Cavitation with low-energy sonication during focused ultrasound thalamotomy for a patient with tremor-dominant Parkinson's disease: a potential risk.

We report a patient with tremor-dominant Parkinson's disease who had a mild cavitation bioeffect during magnetic resonance-guided focused ultrasound thalamotomy. During the aligning phase with low-energy sonication, cavitation caused mild dysarthria and paresthesia, prompting treatment cessation. At the same time, tremor and rigidity improved. MRI revealed extensive high-intensity lesions in the thalamus 1 day after the procedure followed by steroid infusion, which resulted in resolution of adverse events. Tremor and rigidity improved 1.5 years after the procedure. Although cavitation can relieve tremors and rigidity, it should be carefully monitored due to potential permanent adverse events by unpredictable and unknown behaviors.

A Study on the Contributions of Sonication to the Identification of Bacteria Associated with Intubation Cannula Biofilm and the Risk of Ventilator-Associated Pneumonia.

Ventilator-associated pneumonia is one of the most severe complications of critically ill patients that need mechanical respiratory support, as it poses a significant risk of prolonging hospitalization, disability, and even death. This is why physicians worldwide target newer methods for prevention, early diagnosis, and early target treatment for this condition. There are few methods for a quick etiological diagnosis of pneumonia, especially point of care, and most are only readily available in some intensive care units. This is why a new, simple, and cheap method is needed for determining the bacteria that might be infectious in a particular patient. The manner in question is sonication. Method: In this prospective, observational, single-center study, endotracheal cannula specimens will be collected from at least 100 patients in our intensive care unit. This specimen will be submitted to a specific sonication protocol for bacteria to dislodge the biofilm inside the cannula. The resulting liquid will be seeded on growth media, and then a comparison will be made between the germs in the biofilm and the ones in the tracheal secretion of the patient. The primary purpose is to determine the bacteria before the appearance of a manifest infection.

High intensity focused ultrasound combined with ultrasound-guided suction curettage treatment for cesarean scar pregnancy: a comparison of different HIFU sonication strategies.

OBJECTIVE: To explore a new high-intensity focused ultrasound (HIFU) sonication strategy for cesarean scar pregnancy (CSP) and to compare the clinical effectiveness and safety of this new HIFU sonication strategy with the conventional HIFU sonication strategy followed by ultrasound-guided dilation and curettage (USg-D&C) for CSP. MATERIALS AND METHODS: 91 patients with CSP treated by HIFU and USg-D&C in People's Hospital of Deyang City between January 2017 and December 2019 were retrospectively reviewed in this study. Based on the HIFU sonication strategy, patients were divided to two groups: 44 patients were exposed to 'C-shape' sonication layer by layer around the implantation location of the pregnancy sac (control group), while the other 47 patients were exposed to 'I-shape' sonication layer by layer only on the deep part which close to the bladder of the implantation location of the pregnancy sac (experimental group). The differences in clinical efficacy between the two groups were analyzed. Baseline characteristics, technical parameters of HIFU treatment and USg-D&C data were recorded. Adverse events were also recorded. RESULTS: No statistically significant difference was observed between the two groups in baseline characteristics including age, body mass index (BMI), menopause time, largest diameter of gestational sac, pretreatment serum ß-hCG, thickness of gestational sac, embedding myometrium, previous cesarean sections and interval from last cesarean section (CS). The average treatment intensity in the experimental group was significantly lower than that in the control group (p < .05). The median sonication time, total energy used for HIFU ablation, and energy efficiency factor (EEF) in the experimental group were significantly lower than the control group (p < .05). No statistically significant difference was observed between the two groups in treatment power and treatment time (p > .05). Sciatic/buttock pain and postoperative lower abdominal pain in the control group were significantly stronger than that in the experimental group (p < .05). There were no statistically significant differences in post-HIFU vaginal bleeding and discharging, urinary tract irritation, the operation time of USg-D&C, the amount of vaginal bleeding during USg-D&C, and the time for serum ß-hCG back to a normal level between the two groups (p > .05). CONCLUSIONS: The 'I-shape' strategy of HIFU treatment for CSP was effective and safe, with shorter sonication time, less energy input and lower incidence of sonication-related pain occurred in postoperative lower abdominal and sciatic nerve/buttock.

