 segments versus 41/88. Coronary sharpness and length were always superior for the respiratory-resolved datasets, reaching statistical significance (P < 0.05) in most cases. CONCLUSION: XD-GRASP represents an attractive alternative for handling respiratory motion in free-breathing whole heart MRI and provides an effective alternative to self-navigation. Magn Reson Med, 2016. (c) 2016 Wiley Periodicals, Inc.

OBJECTIVE: High channel count electrode arrays allow for the monitoring of large-scale neural activity at high spatial resolution. Implantable arrays featuring many recording sites require compact, high bandwidth front-end electronics. In the present study, we investigated the use of a small, light weight, and low cost digital current-sensing integrated circuit for acquiring cortical surface signals from a 61-channel micro-electrocorticographic (ECoG) array. APPROACH: We recorded both acute and chronic ECoG signal from rat auditory cortex using our novel digital current-sensing headstage. For direct comparison, separate recordings were made in the same anesthetized preparations using an analog voltage headstage. A model of electrode impedance explained the transformation between current- and voltage-sensed signals, and was used to reconstruct cortical potential. We evaluated the digital headstage using several metrics of the baseline and response signals. MAIN RESULTS: The digital current headstage recorded neural signal with similar spatiotemporal stastics and auditory frequency tuning compared to the voltage signal. The signal-to-noise ratio of auditory evoked responses (AERs) was significantly stronger in the current signal. Stimulus decoding based on true and reconstructed voltage signals were not significantly different. Recordings from an implanted system showed AERs that were detectable and decodable for 52 days. The reconstruction filter mitigated the thermal current noise of the electrode impedance and enhanced overall SNR. SIGNIFICANCE: We developed and validated a novel approach to headstage acquisition that used current-input circuits to independently digitize 61 channels of ECoG measurements of the cortical field. These low-cost circuits, intended to measure photo-currents in digital imaging, not only provided a signal representing the local cortical field with virtually the same sensitivity and specificity as a traditional voltage headstage but also resulted in a small, light headstage that can easily be scaled to record from hundreds of channels.

INTRODUCTION: Oxygen (O2 ) nanobubbles offer a new method for tissue oxygenation. The effects of O2 nanobubbles on transmission at neuromuscular junctions (NMJs) and muscle function were explored in murine diaphragm. METHODS: Electrophysiological parameters, NMJ ultrastructure, muscle force, and muscle fatigue were studied during superfusion with solutions with different oxygen levels or oxygen nanobubbles. RESULTS: High frequency nerve stimulation of muscles superfused with O2 nanobubble solution slowed neurotransmission decline over those with either control or hyperoxic solution. O2 nanobubble solution increased the amplitude of evoked excitatory junction potentials and quantal content but did not affect spontaneous activity. Electron microscopy of stimulated O2 nanobubble treated NMJs showed accumulation of large synaptic vesicles and endosome-like structures. O2 nanobubble solution had no effects on isometric muscle force, but it significantly decreased fatigability and maximum force recovery time in nerve stimulated muscles. CONCLUSIONS: O2 nanobubbles increase neurotransmission and reduce the probability of neurotransmission failure in muscle fatigue