An easy-to-handle speed of sound test object for skills labs using additive manufacturing (RAPTUS-SOS).

A new generation of speed of sound (SOS) test object is presented that is fully constructed using additive manufacturing processes with a 3D-printer. The object contains 2 compartments with thin filaments and tubes that can be filled with fluid substances. The filaments are located at equal distances to each other; the tubes have fixed diameters. Depending on the chosen fluids (e.g. water, glycerol-water, corn oil, salt water) and room temperature, the mismatch in distance or diameter depending on the SOS error has been measured using ultrasound imaging equipment. The velocity of the fluid could be calculated deductively with high accuracy (range of total error: 0.1-3.4%). The results show that 3D-printed objects or additive manufacturing techniques can be suitable to use as teaching test objects within skills labs.

The focal adhesion-associated proteins DOCK5 and GIT2 comprise a rheostat in control of epithelial invasion.

DOCK proteins are guanine nucleotide exchange factors for Rac and Cdc42 GTPases. DOCK1 is the founding member of the family and acts downstream of integrins via the canonical Crk-p130Cas complex to activate Rac GTPases in numerous contexts. In contrast, DOCK5, which possesses the greatest similarity to DOCK1, remains sparingly studied. Here we establish that DOCK5 has a non-redundant role in regulating motile and invasive capacities of epithelial cells. DOCK1 is constitutively associated with sites of integrin attachment termed focal adhesions (FAs). In contrast, we demonstrate that DOCK5 recruitment to FAs in Hela cells is restricted by GIT2, an established regulator of FA signaling. We determine that GIT2 is targeted to FAs in response to Rho-ROCK signaling and actomyosin contractility. Accordingly, inhibition of ROCK activity or MLC function promotes enrichment of DOCK5 in membrane protrusions and nascent cell-substratum adhesions. We further demonstrate that GIT2 inhibits the interaction of DOCK5 with Crk. Moreover, we show that depletion of GIT2 promotes DOCK5-dependent activation of the Crk-p130Cas signaling cascade to promote Rac1-mediated lamellipodial protrusion and FA turnover. The antagonism between GIT2 and DOCK5 extends to non-transformed MCF10A mammary epithelial cells, with DOCK5 'dialing-up' and GIT2 'dialing-down' invasiveness. Finally, we determine that DOCK5 inhibition attenuates invasion and metastasis of MDA-MB-231 cells and prolongs life span of mice injected with these cells. Collectively, our work identifies DOCK5 as a key regulator of epithelial invasion and metastasis, and demonstrates that suppression of DOCK5 by GIT2 represents a previously unappreciated mechanism for coordination of Rho and Rac GTPases.

Transtemporal ultrasound application potentially elevates brain temperature: results of an anthropomorphic skull model.

PURPOSE: Transtemporal sonothrombolysis is a tool for a more effective treatment in acute stroke patients. However, some reports revealed side effects, which might be potentially connected to temperature elevation. To gain better insight into cerebral temperature changes during transtemporal sonication, diagnostic and therapeutic ultrasound (US) applications were evaluated using an anthropomorphic skull model. MATERIALS AND METHODS: The impact of diagnostic (PW-Doppler, 1.8-MHz, 0.11 W/cm², TIC 1.2) and therapeutic (1-MHz and 3-MHz, 0.07 - 0.71 W/cm², continuous and pulsed mode) US application on temperature changes was evaluated at the level of muscle/temporal bone (TB), TB/brain, brain and at the middle cerebral artery (MCA) using 4 miniature thermocouples along the US beam. Sonication lasted 120 minutes. RESULTS: Diagnostic ultrasound revealed a maximum temperature increase of 1.45°/0.60°/0.39°/0.41°C (muscle/TB, TB/brain, brain, MCA) after 120 minutes. Therapeutic-1-MHz ultrasound raised temperature by 4.33°/2.02°/1.05 °C/0.81°C (pulsed 1:20) and by 10.38°/4.95°/2.43°/2.08°C (pulsed 1:5) over 120 minutes. Therapeutic-3-MHz US raised temperature by 4.89°/2.56°/1.24/1.25°C (pulsed 1:20) and by 14.77°/6.59°/3.56°/2.86°C (pulsed 1:5) over 120 minutes, respectively. Continuous application of therapeutic US (1-MHz and 3-MHz) led to a temperature increase of 13.86°/3.63°/1.66°/1.48°C and 17.09°/4.28°/1.38/0.99°C within 3 minutes. CONCLUSION: Diagnostic PW-Doppler showed only a moderate temperature increase and can be considered as safe. Therapeutic sonication is very powerful in delivering energy so that even pulsed application modes resulted in significant and potentially harmful temperature increases.

