Common acoustic phonon lifetimes in inorganic and hybrid lead halide perovskites.

The acoustic phonons in the organic-inorganic lead halide perovskites have been reported to have anomalously short lifetimes over a large part of the Brillouin zone. The resulting shortened mean free paths of the phonons have been implicated as the origin of the low thermal conductivity. We apply neutron spectroscopy to show that the same acoustic phonon energy linewidth broadening (corresponding to shortened lifetimes) occurs in the fully inorganic CsPbBr3 by comparing the results on the organic-inorganic CH3NH3PbCl3. We investigate the critical dynamics near the three zone boundaries of the cubic P m 3 ¯ m Brillouin zone of CsPbBr3 and find energy and momentum broadened dynamics at momentum points where the Cs-site (A-site) motions contribute to the cross section. Neutron diffraction is used to confirm that both the Cs and Br sites have unusually large thermal displacements with an anisotropy that mirrors the low temperature structural distortions. The presence of an organic molecule is not necessary to disrupt the low-energy acoustic phonons at momentum transfers located away from the zone center in the lead halide perovskites and such damping may be driven by the large displacements or possibly disorder on the A site.

Agreement Among 4 Sampling Methods to Identify Respiratory Pathogens in Dairy Calves with Acute Bovine Respiratory Disease.

BACKGROUND: Four sampling techniques commonly are used for antemortem identification of pathogens from cattle with bovine respiratory disease (BRD): the nasal swab (NS), guarded nasopharyngeal swab (NPS), bronchoalveolar lavage (BAL), and transtracheal wash (TTW). Agreement among these methods has not been well characterized. OBJECTIVE: To evaluate agreement among TTW and NS, NPS, or BAL for identification of viral and bacterial pathogens in dairy calves with BRD. ANIMALS: One hundred dairy calves with naturally acquired BRD. METHODS: Calves were sampled by all 4 methods. Viral agents were identified by real-time RT-PCR, bacteria were identified by aerobic culture, and Mycoplasma bovis (M. bovis) isolates were speciated by PCR. Agreement among TTW and NS, NPS, or BAL was evaluated by calculating the kappa statistic and percent positive agreement. McNemar's exact test was used to compare the proportions of positive results. RESULTS: Agreement among TTW and NS, TTW and NPS, and TTW and BAL, was very good for identification of P. multocida, M. haemolytica, and M. bovis. For bovine respiratory syncytial virus (BRSV), agreement with TTW was moderate for NS, good for NPS, and very good for BAL. For bovine coronavirus (BCV), agreement with TTW was moderate for NS and NPS, and good for BAL. McNemar's test was significant only for BCV, indicating that for this pathogen the proportion of positive results from NS and NPS could not be considered comparable to TTW. CONCLUSIONS AND CLINICAL IMPORTANCE: This study provides guidance for veterinarians selecting diagnostic tests for antemortem identification of pathogens associated with BRD.

Increased variability in Apc(Min)/+ intestinal tissue can be measured with microultrasound.

Altered tissue structure is a feature of many disease states and is usually measured by microscopic methods, limiting analysis to small areas. Means to rapidly and quantitatively measure the structure and organisation of large tissue areas would represent a major advance not just for research but also in the clinic. Here, changes in tissue organisation that result from heterozygosity in Apc, a precancerous situation, are comprehensively measured using microultrasound and three-dimensional high-resolution microscopy. Despite its normal appearance in conventionally examined cross-sections, both approaches revealed a significant increase in the variability of tissue organisation in Apc heterozygous tissue. These changes preceded the formation of aberrant crypt foci or adenoma. Measuring these premalignant changes using microultrasound provides a potential means to detect microscopically abnormal regions in large tissue samples, independent of visual examination or biopsies. Not only does this provide a powerful tool for studying tissue structure in experimental settings, the ability to detect and monitor tissue changes by microultrasound could be developed into a powerful adjunct to screening endoscopy in the clinic.

Modelling and characterisation of a ultrasound-actuated needle for improved visibility in ultrasound-guided regional anaesthesia and tissue biopsy.