Time-domain simulation of ultrasound propagation with fractional Laplacians for lossy-medium biological tissues with complicated geometries.

Simulations of ultrasound wave propagation inside biological tissues have a wide range of practical applications. In previous studies, wave propagation equations in lossy biological media are solved either with convolutions, which consume a large amount of memory, or with pseudo-spectral methods, which cannot handle complicated geometries effectively. The approach described in the paper employed a fractional central difference method (FCD), combined with the immersed boundary (IB) method for the finite-difference, time-domain simulation. The FCD method can solve the fractional Laplace terms in Chen and Holm's lossy-medium equations directly in the physical domain without integral transforms. It also works naturally with the IB method, which enables a simple Cartesian-type grid mesh to be used to solve problems with complicated geometries. The numerical results agree very well with the analytical solutions for frequency power-law attenuation lossy media.

Evaluation of viral contamination in a baculovirus expression system.

Insect expression systems based on baculovirus are widely used for generating recombinant proteins. Here, the infectivity of baculoviruses under the physiological stresses of 'freeze-thaw' and sonication and the baculoviral contamination of recombinant proteins after protein purification were evaluated. Our findings suggest that Nonidet P-40 (NP-40) treatment of baculoviruses completely abolishes their infectivity and that recombinant proteins purified with affinity beads do not include infectious baculoviruses. We therefore suggest that baculovirus is completely inactivated by NP-40 treatment and that recombinant proteins are unlikely to be contaminated with infectious baculoviruses after their affinity purification.

Frequency bands for ultrasound, suitable for the consideration of its health effects.

It is proposed that the ultrasound frequency spectrum should be divided into three bands in order to facilitate a more rational assessment of its health effects. Whilst statement of the frequencies at the borders of these bands facilitates their definition, it is recognized that these observables vary continuously with frequency and consequently these border frequencies should not be used to rule out the possibility of a given effect occurring. The lowest band, US(A), lies between 17.8 and 500 kHz. In this band acoustic cavitation and its associated forces form the dominant process resulting in biological effects in liquids and soft tissues, whereas health effects from airborne ultrasound have been reported but are far less researched. In the middle band, US(B), between 500 kHz and 100 MHz, temperature rise in tissues becomes the most important biological effect of exposure. The highest band, US(C), covers frequencies above 100 MHz, for which the radiation force becomes an increasingly important biophysical mechanism. A justification for the selection of 17.8 kHz in preference to any other threshold for the lower frequency limit for ultrasound is given.

A pilot study of endoluminal US for stool liquefaction.

BACKGROUND: There is a need to cleanse patients who are poorly prepared for colonoscopy safely and efficiently during the procedure to minimize rescheduling. US is already being used in catheter-based intravascular thrombolysis, and time-reversal acoustic (TRA) has been explored in assisting drug delivery to the brain. OBJECTIVE: To explore the efficacy and safety of a miniaturized endoluminal US device in stool dissolution as a means to salvage poor bowel preparation. DESIGN: Proof of concept experimental study. SETTINGS: Animal laboratory. INTERVENTIONS: Low-frequency US and TRAs. MAIN OUTCOME MEASUREMENTS: Feasibility, efficacy, and safety of US to liquefy stools ex vivo. RESULTS: Depending on parameters, such as pulse rate, acoustic intensity, and duration, increases in liquefaction speeds by a factor of 50 and 100 times were obtained. There was a significant difference in weight change between the 20-kHz-treated sample compared with controls (P ≤ .0001). There was no difference in sloughing of mucosa and mechanical injury among the US, water spray, and control groups. LIMITATIONS: Animal model. CONCLUSION: Endoluminal US can liquefy stools at acoustic exposure levels that do not damage ex vivo colonic mucosa. Endoluminal US should be able to dissolve stools more rapidly than water spray alone, thereby optimizing colonoscopic evaluation in vivo.

Study on combined effects of blanching and sonication on different quality parameters of carrot juice.

