Which Confounders Have the Largest Impact in Shear Wave Elastography of Muscle and How Can They be Minimized? An Elasticity Phantom, Ex Vivo Porcine Muscle and Volunteer Study Using a Commercially Available System.

The goal of the study was to investigate the quantitative impact of region of interest (ROI), software choice, muscle fiber orientation and preload tension on shear wave velocity (SWV). First, SWV was assessed in an isotropic elasticity phantom and ex vivo porcine muscle using a commercially available clinical ultrasound system. Secondly, SWV was acquired in relaxed and stretched calf muscles of healthy volunteers (dorsal extension of the talocrural joint), for both parallel and transverse probe direction to the fibers, as well as for different ROIs and software versions. The effect of intermediate probe-fiber alignments was also analyzed. Finally, the impact of confounding factors on SWV reproducibility was minimized with a second force-controlled volunteer study, in which the calf was isometrically loaded, and fiber orientation and ROI were well-defined. 2046 in vivoSWE images were acquired to analyze SWV reproducibility with different confounder settings. In healthy volunteers, the main variance-contributing factors were in order of importance muscle tension, fiber orientation, horizontal ROI size and insertion depth. Regression analysis showed significantly reduced SWV with increasing insertion depth for each study material. Parallel probe-fiber orientation, muscle stretch and increasing horizontal ROI size led to significantly higher SWV. Based on the results of the study, we provide recommendations to minimize the impact of confounders in musculoskeletal elastography and discuss the main confounding mechanisms and trade-offs between confounding variables. Coefficients of variation can be significantly reduced with a controlled protocol, if the confounders are clinically taken into account.

Influencing Factors of 2D Shear Wave Elastography of the Muscle - An Ex Vivo Animal Study.

OBJECTIVE: To evaluate measurement confounders on 2D shear wave elastography (2D-SWE) elastography of muscle. MATERIALS AND METHODS: Ex vivo , porcine muscle was examined with a GE LOGIQ E9 ultrasound machine with a 9 L linear (9 MHz) and C1-6 convex probe (operating at 2.5 or 6 MHz). The influence of different confounders on mean shear wave velocity (SWVmean) was analyzed: probes, pressure applied by probe, muscle orientation, together with the impact of different machine settings such as frequency, placement depth and size of region of interest (ROI). The mean of twelve repeated SWVmean measurements (m/s) and coefficient of variation (CV; standard deviation/mean in %) were assessed for each test configuration. RESULTS: Reproducibility (CV) and maximum possible tissue depth of the linear probe were inferior to the convex probe. With the linear probe, there was a linear decrease of SWVmean with placement depth from 4.56 m/s to 1.81 m/s. A significant increase of SWVmean (p<0.001) was observed for larger ROI widths (range 3.96 m/s to 6.8 m/s). A change in the machine operation mode ('penetration' instead of 'general') led to a significant increase of SWVmean (p=0.04). SWVmean in the longitudinal direction of muscle was significantly higher than in cross section (p<0.001) (e. g. 4.56 m/s versus 3.42 m/s). An increase of linear probe pressure significantly increased muscle SWVmean from 5.29 m/s to 7.21 m/s (p<0.001). CONCLUSIONS: 2D-SWE of muscle is influenced by a wealth of parameters. Therefore, standardization of measurement is advisable before application in clinical research studies and routine patient assessment.

Economical Sponge Phantom for Teaching, Understanding, and Researching A- and B-Line Reverberation Artifacts in Lung Ultrasound.

This project evaluated a low-cost sponge phantom setup for its capability to teach and study A- and B-line reverberation artifacts known from lung ultrasound and to numerically simulate sound wave interaction with the phantom using a finite-difference time-domain (FDTD) model. Both A- and B-line artifacts were reproducible on B-mode ultrasound imaging as well as in the FDTD-based simulation. The phantom was found to be an easy-to-set up and economical tool for understanding, teaching, and researching A- and B-line artifacts occurring in lung ultrasound. The FDTD method-based simulation was able to reproduce the artifacts and provides intuitive insight into the underlying physics.

Ultrasound Needle Visibility in Contrast Mode Imaging: An In Vitro and Ex Vivo Study.