Clear needle visualisation is recognised as an unmet need for ultrasound guided percutaneous needle procedures including regional anaesthesia and tissue biopsy. With inadequate needle visibility, these procedures may result in serious complications or a failed operation. This paper reports analysis of the modal behaviour of a previously proposed ultrasound-actuated needle configuration, which may overcome this problem by improving needle visibility in colour Doppler imaging. It uses a piezoelectric transducer to actuate longitudinal resonant modes in needles (outer diameter 0.8-1.2mm, length>65mm). The factors that affect the needle's vibration mode are identified, including the needle length, the transducer's resonance frequency and the gripping position. Their effects are investigated using finite element modelling, with the conclusions validated experimentally. The actuated needle was inserted into porcine tissue up to 30mm depth and its visibility was observed under colour Doppler imaging. The piezoelectric transducer is able to generate longitudinal vibration with peak-to-peak amplitude up to 4µm at the needle tip with an actuating voltage of 20Vpp. Actuated in longitudinal vibration modes (distal mode at 27.6kHz and transducer mode at 42.2kHz) with a drive amplitude of 12-14Vpp, a 120mm needle is delineated as a coloured line in colour Doppler images, with both needle tip and shaft visualised. The improved needle visibility is maintained while the needle is advanced into the tissue, thus allowing tracking of the needle position in real time. Moreover, the needle tip is highlighted by strong coloured artefacts around the actuated needle generated by its flexural vibration. A limitation of the technique is that the transducer mode requires needles of specific lengths so that the needle's resonance frequency matches the transducer. This may restrict the choice of needle lengths in clinical applications.

Tunable beam shaping with a phased array acousto-optic modulator.

We demonstrate the generation of Bessel beams using an acousto-optic array based on a liquid filled cavity surrounded by a cylindrical multi-element ultrasound transducer array. Conversion of a Gaussian laser mode into a Bessel beam with tunable order and position is shown. Also higher-order Bessel beams up to the fourth order are successfully generated with experimental results very closely matching simulations.

A randomised, single-blind technical study comparing the ultrasonic visibility of smooth-surfaced and textured needles in a soft embalmed cadaver model.

Visibility of the needle tip and shaft is important during ultrasound-guided regional anaesthesia in order to prevent nerve trauma. Tip and shaft visibility is reduced when needles are inserted in-plane at wide angles and out-of-plane at narrow angles to the ultrasound probe. Although textured needles are more reflective than smooth needles, we hypothesised that poor visibility of the tip and shaft still remained using the above angle-probe combinations. In a single-blind study, we compared the visibility of a textured Tuohy needle, a textured single-shot needle and a conventional smooth-surfaced Tuohy needle when inserted into the biceps and deltoid muscles of a soft embalmed cadaver. One hundred and forty-four needles were block-randomised to in-plane and out-of-plane insertions at 30°, 45°, 60° and 75° to the ultrasound beam. Two blinded raters assessed needle tip visibility on video recordings of the insertions using a binary scale (0 = not visible, 1 = visible) and shaft visibility using a 5-point Likert scale. The median (IQR [range]) proportions of visible needle tips were 83% (67-83 [50-100]%) for the textured Tuohy, 75% (67-83 [33-83]%) for the textured single-shot needle and 33% (33-46 [0-50]%) for the smooth-surfaced Tuohy (p = 0.0007). Median (IQR [range]) needle shaft visibility was rated as 4.0 (3.5-4.7 [3.0-4.9]) for the textured Tuohy, 4.0 (3.8-4.5 [2.7-4.9]) for the textured single-shot needle and 3.0 (2.4-3.3 [2.3-3.5]) for the smooth-surfaced Tuohy (p = 0.015). Nevertheless, visibility was reduced at wide angles in-plane and narrow angles out-of-plane both for needle tips (p = 0.004) and shafts (p = 0.005).

Alignment of an acoustic manipulation device with cepstral analysis of electronic impedance data.

Acoustic particle manipulation is an emerging technology that uses ultrasonic standing waves to position objects with pressure gradients and acoustic radiation forces. To produce strong standing waves, the transducer and the reflector must be aligned properly such that they are parallel to each other. This can be a difficult process due to the need to visualise the ultrasound waves and as higher frequencies are introduced, this alignment requires higher accuracy. In this paper, we present a method for aligning acoustic resonators with cepstral analysis. This is a simple signal processing technique that requires only the electrical impedance measurement data of the resonator, which is usually recorded during the fabrication process of the device. We first introduce the mathematical basis of cepstral analysis and then demonstrate and validate it using a computer simulation of an acoustic resonator. Finally, the technique is demonstrated experimentally to create many parallel linear traps for 10 µm fluorescent beads inside an acoustic resonator.

