Printed Receive Coils with High Acoustic Transparency for Magnetic Resonance Guided Focused Ultrasound
2018; 8: 3392
In magnetic resonance guided focused ultrasound (MRgFUS) therapy sound waves are focused through the body to selectively ablate difficult to access lesions and tissues. A magnetic resonance imaging (MRI) scanner non-invasively tracks the temperature increase throughout the tissue to guide the therapy. In clinical MRI, tightly fitted hardware comprised of multichannel coil arrays are required to capture high quality images at high spatiotemporal resolution. Ablating tissue requires a clear path for acoustic energy to travel but current array materials scatter and attenuate acoustic energy. As a result coil arrays are placed outside of the transducer, clear of the beam path, compromising imaging speed, resolution, and temperature accuracy of the scan. Here we show that when coil arrays are fabricated by additive manufacturing (i.e., printing), they exhibit acoustic transparency as high as 89.5%. This allows the coils to be placed in the beam path increasing the image signal to noise ratio (SNR) five-fold in phantoms and volunteers. We also characterize printed coil materials properties over time when submerged in the water required for acoustic coupling. These arrays offer high SNR and acceleration capabilities, which can address current challenges in treating head and abdominal tumors allowing MRgFUS to give patients better outcomes.
View details for DOI 10.1038/s41598-018-21687-1
View details for Web of Science ID 000425590600016
View details for PubMedID 29467432
View details for PubMedCentralID PMC5821831
Pilot Findings of Brain Displacements and Deformations during Roller Coaster Rides
JOURNAL OF NEUROTRAUMA
2017; 34 (22): 3198–3205
With 300,000,000 riders annually, roller coasters are a popular recreational activity. Although the number of roller coaster injuries is relatively low, the precise effect of roller coaster rides on our brains remains unknown. Here we present the quantitative characterization of brain displacements and deformations during roller coaster rides. For two healthy adult male subjects, we recorded head accelerations during three representative rides, and, for comparison, during running and soccer headers. From the recordings, we simulated brain displacements and deformations using rigid body dynamics and finite element analyses. Our findings show that despite having lower linear accelerations than sports head impacts, roller coasters may lead to brain displacements and strains comparable to mild soccer headers. The peak change in angular velocity on the rides was 9.9 rad/sec, which was higher than the 5.6 rad/sec in soccer headers with ball velocities reaching 7 m/sec. Maximum brain surface displacements of 4.0 mm and maximum principal strains of 7.6% were higher than in running and similar to soccer headers, but below the reported average concussion strain. Brain strain rates during roller coaster rides were similar to those in running, and lower than those in soccer headers. Strikingly, on the same ride and at a similar position, the two subjects experienced significantly different head kinematics and brain deformation. These results indicate that head motion and brain deformation during roller coaster rides are highly sensitive to individual subjects. Although our study suggests that roller coaster rides do not present an immediate risk of acute brain injury, their long-term effects require further longitudinal study.
View details for DOI 10.1089/neu.2016.4893
View details for Web of Science ID 000414560000016
View details for PubMedID 28683585
FREQUENCY DEPENDENCE OF ULTRASOUND NEUROSTIMULATION IN THE MOUSE BRAIN
ULTRASOUND IN MEDICINE AND BIOLOGY
2016; 42 (7): 1512-1530
Ultrasound neuromodulation holds promise as a non-invasive technique for neuromodulation of the central nervous system. However, much remains to be determined about how the technique can be transformed into a useful technology, including the effect of ultrasound frequency. Previous studies have demonstrated neuromodulation in vivo using frequencies <1 MHz, with a trend toward improved efficacy with lower frequency. However, using higher frequencies could offer improved ultrasound spatial resolution. We investigate the ultrasound neuromodulation effects in mice at various frequencies both below and above 1 MHz. We find that frequencies up to 2.9 MHz can still be effective for generating motor responses, but we also confirm that as frequency increases, sonications require significantly more intensity to achieve equivalent efficacy. We argue that our results provide evidence that favors either a particle displacement or a cavitation-based mechanism for the phenomenon of ultrasound neuromodulation.
View details for DOI 10.1016/j.ultrasmedbio.2016.02.012
View details for Web of Science ID 000377305500011
View details for PubMedID 27090861
View details for PubMedCentralID PMC4899295
Ultrasound-based neurostimulation in the mouse model.
journal of the Acoustical Society of America
2013; 134 (5): 4090-?
Ultrasound-based neurostimulation would be a useful tool prior to MR-guided focused ultrasound treatments in the brain. In this work, we report on our studies on ultrasound-based neurostimulation in the mouse model. We define the success rate as the ratio of the number of positive EMG responses to the number of sonications. A single element ultrasound transducer with a center frequency of 500 kHz was applied to the mouse head via a coupling column and coupling gel on the mouse head. EMG electrodes were placed in the mouse neck and tail muscles to measure contraction of the relevant muscles as the ultrasound transducer is moved across the mouse head. The success rate increases with ultrasound intensity or with ultrasound duration, following a sigmoidal curve. As the ultrasound frequency is increased, the ultrasound intensity must be increased for the same success rate. Movement of the ultrasound transducer across the brain changes the response in the relevant EMG systems such that the neck EMG response is stronger when the transducer is more rostrally placed, while the tail EMG response is stronger when the transducer is more caudally placed. Our findings present evidence for selective targeting in the mouse model of ultrasound-based neurostimulation.