Guideline for Technical Quality Assurance (TQA) of ultrasound devices (B-Mode)--version 1.0 (July 2012): EFSUMB Technical Quality Assurance Group--US-TQA/B.

The Technical Quality Assurance group was initiated by the EFSUMB Board in 2007 and met firstly in 2008 to discuss and evaluate methods and procedures published for performing technical quality assurance for diagnostic ultrasound devices. It is the aim of this group of experts to advise the EFSUMB Board of effective and efficacious methods for routine use and to make recommendations regarding the technical aspects of EFSUMB by-law 9, parts 11.6. & 11.7. The group's work focused on new developments and related European projects to establish a common guideline. There is a great need of a well established protocol and dedicated processing software for the performance testing of medical ultrasound equipment. The measurements should be user independent as much as physically possible. Only if these goals are achieved in an international (firstly European) context, the optimal quality of ultrasound imaging can be offered and maintained to the medical community. This guideline aims to offer and summarize suitable procedures and evaluation processes to lend support for an optimal Technical Quality Assurance (TQA) scheme. The content of this guideline was presented to the EFSUMB Board of Directors (delegates) and approved by the EFSUMB Executive Board (ExB) at the regular meeting during EUROSON 2012 in Madrid April 2012.

Thermal effects of diagnostic ultrasound in an anthropomorphic skull model.

PURPOSE: Exposure to diagnostic ultrasound (US) can significantly heat biological tissue although conventional routine examinations are regarded as safe. The risk of unwanted thermal effects increases with a high absorption coefficient and extended insonation time. Certain applications of transcranial diagnostic US (TC-US) require prolonged exposure. An anthropomorphic skull model (ASM) was developed to evaluate thermal effects induced by TC-US of different modalities. The objective was to determine whether prolonged continuous TC-US application results in potentially harmful temperature increases. MATERIALS AND METHODS: The ASM consists of a human skull with tissue mimicking material and exhibits acoustic and anatomical characteristics of the human skull and brain. Experiments are performed with a diagnostic US device testing four different US modalities: Duplex PW (pulsed wave) Doppler, PW Doppler, color flow Doppler and B-mode. Temperature changes are recorded during 180 minutes of insonation. RESULTS: All measurements revealed significant temperature increases during insonation independent of the US modality. The maximum temperature elevation of + 5.25° C (p < 0.001) was observed on the surface of the skull exposed to duplex PW Doppler. At the bone-brain border a maximum temperature increae of + 2.01 °C (p < 0.001) was noted. Temperature increases within the brain were < 1.23 °C (p = 0.001). The highest values were registered using the duplex PW Doppler modality. CONCLUSION: TC-US induces significant local heating effects in an ASM. An application duration that extends routine clinical periods causes potentially harmful heating especially in tissue close to bone. TC-US elevates the temperature in the brain mimicking tissue but is not capable of producing harmful temperature increases during routine examinations. However, the risk of thermal injury in brain tissue increases significantly after an exposure time of > 2 hours.

[Ultrasound contrast agents--physical basics]. / Ultraschallkontrastmittel -- physikalische Grundlagen.

