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  • 1.
    Härmark, Johan
    et al.
    KTH, Strukturell bioteknik.
    Larsson, Malin K.
    KTH, Medicinsk bildteknik.
    Razuvajev, Anton
    Koeck, Philip JB
    KTH, Strukturell bioteknik.
    Paradossi, Gaio
    Brodin, Lars-Åke
    KTH, Medicinsk bildteknik.
    Caidahl, Kenneth
    Hebert, Hans
    KTH, Strukturell bioteknik.
    Bjällmark, Anna
    KTH, Medicinsk bildteknik.
    Investigation of the elimination process of a multimodal polymer-shelled contrast agent in rats using ultrasound and transmission electron microscopy2015Inngår i: Biomedical Spectroscopy and Imaging, ISSN 2212-8794, Vol. 4, nr 1, s. 81-93Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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.

  • 2.
    Josefsson, Leila
    et al.
    KTH, Tillämpad fysikalisk kemi.
    Larsson, Malin K.
    KTH, Medicinsk bildteknik.
    Bjällmark, Anna
    KTH, Medicinsk bildteknik.
    Emmer, Åsa
    KTH, Tillämpad fysikalisk kemi.
    Analysis of polyvinyl alcohol microbubbles in human blood plasma using capillary electrophoresis2016Inngår i: Journal of Separation Science, ISSN 1615-9306, E-ISSN 1615-9314, Vol. 39, nr 8, s. 1551-1558Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Recently, a new type of ultrasound contrast agent that consists of air-filled microbubbles stabilized with a shell of polyvinyl alcohol was developed. When superparamagnetic nanoparticles of iron oxide are incorporated in the polymer shell, a multimodal contrast agent can be obtained. The biodistribution and elimination pathways of the polyvinyl alcohol microbubbles are essential to investigate, which is limited with today's techniques. The aim of the present study was, therefore, to develop a method for qualitative and quantitative analysis of microbubbles in biological samples using capillary electrophoresis with ultraviolet detection. The analysis parameters were optimized to a wavelength at 260 nm and pH of the background electrolyte ranging between 11.9 and 12. Studies with high-intensity ultrasonication degraded microbubbles in water showed that degraded products and intact microbubbles could be distinguished, thus it was possible to quantify the intact microbubbles solely. Analysis of human blood plasma spiked with either plain microbubbles or microbubbles with nanoparticles demonstrated that it is possible to separate them from biological components like proteins in these kinds of samples.

  • 3.
    Larsson, Malin
    et al.
    KTH, Medicinsk teknik.
    Bjällmark, Anna
    KTH, Medicinsk teknik.
    Larsson, Matilda
    KTH, Medicinsk teknik.
    Caidahl, Kenneth
    Karolinska Institutet.
    Winter, Reidar
    KTH, Medicinsk teknik.
    Brodin, Lars-Åke
    KTH, Medicinska sensorer, signaler och system (MSSS) (Stängd 20130701).
    A new ultrasound-based approach to visualize target specific polymeric contrast agent2011Inngår i: 2011 IEEE International Ultrasonics Symposium (IUS), IEEE , 2011, s. 1626-1629Konferansepaper (Fagfellevurdert)
    Abstract [en]

    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.

  • 4.
    Larsson, Malin K.
    et al.
    KTH, Medicinsk teknik.
    Da Silva, Cristina
    Gunyeli, Elif
    Bin Ilami, Ali Akebat
    Szummer, Karolina
    Winter, Reidar
    KTH, Medicinsk teknik.
    Bjällmark, Anna
    KTH, Medicinsk teknik.
    The potential clinical value of contrast-enhanced echocardiography beyond current recommendations2016Inngår i: Cardiovascular Ultrasound, ISSN 1476-7120, E-ISSN 1476-7120, Vol. 14, artikkel-id 2Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Contrast agents are used in resting echocardiography to opacify the left ventricular (LV) cavity and to improve LV endocardial border delineation in patients with suboptimal image quality. If a wider use of contrast-enhanced echocardiography would be adopted instead of the current selective approach, diagnoses such as myocardial ischemia and LV structural abnormalities could potentially be detected earlier. The aim was therefore to retrospectively investigate if contrast- enhanced echocardiography beyond the current recommendations for contrast agent usage affects assessment of wall motion abnormalities, ejection fraction (EF) and detection of LV structural abnormalities. A secondary aim was to evaluate the user dependency during image analysis. Methods: Experienced readers (n = 4) evaluated wall motion score index (WMSI) and measured EF on greyscale and contrast-enhanced images from 192 patients without indications for contrast-enhanced echocardiography. Additionally, screening for LV structural abnormalities was performed. Repeated measurements were performed in 20 patients by the experienced as well as by inexperienced (n = 2) readers. Results: Contrast analysis resulted in significantly higher WMSI compared to greyscale analysis (p < 0.003). Of the 83 patients, classified as healthy by greyscale analysis, 55 % were re-classified with motion abnormalities by contrast analysis. No significant difference in EF classification (>= 55 %, 45-54 %, 30-44 %, < 30 %) was observed. LV structural abnormalities, such as increased trabeculation (n = 21), apical aneurysm (n = 4), hypertrophy (n = 1) and thrombus (n = 1) were detected during contrast analysis. Intra- and interobserver variability for experienced readers as well as the variability between inexperienced and experienced readers decreased for WMSI and EF after contrast analysis. Conclusions: Contrast-enhanced echocardiography beyond current recommendations for contrast agent usage increased the number of detected wall motion and LV structural abnormalities. Moreover, contrast- enhanced echocardiography increased reproducibility for assessment of WMSI and EF.

  • 5.
    Larsson, Malin K.
    et al.
    KTH, Medicinsk bildteknik.
    Larsson, Matilda
    KTH, Medicinsk bildteknik.
    Nowak, Greg
    Paradossi, Gaio
    Brodin, Lars-Åke
    KTH, Medicinsk bildteknik.
    Janerot Sjöberg, Birgitta
    KTH, Medicinsk teknik.
    Caidahl, Kenneth
    Bjällmark, Anna
    KTH, Medicinsk bildteknik.
    Endocardial border delineation capability of a novel multimodal polymer-shelled contrast agent2014Inngår i: Cardiovascular Ultrasound, ISSN 1476-7120, E-ISSN 1476-7120, Vol. 12, s. 24-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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.

  • 6.
    Larsson, Malin
    et al.
    KTH, Medicinsk teknik.
    Larsson, Matilda
    KTH, Medicinsk teknik.
    Oddo, Letizia
    Margheritelli, Silvia
    Paradossi, Gaio
    Nowak, Jacek
    Brodin, Lars-Åke
    KTH, Medicinsk teknik.
    Caidahl, Kenneth
    Bjällmark, Anna
    KTH, Medicinsk teknik.
    Visualization of multimodal polymer-shelled contrast agents using ultrasound contrast sequences: An experimental study in a tissue mimicking flow phantom2013Inngår i: Cardiovascular Ultrasound, ISSN 1476-7120, E-ISSN 1476-7120, Vol. 11, s. 33-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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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