PURPOSE: To evaluate needle visibility in ultrasound under contrast mode conditions. MATERIALS AND METHODS: Needle visibility was evaluated for bevel, EchoTip ® and shaft of 18G Chiba biopsy needle with a 9 MHz linear probe (GE Logiq E9). Insertion angles varied between 30°(steep) and 90°(parallel to the probe surface). The acoustic output varied from 5-28%. 2 different contrast mode presets with either 'Amplitude Modulation' (Penetration) or 'Phase Inversion Harmonics' (High Resolution) were assessed. All other imaging parameters were kept constant. The visibility of bevel, EchoTip ® and shaft was assessed for grayscale and color-coded images with a 3-point Likert-like scale (not, poorly, well visible) by 2 independent readers. The echogenicity of the needle bevel, EchoTip ® and shaft was assessed in deciBel (dB) on the color-coded images. RESULTS: With the parallel insertion angle, all needle areas were well visible. With steep insertion the EchoTip ® was the only visible area. High Resolution was superior to Penetration (p<0.001). The visibility and echogenicity of the needle bevel ( rgrayscale =0.109, p grayscale =0.178; rcolor-coded =0.236, p color-coded =0.266; rdB =0.956, p dB =0.001), EchoTip ® ( rgrayscale += 0.477, p grayscale += 0.018; rcolor-coded =0.540, p color-coded += 0.006; rdB =0.911, p dB =0.001) and shaft ( rgrayscale =0.124, p grayscale =0.563; rcolor-coded =0.061, p color-coded += 0.775; rdB += 0.926, p dB =0.001) increased with increasing acoustic output. Grayscale images were superior to color-coded images for needle visibility (p=0.004). CONCLUSION: Parallel needle insertion, use of an echogenic tip, adequate choice of presets, increased acoustic output, and dual view of grayscale and color-coded images improve needle visibility in ultrasound under contrast mode conditions.

Measurement of real-time tissue elastography in a phantom model and comparison with transient elastography in pediatric patients with liver diseases.

PURPOSE: We aimed to determine the comparability of real-time tissue elastography (RTE) and transient elastography (TE) in pediatric patients with liver diseases. MATERIALS AND METHODS: RTE was performed on the Elasticity QA Phantom Model 049 (Computerized Imaging Reference Systems Company Inc., Norfolk, Virginia, USA), which has five areas with different levels of stiffness. RTE measurements of relative stiffness (MEAN [mean value of tissue elasticity], AREA [% of blue color-coded stiffer tissue]) in the phantom were compared with the phantom stiffness specified in kPa (measurement unit of TE). RTE and TE were performed on 147 pediatric patients with various liver diseases. A total of 109 measurements were valid. The participants had following diseases: metabolic liver disease (n=25), cystic fibrosis (n=20), hepatopathy of unknown origin (n=11), autoimmune hepatitis (n=12), Wilson's disease (n=11), and various liver parenchyma alterations (n=30). Correlations between RTE and TE measurements in the patients were calculated. In addition, RTE was performed on a control group (n=30), and the RTE values between the patient and control groups were compared. RESULTS: The RTE parameters showed good correlation in the phantom model with phantom stiffness (MEAN/kPa, r=-0.97; AREA/kPa, r=0.98). However, the correlation of RTE and TE was weak in the patient group (MEAN/kPa, r=-0.23; AREA/kPa, r=0.24). A significant difference was observed between the patient and control groups (MEAN, P = 5.32 e-7; AREA, P = 1.62 e-6). CONCLUSION: In the phantom model, RTE was correlated with kPa, confirming the presumed comparability of the methods. However, there was no direct correlation between RTE and TE in patients with defined liver diseases under real clinical conditions.

Diagnostic ultrasound activates pure prekallikrein.

Diagnostic ultrasound activates the contact phase of human coagulation. This has been seen in human blood or plasma or with purified factor 12. The present work aimed to quantify a possibly triggering action of ultrasound on purified prekallikrein, the second of the two main triggers of the intrinsic hemostasis cascade. Either 2.7 µg/ml human prekallikrein or for control 1 µg/ml kallikrein in 26% glycerol - 0.54% NaCl-10.6 mmol/l Na3 citrate pH 7.4, in emptied polypropylene coagulation monovettes (Sarstedt) were exposed to diagnostic ultrasound (Siemens Acouson Antares, 5 MHz, 0.6 TIB, 0.6 TIS) for 0-5 min at room temperature (RT). Fifty microliter samples were withdrawn in duplicate and placed into an U-wells high quality microtiter plate (Brand 781600). Then 10 µl 2 mmol/l chromogenic substrate HD-CHG-Ala-Arg-pNA in 0.45% NaCl were added, and the increase in absorbance with time (ΔA405 nm /t at 37°C) was determined by a microtiterplate photometer with a 1 mA resolution (PHOmo; anthos). Exposure to diagnostic ultrasound biphasically increased the chromogenic activity of a prekallikrein solution in 26% glycerol. About 3-4 min ultrasound at 23 °C generated about 0.02 µg/ml kallikrein, that means that about 1% of pure prekallikrein in glycerol was converted into kallikrein. Thus, diagnostic ultrasound activates purified human prekallikrein to kallikrein. The ultrasound energy seems to fold the latent proenzyme prekallikrein into the active enzyme kallikrein. This contributes to explain the triggering action of ultrasound on the contact system of plasmatic human coagulation. Conversion of only 1% of prekallikrein into kallikrein is absolutely sufficient to start the intrinsic coagulation cascade. The clinical consequence of this action of ultrasound on intrinsic coagulation is that patients at risk for thrombosis, for example, patients with insufficiencies of hepatocytes, AT-3, C1-ina, or fibrinolysis should be protected by low-molecular-weight-heparin prior to the exposure of ultrasound, especially upon its prolonged exposure.