This study was conducted to evaluate the combined effects of blanching and sonication on carrot juice quality. Carrots were blanched at 100 °C for 4 min in normal and acidified water. Juice was extracted and sonicated at 15 °C for 2 min keeping pulse duration 5 s on and 5 s off (70% amplitude level and 20 kHz frequency). No significant effect of blanching and sonication was observed on Brix, pH and titratable acidity except acidified blanching that decreased pH and increased acidity significantly. Peroxidase was inactivated after blanching that also significantly decreased total phenol, flavonoids, tannins, free radical scavenging activity, antioxidant capacity and ascorbic acid and increased cloud and color values. Sonication could improve all these parameters significantly. The present results suggest that combination of blanching and sonication may be employed in food industry to produce high-quality carrot juice with reduced enzyme activity and improved nutrition.

Scalp Nerve Block Alleviates Headaches Associated With Sonication During Transcranial Magnetic Resonance-Guided Focused Ultrasound.

BACKGROUND AND OBJECTIVES: In magnetic resonance-guided focused ultrasound (MRgFUS) procedures, headache is a frequent symptom and cause of treatment discontinuation. Herein, we assessed the efficacy of scalp nerve block (SNB) for alleviating headache during MRgFUS procedures. METHODS: The effect of SNB on intraprocedural headache was examined by retrospectively comparing 2 patient cohorts at a single institution. During the study period from April 2020 to February 2022, an SNB protocol for all patients with a skull density ratio ≤0.55 was instituted on October 6, 2021. The number of patients with a skull density ratio ≤0.55 was 34 before the protocol and 36 afterward. Headache intensity was evaluated using a numerical rating scale (NRS) after each sonication. To evaluate the effect of SNB on headache intensity, multiple regression analysis was performed per patient and per sonication. In the per-patient analysis, the effect of SNB was evaluated using the maximum NRS, mean NRS, and NRS at the first ultrasound exposure that reached 52.5°C. In the per-sonication analysis, the effect of SNB was evaluated not only for the entire sonication but also for sonications classified into ≤9999 J, 10 000 to 29 999 J, and ≥30 000 J energy doses. RESULTS: With SNB, headache alleviation was observed in the NRS after the first sonication that reached 52.5°C in each patient (ß = -2.40, 95% CI -4.05 to -0.758, P = .00499), in the NRS when all sonications were evaluated (ß = -0.647, 95% CI -1.19 to -0.106, P = .0201), and in the NRS when all sonications were classified into 10 000 to 29 999 J (ß = -1.83, 95% CI -3.17 to -0.485, P = .00889). CONCLUSION: SNB significantly reduced headache intensity during MRgFUS, especially that caused by sonication with a moderate-energy dose. These findings suggest that scalp nerves play a role in headache mechanisms during MRgFUS.

Ultrasonication and the quality of human milk: variation of power and time of exposure.

Donor human milk is pasteurized to prevent the potential risk of the transmission of pathogens to preterm infants. Currently, Holder pasteurization (human milk held at 62·5°C for 30 min) is used in most human milk banks, but has the disadvantage that it results in excessive inactivation of important bioactive components. Power-ultrasound (20-100 kHz) is an emerging technology for the preservation of foods and could be an alternative method for the treatment of human milk. The aim of this study was to investigate the effect of different ultrasound settings on the elimination of Escherichia coli and the retention of bile salt stimulated lipase (BSSL) activity. Ultrasonication with a constant power decreased Esch. coli viability exponentially over time until the processing temperature increased to sub-pasteurization level to between 51·4 and 58·5°C, then a log10 1·3 decrease was observed (P<0·05). BSSL activity decreased to 91% until a temperature of 51·4°C and then it decreased to 8% between 51·4 and 64·9°C. Ultrasonication with a constant energy and various power and exposure times showed the highest temperature (53·7°C) when treated with the longest exposure time and lowest ultrasound-power (276 s at 3·62 W) compared with 37·6°C for 39 s at 25·64 W. The findings predict that the viability of Esch. coli could be reduced by log10 5 with a minimal loss of activity of BSSL by applying 13·8 kJ of energy in 12 ml of human milk using high ultrasound power over a short exposure time to ensure that the temperature remains below the critical level for protein denaturation. Alternatively, the use of lower power settings such as the 26 W used in the present studies would require a cooling system to ensure the human milk BSSL was protected against temperature denaturation.