Resonance tracking and vibration stablilization for high power ultrasonic transducers.

Resonant frequency shift and electrical impedance variation are common phenomena in the application of high power ultrasonic transducers, e.g. in focused ultrasound surgery and in cutting. They result in low power efficiency and unstable vibration amplitude. To solve this problem, a driving and measurement system has been developed to track the resonance of high power transducers and to stabilise their vibration velocity. This has the ability to monitor the operating and performance parameters of the ultrasonic transducers in real time. The configuration of the system, with its control algorithm implemented in LabVIEW (National Instruments, Newbury, UK), ensures flexibility to suit different transducers and load conditions. In addition, with different programs, it can be utilised as a high power impedance analyser or an instantaneous electrical power measurement system for frequencies in the MHz range. The effectiveness of this system has been demonstrated in detailed studies. With it, high transducer performance at high power can be achieved and monitored in real time.

Automated performance assessment of ultrasound systems using a dynamic phantom.

Quality assurance of medical ultrasound imaging systems is limited by repeatability, difficulty in quantifying results, and the time involved. A particularly interesting approach is demonstrated in the Edinburgh pipe phantom which, with an accompanying mathematical transformation, produces a single figure of merit for image quality from individual measurements of resolution over a range of depths. However, the Edinburgh pipe phantom still requires time-consuming manual scanning, mitigating against its routine use. This paper presents a means to overcome this limitation with a new device, termed the Dundee dynamic phantom, allowing rapid set-up and automated operation. The Dundee dynamic phantom is based on imaging two filamentary targets, positioned by computer control at different depths in a tank of 9.4% ethanol-water solution. The images are analysed in real time to assess if the targets are resolved, with individual measurements at different depths again used to calculate a single figure of merit, in this case for lateral resolution only. Test results are presented for a total of 18 scanners in clinical use for different applications. As a qualitative indication of viability, the figure of merit produced by the Dundee dynamic phantom is shown to differentiate between scanners operating at different frequencies and between a relatively new, higher quality system and an older, lower quality system.

Translation of sonoelastography from Thiel cadaver to patients for peripheral nerve blocks.

Ultrasound guidance is now common in regional anaesthesia practice, but remains limited by poor visibility of the needle tip and poor quantification of local anaesthetic spread. Sonoelastography based on tissue compression is a technique depicting tissue strain. Hitherto used largely for tumour diagnosis, we used it in both Thiel embalmed cadavers and two patients receiving interscalene and femoral blocks to observe changes in tissue strain during local anaesthetic injection. The primary aim of our study was to measure the area under the curve (weighted for time) of the strain pattern in Thiel perineural tissue when using a range of volumes of embalming fluid (0.25, 0.5, 1, 2.5, 5 and 7.5 ml) for interscalene and femoral blocks using sonoelastography. Our secondary aims were to evaluate static images of anatomy and videos of needle insertion and perineural injection using combined B-Mode ultrasound and sonoelastography. Independent raters assessed the anatomy and spread using a 7-point Likert scale, ranked from extremely poor to extremely good. We performed 83 blocks in cadavers. Concordance between both raters was good, with weighted Kappa (95% CI) 0.66 (0.61-0.71). The characteristics of spread were similar with both interscalene and femoral block; spread increased with injectate volume up to 1 ml. Analysis of variance showed differences in spread between injection volumes (p = 0.009), but not between regional blocks (p = 0.05). Post-hoc analysis showed greater spread with 1 and 2.5 ml volumes compared with 0.25 ml. In patients, visibility of strain during injection was better with sonoelastography than with B-Mode ultrasound and showed a dose response from 1 to 5 ml volumes of local anaesthetic. Colour strain recognition using sonoelastography offers the ability to differentiate between nerve and surrounding tissue during local anaesthetic injection by improving visibility of spread (p = 0.04).

Manipulation of microparticles using phase-controllable ultrasonic standing waves.