The ultrasound frequency determines the degree of intrinsic coagulation activation.

Diagnostic ultrasound activates intrinsic coagulation. The aim of the present work was to quantify the action of different ultrasound frequencies on the contact phase of human blood coagulation. Pooled normal citrated platelet-poor plasma in 2 ml aliquots in polypropylene monovettes was exposed to diagnostic ultrasound, changing the ultrasound frequency from 17 to 15 to 12 to 8 to 7 MHz (at an intensity of 1.1 MI). After 0-2 min (23°C), 400 µl samples were withdrawn and placed into polypropylene Eppendorf cups. Forty microliters of plasma sample was pipetted into U-wells polystyrene microtiter plates of high purity (Brand781600). Immediately thereafter, the recalcified coagulation activity assay (RECA) was performed. Seventeen megahertz ultrasound exposure was the weakest activator of intrinsic coagulation of all frequencies tested: even 2 min of exposure at 23°C enhanced F2a generation by only about three-fold. The shorter the ultrasound exposure, the better the action against intrinsic hemostasis: 0.5 min of ultrasound exposure at 23°C induced less than two-fold thrombin generation in all frequencies tested. One minute ultrasound exposure (23°C) triggered intrinsic coagulation strongest at 8 MHz, showing an approximately four-fold increase in F2a generation. A 1.5 min of ultrasound exposure (23°C) triggered coagulation strongest at 7 MHz, showing an approximately 14-fold increase in F2a generation. Two minute of ultrasound exposure (23°C) triggered coagulation strongest at 15 MHz, showing an approximately 18-fold increase in F2a generation. Ultrasound has to be considered as a potential inducer of pathologic systemic coagulation. Patients at risk for increased coagulation activation and/or liver insufficiency should be protected with low molecular weight heparin, if a prolonged ultrasound diagnostic is planned. Ultrasound frequencies of about 17 MHz are the weakest activators of intrinsic coagulation. Ultrasound frequencies of about 7 MHz might be used for therapeutic induction of coagulation activation, such as in patients with severe cerebral or hepatic hemorrhages.

Functional and anatomical investigations in racemose haemangioma.

PURPOSE: To determine the vascular morphology of racemose haemangioma and related functional alterations in arteriovenous (AV) malformation type 3. METHODS: A 17-year-old patient with unilateral racemose haemangioma received a full ophthalmic examination including Snellen visual acuity (VA) and Goldmann visual field. The central vision was investigated by scanning laser ophthalmoscope (SLO) and multifocal electroretinogram (mfERG). The ocular haemodynamics were examined by fluorescence angiography and Doppler ultrasound. The tomographic contour of the vascular architecture was visualized using B-scan ultrasound, Stratus optical coherence tomography (OCT) and three-dimensional Heidelberg retina tomograph (3D-HRT II). RESULTS: The VA of the patient's right eye was reduced to 20/400 and her visual field was constricted concentrically. Microperimetry revealed a small central field with good central fixation. The mfERG demonstrated reduced amplitudes of the central retina. On fluorescein angiography, there was a fast filling of the retinal branches related to the racemose vessels. Doppler ultrasound confirmed a significantly changed haemodynamic flow in the racemose vessels. Ultrasound, OCT and HRT demonstrated a prominent optic nerve head. CONCLUSION: The racemose haemangioma led to a marked visual field defect. Racemose haemangiomas are associated with severe changes in the haemodynamics of the retinal vasculature.

Short posterior ciliary artery, central retinal artery, and choroidal hemodynamics in brimonidine-treated primary open-angle glaucoma patients.

PURPOSE: Malfunction in peripapillary hemodynamics has been suggested to play a major part in the pathogenesis of primary open-angle glaucoma (POAG). The aim of this study was to determine whether topically applied brimonidine can influence blood hemodynamic characteristics associated with the perioptic short posterior ciliary arteries (SPCAs), central retinal artery (CRA), and choroidal vascular system in POAG patients. DESIGN: Randomized clinical trial. In this prospective, institutional, double-masked, vehicle-controlled, randomized clinical trial, the intraocular pressure (IOP) and vascular dynamics of the SPCAs, CRA, and choroidal vascular system were analyzed in both eyes of 17 POAG patients, before and after treatment with 0.2% brimonidine for 4 weeks. RESULTS: Mean IOP reduction was significant (18.7%) following treatment with brimonidine. However, no clear changes were recorded with respect to blood perfusion parameters (peak systolic velocity, end-diastolic velocity, pulsatility, and resistance indices) associated with the SPCAs and CRA or the choroidal ocular pulse amplitude. CONCLUSIONS: Topical treatment of brimonidine to POAG patients causes a significant reduction of IOP, but blood hemodynamic properties associated with the SPCAs, CRA, and choroidal vascular systems appeared unaffected. Topically applied brimonidine, therefore, appears not to constrict or dilate peripapillary blood vessels.