Detecting blood-brain barrier disruption within minimal hemorrhage following transcranial focused ultrasound: a correlation study with contrast-enhanced MRI.

Focused ultrasound combined with an intravascular ultrasound contrast agent can induce transient disruption of the blood-brain barrier, and the blood-brain barrier disruption can be detected by contrast-enhanced MRI. There is, however, no study investigating the ability of various MR methods to detect focused ultrasound-induced blood-brain barrier disruption within minimal hemorrhage. Sonication was applied to 15 rat brains with four different doses of ultrasound contrast agent (0, 10, 30, or 50 µL/kg), and contrast-enhanced T1-weighted spin echo, gradient echo images, and longitudinal relaxation rate mapping along with effective transverse relaxation time-weighted and susceptibility-weighted images were acquired. Volume-of-interest-based and threshold-based analyses were performed to quantify the contrast enhancement, which was then correlated with the ultrasound contrast agent dose and with the amount of Evans blue extravasation. Both effective transverse relaxation time-weighted and susceptibility-weighted images did not detect histology-proved intracranial hemorrhage at 10 µL/kg, but MRI failed to detect mild intracranial hemorrhage at 30 µL/kg. All tested sequences showed detectable contrast enhancement increasing with ultrasound contrast agent dose. In correlating with Evans blue extravasation, the gradient echo sequence was slightly better than the spin echo sequence and was comparable to longitudinal relaxation rate mapping. In conclusion, both gradient echo and spin echo sequences were all reliable in indicating the degree of focused ultrasound-induced blood-brain barrier disruption within minimal hemorrhage.

Pre-treatment of sperm reduces success of ICSI in the pig.

In pigs, although ICSI is a feasible fertilization technique, its efficiency is low. In general, injected pig sperm are insufficient to induce oocyte activation and embryonic development. Pretreatments for disrupting sperm membranes have been applied to improve the fertility of ICSI oocytes; however, we hypothesize that such pretreatment(s) may reduce the ability of the sperm to induce oocyte activation. We first evaluated the effects of sperm pretreatments (sonication (SO) to isolate the sperm heads from the tails, Triton X-100 (TX), and three cycles of repeated freezing/thawing (3×-FT) for disrupting sperm membranes) on the rate of pronucleus (PN) formation after ICSI. We found that oocytes injected with control (whole) sperm had higher rates of PN formation than those obtained after subjecting the sperm to SO, TX, and 3×-FT. The amounts of phospholipase Cζ (PLCζ), which is thought to be the oocyte-activating factor in mammalian sperm, in sperm treated by each method was significantly lower than that in whole untreated sperm. Furthermore, using immunofluorescence, it was found that in pig sperm, PLCζ was localized to both the post-acrosomal region and the tail area. Thus we demonstrated for the first time that sperm pretreatment leads to a reduction of oocyte-activating capacity. Our data also show that in addition to its expected localization to the sperm head, PLCζ is also localized in the tail of pig sperm, thus raising the possibility that injection of whole sperm may be required to attain successful activation in pigs.

Cavitation-modulated inflammatory response following focused ultrasound blood-brain barrier opening.

Focused ultrasound (FUS) in combination with systemically injected microbubbles can be used to non-invasively open the blood-brain barrier (BBB) in targeted regions for a variety of therapeutic applications. Over the past two decades, preclinical research into the safety and efficacy of FUS-induced BBB opening has proven this technique to be transient and efficacious, propelling FUS-induced BBB opening into several clinical trials in recent years. However, as clinical trials further progress, the neuroinflammatory response to FUS-induced BBB opening needs to be better understood. In this study, we provide further insight into the relationship of microbubble cavitation and the resulting innate immune response to FUS-induced BBB opening. By keeping ultrasound parameters fixed (i.e. frequency, pressure, pulse length, etc.), three groups of mice were sonicated using a real-time cavitation controller until a target cavitation dose was reached (1 x 107 V2•s, 5 x 107 V2•s, 1 x 108 V2•s). The change in relative gene expression of the mouse inflammatory cytokines and receptors were evaluated at three different time-points (6 h, 24 h, and 72 h) after FUS. At both 6 and 24 h time-points, significant changes in relative gene expression of inflammatory cytokines and receptors were observed across all cavitation groups. However, the degree of changes in relative expression levels and the number of genes with significant changes in expression varied across the cavitation groups. Groups with a higher cavitation dose exhibited both greater changes in relative expression levels and greater number of significant changes. By 72 h post-opening, the gene expression levels returned to baseline in all cavitation dose groups, signifying a transient inflammatory response to FUS-induced BBB opening at the targeted cavitation dose levels. Furthermore, the real-time cavitation controller was able to produce consistent and significantly different BBB permeability enhancement volumes across the three different cavitation dose groups. These results indicate that cavitation monitoring and controlling during FUS-induced BBB opening can be used to potentially modulate or limit the degree of neuroinflammation, further emphasizing the importance of implementing cavitation controllers as FUS-induced BBB opening is translated into the clinic.