The concept of ultrasound contrast agents (UCA) is based on the inherent physical and acoustical properties of gas-filled microbubbles within an ultrasonic (US) field. Depending on the magnitude of the incident US wave different scattering behavior occurs. While it is linear for low acoustic pressures, increasing it leads to the occurrence of nonlinear effects, such as emission of harmonics. High pressure results in destruction of the bubbles producing a highly nonlinear echo signal. Using these specific acoustic signatures opens new perspectives for the development of bubble-specific imaging techniques such as harmonic or intermittent imaging. This review deals with the physical properties of the gas-filled microbubbles, their behavior within an ultrasonic field, and the use of the bubbles' acoustic signatures for contrast-specific imaging. Novel applications such as tissue-specific microbubbles, targeted imaging, and therapeutic applications using the bubbles as vehicles for drug or gene delivery are discussed as well as acoustically induced bioeffects and considerations for the safe use of UCA from an acoustic standpoint.

[A testing device for quality assurance of 3D-ultrasound equipment]. / Ein Testobjekt zur Qualitätssicherung von 3D-Ultraschallgeräten.

A test object for 3D-ultrasound (US) imaging equipment was constructed, that could be used for various purposes: For training of the correct technical setup procedures and practical handling of a 3D-US equipment, as well as for various quality assurance procedures. The size and volume of these structures were known precisely (+/- 0.1 mm resp. +/- 0.06 mL, respectively; smallest volume: 0.1 mL). The stability of the structures was in agreement with guideline IEC 854 and allowed to quantify exactly the imaging and measurement errors of size and volume measurements performed with commercial 3D-equipment. The test object is well suited to validate measured volume data, as well as to perform procedures of technical quality assurance in a reproducible manner.

In vitro measurement accuracy of three-dimensional ultrasound.

OBJECTIVES: We sought to validate distance and volume measurements in three-dimensional (3-D) ultrasound images. BACKGROUND: Even with the latest equipment, it is not known how accurate 3-D echocardiographic measurements are. METHODS: Six models were imaged in ethanol solution and two within a tissue phantom using a mechanical rotation device rotating in 1 degrees intervals and a real-time 3-D scanner. Distance and volume measurements (n = 60) were performed in two-dimensional (2-D) and 3-D images using TomTec and InViVo software. RESULTS: Distance measurements had a mean total error between 1.12% and 2.31% for Acuson (2.5 MHZ, 3 MHZ, and 4 MHZ) and Hewlett Parkard (HP) fusion frequencies h and m, HP fusion harmonic B in the axial, and between 3.5% and 4.9% in the lateral dimension. HP Harmonic A and B, Volumetrics (2.5 MHZ), and HP fusion Harmonic A exhibited significantly higher differences to reality with a mean difference between 5.1% and 8.9% in the axial and between 6.2% and 7.9% in the lateral direction. Axial 2-D measurements were not different from real dimensions except Volumetrics model 1. In the lateral axis, all imaging modalities were different from reality except the fusion harmonic modus B. Using the HP fusion frequency h and HP fusion Harmonic B-mode, volume measurements in 3-D images significantly underestimated reality, while Acuson's fundamental frequency 3.5 MHZ was not different from real volumes. CONCLUSION: Three-dimensional visualization using different ultrasound settings results in different accuracy.

Strong in vitro synergy between the fusion inhibitor T-20 and the CXCR4 blocker AMD-3100.

Attachment and entry of HIV-1 into CD4 cells involve a series of events in which different viral envelope proteins interact with specific cell receptors, culminating in fusion of viral and cell membranes. AMD-3100 is a small molecule inhibitor of HIV-1 attachment to the CXCR4 chemokine receptor, and T-20 is a synthetic peptide corresponding to a region of HIV-1 gp41 that blocks fusion to cell membranes. To evaluate the interaction between agents acting at two different steps of the entry process, we conducted in vitro studies of the combination of T-20 and AMD-3100 against an X4 HIV-1 isolate. Single drugs or multiply diluted fixed ratio combinations of drugs were added to peripheral blood mononuclear cells infected with a clinical isolate, 14aPre. Drug interactions were evaluated using the median-effect principle and the combination index technique. The 50% inhibitory concentration (IC50) for T-20 was 0.10 microg/ml and for AMD-3100 was 0.19 microg/ml. Synergy was observed between T-20 and AMD-3100 and this increased with higher inhibitory concentrations, with combination indices ranging from 0.62 at IC50 to 0.02 at IC95. Whether these synergistic interactions translate into clinical benefit will need to be addressed in the context of clinical trials.

