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| 2. |
- Härmark, Johan, et al.
(författare)
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Investigation of the elimination process of a multimodal polymer-shelled contrast agent in rats using ultrasound and transmission electron microscopy
- 2015
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Ingår i: Biomedical Spectroscopy and Imaging. - 2212-8794. ; 4:1, s. 81-93
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A novel polymer-shelled contrast agent (CA) with multimodal imaging and target specific potential was developed recently and tested for its acoustical properties using different in-vitro setups.OBJECTIVE: The aim of this study was to investigate the elimination of three types of the novel polymer-shelled CA, one unmodified and two shell modified versions, in rats.METHODS: The blood elimination time was estimated by measuring the image intensity, from ultrasound images of the common carotid artery, over time after a bolus injection of the three types of the novel CA. The commercially available CA SonoVue was used as a reference. The subcellular localization of the three CAs was investigated using transmission electron microscopy.RESULTS: The ultrasound measurements indicated a blood half-life of 17–85 s for the different types of the novel CA, which was significant longer than the blood half-life time for SonoVue. Additionally, CAs were exclusively found in the circulatory system, either taken up by, or found in the vicinity of macrophages.CONCLUSIONS: Compared to the commercially available CA SonoVue, the blood circulation times for the three types of the novel polymer-shelled CA were prolonged. Moreover, macrophages were suggested to be responsible for the elimination of the CA.
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| 3. |
- Larsson, Malin, 1983-, et al.
(författare)
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A new ultrasound-based approach to visualize target specific polymeric contrast agent
- 2011
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Ingår i: 2011 IEEE International Ultrasonics Symposium (IUS). - : IEEE. - 9781457712524 ; , s. 1626-1629
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Konferensbidrag (refereegranskat)abstract
- There are advantages of using a polymeric shelled contrast agent (CA) during ultrasound imaging instead of lipid shelled CA, e.g. particles can be attached to the surface, which enables an introduction of antibodies to the surface making the CA target specific. For this application it is essential to have a sensitive imaging technique suitable for polymeric CA. However, previously presented results have indicated difficulties in visualizing polymeric CA with commercially available contrast algorithms. Therefore a new subtraction algorithm (SA), was developed that define the difference between contrast and reference images. The aim of this study was to evaluate the response from a polymeric CA, when using the SA and compare it with existing contrast algorithms. Moreover, the possibility to detect a thin layer of CA was tested using the SA.Ultrasound short-axis images of a tissue-mimicking vessel phantom with a pulsating flow were obtained using a GE Vivid7 system (M12L) and a Philips iE33 system (S5-1). Repeated (n=91) contrast to tissue ratios (CTR) calculated at various mechanical index (MI) using the contrast algorithms pulse inversion (PI), power modulation (PM) and SA at a concentration of 105microbubbles/ml.The developed SA showed improvements in CTR compared to existing contrast algorithms. The CTRs were -0.99 dB ± 0.67 (MI 0.2), 9.46 dB ± 0.77 (MI 0.4) and 2.98 dB ± 0.60 (MI 0.8) with PI, 8.17 dB ± 1.15 (MI 0.2), 15.60 dB ± 1.29 (MI0.4) and 11.60 dB ± 0.73 (MI 0.8) with PM and 14.97 dB ± 3.97 (MI 0.2), 20.89 dB ± 3.54 (MI 0.4) and 21.93 dB ± 4.37 (MI 0.8) with the SA. In addition to this, the layer detection, when using the SA was successful.
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| 4. |
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| 5. |
- Larsson, Malin K., et al.
(författare)
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Endocardial border delineation capability of a multimodal polymer-shelled contrast agent
- 2014
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundA novel polymer-shelled contrast agent (CA) with high mechanical and chemical stability was recently developed [1]. In excess to its ultrasound properties, it also supports targeted and multimodal imaging [2-4]. Even though these new possibilities have the potential to lead to new methodologies and approaches for non-invasive diagnosis, it is important that the fundamental diagnostic features in contrast-enhanced ultrasound are preserved. The aim of this study was therefore to examine the clinical use of the polymer-shelled CA by analyzing the left ventricular endocardial border delineation capability in a porcine model. In addition, physiological effects due to CA injections were studied.MethodsThe endocardial border delineation capability was assessed in a comparative study, which included three doses (1.5 ml, 3 ml and 5 ml, [5x108 MBs/ml]) of the polymer-shelled CA and the commercially available CA SonoVue® (1.5 ml, [2-5x108 MBs/ml]). Ultrasound images of the left ventricle were evaluated manually by blinded observers (n=3) according to a 6-segment model, in which each segment was graded as 0=not visible, 1=barely visible or 2=well visible, as well as semi-automatically by a segmentation software. Furthermore, duration of clinically useful contrast enhancement and changes in physiological parameters were evaluated.ResultsFor the highest dose of the polymer-shelled CA, the obtained segment scores, time for clinically sufficient contrast enhancement and semi-automatic delineation capability were comparable to SonoVue®. Moreover, neither dose of the polymer-shelled CA did affect the physiological parameters.ConclusionThis study demonstrated that the polymer-shelled CA can be used in contrast-enhanced diagnostic imaging without influence on major physiological parameters.