Ultrasound energy in phacoemulsification: a comparative analysis of phaco-chop and stop-and-chop techniques according to the degree of nuclear density.

BACKGROUND AND OBJECTIVE: To evaluate the amount of ultrasound energy used, corneal endothelial cell loss, and central corneal thickness using the phaco-chop and stop-and-chop techniques for cataracts with different degrees of nuclear density. PATIENTS AND METHODS: One hundred two eyes of 51 patients with bilateral senile cataract were included. Each eye was randomly assigned to have either phaco-chop or stop-and-chop nucleofractis during phacoemulsification. The groups were divided into two subgroups according to the nuclear density. The effective phacoemulsification time, endothelial cell density, and central corneal thickness were analyzed. RESULTS: The mean effective phacoemulsification time was similar between the groups in moderately dense nuclei (2.17 +/- 1.33 vs 1.33 +/- 1.05 seconds; P = .41). However, the phaco-chop technique required less effective phacoemulsification time than the stop-and-chop technique in dense nuclei (3.86 +/- 4.18 vs 6.70 +/- 5.43 seconds; P = .01). The endothelial cell loss and the central corneal thickness did not vary significantly between the groups. CONCLUSION: The phaco-chop technique requires lower ultrasound energy for nuclear management than the stop-and-chop technique in dense cataracts and the resulting endothelial loss was similar in both techniques.

Lithotripsy.

Shock wave lithotripsy (SWL) is the process of fragmentation of renal or ureteric stones by the use of repetitive shock waves generated outside the body and focused onto the stone. Following its introduction in 1980, SWL revolutionized the treatment of kidney stones by offering patients a non-invasive procedure. It is now seen as a mature technology and its use is perceived to be routine. It is noteworthy that, at the time of its introduction, there was a great effort to discover the mechanism(s) by which it works, and the type of sound field that is optimal. Although nearly three decades of subsequent research have increased the knowledge base significantly, the mechanisms are still controversial. Furthermore there is a growing body of evidence that SWL results in injury to the kidney which may have long-term side effects, such as new onset hypertension, although again there is much controversy within the field. Currently, use of lithotripsy is waning, particularly with the advent of minimally invasive ureteroscopic approaches. The goal here is to review the state of the art in SWL and to present the barriers and challenges that need to be addressed for SWL to deliver on its initial promise of a safe, effective, non-invasive treatment for kidney stones.

Consistent opening of the blood brain barrier using focused ultrasound with constant intravenous infusion of microbubble agent.

The blood brain barrier (BBB) is a major obstacle to the delivery of therapeutics to the brain. Focused ultrasound (FUS) in combination with microbubbles can non-invasively open the BBB in a targeted manner. Bolus intravenous injections of microbubbles are standard practice, but dynamic influx and clearance mechanisms prevent delivery of a uniform dose with time. When multiple targets are selected for sonication in a single treatment, uniform serum concentrations of microbubbles are important for consistent BBB opening. Herein, we show that bubble infusions were able to achieve consistent BBB opening at multiple target sites. FUS exposures were conducted with different Definity microbubble concentrations at various acoustic pressures. To quantify the effects of infusion on BBB opening, we calculated the MRI contrast enhancement rate. When infusions were performed at rates of 7.2 µl microbubbles/kg/min or below, we were able to obtain consistent BBB opening without injury at all pressures. However, when infusion rates exceeded 20 µl/kg/min, signs of injury occurred at pressures from 0.39 to 0.56 MPa. When compared to bolus injections, a bubble infusion offers a more controlled and consistent approach to multi-target BBB disruption.