Amplitude-coded color doppler: clinical applications.

Amplitude-coded color Doppler sonography (ACD) has become an useful adjunct to gray-scale US and conventional color Doppler sonography (CD) for the assessment of vascular diseases and pathologic conditions that might affect or alter tissue vascularization or perfusion. Basically, all US units that generate conventional color Doppler information through autocorrelation technique are capable of displaying ACD. This technique is also referred to as power Doppler, amplitude-mode color Doppler US, color Doppler energy (CDE), or US angiography. Amplitude-coded color Doppler sonography has already emerged as a valuable adjunct to conventional CD, particularly for evaluating flow in parts of the body where CD signal is weak because of slow flow, small blood vessels, or both.

[A test object for quality control of the instrument for doppler (duplex) ultrasonography, based on the Draft IEC 61685 Standard]. / Ein Testobjekt für die apparative Qualitätssicherung bei Ultraschall-Doppler(Duplex)-Geräten, ausgehend vom Normenentwurf IEC 61685.

PURPOSE: The authors, forming part of a multicenter project funded by the European Community, summarize the validation of a tissue-mimicking flow Doppler test object and of procedures for testing medical diagnostic Doppler equipment. The results of the project are expected to contribute to a future international IEC Standard concerning flow Doppler test objects (Draft IEC 61685 Standard) and for the European Medical Device Directive (MD 93/42/EEC). METHODS: Within this project a test protocol was developed that includes a set of different procedures, suitable for checking Spectral and Colour Doppler systems. The performance parameters for describing the image quality as well as the accuracy and the correct functioning of a system are in accordance with the definitions made in the Draft IEC 61685 Standard. RESULTS: A survey of the design and materials used for this Doppler test object will be presented with a special emphasis on the suitability of the procedures for routine measurement of performance parameters in hospitals. CONCLUSION: The test object satisfies the requirements of the Draft IEC 61685 Standard. The test procedures in combination with this test object can be used for checking different transducer models with nominal frequencies between 2.5-10.0 MHz.

Systematic distortions in magnetic position digitizers.

Medical devices equipped with position sensors enable applications like image guided surgical interventions, reconstruction of three-dimensional 3D ultrasound (US) images, and virtual or augmented reality systems. The acquisition of three-dimensional position data in real time is one of the key technologies in this field. The systematic distortions induced by various metals, surgical tools, and US scan probes in different commercial electromagnetic tracking systems were assessed in the presented work. A precise nonmetallic six degree-of-freedom measurement rack was built that allowed a quantitative comparison of different electromagnetic trackers. Also, their performance in the presence of large metallic structures was quantified in a phantom study on an acrylic skull model in an operating room (OR). The trackers used were alternating current (ac) and direct current (dc) based systems. The ac trackers were, on average, distorted by 0.7 mm and 0.5 degree by metallic objects positioned at a distance greater than 120 mm between the geometrical center of the sample and the sensor. In the OR environment, the ac system exhibits mean errors of 3.2 +/- 2.4 mm and 2.9 degrees +/- 1.9 degrees. The dc trackers are more sensitive to distortions caused by ferromagnetic materials (averaged value: 1.6 mm and 0.5 degree beyond a distance of 120 mm). The dc tracker shows no distortions from other conductive materials but was less accurate in the OR environment (typical error: 6.4 +/- 2.5 mm and 4.9 degrees +/- 2.0 degrees). At distances smaller than approximately 100 mm between sample and sensor error increases quickly. It is also apparent from our measurements that the influence of US scan probes is governed by their shielding material. The results show that surgical instruments not containing conductive material are to be preferred when using an ac tracker. Nonferromagnetic instruments should be used with dc trackers. Static distortions caused by the OR environment have to be compensated by precise calibration methods.

Development of an example flow test object and comparison of five of these test objects, constructed in various laboratories.