A method of manipulating microparticles in a liquid using ultrasound is proposed and demonstrated. An ultrasonic standing wave with nodal planes whose positions are controllable by varying the relative phase of two applied sinusoidal signals is generated using a pair of acoustically matched piezoelectric transducers. The resulting acoustic radiation force is used to trap micron scale particles at a series of arbitrary positions (determined by the relative phase) and then move them in a controlled manner. This method is demonstrated experimentally and 5 µm polystyrene particles are trapped and moved in one dimension through 140 µm.

Etomidate unmasks intraadrenal regulation of steroidogenesis and proliferation in adrenal cortical cell lines.

To characterize intraadrenal adaptations for inhibition of cortisol synthesis, we analyzed the effects of etomidate (ETO) on steroid hormone secretion and expression of key regulators of steroidogenesis and proliferation in human NCI-h295 adrenocortical cancer cells. Etomidate potently blocked 11beta-hydroxylase (CYP11B1), aldosterone synthase (CYP11B2), and side chain cleavage enzyme (CYP11A1). This inhibition of steroidogenesis was associated with increased expression of steroidogenic acute regulatory protein (StAR), and CYP11A1 and 17alpha-hydroxylase/17, 20-lyase (CYP17A1) protein levels, but not of the respective mRNA levels. Promoter activity of CYP11A1 and melanocortin 2 receptor (MC2R) was not increased by etomidate in treated cells compared to controls. The increase in protein levels was partially reversed by cycloheximide suggesting post-transcriptional mechanisms but also protein stabilization as underlying cause. Furthermore, ETO exhibited antiproliferative activity paralleled by a decrease in phosphorylation of MEK and ERK1, 2. In summary, ETO exhibits pleiotropic effects on adrenal function in vitro. Inhibition of steroidogenesis is followed by increased levels of steroidogenic key proteins and reduced proliferation. These changes reflect adaptations to maintain steroidogenesis at the cost of adrenal proliferation.

Albuterol metered dose inhaler performance under hyperbaric pressures.

The weight change per actuation and aerosol particle size and number delivered by albuterol metered dose inhalers (MDIs) were measured in a multiplace hyperbaric chamber at pressures ranging from one atmosphere absolute (1 ATA, 0 feet of seawater, fsw, 101 kPa) to three ATA (66 fsw, 304 kPa). Weight change per actuation by CFC (chlorofluorocarbon) and long canister HFA (hydrofluoroalkane) powered MDIs was 13 +/- 1% and 12 +/- 1% less, respectively, at 3 ATA compared to 1 ATA. However, weight change per actuation by short canister HFA MDIs was not significantly changed with pressure. The geometric mean diameters of nano particles from the CFC and short canister HFA MDIs decreased from 50 nm at 0 fsw to 32 nm at 66 fsw whereas the long canister HFA aerosol diameters were not affected. The numbers of nanometer size particles delivered at 66 fsw were only 4-7% of those delivered at 0 fsw for the CFC and long canister HFA MDIs whereas for the short canister MDIs it was 26%. We conclude that the weight change per actuation of albuterol and the sizes and numbers of aerosol particles emitted from albuterol MDIs actuated in a hyperbaric environment vary by canister type.

Investigation of dental samples using a 35MHz focussed ultrasound piezocomposite transducer.

Dental erosion and decay are increasingly prevalent but as yet there is no quantitative monitoring tool. Such a tool would allow earlier diagnosis and treatment and ultimately the prevention of more serious disease and pain. Despite ultrasound having been demonstrated as a method of probing the internal structures of teeth more than 40 years ago, development of a clinical tool has been slow. The aim of the study reported here was to investigate the use of a novel high frequency ultrasound transducer and validate it using a known dental technique. A tooth extracted for clinical reasons was sectioned to provide a sample that contained an enamel and dentine layer such that the enamel-dentine junction (EDJ) was of a varying depth. The sample was then submerged in water and a B-scan recorded using a custom-designed piezocomposite ultrasound transducer with a centre frequency of 35 MHz and a -6 dB bandwidth of 24 MHz. The transducer has an axial resolution of 180 microm and a spatial resolution of 110 microm, a significant advance on previous work using lower frequencies. The depth of the EDJ was measured from the resulting data set and compared to measurements from the sequential grinding and imaging (SGI) method. The B-scan showed that the EDJ was of varying depth. Subsequently, the EDJ measurements were found to have a correlation of 0.89 (p<0.01) against the SGI measurements. The results indicate that high frequency ultrasound is capable of measuring enamel thickness to an accuracy of within 10% of the total enamel thickness, whereas currently there is no clinical tool available to measure enamel thickness.