Focused ultrasound as a novel strategy for noninvasive gene delivery to retinal Müller glia.

Müller glia are specialized retinal cells with stem cell properties in fish and frogs but not in mammals. Current efforts to develop gene therapies to activate mammalian Müller glia for retinal repair will require safe and effective delivery strategies for recombinant adeno-associated viruses (AAVs), vectors of choice for clinical translation. Intravitreal and subretinal injections are currently used for AAV gene delivery in the eye, but less invasive methods efficiently targeting Müller glia have yet to be developed. Methods: As gene delivery strategies have been more extensively studied in the brain, to validate our vectors, we initially compared the glial tropism of AAV-PHP.eB, an AAV9 that crosses the blood-brain and blood-retinal barriers, for its ability to drive fluorescent protein expression in glial cells in both the brain and retina. We then tested the glial transduction of AAV2/8-GFAP-mCherry, a virus that does not cross blood-brain and blood-retinal barriers, for its effectiveness in transducing Müller glia in murine retinal explants ex vivo. For in vivo assays we used larger rat eyes, performing invasive intravitreal injections, and non-invasive intravenous delivery using focused ultrasound (FUS) (pressure amplitude: 0.360 - 0.84 MPa) and microbubbles (Definity, 0.2 ml/kg). Results: We showed that AAV-PHP.eB carrying a ubiquitous promoter (CAG) and green fluorescent protein (GFP) reporter, readily crossed the blood-brain and blood-retinal barriers after intravenous delivery in mice. However, murine Müller glia did not express GFP, suggesting that they were not transduced by AAV-PHP.eB. We thus tested an AAV2/8 variant, which was selected based on its safety record in multiple clinical trials, adding a glial fibrillary acidic protein (GFAP) promoter and mCherry (red fluorescent protein) reporter. We confirmed the glial specificity of AAV2/8-GFAP-mCherry, showing effective expression of mCherry in astrocytes after intracranial injection in the mouse brain, and of Müller glia in murine retinal explants. For in vivo experiments we switched to rats because of their larger size, injecting AAV2/8-GFAP-mCherry intravitreally, an invasive procedure, demonstrating passage across the inner limiting membrane, leading to Müller glia transduction. We then tested an alternative non-invasive delivery approach targeting a different barrier - the inner blood-retinal-barrier, applying focused ultrasound (FUS) to the retina after intravenous injection of AAV2/8 and microbubbles in rats, using magnetic resonance imaging (MRI) for FUS targeting. FUS permeabilized the rat blood-retinal-barrier and allowed the passage of macromolecules to the retina (Evans blue, IgG, IgM), with minimal extravasation of platelets and red blood cells. Intravenous injection of microbubbles and AAV2/8-GFAP-mCherry followed by FUS resulted in mCherry expression in rat Müller glia. However, systemic delivery of AAV2/8 also had off-target effects, transducing several murine peripheral organs, particularly the liver. Conclusions: Retinal permeabilisation via FUS in the presence of microbubbles is effective for delivering AAV2/8 across the inner blood-retinal-barrier, targeting Müller glia, which is less invasive than intravitreal injections that bypass the inner limiting membrane. However, implementing FUS in the clinic will require a comprehensive consideration of any off-target tropism of the AAV in peripheral organs, combined ideally, with the development of Müller glia-specific promoters.

Blood-brain barrier disruption and delivery of irinotecan in a rat model using a clinical transcranial MRI-guided focused ultrasound system.

