The term Enterprise Architecture (EA) Debts has been coined to grasp the difference between the actual state of the EA and its hypothetical, optimal state. So far, different methods have been proposed to identify such EA Debts in organizations. However, these methods either are based on the transfer of known concepts from other domains to EA or are time and resource intensive. To overcome these shortcomings, we propose an approach that uses an interview format to identify EA Debts in enterprises and a method that allows a qualitative assessment of identified EA Debts. The proposed approach is supported by the designed framework that consists of an interview format and a process for determining thresholds of certain EA Smells.

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.

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.

Air-filled polyvinyl alcohol microbubbles (PVA-MBs) were recently introduced as a contrast agent for ultrasound imaging. In the present study, we explore the possibility of extending their application in multimodal imaging by labeling them with a near infrared (NIR) fluorophore, VivoTag-680. PVA-MBs were injected intravenously into FVB/N female mice and their dynamic biodistribution over 24 h was determined by 3D-fluorescence imaging co-registered with 3D-mu CT imaging, to verify the anatomic location. To further confirm the biodistribution results from in vivo imaging, organs were removed and examined histologically using bright field and fluorescence microscopy. Fluorescence imaging detected PVA-MB accumulation in the lungs within the first 30 min post-injection. Redistribution to a low extent was observed in liver and kidneys at 4 h, and to a high extent mainly in the liver and spleen at 24 h. Histology confirmed PVA-MB localization in lung capillaries and macrophages. In the liver, they were associated with Kupffer cells; in the spleen, they were located mostly within the marginal-zone. Occasional MBs were observed in the kidney glomeruli and interstitium. The potential application of PVA-MBs as a contrast agent was also studied using ultrasound (US) imaging in subcutaneous and orthotopic pancreatic cancer mouse models, to visualize blood flow within the tumor mass. In conclusion, this study showed that PVA-MBs are useful as a contrast agent for multimodal imaging. (C) 2015 Elsevier Inc. All rights reserved.

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.

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.

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.

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.

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.