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| 6. |
- Larsson, Malin K., et al.
(författare)
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Endocardial border delineation capability of a novel multimodal polymer-shelled contrast agent
- 2014
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Ingår i: Cardiovascular Ultrasound. - : Springer Science and Business Media LLC. - 1476-7120. ; 12, s. 24-
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Tidskriftsartikel (refereegranskat)abstract
- Background: A novel polymer-shelled contrast agent (CA) with multimodal and target-specific potential was developed recently. To determine its ultrasonic diagnostic features, we evaluated the endocardial border delineation as visualized in a porcine model and the concomitant effect on physiological variables. Methods: Three doses of the novel polymer-shelled CA (1.5 ml, 3 ml, and 5 ml [5 x 10(8) microbubbles (MBs)/ml]) and the commercially available CA SonoVue (1.5 ml [2-5 x 10(8) MBs/ml]) were used. Visual evaluations of ultrasound images of the left ventricle were independently performed by three observers who graded each segment in a 6-segment model as either 0 = not visible, 1 = weakly visible, or 2 = visible. Moreover, the duration of clinically useful contrast enhancement and the left ventricular opacification were determined. During anesthesia, oxygen saturation, heart rate, and arterial pressure were sampled every minute and the effect of injection of CA on these physiological variables was evaluated. Results: The highest dose of the polymer-shelled CA gave results comparable to SonoVue. Thus, no significant difference in the overall segment score distribution (2-47-95 vs. 1-39-104), time for clinically sufficient contrast enhancement (20-40 s for both) and left ventricular overall opacification was found. In contrast, when comparing the endocardial border delineation capacity for different regions SonoVue showed significantly higher segment scores for base and mid, except for the mid region when injecting 1.5 ml of the polymer-shelled CA. Neither high nor low doses of the polymer-shelled CA significantly affected the investigated physiological variables. Conclusions: This study demonstrated that the novel polymer-shelled CA can be used in contrast-enhanced diagnostic imaging without influence on major physiological variables.
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| 7. |
- Larsson, Malin, 1983-
(författare)
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Toward increased applicability of ultrasound contrast agents
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ultrasound is one of the most widely used modalities in medical imaging because of its high cost-effectiveness, wide availability in hospitals, generation of real-time images, and use of nonionizing radiation. However, the image quality can be insufficient in some patients. Introducing a contrast agent (CA), which comprises a suspension of 2–6 mm-sized microbubbles, improves the image quality and thus the image analysis. At present, contrast-enhanced ultrasound is frequently used during standard clinical procedures such as kidney, liver, and cardiac (echocardiography) imaging. Multimodality and targeted imaging are future areas for ultrasound CAs. Multimodality imaging may improve diagnostics by simultaneously providing anatomical and functional information. Targeted imaging may allow for identification of particular diseases.The work within this thesis focused mainly on a novel multimodal polymer-shelled CA with the potential to be target specific. In Study I, the acoustic response was determined in a flow phantom by evaluating the contrast-to-tissue-ratio when using contrast sequences available in clinical ultrasound systems. This study showed that a high acoustic pressure is needed for optimal visualization of the polymer-shelled CA. In Study II, the in vivo performance of this CA was evaluated in a rat model, and the blood elimination time and subcellular distribution were determined. In Study III, the efficiency in endocardial border delineation was assessed in a pig model. The polymer-shelled CA had a significantly longer blood circulation time than the commercially available CA SonoVue, which is favorable for target-specific CA, in which a long circulation time increases the probability of target-specific binding. Transmission electron microscopic analysis of tissue sections from liver, kidney, spleen and lungs, obtained at different time points after CA injection showed that macrophages were responsible for the elimination of the polymer-shelled CA. A higher dose of the polymer-shelled CA was needed to obtain similar endocardial border delineation efficiency as that obtained using SonoVue. The results of Studies I–III demonstrate that the polymer-shelled CA has potential applicability in medical imaging.Current guidelines for contrast-enhanced echocardiography are limited to cases of suboptimal image quality or when there is a suspicion of structural abnormalities within the left ventricle. It may be hypothesized that the wider use of contrast-enhanced echocardiography may help to detect some diseases earlier. Study IV assessed the diagnostic outcomes after contrast administration in patients without indications for CA use. The myocardial wall motion score index and ejection fraction were evaluated by experienced and inexperienced readers, and a screening for left ventricular structural abnormalities was performed. More cases of wall motion and structural abnormalities were detected in the contrast-enhanced analysis. Intra- and interobserver variability was lower with the use of CAs. This study suggests that the more widespread use of CAs instead of the current selective approach may contribute to earlier detection of cardiovascular disease.
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| 8. |
- Larsson, Malin, et al.