We investigated controlled blood-brain barrier (BBB) disruption using a low-frequency clinical transcranial MRI-guided focused ultrasound (TcMRgFUS) device and evaluated enhanced delivery of irinotecan chemotherapy to the brain and a rat glioma model. Animals received three weekly sessions of FUS, FUS and 10 mg/kg irinotecan, or irinotecan alone. In each session, four volumetric sonications targeted 36 locations in one hemisphere. With feedback control based on recordings of acoustic emissions, 98% of the sonication targets (1045/1071) reached a pre-defined level of acoustic emission, while the probability of wideband emission (a signature for inertial cavitation) was than 1%. BBB disruption, evaluated by mapping the R1 relaxation rate after administration of an MRI contrast agent, was significantly higher in the sonicated hemisphere (P < 0.01). Histological evaluation found minimal tissue effects. Irinotecan concentrations in the brain were significantly higher (P < 0.001) with BBB disruption, but SN-38 was only detected in <50% of the samples and only with an excessive irinotecan dose. Irinotecan with BBB disruption did not impede tumor growth or increase survival. Overall these results demonstrate safe and controlled BBB disruption with a low-frequency clinical TcMRgFUS device. While irinotecan delivery to the brain was not neurotoxic, it did not improve outcomes in the F98 glioma model.

Cardiac arrhythmia and injury induced in rats by burst and pulsed mode ultrasound with a gas body contrast agent.

OBJECTIVE: Premature complexes (PCs) in the electrocardiogram (ECG) signal have been reported for myocardial contrast echocardiography and also for burst mode (physical therapy) ultrasound with gas body contrast agents at lower peak rarefactional pressure amplitudes (PRPAs). For contrast echocardiography, irreversibly injured cardiomyocytes have been associated with the arrhythmia. The objective was to determine whether cardiomyocyte injury is associated with the PCs induced by the burst mode at lower PRPAs. METHODS: Anesthetized rats were exposed to focused 1.5-MHz ultrasound in a water bath. Evans blue dye was injected intraperitoneally to stain injured cardiomyocytes, and a perflutren lipid microsphere ultrasound contrast agent was infused intravenously. The continuous burst mode simulated physical therapy ultrasound. Intermittent 2-millisecond bursts, or envelopes of pulses simulating diagnostic ultrasound, were triggered 1:4 at end systole. Premature complexes were observed on ECG recordings, and stained cardiomyocytes were counted in frozen sections. RESULTS: The continuous burst mode produced variable PCs and stained cells above a 0.3-MPa PRPA. The triggered bursts above 0.3 MPa and pulse envelopes above 1.2 MPa produced statistically significant (P < .01) PCs and stained cardiomyocytes. CONCLUSIONS: Irreversible cardiomyocyte injury was associated with the development of PCs for the burst mode and occurred at substantially lower PRPAs than for pulsed ultrasound.

Evaluation of Crack Formation and Propagation with Ultrasonic Root-End Preparation and Obturation Using a Digital Microscope and Optical Coherence Tomography.

OBJECTIVE: This study is aimed at determining (1) the effect of root-end resection, ultrasonic root-end preparation, and root-end filling on the incidence of crack formation and propagation by using a digital microscope (DM) and optical coherence tomography (OCT) and (2) the performance of OCT on the detection of cracks by comparing with microcomputed tomography (micro-CT) as a reference standard. METHODOLOGY: Thirty extracted lower incisors were endodontically treated and subjected to root-end resection and ultrasonic root-end cavity preparation. Then, the teeth were divided into three groups (n = 10, each), and the root-end cavity was either left unfilled or filled with mineral trioxide aggregate (MTA) or super-EBA. The resected surface was observed with OCT and DM after the root-end resection, ultrasonic root-end preparation, and root-end filling, and the frequency of incomplete and complete cracks were recorded. The observation was repeated after two weeks, one month, and two months, and micro-CT scans after two months were taken as the gold standard. RESULTS: The DM results show dentinal crack formation in 47% of the samples following root-end resection and in 87% following ultrasonic preparation. After the ultrasonic preparation, no existing crack propagated to a complete crack, but new cracks were formed. MTA and super-EBA had no effect on crack formation. The Spearman correlation coefficient between OCT and DM was 0.186 (very weak correlation; p = 0.015). Sensitivity and specificity in comparison to micro-CT were 0.50 and 0.55 in OCT and 1.00 and 0.35 in DM, respectively. McNemar's test showed a significant difference between OCT and DM (p < 0.05). CONCLUSION: Apical resection and ultrasonic preparation could form dentinal cracks. OCT and DM showed different detection frequencies of cracks with very weak correlation. DM showed superior sensitivity compared with OCT.