Modelling prefrontal cortex deficits in schizophrenia: implications for treatment.

Current treatments of schizophrenia are compromised by their inability to treat all symptoms of the disease and their side-effects. Whilst existing antipsychotic drugs are effective against positive symptoms, they have negligible efficacy against the prefrontal cortex (PFC)-associated cognitive deficits and negative symptoms. New models that reproduce core pathophysiological features of schizophrenia are more likely to have improved predictive validity in identifying new treatments. We have developed a NMDA receptor antagonist model that reproduces core PFC deficits of schizophrenia and discuss this in relation to pathophysiology and treatments. Subchronic and chronic intermittent PCP (2.6 mg/kg i.p.) was administered to rats. PFC activity was assessed by 2-deoxyglucose imaging, parvalbumin and Kv3.1 mRNA expression, and the attentional set-shifting test (ASST) of executive function. Affymetrix gene array technology was employed to examine gene expression profile patterns. PCP treatment reduced glucose utilization in the PFC (hypofrontality). This was accompanied by a reduction in markers of GABAergic interneurones (parvalbumin and Kv3.1 mRNA expression) and deficits in the extradimensional shift dimension of the ASST. Consistent with their clinical profile, the hypofrontality was not reversed by clozapine or haloperidol. Transcriptional analysis revealed patterns of change consistent with current neurobiological theories of schizophrenia. This model mirrors core neurobiological deficits of schizophrenia; hypofrontality, altered markers of GABAergic interneurone activity and deficits in executive function. As such it is likely to be a valuable translational model for understanding the neurobiological mechanisms underlying hypofrontality and for identifying and validating novel drug targets that may restore PFC deficits in schizophrenia.

1-3 connectivity lithium niobate composites for high temperature operation.

Lithium niobate, LiNbO(3), is a piezoelectric material well known for its high Curie temperature. However, it has often been neglected for use in ultrasonic transducers because of its low electro-mechanical coupling coefficients. Recent advances in signal processing have made this disadvantage less significant and we now report an investigation of the potential of LiNbO(3) composites for use in high temperature transducers for non-destructive testing (NDT). LiNbO(3) composites of 1-3 connectivity in room temperature vulcanising (RTV) sealant and cement matrices were fabricated by the dice and fill method. The RTV and the cement are specified to withstand temperatures up to 350 degrees C and 1600 degrees C, respectively. The composites have been characterized by electrical impedance measurement at ambient and elevated temperatures. In array configuration, transmit-receive signals from the back wall of a steel specimen were obtained at room temperature with good signal to noise ratio. High temperature measurements were made at temperatures up to 180 degrees C for the RTV composite and 360 degrees C for the cement composite configured as single element transducers. Temperature cycling has also been investigated and the new composite materials have been demonstrated to withstand several cycles without deterioration. It is concluded that they may contribute toward a solution to presently unsolved problems in NDT at elevated temperatures.

Multilayer piezocomposite structures with piezoceramic volume fractions determined by mathematical optimisation.

Piezocomposite materials are now widely used in broadband underwater sonar for ultrasound generation and detection because of their recognised advantages over piezoceramic devices. However, it is difficult to make single-layer piezocomposite devices to operate effectively at frequencies below 100 kHz. Instead, multilayer composite stacks can be used. If this solution is adopted, interesting effects can be achieved by choosing appropriate ceramic volume fractions for different layers in the stack, as volume fraction plays a key role in achieving the desired performance. In this paper we describe a theoretical study of 1-3 piezocomposite transducers with five layers each with a different volume fraction. Our work is based mainly on our own special purpose computer code which solves the one-dimensional wave equation by matrix manipulation, with additional support from the PZ Flex finite element analysis package. The choice of volume fractions is difficult because of the multifaceted nature of the problem, with a very large number of possible combinations and complex dependence of material properties, and hence transducer sensitivity and frequency response on the volume fractions. Therefore, we have used the stochastic optimisation technique of simulated annealing implemented in MATLAB code to determine the volume fraction of each layer. The optimisation cost function we have used is maximisation of gain-bandwidth product. We have found that significant increases in gain-bandwidth product can be achieved compared with the use of the same volume fraction in each layer, far exceeding the 35% reported previously with trial-and-error volume fraction adjustment. This suggests that improvements in practical device performance are possible.