Doppler test objects are used to characterise Doppler systems, both stand-alone systems and the Doppler part of so-called duplex scanners. The aim of the project partially presented here is the development and validation of an example of a Doppler test object fulfilling the requirements of the IEC 1685. The project has been carried out by nine partners of five European countries and has been funded by the European Commission. The flow Doppler test object is composed of: tissue mimicking material (TMM), blood mimicking fluid (BMF), tube (embedded in the TMM and carrying the BMF), tank flow system, including a pump and a flow meter. In the normative part of the IEC 1685, requirements are given for the values of acoustical parameters of TMM and BMF such as sound velocity, attenuation and backscattering. For BMF, requirements are given also for values of density and viscosity. In an informative (but not compulsory) annex, a description is given of a flow test object meeting these requirements as an example. 'example test object' developed during the project is composed of TMM based on agar and including SiC- and Al2O3-powders, BMF based on nylon particles suspended in water and glycerine, and a tube of c-flex, a silicon copolymer. Two tube sizes are used: 4.0 mm ID and 8.0 mm ID. During the project, very precise recipes have been developed for the composition and preparation of both TMM and BMF. Based on these recipes and a description of the construction in a design five flow test objects have been constructed in the laboratories of five participants. The test objects have been compared by measurements of the physical parameters and by Doppler measurements of the five test objects with the Doppler system. The measurements have been carried out by five observers. Inter-test object and inter-observer variabilities are determined, yielding information about usefulness of the parameters.

Amplitude-coded colour Doppler sonography: physical principles and technique.

The purpose of this review is to help in understanding the principles of a new ultrasound Doppler technique called amplitude-coded colour Doppler (power) mode. All pertinent information available in the literature on the physical principles of this technique has been revised in order to give a detailed survey. The main components and the key characteristics of this mode are discussed together with illustrative examples. In addition, work-in-progress developments and other future aspects of US imaging in combination with this technique are discussed.

[Results of a study of quality control of diagnostic ultrasound equipment]. / Ergebnisse einer Studie zur Qualitätskontrolle von diagnostischen Ultraschall-Geräten.

AIMS: In this paper results of a quality control programme for B-mode ultrasound equipment used in clinical routine are presented. Over a period of 18 months 5 modern scanners with altogether 19 scanheads were periodically controlled. METHODS: The methods used for measuring the various performance parameters of an ultrasound equipment followed closely standard methods. All measurements were carried out with commercially available tissue-mimicking phantoms, and documented in a uniform protocol. RESULTS: Based on the results it was found that 11 of the scanheads did not operate correctly; 2 additional ones were severely defective. Only 6 scanheads were without loss of image quality or function. For the 13 malfunctioning scanheads adjustments, repair or even an exchange was necessary. CONCLUSION: The study demonstrates that quality control performed periodically is necessary to ensure optimal image quality and safe operation of the equipment.

[Effects of various alfentanil doses on blood pressure, heart rate and plasma catecholamine level in endotracheal intubation]. / Der Einfluss unterschiedlicher Alfentanildosen auf Blutdruck, Herzfrequenz und Plasmakatecholaminspiegel bei der endotrachealen Intubation.

METHOD: In 56 patients undergoing arthroscopy of the knee blood pressure (BP), heart rate (HR) and plasma catecholamines were measured during induction of anaesthesia. To a standard treatment including etomidate (K), either 1 (A1), 2 (A2) or 3 (A3) mg alfentanil were added. The control-group included 8 patients, the other groups consisted of 16 patients. Blood pressure and heart rate were measured the day before anaesthesia (T1), at the arrival in the operation theatre (T2), 1 minute after the induction (T3) and 1 minute after intubation (T4). Catecholamines were analysed at T2 and T4. - RESULTS: At T1 and T2 no significant differences were measured. The control-group had a significant rise of BP, HR and adrenalin at T4. In group A1 (1 mg alfentanil) BP and catocholamines remained at the same levels, HR rose significantly. In group A2 all parameters did not change. The group A3, BP dropped significantly, whereas the other parameters remained stable.- DISCUSSION: 2 mg Alfentanil given 1 minute before endotracheal intubation depress the sympathoadrenergic reactions but do not impair the circulation.