View details for DOI 10.1121/1.4830937
View details for PubMedID 24181342
Data-Driven Prediction of Drug Effects and Interactions
SCIENCE TRANSLATIONAL MEDICINE
2012; 4 (125)
Adverse drug events remain a leading cause of morbidity and mortality around the world. Many adverse events are not detected during clinical trials before a drug receives approval for use in the clinic. Fortunately, as part of postmarketing surveillance, regulatory agencies and other institutions maintain large collections of adverse event reports, and these databases present an opportunity to study drug effects from patient population data. However, confounding factors such as concomitant medications, patient demographics, patient medical histories, and reasons for prescribing a drug often are uncharacterized in spontaneous reporting systems, and these omissions can limit the use of quantitative signal detection methods used in the analysis of such data. Here, we present an adaptive data-driven approach for correcting these factors in cases for which the covariates are unknown or unmeasured and combine this approach with existing methods to improve analyses of drug effects using three test data sets. We also present a comprehensive database of drug effects (Offsides) and a database of drug-drug interaction side effects (Twosides). To demonstrate the biological use of these new resources, we used them to identify drug targets, predict drug indications, and discover drug class interactions. We then corroborated 47 (P < 0.0001) of the drug class interactions using an independent analysis of electronic medical records. Our analysis suggests that combined treatment with selective serotonin reuptake inhibitors and thiazides is associated with significantly increased incidence of prolonged QT intervals. We conclude that confounding effects from covariates in observational clinical data can be controlled in data analyses and thus improve the detection and prediction of adverse drug effects and interactions.
View details for DOI 10.1126/scitranslmed.3003377
View details for Web of Science ID 000301538300005
View details for PubMedID 22422992
View details for PubMedCentralID PMC3382018
Cutting edge: TLR2 is a functional receptor for acute-phase serum amyloid A
JOURNAL OF IMMUNOLOGY
2008; 181 (1): 22-26
Induced secretion of acute-phase serum amyloid A (SAA) is a host response to danger signals and a clinical indication of inflammation. The biological functions of SAA in inflammation have not been fully defined, although recent reports indicate that SAA induces proinflammatory cytokine expression. We now show that TLR2 is a functional receptor for SAA. HeLa cells expressing TLR2 responded to SAA with potent activation of NF-kappaB, which was enhanced by TLR1 expression and blocked by the Toll/IL-1 receptor/resistance (TIR) deletion mutants of TLR1, TLR2, and TLR6. SAA stimulation led to increased phosphorylation of MAPKs and accelerated IkappaBalpha degradation in TLR2-HeLa cells, and results from a solid-phase binding assay showed SAA interaction with the ectodomain of TLR2. Selective reduction of SAA-induced gene expression was observed in tlr2-/- mouse macrophages compared with wild-type cells. These results suggest a potential role for SAA in inflammatory diseases through activation of TLR2.
View details for Web of Science ID 000257404900006
View details for PubMedID 18566366
View details for PubMedCentralID PMC2464454
Pharmacological characterization of a novel nonpeptide antagonist for formyl peptide receptor-like 1
2007; 72 (4): 976-983
A series of quinazolinone derivatives were synthesized based on a hit compound identified from a high-throughput screening campaign targeting the human formyl peptide receptor-like 1 (FPRL1). Based on structure-activity relationship analysis, we found that substitution on the para position of the 2-phenyl group of the quinazolinone backbone could alter the pharmacological properties of the compound. The methoxyl substitution produced an agonist 4-butoxy-N-[2-(4-methoxy-phenyl)-4-oxo-1,4-dihydro-2H-quinazolin-3-yl]-benzamide (Quin-C1; C1), whereas a hydroxyl substitution resulted in a pure antagonist, Quin-C7 (C7). Several partial agonists were derived from other substitutions on the para position. C7 partially displaced [(125)I]Trp-Lys-Tyr-Met-Val-d-Met-NH(2) (WKYMVm) binding to FPRL1 but not [(3)H]N-formyl-Met-Leu-Phe to formyl peptide receptor. In functional assays using FPRL1-expressing RBL-2H3 cells, C7 inhibited calcium mobilization and chemotaxis induced by WKYMVm and C1 and degranulation elicited by C1. C7 also suppressed C1-induced extracellular signal-regulated kinase phosphorylation and reduced arachidonic acid-induced ear edema in mice. This study represents the first characterization of a nonpeptidic antagonist for FPRL1 and suggests the prospect of using low molecular weight compounds as modulators of chemoattractant receptors in vitro and in vivo.
View details for DOI 10.1124/mol.107.037564
View details for Web of Science ID 000249561500018
View details for PubMedID 17652444