Imaging with lithium niobate/epoxy composites.

Lithium niobate, LiNbO3, is a very promising material for high temperature applications in non-destructive testing because of its high Curie temperature. However, for commercial applications LiNbO3 has often been neglected because of its low electromechanical coupling coefficients. This paper explores the potential of LiNbO3 composites, by means of room temperature characterization and measurements, for further use in operation in high temperature transducers. LiNbO3 composites of 1-3 connectivity in an epoxy matrix with volume fractions of LiNbO3 of 33% and 54% were fabricated. The composites were characterized by electrical impedance measurements and the results were compared with modelled impedance characteristics. Many parameters were predicted accurately, including an improvement of more than 75% in thickness mode electromechanical coupling coefficient, from kT=0.17 for bulk LiNbO3 to kT=0.32 for composite material. Some large discrepancies between simulation and experiment were also identified when a conventional one-dimensional model was used to calculate equivalent composite material parameters; however, finite element modelling was more accurate. After characterization, the composite was configured for use as a linear array. Functional measurements were conducted on steel blocks with a side drilled hole to represent a crack tip. This was detected by the array and visualized in time-of-flight diffraction B-scan images.

1-3 connectivity piezoelectric ceramic-polymer composite transducers made with viscous polymer processing for high frequency ultrasound.

Potential applications of high frequency ultrasound exist because of the high spatial resolution consequent upon short wavelength. The frequencies of interest, typically from 25 MHz upwards, are easily supported by modern instrumentation but the capabilities of ultrasonic transducers have not kept pace and the transducers in high frequency commercial ultrasonic systems are still made with single-phase crystal, ceramic or piezopolymer materials. Despite potential performance advantages, the 1-3 connectivity piezoelectric ceramic-polymer composite materials now widely used at lower ultrasonic frequencies have not been adopted because of manufacturing difficulties. These difficulties are centred on fabrication of the 1-3 piezoceramic bristle-block comprising tall, thin pillars upstanding from a supporting stock. Fabrication techniques which have been explored already include injection moulding, mechanical dicing, and laser machining. Here, we describe an alternative technique based on viscous polymer processing (VPP) to produce net shape ceramic bristle-blocks. VPP produces green-state ceramic with rheological properties suitable for embossing. We outline how this can be created then report on our work to fabricate PZT bristle-blocks with lateral pillar dimensions of the order of 50 microm and height-to-width ratios of the order of 10. These have been backfilled with low pre-cure viscosity polymer and made into complete 1-3 piezocomposite transducer elements. We outline the performance of the transducers in terms of electrical impedance and pulse-echo behaviour and show that it corresponds well with computer modelling. We conclude that VPP is a promising technique to allow the established advantages of piezocomposite material to be exploited at higher frequencies than have been possible so far.

Thick aluminium nitride films deposited by room-temperature sputtering for ultrasonic applications.

Materials in film form for electromechanical transduction have a number of potential applications in ultrasound. They are presently under investigation in flexural transducers for air-coupled ultrasound and underwater sonar operating at frequencies up to a few megahertz. At higher frequencies, they have the potential to be integrated with electronics for applications of ultrasound requiring high spatial resolution. However, a number of fabrication difficulties have arisen in studies of such films. These include the high temperatures required in many thick and thin film deposition processes, making them incompatible with other stages in transducer fabrication, and difficulties maintaining film quality when thin film--typically sub-1 microm--processes are extended to higher thicknesses. In this paper, we first outline a process which has allowed us to deposit aluminium nitride (AlN) films capable of electromechanical transduction at thicknesses up to more than 5 microm without substrate heating. As an ultrasonic transduction material, AlN has functional disadvantages, particularly a high acoustic velocity and weak electromechanical transduction. However, it also has a number of advantages relating to practicality of fabrication and functionality. These include the ability to be deposited on a variety of amorphous substrates, a very high Curie temperature, low permittivity, and low electrical and mechanical losses. Here, we present experimental results highlighting the transduction capabilities of AlN deposited on aluminium electrodes on glass and lithium niobate. We compare the results with those from standard simulation processes, highlighting the reasons for discrepancies and discussing the implications for incorporation of AlN into standard ultrasonic transducer design processes.