(författare)
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Visualization of multimodal polymer-shelled contrast agents using ultrasound contrast sequences : an experimental study in a tissue mimicking flow phantom
- 2013
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Ingår i: Cardiovascular Ultrasound. - : Springer Science and Business Media LLC. - 1476-7120. ; 11, s. 33-
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Tidskriftsartikel (refereegranskat)abstract
- Background: A multimodal polymer-shelled contrast agent (CA) with target specific potential was recently developed and tested for its acoustic properties in a single element transducer setup. Since the developed polymeric CA has different chemical composition than the commercially available CAs, there is an interest to study its acoustic response when using clinical ultrasound systems. The aim of this study was therefore to investigate the acoustic response by studying the visualization capability and shadowing effect of three polymer-shelled CAs when using optimized sequences for contrast imaging. Methods: The acoustic response of three types of the multimodal CA was evaluated in a tissue mimicking flow phantom setup by measuring contrast to tissue ratio (CTR) and acoustic shadowing using five image sequences optimized for contrast imaging. The measurements were performed over a mechanical index (MI) range of 0.2-1.2 at three CA concentrations (10(6), 10(5), 10(4) microbubbles/ml). Results: The CTR-values were found to vary with the applied contrast sequence, MI and CA. The highest CTR-values were obtained when a contrast sequence optimized for higher MI imaging was used. At a CA concentration of 106 microbubbles/ml, acoustic shadowing was observed for all contrast sequences and CAs. Conclusions: The CAs showed the potential to enhance ultrasound images generated by available contrast sequences. A CA concentration of 106 MBs/ml implies a non-linear relation between MB concentration and image intensity.
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| 9. |
- Widman, Erik, et al.
(författare)
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Feasibility of shear wave elastography for plaque characterization
- 2014
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Ingår i: IEEE International Ultrasonics Symposium, IUS. - 9781479970490 ; , s. 1818-1821
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Konferensbidrag (refereegranskat)abstract
- Determining plaque vulnerability is critical when selecting the most suitable treatment for patients with atherosclerotic plaque in the common carotid artery and quantitative characterization methods are needed. In this study, shear wave elastography (SWE) was used to characterize soft plaque mimicking inclusions in three atherosclerotic arterial phantoms by using phase velocity analysis in a static environment. The results were validated with axial tensile mechanical testing (MT). SWE measured a mean shear modulus of 5.8 ± 0.3 kPa and 25.0 ± 1.2 kPa versus 3.0 kPa and 30.0 kPa measured by mechanical testing in the soft plaques and phantom walls respectively. The results show good agreement between MT and SWE for both the plaque and phantom wall.
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| 10. |
- Widman, Erik, 1981-, et al.
(författare)
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SHEAR WAVE ELASTOGRAPHY OF THE ARTERIAL WALL – WHERE WE ARE TODAY
- 2013
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Konferensbidrag (refereegranskat)abstract
- 1. IntroductionShear Wave Elastography (SWE) is a recently developed noninvasive method for elastography assessment using ultrasound. The technique consists of sending an acoustic radiation force (pushing sequence) into the tissue that in turn generates an orthogonal low frequency propagating shear wave. The shear wave propagation is measured real time by high speed B-mode imaging. From the B-mode images, the shear wave is tracked via normalized cross-correlation and the speed is calculated, which is used to generate an elasticity map of the tissue’s shear modulus. To date, the technique has mostly been used in large homogeneous tissues such as breast and liver where it successfully detects lesions and tumors that are easily missed with normal B-mode ultrasound [1]. SWE could potentially be applied in vascular applications to assess elasticity of the arterial wall to characterize the stiffness as an early indicator of cardiac disease. Furthermore, SWE could aid in the characterization of plaques in the carotid artery, which is critical for the prevention of ischemic stroke2. Methods and ResultsAn initial study was performed using an Aixplorer SWE system (Supersonic Imagine, France) to measure the shear modulus in a polyvinyl alcohol phantom (PVA) vessel with a plaque inclusion (Figure 1). It was possible to distinguish the softer inclusion mean shear wave speed (2.1 m/s) from the arterial wall (3.5 m/s) on the SWE colour-map, but the Young’s Modulus calculation of the arterial wall (E=19.8 kPa) did not match the measured Young’s Modulus (E=53.1 kPa) from comparative mechanical testing.We have begun implementing various pushing sequences (single unfocused push, single focused push, line push, comb push) on a programmable ultrasound machine (Verasonics, USA) using a linear transducer (Philips L7-4) in a homogeneous PVA phantom. An algorithm for one dimensional cross-correlation tracking and shear wave speed estimation has been developed and initially tested in an experimental setup3. DiscussionAccording to our initial results, it is possible that SWE could be applied in vascular applications. However, the initial mechanical testing vs. SWE comparison indicated that further development to the post processing is needed before applying it on the carotid artery, which is a heterogeneous tissue with other wave propagation properties than e.g. breast tissue. The carotid artery has a difficult geometry to study for several reasons. The intima-media complex is very thin (< 1mm), and the vessel wall is not stationary. Furthermore, the cylindrical shape of the artery produces complex wave reflections within the arterial wall, which result in a polychromatic propagation of the shear wave. A few studies have applied techniques based on SWE to the arterial wall with promising results and a pilot study demonstrating the feasibility of the technique in-vivo has been published [2]. Still, a considerable effort is needed to validate and optimize the technique for the clinical vascular setting.
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